-% Define some publisher name shortcuts (useful for consistency)
-% Listed in alphebetical order.
-@String{AIP = "AIP"}
-@String{APS = "American Physical Society"}
-@String{SPRINGER = "Springer Science + Business Media, LLC"}
-
-% Define some journal name shortcuts (useful for consistency)
-% Listed in alphebetical order.
-@String{ACIEE = "Angewandte Chemie International Edition in English"}
-@String{ACIEE = "Angew. Chem. Int. Ed. Engl."}
-@String{ARBC = "Annual Review of Biochemistry"}
-@String{BCBPRC = "Biochemical and Biophysical Research Communications"}
-@String{BPJ = "Biophys. J."}
-@String{BIOSENSE = "Biosensors and Bioelectronics"}
-@String{EMBO = "EMBO Rep."}
-@String{IJBMM = "International Journal of Biological Macromolecules"}
-@String{JCS = "Journal of Cell Science"}
-@String{JCP = "The Journal of Chemical Physics"}
-@String{JCPPCB = "Journal de Chimie Physique et de Physico-Chimie Biologique"}
-@String{JMB = "Journal of Molecular Biology"}
-@String{JPCM = "Journal of Physics: Condensed Matter"}
-@String{LANG = "Langmuir"}
-@String{NANOTECH = "Nanotechnology"}
-@String{NAT = "Nature"}
-@String{NSB = "Nature Structural Biology"}
-@String{NSMB = "Nature Structural Molecular Biology"}
-@String{NAR = "Nucleic Acids Research"}
-@String{PRL = "Phys. Rev. Lett."}
-@String(PNAS = "Proceedings of the National Academy of Sciences USA")
-@String{PBPMB = "Progress in Biophysics and Molecular Biology"}
-@String{PS = "Protein Sci."}
-@String{PROT = "Proteins"}
-@String{RMP = "Rev. Mod. Phys."}
-@String{RSI = "Review of Scientific Instruments"}
-@String{SCI = "Science"}
-@String{STR = "Structure"}
-@String{ULTRAMIC = "Ultramicroscopy"}
-
-
-% Define some author name shortcuts (useful for consistency)
-% Format: "von Last, Jr., First", sorted alphabetically by Last.
-@String{DAbramavicius = "Abramavicius, Darius"}
-@String{SArcidiacono = "Arcidiacono, S"}
-@String{CArciola = "Arciola, Carla Renata"}
-@String{SAinavarapu = "Ainavarapu, Sri Rama Koti"}
-@String{MAllen = "Allen, Mark D."}
-@String{WBaase = "Baase, Walter A."}
-@String{CBadilla = "Badilla, Carmen L."}
-@String{MBalamurali = "Balamurali, M. M."}
-@String{GBaneyx = "Baneyx, Gretchen"}
-@String{TBasche = "Basche, Th."}
-@String{LBaugh = "Baugh, Loren"}
-@String{JBechhoefer = "Bechhoefer, John"}
-@String{VBenes = "Benes, Vladimir"}
-@String{FBerkemeier = "Berkemeier, Felix"}
-@String{BBerne = "Berne, Bruce J."}
-@String{MBertz = "Bertz, Morten"}
-@String{RBest = "Best, Robert B."}
-@String{NBhasin = "Bhasin, Nishant"}
-@String{KBillings = "Billings, Kate S."}
-@String{JBirchler = "Birchler, James A."}
-@String{WBreyer = "Breyer, Wendy A."}
-@String{SBroedel = "Broedel, Sheldon E."}
-@String{BDBrowerToland = "Brower-Toland, Brent D."}
-@String{VBrumfeld = "Brumfeld, Vlad"}
-@String{BBullard = "Bullard, Belinda"}
-@String{CBustamante = "Bustamante, Carlos"}
-@String{YBustanji = "Bustanji, Yasser"}
-@String{HJButt = {Butt, Hans-J\"urgen}}
-@String{ICampbell = "Campbell, Iain D."}
-@String{YCao = "Cao, Yi"}
-@String{PCarl = "Carl, Philippe"}
-@String{MCarrionVazquez = "Carrion-Vazquez, Mariano"}
-@String{CCecconi = "Cecconi, Ciro"}
-@String{EChapman = "Chapman, Edwin R."}
-@String{JChoy = "Choy, Jason"}
-@String{JClarke = "Clarke, Jane"}
-@String{EDCola = "{\uppercase{d}}i Cola, Emanuela"}
-@String{MConti = "Conti, Matteo"}
-@String{DCraig = "Craig, David"}
-@String{FDahlquist = "Dahlquist, Frederick W."}
-@String{WDeGrado = "DeGrado, William F."}
-@String{HDietz = "Dietz, Hendrik"}
-@String{RDima = "Dima, Ruxandra I."}
-@String{DDischer = "Discher, Dennis E."}
-@String{CDornmair = "Dornmair, C."}
-@String{LDougan = "Dougan, Lorna"}
-@String{TDrobek = "Drobek, T."}
-@String{MElbaum = "Elbaum, Michael"}
-@String{TEndo = "Endo, Toshiya"}
-@String{HErickson = "Erickson, Harold P."}
-@String{MEsaki = "Esaki, Masatoshi"}
-@String{JFernandez = "Fernandez, Julio M."}
-@String{GFranzen = "Franzen, Gereon"}
-@String{ELFlorin = "Florin, Ernst-Ludwig"}
-@String{SFossey = "Fossey, S. A."}
-@String{SFowler = "Fowler, Susan B."}
-@String{HFujita = "Fujita, Hideaki"}
-@String{TFunck = "Funck, Theodor"}
-@String{MGao = "Gao, Mu"}
-@String{TGarcia = "Garcia, Tzintzuni"}
-@String{HGaub = "Gaub, Hermann E."}
-@String{MGautel = "Gautel, Mathias"}
-@String{CGergely = "Gergely, C."}
-@String{HGranzier = "Granzier, Henk"}
-@String{FGrater = "Grater, Frauke"}
-@String{HJGuntherodt = "Guntherodt, Hans-Joachim"}
-@String{JHaack = "Haack, Julie A."}
-@String{RHajjar = "Hajjar, Roger J."}
-@String{FHan = "Han, Fangpu"}
-@String{HHansma = "Hansma, H. G."}
-@String{PHansma = "Hansma, Paul K."}
-@String{WHeckl = "Heckl, W. M."}
-@String{JHemmerle = "Hemmerle, J."}
-@String{HHinssen = "Hinssen, Horst"}
-@String{PHinterdorfer = "Hinterdorfer, Peter"}
-@String{RHochstrasser = "Hochstrasser, Robin M."}
-@String{WHoff = "Hoff, Wouter D."}
-@String{JHorber = "Horber, J. K. H."}
-@String{CKHu = "Hu, Chin-Kun"}
-@String{HHuang = "Huang, Hector Han-Li"}
-@String{GHummer = "Hummer, Gerhard"}
-@String{JHutter = "Hutter, Jeffrey L."}
-@String{CHyeon = "Hyeon, Changbong"}
-@String{AIrback = "Irback, Anders"}
-@String{MJaschke = "Jaschke, Manfred"}
-@String{YJia = "Jia, Yiwei"}
-@String{CJohnson = "Johnson, Colin P."}
-@String{DKaftan = "Kaftan, David"}
-@String{RKapon = "Kapon, Ruti"}
-@String{MKarplus = "Karplus, Martin"}
-@String{FKienberger = "Kienberger, Ferry"}
-@String{WKing = "King, William Trevor"}
-@String{DKlimov = "Klimov, Dmitri K."}
-@String{AKrammer = "Krammer, Andre"}
-@String{MKulke = "Kulke, Michael"}
-@String{CKwok = "Kwok, Carol H."}
-@String{DLabeit = "Labeit, Dietmar"}
-@String{SLabeit = "Labeit, Siegfried"}
-@String{SLahmers = "Lahmers, Sunshine"}
-@String{CLam = "Lam, Canaan"}
-@String{JLamb = "Lamb, Jonathan C."}
-@String{WLau = "Lau, Wai Leung"}
-@String{MLeake = "Leake, Mark C."}
-@String{HLee = "Lee, Haeshin"}
-@String{HLehmann = "Lehmann, H."}
-@String{OLequin = "Lequin, Olivier"}
-@String{RLevy = "L\'evy, R"}
-@String{HLi = "Li, Hongbin"}
-@String{MSLi = "Li, Mai Suan"}
-@String{FCLin = "Lin, Fan-Chi"}
-@String{WLinke = "Linke, Wolfgang A."}
-@String{JLis = "Lis, John T."}
-@String{WLiu = "Liu, W."}
-@String{HLu = "Lu, Hui"}
-@String{MLudwig = "Ludwig, M."}
-@String{MMaaloum = "Maaloum, Mounir"}
-@String{SMajid = "Majid, Sophia"}
-@String{EMandello = "Mandello, Enrico"}
-@String{GManderson = "Manderson, Gavin"}
-@String{PMarszalek = "Marszalek, Piotr E."}
-@String{BMatthews = "Matthews, Brian W."}
-@String{AMatouschek = "Matouschek, Andreas"}
-@String{MMickler = "Mickler, Moritz"}
-@String{SMitternacht = "Mitternacht, Simon"}
-@String{SMohanty = "Mohanty, Sandipan"}
-@String{UMohideen = "Mohideen, U."}
-@String{VMontana = "Montana, Vedrana"}
-@String{LMontanaro = "Montanaro, Lucio"}
-@String{VMoy = "Moy, Vincent T."}
-@String{SMukamel = "Mukamel, Shaul"}
-@String{CNeagoe = "Neagoe, Ciprian"}
-@String{RNevo = "Nevo, Reinat"}
-@String{SNg = "Ng, Sean P."}
-@String{SNie = "Nie, S."}
-@String{RNome = "Nome, Rene A."}
-@String{ANoy = "Noy, Aleksandr"}
-@String{AOberhauser = "Oberhauser, Andres F."}
-@String{FOesterhelt = "Oesterhelt, Filipp"}
-@String{TOhashi = "Ohashi, Tomoo"}
-@String{BOhler = "Ohler, Benjamin"}
-@String{COpitz = "Optiz, Christiane A."}
-@String{KOroszlan = "Oroszlan, Krisztina"}
-@String{EOroudjev = "Oroudjev, E."}
-@String{EPaci = "Paci, Emanuele"}
-@String{VParpura = "Parpura, Vladimir"}
-@String{QPeng = "Peng, Qing"}
-@String{OPerisic = "Perisic, Ognjen"}
-@String{CPeterson = "Peterson, Craig L."}
-@String{EPuchner = "Puchner, Elias M."}
-@String{LRandles = "Randles, Lucy G."}
-@String{SRedick = "Redick, Sambra D."}
-@String{ZReich = "Reich, Ziv"}
-@String{MRief = "Rief, Matthias"}
-@String{HRoder = "Roder, Heinrich"}
-@String{RRobertson = "Robertson, Ragan B."}
-@String{BSamori = "Samori, Bruno"}
-@String{ASarkar = "Sarkar, Atom"}
-@String{TSato = "Sato, Takehiro"}
-@String{PSchaaf = "Schaaf, P."}
-@String{RSchafer = "Schafer, Rolf"}
-@String{NScherer = "Scherer, Norbert F."}
-@String{MSchlierf = "Schlierf, Michael"}
-@String{KSchulten = "Schulten, Klaus"}
-@String{BSenger = "Senger, B."}
-@String{DSharma = "Sharma, Deepak"}
-@String{CSmith = "Smith, Corey L."}
-@String{JSoares = "Soares, J."}
-@String{DSpeicher = "Speicher, David W."}
-@String{RStark = "Stark, R. W."}
-@String{CStroh = "Stroh, Cordula"}
-@String{TStrunz = "Strunz, Torsten"}
-@String{MSu = "Su, Meihong"}
-@String{ASzabo = "Szabo, Attila"}
-@String{DTalaga = "Talaga, David S."}
-@String{JTang = "Tang, Jianyong"}
-@String{DThirumalai = "Thirumalai, Devarajan"} % http://biotheory.umd.edu
-@String{JThompson = "Thompson, J. B."}
-@String{JTocaHerrera = "Toca-Herrera, Jose L."}
-@String{IVetter = "Vetter, Ingrid R."}
-@String{JCVoegel = "Voegel, J.-C."}
-@String{VVogel = "Vogel, Viola"}
-@String{KWalther = "Walther, Kirstin A."}
-@String{MWang = "Wang, Michelle D."}
-@String{KWatanabe = "Watanabe, Kaori"}
-@String{AWiita = "Wiita, Arun P."}
-@String{AWilcox = "Wilcox, Alexander J."}
-@String{CWitt = "Witt, Christian"}
-@String{YWu = "Wu, Yiming"}
-@String{GYang = "Yang, Guoliang"} % Drexel
-@String{YYang = "Yang, Yao"} % Drexel
-@String{RYeh = "Yeh, Richard C."}
-@String{WYu = "Yu, Weichang"}
-@String{JZhao = "Zhao, Jason Ming"}
-@String{WZhuang = "Zhuang, Wei"}
-
-
-% And now, off to the races with assorted entries, sorted by date
-
-@Article{hyeon03,
- author = CHyeon #" and "# DThirumalai,
- title = "Can energy landscape roughness of proteins and {RNA}
- be measured by using mechanical unfolding
- experiments?",
- journal = PNAS,
- year = 2003,
- month = sep,
- day = "02",
- volume = 100,
- number = 18,
- pages = "10249--10253",
- keywords = "Protein Folding; Proteins; RNA; Temperature; Thermodynamics",
- abstract = "By considering temperature effects on the mechanical
- unfolding rates of proteins and RNA, whose energy
- landscape is rugged, the question posed in the title is
- answered in the affirmative. Adopting a theory by
- Zwanzig [Zwanzig, R. (1988) Proc. Natl. Acad. Sci. USA
- 85, 2029-2030], we show that, because of roughness
- characterized by an energy scale epsilon, the unfolding
- rate at constant force is retarded. Similarly, in
- nonequilibrium experiments done at constant loading
- rates, the most probable unfolding force increases
- because of energy landscape roughness. The effects are
- dramatic at low temperatures. Our analysis suggests
- that, by using temperature as a variable in mechanical
- unfolding experiments of proteins and RNA, the
- ruggedness energy scale epsilon, can be directly
- measured.",
- ISSN = "0027-8424",
- doi = "10.1073/pnas.1833310100",
- URL = "http://www.pnas.org/cgi/content/abstract/100/18/10249",
- eprint = "http://www.pnas.org/cgi/reprint/100/18/10249.pdf",
- note = "Derives the major theory behind my thesis. The Kramers rate equation is \citet{hanggi90} Eq.~4.56c (page 275).",
- project = "Energy Landscape Roughness",
-}
-
-@Article{nevo05,
- author = RNevo #" and "# VBrumfeld #" and "# RKapon #" and "#
- PHinterdorfer #" and "# ZReich,
- title = "Direct measurement of protein energy landscape
- roughness",
- journal = EMBO,
- year = 2005,
- month = may,
- volume = 6,
- number = 5,
- pages = "482--486",
- keywords = "Models, Molecular; Protein Binding; Protein Folding; Spectrum Analysis; Thermodynamics; beta Karyopherins; ran GTP-Binding Protein",
- abstract = "The energy landscape of proteins is thought to have an
- intricate, corrugated structure. Such roughness should
- have important consequences on the folding and binding
- kinetics of proteins, as well as on their equilibrium
- fluctuations. So far, no direct measurement of protein
- energy landscape roughness has been made. Here, we
- combined a recent theory with single-molecule dynamic
- force spectroscopy experiments to extract the overall
- energy scale of roughness epsilon for a complex
- consisting of the small GTPase Ran and the nuclear
- transport receptor importin-beta. The results gave
- epsilon > 5k(B)T, indicating a bumpy energy surface,
- which is consistent with the ability of importin-beta
- to accommodate multiple conformations and to interact
- with different, structurally distinct ligands.",
- ISSN = "1469-221X",
- doi = "10.1038/sj.embor.7400403",
- URL = "http://www.nature.com/embor/journal/v6/n5/abs/7400403.html",
- eprint = "http://www.nature.com/embor/journal/v6/n5/pdf/7400403.pdf",
- note = "Applies \citet{hyeon03} to ligand-receptor
- binding.",
- project = "Energy Landscape Roughness",
-}
-
-@Article{yang06,
- author = YYang #" and "# FCLin #" and "# GYang,
- collaboration = "",
- title = "Temperature control device for single molecule
- measurements using the atomic force microscope",
- publisher = AIP,
- year = 2006,
- journal = RSI,
- volume = 77,
- number = 6,
- numpages = 5,
- pages = "063701",
- keywords = "temperature control; atomic force microscopy;
- thermocouples; heat sinks",
- eid = "063701",
- URL = "http://link.aip.org/link/?RSI/77/063701/1",
- doi = "10.1063/1.2204580",
- note = "Introduces our temperature control system",
- project = "Energy Landscape Roughness",
-}
-
-@Article{rief97b,
- author = MRief #" and "# MGautel #" and "# FOesterhelt
- #" and "# JFernandez #" and "# HGaub,
- title = "Reversible Unfolding of Individual Titin
- Immunoglobulin Domains by {AFM}",
- journal = SCI,
- volume = 276,
- number = 5315,
- pages = "1109--1112",
- year = 1997,
- doi = "10.1126/science.276.5315.1109",
- URL = "http://www.sciencemag.org/cgi/content/abstract/276/5315/1109",
- eprint = "http://www.sciencemag.org/cgi/reprint/276/5315/1109.pdf",
- note = "Seminal paper for force spectroscopy on Titin. Cited
- by \citet{dietz04} (ref 9) as an example of how
- unfolding large proteins is easily interpreted (vs.\
- confusing unfolding in bulk), but Titin is a rather
- simple example of that, because of its globular-chain
- structure.",
- project = "Energy Landscape Roughness",
-}
-
-@Article{hutter93,
- author = JHutter #" and "# JBechhoefer,
- collaboration = "",
- title = "Calibration of atomic-force microscope tips",
- publisher = AIP,
- year = 1993,
- journal = RSI,
- volume = 64,
- number = 7,
- pages = "1868--1873",
- keywords = "ATOMIC FORCE MICROSCOPY; CALIBRATION; QUALITY FACTOR;
- PROBES; RESONANCE; SILICON NITRIDES; MICA; VAN DER
- WAALS FORCES",
- doi = "10.1063/1.1143970",
- URL = "http://link.aip.org/link/?RSI/64/1868/1",
- project = "Cantilever Calibration",
- note = "Original equipartition-based calibration method (thermal
- calibration).",
-}
-
-@Article{dietz04,
- author = HDietz #" and "# MRief,
- title = "Exploring the energy landscape of {GFP} by
- single-molecule mechanical experiments",
- journal = PNAS,
- volume = 101,
- number = 46,
- pages = "16192--16197",
- year = 2004,
- abstract = "We use single-molecule force spectroscopy to drive
- single GFP molecules from the native state through
- their complex energy landscape into the completely
- unfolded state. Unlike many smaller proteins,
- mechanical GFP unfolding proceeds by means of two
- subsequent intermediate states. The transition from the
- native state to the first intermediate state occurs
- near thermal equilibrium at {approx}35 pN and is
- characterized by detachment of a seven-residue
- N-terminal {alpha}-helix from the beta barrel. We
- measure the equilibrium free energy cost associated
- with this transition as 22 kBT. Detachment of this
- small {alpha}-helix completely destabilizes GFP
- thermodynamically even though the {beta}-barrel is
- still intact and can bear load. Mechanical stability of
- the protein on the millisecond timescale, however, is
- determined by the activation barrier of unfolding the
- {beta}-barrel out of this thermodynamically unstable
- intermediate state. High bandwidth, time-resolved
- measurements of the cantilever relaxation phase upon
- unfolding of the {beta}-barrel revealed a second
- metastable mechanical intermediate with one complete
- {beta}-strand detached from the barrel. Quantitative
- analysis of force distributions and lifetimes lead to a
- detailed picture of the complex mechanical unfolding
- pathway through a rough energy landscape.",
- doi = "10.1073/pnas.0404549101",
- URL = "http://www.pnas.org/cgi/content/abstract/101/46/16192",
- eprint = "http://www.pnas.org/cgi/reprint/101/46/16192.pdf",
- note = "Nice energy-landscape-to-one-dimension compression
- graphic. Unfolding Green Flourescent Protein (GFP)
- towards using it as an embedded force probe.",
- project = "Energy landscape roughness",
-}
-
-@Article{sato05,
- author = TSato #" and "# MEsaki #" and "# JFernandez #" and "# TEndo,
- title = "{Comparison of the protein-unfolding pathways between
- mitochondrial protein import and atomic-force
- microscopy measurements}",
- journal = PNAS,
- volume = 102,
- number = 50,
- pages = "17999--18004",
- year = 2005,
- abstract = "Many newly synthesized proteins have to become
- unfolded during translocation across biological
- membranes. We have analyzed the effects of various
- stabilization/destabilization mutations in the Ig-like
- module of the muscle protein titin upon its import from
- the N terminus or C terminus into mitochondria. The
- effects of mutations on the import of the titin module
- from the C terminus correlate well with those on forced
- mechanical unfolding in atomic-force microscopy (AFM)
- measurements. On the other hand, as long as turnover of
- the mitochondrial Hsp70 system is not rate-limiting for
- the import, import of the titin module from the N
- terminus is sensitive to mutations in the N-terminal
- region but not the ones in the C-terminal region that
- affect resistance to global unfolding in AFM
- experiments. We propose that the mitochondrial-import
- system can catalyze precursor-unfolding by reducing the
- stability of unfolding intermediates.",
- doi = "10.1073/pnas.0504495102",
- URL = "http://www.pnas.org/cgi/content/abstract/102/50/17999",
- eprint = "http://www.pnas.org/cgi/reprint/102/50/17999.pdf",
-}
-
-@Article{peng08,
- author = QPeng #" and "# HLi,
- title = "Atomic force microscopy reveals parallel mechanical
- unfolding pathways of T4 lysozyme: Evidence for a
- kinetic partitioning mechanism",
- journal = PNAS,
- volume = 105,
- number = 6,
- pages = "1885--1890",
- year = 2008,
- abstract = "Kinetic partitioning is predicted to be a general
- mechanism for proteins to fold into their well defined
- native three-dimensional structure from unfolded states
- following multiple folding pathways. However,
- experimental evidence supporting this mechanism is
- still limited. By using single-molecule atomic force
- microscopy, here we report experimental evidence
- supporting the kinetic partitioning mechanism for
- mechanical unfolding of T4 lysozyme, a small protein
- composed of two subdomains. We observed that on
- stretching from its N and C termini, T4 lysozyme
- unfolds by multiple distinct unfolding pathways: the
- majority of T4 lysozymes unfold in an all-or-none
- fashion by overcoming a dominant unfolding kinetic
- barrier; and a small fraction of T4 lysozymes unfold in
- three-state fashion involving unfolding intermediate
- states. The three-state unfolding pathways do not
- follow well defined routes, instead they display
- variability and diversity in individual unfolding
- pathways. The unfolding intermediate states are local
- energy minima along the mechanical unfolding pathways
- and are likely to result from the residual structures
- present in the two subdomains after crossing the main
- unfolding barrier. These results provide direct
- evidence for the kinetic partitioning of the mechanical
- unfolding pathways of T4 lysozyme, and the complex
- unfolding behaviors reflect the stochastic nature of
- kinetic barrier rupture in mechanical unfolding
- processes. Our results demonstrate that single-molecule
- atomic force microscopy is an ideal tool to investigate
- the folding/unfolding dynamics of complex multimodule
- proteins that are otherwise difficult to study using
- traditional methods.",
- doi = "10.1073/pnas.0706775105",
- URL = "http://www.pnas.org/cgi/content/abstract/105/6/1885",
- eprint = "http://www.pnas.org/cgi/reprint/105/6/1885.pdf",
-}
-
-@Article{sharma07,
- author = DSharma #" and "# OPerisic #" and "# QPeng #" and "#
- YCao #" and "# CLam #" and "# HLu #" and "# HLi,
- title = "Single-molecule force spectroscopy reveals a
- mechanically stable protein fold and the rational
- tuning of its mechanical stability",
- journal = PNAS,
- volume = 104,
- number = 22,
- pages = "9278--9283",
- year = 2007,
- abstract = "It is recognized that shear topology of two directly
- connected force-bearing terminal [beta]-strands is a
- common feature among the vast majority of mechanically
- stable proteins known so far. However, these proteins
- belong to only two distinct protein folds, Ig-like
- [beta] sandwich fold and [beta]-grasp fold,
- significantly hindering delineating molecular
- determinants of mechanical stability and rational
- tuning of mechanical properties. Here we combine
- single-molecule atomic force microscopy and steered
- molecular dynamics simulation to reveal that the de
- novo designed Top7 fold [Kuhlman B, Dantas G, Ireton
- GC, Varani G, Stoddard BL, Baker D (2003) Science
- 302:13641368] represents a mechanically stable protein
- fold that is distinct from Ig-like [beta] sandwich and
- [beta]-grasp folds. Although the two force-bearing
- [beta] strands of Top7 are not directly connected, Top7
- displays significant mechanical stability,
- demonstrating that the direct connectivity of
- force-bearing [beta] strands in shear topology is not
- mandatory for mechanical stability. This finding
- broadens our understanding of the design of
- mechanically stable proteins and expands the protein
- fold space where mechanically stable proteins can be
- screened. Moreover, our results revealed a
- substructure-sliding mechanism for the mechanical
- unfolding of Top7 and the existence of two possible
- unfolding pathways with different height of energy
- barrier. Such insights enabled us to rationally tune
- the mechanical stability of Top7 by redesigning its
- mechanical unfolding pathway. Our study demonstrates
- that computational biology methods (including de novo
- design) offer great potential for designing proteins of
- defined topology to achieve significant and tunable
- mechanical properties in a rational and systematic
- fashion.",
- doi = "10.1073/pnas.0700351104",
- URL = "http://www.pnas.org/cgi/content/abstract/104/22/9278",
- eprint = "http://www.pnas.org/cgi/reprint/104/22/9278.pdf",
-}
-
-@Article{oberhauser01,
- author = AOberhauser #" and "# PHansma #" and "# MCarrionVazquez
- #" and "# JFernandez,
- title = "Stepwise unfolding of titin under force-clamp atomic
- force microscopy",
- journal = PNAS,
- volume = 98,
- number = 2,
- pages = "468--472",
- year = 2001,
- abstract = "",
- doi = "10.1073/pnas.021321798",
- URL = "http://www.pnas.org/cgi/content/abstract/98/2/468",
- eprint = "http://www.pnas.org/cgi/reprint/98/2/468.pdf",
-}
-
-@Article{walther07,
- author = KWalther #" and "# FGrater #" and "# LDougan #" and "#
- CBadilla #" and "# BBerne #" and "# JFernandez,
- title = "Signatures of hydrophobic collapse in extended
- proteins captured with force spectroscopy",
- journal = PNAS,
- volume = 104,
- number = 19,
- pages = "7916--7921",
- year = 2007,
- abstract = "We unfold and extend single proteins at a high force
- and then linearly relax the force to probe their
- collapse mechanisms. We observe a large variability in
- the extent of their recoil. Although chain entropy
- makes a small contribution, we show that the observed
- variability results from hydrophobic interactions with
- randomly varying magnitude from protein to protein.
- This collapse mechanism is common to highly extended
- proteins, including nonfolding elastomeric proteins
- like PEVK from titin. Our observations explain the
- puzzling differences between the folding behavior of
- highly extended proteins, from those folding after
- chemical or thermal denaturation. Probing the collapse
- of highly extended proteins with force spectroscopy
- allows separation of the different driving forces in
- protein folding.",
- doi = "10.1073/pnas.0702179104",
- URL = "http://www.pnas.org/cgi/content/abstract/104/19/7916",
- eprint = "http://www.pnas.org/cgi/reprint/104/19/7916.pdf",
-}
-
-@Article{dietz06a,
- author = HDietz #" and "# FBerkemeier #" and "# MBertz #" and "# MRief,
- title = "Anisotropic deformation response of single protein
- molecules",
- journal = PNAS,
- volume = 103,
- number = 34,
- pages = "12724--12728",
- year = 2006,
- abstract = "Single-molecule methods have given experimental access
- to the mechanical properties of single protein
- molecules. So far, access has been limited to mostly
- one spatial direction of force application. Here, we
- report single-molecule experiments that explore the
- mechanical properties of a folded protein structure in
- precisely controlled directions by applying force to
- selected amino acid pairs. We investigated the
- deformation response of GFP in five selected
- directions. We found fracture forces widely varying
- from 100 pN up to 600 pN. We show that straining the
- GFP structure in one of the five directions induces
- partial fracture of the protein into a half-folded
- intermediate structure. From potential widths we
- estimated directional spring constants of the GFP
- structure and found values ranging from 1 N/m up to 17
- N/m. Our results show that classical continuum
- mechanics and simple mechanistic models fail to
- describe the complex mechanics of the GFP protein
- structure and offer insights into the mechanical design
- of protein materials.",
- doi = "10.1073/pnas.0602995103",
- URL = "http://www.pnas.org/cgi/content/abstract/103/34/12724",
- eprint = "http://www.pnas.org/cgi/reprint/103/34/12724.pdf",
-}
-
-
-@Article{labeit03,
- author = DLabeit #" and "# KWatanabe #" and "# CWitt #" and "#
- HFujita #" and "# YWu #" and "# SLahmers #" and "#
- TFunck #" and "# SLabeit #" and "# HGranzier,
- title = "Calcium-dependent molecular spring elements in the
- giant protein titin",
- journal = PNAS,
- volume = 100,
- number = 23,
- pages = "13716--13721",
- year = 2003,
- abstract = "Titin (also known as connectin) is a giant protein
- with a wide range of cellular functions, including
- providing muscle cells with elasticity. Its
- physiological extension is largely derived from the
- PEVK segment, rich in proline (P), glutamate (E),
- valine (V), and lysine (K) residues. We studied
- recombinant PEVK molecules containing the two conserved
- elements: {approx}28-residue PEVK repeats and E-rich
- motifs. Single molecule experiments revealed that
- calcium-induced conformational changes reduce the
- bending rigidity of the PEVK fragments, and
- site-directed mutagenesis identified four glutamate
- residues in the E-rich motif that was studied (exon
- 129), as critical for this process. Experiments with
- muscle fibers showed that titin-based tension is
- calcium responsive. We propose that the PEVK segment
- contains E-rich motifs that render titin a
- calcium-dependent molecular spring that adapts to the
- physiological state of the cell.",
- doi = "10.1073/pnas.2235652100",
- URL = "http://www.pnas.org/cgi/content/abstract/100/23/13716",
- eprint = "http://www.pnas.org/cgi/reprint/100/23/13716.pdf",
-}
-
-@Article{mickler07,
- author = MMickler #" and "# RDima #" and "# HDietz #"
- and "# CHyeon #" and "# DThirumalai #" and "# MRief,
- title = "Revealing the bifurcation in the unfolding pathways
- of {GFP} by using single-molecule experiments and
- simulations",
- journal = PNAS,
- volume = 104,
- number = 51,
- pages = "20268--20273",
- year = 2007,
- keywords = "AFM experiments, coarse-grained simulations, cross-link mutants,
- pathway bifurcation, plasticity of energy landscape",
- abstract = "Nanomanipulation of biomolecules by using
- single-molecule methods and computer simulations has
- made it possible to visualize the energy landscape of
- biomolecules and the structures that are sampled during
- the folding process. We use simulations and
- single-molecule force spectroscopy to map the complex
- energy landscape of GFP that is used as a marker in
- cell biology and biotechnology. By engineering internal
- disulfide bonds at selected positions in the GFP
- structure, mechanical unfolding routes are precisely
- controlled, thus allowing us to infer features of the
- energy landscape of the wild-type GFP. To elucidate the
- structures of the unfolding pathways and reveal the
- multiple unfolding routes, the experimental results are
- complemented with simulations of a self-organized
- polymer (SOP) model of GFP. The SOP representation of
- proteins, which is a coarse-grained description of
- biomolecules, allows us to perform forced-induced
- simulations at loading rates and time scales that
- closely match those used in atomic force microscopy
- experiments. By using the combined approach, we show
- that forced unfolding of GFP involves a bifurcation in
- the pathways to the stretched state. After detachment
- of an N-terminal {alpha}-helix, unfolding proceeds
- along two distinct pathways. In the dominant pathway,
- unfolding starts from the detachment of the primary
- N-terminal -strand, while in the minor pathway rupture
- of the last, C-terminal -strand initiates the unfolding
- process. The combined approach has allowed us to map
- the features of the complex energy landscape of GFP
- including a characterization of the structures, albeit
- at a coarse-grained level, of the three metastable
- intermediates.",
- doi = "10.1073/pnas.0705458104",
- URL = "http://www.pnas.org/cgi/content/abstract/104/51/20268",
- eprint = "http://www.pnas.org/cgi/reprint/104/51/20268.pdf",
- note = "Hiccup in unfolding leg corresponds to unfolding intermediate
- (See Figure 2). The unfolding timescale in GFP is about 6 ms.",
-}
-
-@Article{wiita06,
- author = AWiita #" and "# SAinavarapu #" and "# HHuang #" and "# JFernandez,
- title = "From the Cover: Force-dependent chemical kinetics of
- disulfide bond reduction observed with single-molecule
- techniques",
- journal = PNAS,
- volume = 103,
- number = 19,
- pages = "7222--7227",
- year = 2006,
- abstract = "The mechanism by which mechanical force regulates the
- kinetics of a chemical reaction is unknown. Here, we
- use single-molecule force-clamp spectroscopy and
- protein engineering to study the effect of force on the
- kinetics of thiol/disulfide exchange. Reduction of
- disulfide bonds through the thiol/disulfide exchange
- chemical reaction is crucial in regulating protein
- function and is known to occur in mechanically stressed
- proteins. We apply a constant stretching force to
- single engineered disulfide bonds and measure their
- rate of reduction by DTT. Although the reduction rate
- is linearly dependent on the concentration of DTT, it
- is exponentially dependent on the applied force,
- increasing 10-fold over a 300-pN range. This result
- predicts that the disulfide bond lengthens by 0.34 A at
- the transition state of the thiol/disulfide exchange
- reaction. Our work at the single bond level directly
- demonstrates that thiol/disulfide exchange in proteins
- is a force-dependent chemical reaction. Our findings
- suggest that mechanical force plays a role in disulfide
- reduction in vivo, a property that has never been
- explored by traditional biochemistry. Furthermore, our
- work also indicates that the kinetics of any chemical
- reaction that results in bond lengthening will be
- force-dependent.",
- doi = "10.1073/pnas.0511035103",
- URL = "http://www.pnas.org/cgi/content/abstract/103/19/7222",
- eprint = "http://www.pnas.org/cgi/reprint/103/19/7222.pdf",
-}
-
-@Article{bullard06,
- author = BBullard #" and "# TGarcia #" and "# VBenes #" and "#
- MLeake #" and "# WLinke #" and "# AOberhauser,
- title = "The molecular elasticity of the insect flight muscle
- proteins projectin and kettin",
- journal = PNAS,
- volume = 103,
- number = 12,
- pages = "4451--4456",
- year = 2006,
- abstract = "Projectin and kettin are titin-like proteins mainly
- responsible for the high passive stiffness of insect
- indirect flight muscles, which is needed to generate
- oscillatory work during flight. Here we report the
- mechanical properties of kettin and projectin by
- single-molecule force spectroscopy. Force-extension and
- force-clamp curves obtained from Lethocerus projectin
- and Drosophila recombinant projectin or kettin
- fragments revealed that fibronectin type III domains in
- projectin are mechanically weaker (unfolding force, Fu
- {approx} 50-150 pN) than Ig-domains (Fu {approx}
- 150-250 pN). Among Ig domains in Sls/kettin, the
- domains near the N terminus are less stable than those
- near the C terminus. Projectin domains refolded very
- fast [85% at 15 s-1 (25{degrees}C)] and even under high
- forces (15-30 pN). Temperature affected the unfolding
- forces with a Q10 of 1.3, whereas the refolding speed
- had a Q10 of 2-3, probably reflecting the cooperative
- nature of the folding mechanism. High bending
- rigidities of projectin and kettin indicated that
- straightening the proteins requires low forces. Our
- results suggest that titin-like proteins in indirect
- flight muscles could function according to a
- folding-based-spring mechanism.",
- doi = "10.1073/pnas.0509016103",
- URL = "http://www.pnas.org/cgi/content/abstract/103/12/4451",
- eprint = "http://www.pnas.org/cgi/reprint/103/12/4451.pdf",
-}
-
-@Article{dietz06b,
- author = HDietz #" and "# MRief,
- title = "Protein structure by mechanical triangulation",
- journal = PNAS,
- volume = 103,
- number = 5,
- pages = "1244--1247",
- year = 2006,
- abstract = "Knowledge of protein structure is essential to
- understand protein function. High-resolution protein
- structure has so far been the domain of ensemble
- methods. Here, we develop a simple single-molecule
- technique to measure spatial position of selected
- residues within a folded and functional protein
- structure in solution. Construction and mechanical
- unfolding of cysteine-engineered polyproteins with
- controlled linkage topology allows measuring
- intramolecular distance with angstrom precision. We
- demonstrate the potential of this technique by
- determining the position of three residues in the
- structure of green fluorescent protein (GFP). Our
- results perfectly agree with the GFP crystal structure.
- Mechanical triangulation can find many applications
- where current bulk structural methods fail.",
- doi = "10.1073/pnas.0509217103",
- URL = "http://www.pnas.org/cgi/content/abstract/103/5/1244",
- eprint = "http://www.pnas.org/cgi/reprint/103/5/1244.pdf",
-}
-
-@Article{wilcox05,
- author = AWilcox #" and "# JChoy #" and "# CBustamante #" and "# AMatouschek,
- title = "Effect of protein structure on mitochondrial
- import",
- journal = PNAS,
- volume = 102,
- number = 43,
- pages = "15435--15440",
- year = 2005,
- abstract = "Most proteins that are to be imported into the
- mitochondrial matrix are synthesized as precursors,
- each composed of an N-terminal targeting sequence
- followed by a mature domain. Precursors are recognized
- through their targeting sequences by receptors at the
- mitochondrial surface and are then threaded through
- import channels into the matrix. Both the targeting
- sequence and the mature domain contribute to the
- efficiency with which proteins are imported into
- mitochondria. Precursors must be in an unfolded
- conformation during translocation. Mitochondria can
- unfold some proteins by changing their unfolding
- pathways. The effectiveness of this unfolding mechanism
- depends on the local structure of the mature domain
- adjacent to the targeting sequence. This local
- structure determines the extent to which the unfolding
- pathway can be changed and, therefore, the unfolding
- rate increased. Atomic force microscopy studies find
- that the local structures of proteins near their N and
- C termini also influence their resistance to mechanical
- unfolding. Thus, protein unfolding during import
- resembles mechanical unfolding, and the specificity of
- import is determined by the resistance of the mature
- domain to unfolding as well as by the properties of the
- targeting sequence.",
- doi = "10.1073/pnas.0507324102",
- URL = "http://www.pnas.org/cgi/content/abstract/102/43/15435",
- eprint = "http://www.pnas.org/cgi/reprint/102/43/15435.pdf",
-}
-
-@Article{marszalek02,
- author = PMarszalek #" and "# HLi #" and "# AOberhauser #" and "#
- JFernandez,
- title = "Chair-boat transitions in single polysaccharide
- molecules observed with force-ramp {AFM}",
- journal = PNAS,
- volume = 99,
- number = 7,
- pages = "4278--4283",
- year = 2002,
- abstract = "Under a stretching force, the sugar ring of
- polysaccharide molecules switches from the chair to the
- boat-like or inverted chair conformation. This
- conformational change can be observed by stretching
- single polysaccharide molecules with an atomic force
- microscope. In those early experiments, the molecules
- were stretched at a constant rate while the resulting
- force changed over wide ranges. However, because the
- rings undergo force-dependent transitions, an
- experimental arrangement where the force is the free
- variable introduces an undesirable level of complexity
- in the results. Here we demonstrate the use of
- force-ramp atomic force microscopy to capture the
- conformational changes in single polysaccharide
- molecules. Force-ramp atomic force microscopy readily
- captures the ring transitions under conditions where
- the entropic elasticity of the molecule is separated
- from its conformational transitions, enabling a
- quantitative analysis of the data with a simple
- two-state model. This analysis directly provides the
- physico-chemical characteristics of the ring
- transitions such as the width of the energy barrier,
- the relative energy of the conformers, and their
- enthalpic elasticity. Our experiments enhance the
- ability of single-molecule force spectroscopy to make
- high-resolution measurements of the conformations of
- single polysaccharide molecules under a stretching
- force, making an important addition to polysaccharide
- spectroscopy.",
- doi = "10.1073/pnas.072435699",
- URL = "http://www.pnas.org/cgi/content/abstract/99/7/4278",
- eprint = "http://www.pnas.org/cgi/reprint/99/7/4278.pdf",
-}
-
-@Article{craig01,
- author = DCraig #" and "# AKrammer #" and "# KSchulten #" and "#
- VVogel,
- title = "Comparison of the early stages of forced unfolding
- for fibronectin type {III} modules",
- journal = PNAS,
- volume = 98,
- number = 10,
- pages = "5590--5595",
- year = 2001,
- abstract = "",
- doi = "10.1073/pnas.101582198",
- URL = "http://www.pnas.org/cgi/content/abstract/98/10/5590",
- eprint = "http://www.pnas.org/cgi/reprint/98/10/5590.pdf",
-}
-
-@Article{carrion-vazquez99a,
- author = MCarrionVazquez #" and "# PMarszalek #" and
- "# AOberhauser #" and "# JFernandez,
- title = "Atomic force microscopy captures length phenotypes in
- single proteins",
- journal = PNAS,
- volume = 96,
- number = 20,
- pages = "11288--11292",
- year = 1999,
- abstract = "",
- doi = "10.1073/pnas.96.20.11288",
- URL = "http://www.pnas.org/cgi/content/abstract/96/20/11288",
- eprint = "http://www.pnas.org/cgi/reprint/96/20/11288.pdf",
-}
-
-@Article{cao07,
- author = YCao #" and "# MBalamurali #" and "# DSharma #" and "# HLi,
- title = "A functional single-molecule binding assay via force
- spectroscopy",
- journal = PNAS,
- volume = 104,
- number = 40,
- pages = "15677--15681",
- year = 2007,
- abstract = "Protein-ligand interactions, including protein-protein
- interactions, are ubiquitously essential in biological
- processes and also have important applications in
- biotechnology. A wide range of methodologies have been
- developed for quantitative analysis of protein-ligand
- interactions. However, most of them do not report
- direct functional/structural consequence of ligand
- binding. Instead they only detect the change of
- physical properties, such as fluorescence and
- refractive index, because of the colocalization of
- protein and ligand, and are susceptible to false
- positives. Thus, important information about the
- functional state of proteinligand complexes cannot be
- obtained directly. Here we report a functional
- single-molecule binding assay that uses force
- spectroscopy to directly probe the functional
- consequence of ligand binding and report the functional
- state of protein-ligand complexes. As a proof of
- principle, we used protein G and the Fc fragment of IgG
- as a model system in this study. Binding of Fc to
- protein G does not induce major structural changes in
- protein G but results in significant enhancement of its
- mechanical stability. Using mechanical stability of
- protein G as an intrinsic functional reporter, we
- directly distinguished and quantified Fc-bound and
- Fc-free forms of protein G on a single-molecule basis
- and accurately determined their dissociation constant.
- This single-molecule functional binding assay is
- label-free, nearly background-free, and can detect
- functional heterogeneity, if any, among proteinligand
- interactions. This methodology opens up avenues for
- studying protein-ligand interactions in a functional
- context, and we anticipate that it will find broad
- application in diverse protein-ligand systems.",
- doi = "10.1073/pnas.0705367104",
- URL = "http://www.pnas.org/cgi/content/abstract/104/40/15677",
- eprint = "http://www.pnas.org/cgi/reprint/104/40/15677.pdf",
-}
-
-@Article{yu06,
- author = WYu #" and "# JLamb #" and "# FHan #" and "# JBirchler,
- title = "Telomere-mediated chromosomal truncation in maize",
- journal = PNAS,
- volume = 103,
- number = 46,
- pages = "17331--17336",
- year = 2006,
- abstract = "Direct repeats of Arabidopsis telomeric sequence were
- constructed to test telomere-mediated chromosomal
- truncation in maize. Two constructs with 2.6 kb of
- telomeric sequence were used to transform maize
- immature embryos by Agrobacterium-mediated
- transformation. One hundred seventy-six transgenic
- lines were recovered in which 231 transgene loci were
- revealed by a FISH analysis. To analyze chromosomal
- truncations that result in transgenes located near
- chromosomal termini, Southern hybridization analyses
- were performed. A pattern of smear in truncated lines
- was seen as compared with discrete bands for internal
- integrations, because telomeres in different cells are
- elongated differently by telomerase. When multiple
- restriction enzymes were used to map the transgene
- positions, the size of the smears shifted in accordance
- with the locations of restriction sites on the
- construct. This result demonstrated that the transgene
- was present at the end of the chromosome immediately
- before the integrated telomere sequence. Direct
- evidence for chromosomal truncation came from the
- results of FISH karyotyping, which revealed broken
- chromosomes with transgene signals at the ends. These
- results demonstrate that telomere-mediated chromosomal
- truncation operates in plant species. This technology
- will be useful for chromosomal engineering in maize as
- well as other plant species.",
- doi = "10.1073/pnas.0605750103",
- URL = "http://www.pnas.org/cgi/content/abstract/103/46/17331",
- eprint = "http://www.pnas.org/cgi/reprint/103/46/17331.pdf",
-}
-
-@Article{zhao06,
- author = JZhao #" and "# HLee #" and "# RNome #" and "#
- SMajid #" and "# NScherer #" and "# WHoff,
- title = "Single-molecule detection of structural changes
- during {P}er-{A}rnt-{S}im ({PAS}) domain activation",
- journal = PNAS,
- volume = 103,
- number = 31,
- pages = "11561--11566",
- year = 2006,
- abstract = "The Per-Arnt-Sim (PAS) domain is a ubiquitous protein
- module with a common three-dimensional fold involved in
- a wide range of regulatory and sensory functions in all
- domains of life. The activation of these functions is
- thought to involve partial unfolding of N- or
- C-terminal helices attached to the PAS domain. Here we
- use atomic force microscopy to probe receptor
- activation in single molecules of photoactive yellow
- protein (PYP), a prototype of the PAS domain family.
- Mechanical unfolding of Cys-linked PYP multimers in the
- presence and absence of illumination reveals that, in
- contrast to previous studies, the PAS domain itself is
- extended by {approx}3 nm (at the 10-pN detection limit
- of the measurement) and destabilized by {approx}30% in
- the light-activated state of PYP. Comparative
- measurements and steered molecular dynamics simulations
- of two double-Cys PYP mutants that probe different
- regions of the PAS domain quantify the anisotropy in
- stability and changes in local structure, thereby
- demonstrating the partial unfolding of their PAS domain
- upon activation. These results establish a generally
- applicable single-molecule approach for mapping
- functional conformational changes to selected regions
- of a protein. In addition, the results have profound
- implications for the molecular mechanism of PAS domain
- activation and indicate that stimulus-induced partial
- protein unfolding can be used as a signaling
- mechanism.",
- doi = "10.1073/pnas.0601567103",
- URL = "http://www.pnas.org/cgi/content/abstract/103/31/11561",
- eprint = "http://www.pnas.org/cgi/reprint/103/31/11561.pdf",
-}
-
-@Article{gao03,
- author = MGao #" and "# DCraig #" and "# OLequin #" and "#
- ICampbell #" and "# VVogel #" and "# KSchulten,
- title = "Structure and functional significance of mechanically
- unfolded fibronectin type {III1} intermediates",
- journal = PNAS,
- volume = 100,
- number = 25,
- pages = "14784--14789",
- year = 2003,
- abstract = "Fibronectin (FN) forms fibrillar networks coupling
- cells to the extracellular matrix. The formation of FN
- fibrils, fibrillogenesis, is a tightly regulated
- process involving the exposure of cryptic binding sites
- in individual FN type III (FN-III) repeats presumably
- exposed by mechanical tension. The FN-III1 module has
- been previously proposed to contain such cryptic sites
- that promote the assembly of extracellular matrix FN
- fibrils. We have combined NMR and steered molecular
- dynamics simulations to study the structure and
- mechanical unfolding pathway of FN-III1. This study
- finds that FN-III1 consists of a {beta}-sandwich
- structure that unfolds to a mechanically stable
- intermediate about four times the length of the native
- folded state. Considering previous experimental
- findings, our studies provide a structural model by
- which mechanical stretching of FN-III1 may induce
- fibrillogenesis through this partially unfolded
- intermediate.",
- doi = "10.1073/pnas.2334390100",
- URL = "http://www.pnas.org/cgi/content/abstract/100/25/14784",
- eprint = "http://www.pnas.org/cgi/reprint/100/25/14784.pdf",
-}
-
-@Article{opitz03,
- author = COpitz #" and "# MKulke #" and "# MLeake #" and "#
- CNeagoe #" and "# HHinssen #" and "# RHajjar #" and "# WLinke,
- title = "Damped elastic recoil of the titin spring in
- myofibrils of human myocardium",
- journal = PNAS,
- volume = 100,
- number = 22,
- pages = "12688--12693",
- year = 2003,
- abstract = "The giant protein titin functions as a molecular
- spring in muscle and is responsible for most of the
- passive tension of myocardium. Because the titin spring
- is extended during diastolic stretch, it will recoil
- elastically during systole and potentially may
- influence the overall shortening behavior of cardiac
- muscle. Here, titin elastic recoil was quantified in
- single human heart myofibrils by using a high-speed
- charge-coupled device-line camera and a nanonewtonrange
- force sensor. Application of a slack-test protocol
- revealed that the passive shortening velocity (Vp) of
- nonactivated cardiomyofibrils depends on: (i) initial
- sarcomere length, (ii) release-step amplitude, and
- (iii) temperature. Selective digestion of titin, with
- low doses of trypsin, decelerated myofibrillar passive
- recoil and eventually stopped it. Selective extraction
- of actin filaments with a Ca2+-independent gelsolin
- fragment greatly reduced the dependency of Vp on
- release-step size and temperature. These results are
- explained by the presence of viscous forces opposing
- myofibrillar passive recoil that are caused mainly by
- weak actin-titin interactions. Thus, Vp is determined
- by two distinct factors: titin elastic recoil and
- internal viscous drag forces. The recoil could be
- modeled as that of a damped entropic spring consisting
- of independent worm-like chains. The functional
- importance of myofibrillar elastic recoil was addressed
- by comparing instantaneous Vp to unloaded shortening
- velocity, which was measured in demembranated, fully
- Ca2+-activated, human cardiac fibers. Titin-driven
- passive recoil was much faster than active unloaded
- shortening velocity in early phases of isotonic
- contraction. Damped myofibrillar elastic recoil could
- help accelerate active contraction speed of human
- myocardium during early systolic shortening.",
- doi = "10.1073/pnas.2133733100",
- URL = "http://www.pnas.org/cgi/content/abstract/100/22/12688",
- eprint = "http://www.pnas.org/cgi/reprint/100/22/12688.pdf",
-}
-
-@Article{best02,
- author = RBest #" and "# SFowler #" and "# JTocaHerrera #" and "#
- JClarke,
- title = "A simple method for probing the mechanical unfolding
- pathway of proteins in detail",
- journal = PNAS,
- volume = 99,
- number = 19,
- pages = "12143--12148",
- year = 2002,
- abstract = "Atomic force microscopy is an exciting new
- single-molecule technique to add to the toolbox of
- protein (un)folding methods. However, detailed analysis
- of the unfolding of proteins on application of force
- has, to date, relied on protein molecular dynamics
- simulations or a qualitative interpretation of mutant
- data. Here we describe how protein engineering {Phi}
- value analysis can be adapted to characterize the
- transition states for mechanical unfolding of proteins.
- Single-molecule studies also have an advantage over
- bulk experiments, in that partial {Phi} values arising
- from partial structure in the transition state can be
- clearly distinguished from those averaged over
- alternate pathways. We show that unfolding rate
- constants derived in the standard way by using Monte
- Carlo simulations are not reliable because of the
- errors involved. However, it is possible to circumvent
- these problems, providing the unfolding mechanism is
- not changed by mutation, either by a modification of
- the Monte Carlo procedure or by comparing mutant and
- wild-type data directly. The applicability of the
- method is tested on simulated data sets and
- experimental data for mutants of titin I27.",
- doi = "10.1073/pnas.192351899",
- URL = "http://www.pnas.org/cgi/content/abstract/99/19/12143",
- eprint = "http://www.pnas.org/cgi/reprint/99/19/12143.pdf",
- note = "Points out order-of-magnitude errors in $k_{u0}$ estimation
- from fitting Monte Carlo simulations.",
-}
-
-@Article{basche01,
- author = TBasche #" and "# SNie #" and "# JFernandez,
- title = "Single molecules",
- journal = PNAS,
- volume = 98,
- number = 19,
- pages = "10527--10528",
- year = 2001,
- doi = "10.1073/pnas.191365898",
- URL = "http://www.pnas.org/cgi/content/abstract/98/19/10527",
- eprint = "http://www.pnas.org/cgi/reprint/98/19/10527.pdf",
- note = "Mini summary of single-molecule techniques and look to future.
- Focuses on AFM, but mentions others.",
-}
-
-@Article{li01,
- author = HLi #" and "# AOberhauser #" and "# SRedick #" and "#
- MCarrionVazquez #" and "# HErickson #" and "# JFernandez,
- title = "Multiple conformations of {PEVK} proteins detected by
- single-molecule techniques",
- journal = PNAS,
- volume = 98,
- number = 19,
- pages = "10682--10686",
- year = 2001,
- abstract = "An important component of muscle elasticity is the
- PEVK region of titin, so named because of the
- preponderance of these amino acids. However, the PEVK
- region, similar to other elastomeric proteins, is
- thought to form a random coil and therefore its
- structure cannot be determined by standard techniques.
- Here we combine single-molecule electron microscopy and
- atomic force microscopy to examine the conformations of
- the human cardiac titin PEVK region. In contrast to a
- simple random coil, we have found that cardiac PEVK
- shows a wide range of elastic conformations with
- end-to-end distances ranging from 9 to 24 nm and
- persistence lengths from 0.4 to 2.5 nm. Individual PEVK
- molecules retained their distinctive elastic
- conformations through many stretch-relaxation cycles,
- consistent with the view that these PEVK conformers
- cannot be interconverted by force. The multiple elastic
- conformations of cardiac PEVK may result from varying
- degrees of proline isomerization. The single-molecule
- techniques demonstrated here may help elucidate the
- conformation of other proteins that lack a well-defined
- structure.",
- doi = "10.1073/pnas.191189098",
- URL = "http://www.pnas.org/cgi/content/abstract/98/19/10682",
- eprint = "http://www.pnas.org/cgi/reprint/98/19/10682.pdf",
-}
-
-@Article{carl01,
- author = PCarl #" and "# CKwok #" and "# GManderson #" and "#
- DSpeicher #" and "# DDischer,
- title = "Forced unfolding modulated by disulfide bonds in the
- Ig domains of a cell adhesion molecule",
- journal = PNAS,
- volume = 98,
- number = 4,
- pages = "1565--1570",
- year = 2001,
- abstract = "",
- doi = "10.1073/pnas.031409698",
- URL = "http://www.pnas.org/cgi/content/abstract/98/4/1565",
- eprint = "http://www.pnas.org/cgi/reprint/98/4/1565.pdf",
-}
-
-@Article{klimov00,
- author = DKlimov #" and "# DThirumalai,
- title = "Native topology determines force-induced unfolding
- pathways in globular proteins",
- journal = PNAS,
- volume = 97,
- number = 13,
- pages = "7254--7259",
- year = 2000,
- month = jun,
- day = 20,
- keywords = "Animals; Humans; Protein Folding; Proteins; Spectrin",
- abstract = "Single-molecule manipulation techniques reveal that
- stretching unravels individually folded domains in the
- muscle protein titin and the extracellular matrix
- protein tenascin. These elastic proteins contain tandem
- repeats of folded domains with beta-sandwich
- architecture. Herein, we propose by stretching two
- model sequences (S1 and S2) with four-stranded
- beta-barrel topology that unfolding forces and pathways
- in folded domains can be predicted by using only the
- structure of the native state. Thermal refolding of S1
- and S2 in the absence of force proceeds in an
- all-or-none fashion. In contrast, phase diagrams in the
- force-temperature (f,T) plane and steered Langevin
- dynamics studies of these sequences, which differ in
- the native registry of the strands, show that S1
- unfolds in an allor-none fashion, whereas unfolding of
- S2 occurs via an obligatory intermediate. Force-induced
- unfolding is determined by the native topology. After
- proving that the simulation results for S1 and S2 can
- be calculated by using native topology alone, we
- predict the order of unfolding events in Ig domain
- (Ig27) and two fibronectin III type domains ((9)FnIII
- and (10)FnIII). The calculated unfolding pathways for
- these proteins, the location of the transition states,
- and the pulling speed dependence of the unfolding
- forces reflect the differences in the way the strands
- are arranged in the native states. We also predict the
- mechanisms of force-induced unfolding of the
- coiled-coil spectrin (a three-helix bundle protein) for
- all 20 structures deposited in the Protein Data Bank.
- Our approach suggests a natural way to measure the
- phase diagram in the (f,C) plane, where C is the
- concentration of denaturants.",
- ISSN = "0027-8424",
- doi = "10.1073/pnas.97.13.7254",
- URL = "http://www.pnas.org/cgi/content/abstract/97/13/7254",
- eprint = "http://www.pnas.org/cgi/reprint/97/13/7254.pdf",
- note = "Simulated unfolding timescales for Ig27-like S1 and S2 domains",
-}
-
-@Article{li00,
- author = HLi #" and "# AOberhauser #" and "# SFowler #" and "#
- JClarke #" and "# JFernandez,
- title = "Atomic force microscopy reveals the mechanical design
- of a modular protein",
- journal = PNAS,
- volume = 97,
- number = 12,
- year = 2000,
- pages = "6527--6531",
- abstract = "",
- doi = "10.1073/pnas.120048697",
- URL = "http://www.pnas.org/cgi/content/abstract/97/12/6527",
- eprint = "http://www.pnas.org/cgi/reprint/97/12/6527.pdf",
- note = "Unfolding order not from protein-surface interactions. Mechanical unfolding of a chain of interleaved domains $ABABAB\ldots$ yielded a run of $A$ unfoldings followed by a run of $B$ unfoldings.",
-}
-
-@Article{nome07,
- author = RNome #" and "# JZhao #" and "# WHoff #" and "# NScherer,
- title = "Axis-dependent anisotropy in protein unfolding from
- integrated nonequilibrium single-molecule experiments,
- analysis, and simulation",
- journal = PNAS,
- volume = 104,
- number = 52,
- pages = "20799--20804",
- year = 2007,
- month = dec,
- day = 26,
- keywords = "Anisotropy; Bacterial Proteins; Biophysics; Computer Simulation; Cysteine; Halorhodospira halophila; Hydrogen Bonding; Kinetics; Luminescent Proteins; Microscopy, Atomic Force; Molecular Conformation; Protein Binding; Protein Conformation; Protein Denaturation; Protein Folding; Protein Structure, Secondary",
- abstract = "We present a comprehensive study that integrates
- experimental and theoretical nonequilibrium techniques
- to map energy landscapes along well defined pull-axis
- specific coordinates to elucidate mechanisms of protein
- unfolding. Single-molecule force-extension experiments
- along two different axes of photoactive yellow protein
- combined with nonequilibrium statistical mechanical
- analysis and atomistic simulation reveal energetic and
- mechanistic anisotropy. Steered molecular dynamics
- simulations and free-energy curves constructed from the
- experimental results reveal that unfolding along one
- axis exhibits a transition-state-like feature where six
- hydrogen bonds break simultaneously with weak
- interactions observed during further unfolding. The
- other axis exhibits a constant (unpeaked) force profile
- indicative of a noncooperative transition, with
- enthalpic (e.g., H-bond) interactions being broken
- throughout the unfolding process. Striking qualitative
- agreement was found between the force-extension curves
- derived from steered molecular dynamics calculations
- and the equilibrium free-energy curves obtained by
- JarzynskiHummerSzabo analysis of the nonequilibrium
- work data. The anisotropy persists beyond pulling
- distances of more than twice the initial dimensions of
- the folded protein, indicating a rich energy landscape
- to the mechanically fully unfolded state. Our findings
- challenge the notion that cooperative unfolding is a
- universal feature in protein stability.",
- ISSN = "1091-6490",
- doi = "10.1073/pnas.0701281105",
- URL = "http://www.pnas.org/cgi/content/abstract/104/52/20799",
- eprint = "http://www.pnas.org/cgi/reprint/104/52/20799.pdf",
-}
-
-@Article{ng07,
- author = SNg #" and "# KBillings #" and "# TOhashi #" and "#
- MAllen #" and "# RBest #" and "# LRandles #" and "#
- HErickson #" and "# JClarke,
- title = "Designing an extracellular matrix protein with
- enhanced mechanical stability",
- journal = PNAS,
- volume = 104,
- number = 23,
- year = 2007,
- pages = "9633--9637",
- doi = "10.1073/pnas.0609901104",
- abstract = "The extracellular matrix proteins tenascin and
- fibronectin experience significant mechanical forces in
- vivo. Both contain a number of tandem repeating
- homologous fibronectin type III (fnIII) domains, and
- atomic force microscopy experiments have demonstrated
- that the mechanical strength of these domains can vary
- significantly. Previous work has shown that mutations
- in the core of an fnIII domain from human tenascin
- (TNfn3) reduce the unfolding force of that domain
- significantly: The composition of the core is
- apparently crucial to the mechanical stability of these
- proteins. Based on these results, we have used rational
- redesign to increase the mechanical stability of the
- 10th fnIII domain of human fibronectin, FNfn10, which
- is directly involved in integrin binding. The
- hydrophobic core of FNfn10 was replaced with that of
- the homologous, mechanically stronger TNfn3 domain.
- Despite the extensive substitution, FNoTNc retains both
- the three-dimensional structure and the cell adhesion
- activity of FNfn10. Atomic force microscopy experiments
- reveal that the unfolding forces of the engineered
- protein FNoTNc increase by {approx}20% to match those
- of TNfn3. Thus, we have specifically designed a protein
- with increased mechanical stability. Our results
- demonstrate that core engineering can be used to change
- the mechanical strength of proteins while retaining
- functional surface interactions.",
- URL = "http://www.pnas.org/cgi/content/abstract/104/23/9633",
- eprint = "http://www.pnas.org/cgi/reprint/104/23/9633.pdf",
-}
-
-@Article{zhuang06,
- author = WZhuang #" and "# DAbramavicius #" and "# SMukamel,
- title = "Two-dimensional vibrational optical probes for
- peptide fast folding investigation",
- journal = PNAS,
- volume = 103,
- number = 50,
- year = 2006,
- pages = "18934--18938",
- doi = "10.1073/pnas.0606912103",
- abstract = "A simulation study shows that early protein folding
- events may be investigated by using a recently
- developed family of nonlinear infrared techniques that
- combine the high temporal and spatial resolution of
- multidimensional spectroscopy with the
- chirality-specific sensitivity of amide vibrations to
- structure. We demonstrate how the structural
- sensitivity of cross-peaks in two-dimensional
- correlation plots of chiral signals of an {alpha} helix
- and a [beta] hairpin may be used to clearly resolve
- structural and dynamical details undetectable by
- one-dimensional techniques (e.g. circular dichroism)
- and identify structures indistinguishable by NMR.",
- URL = "http://www.pnas.org/cgi/content/abstract/103/50/18934",
- eprint = "http://www.pnas.org/cgi/reprint/103/50/18934.pdf",
-}
-
-@Article{discher06,
- author = DDischer #" and "# NBhasin #" and "# CJohnson,
- title = "Covalent chemistry on distended proteins",
- journal = PNAS,
- volume = 103,
- number = 20,
- pages = "7533--7534",
- doi = "10.1073/pnas.0602388103",
- year = 2006,
- URL = "http://www.pnas.org/cgi/content/abstract/103/20/7533.pdf",
- eprint = "http://www.pnas.org/cgi/reprint/103/20/7533.pdf",
-}
-
-@Article{li06,
- author = MSLi #" and "# CKHu #" and "# DKlimov #" and "#
- DThirumalai,
- title = "Multiple stepwise refolding of immunoglobulin domain
- {I27} upon force quench depends on initial conditions",
- journal = PNAS,
- volume = 103,
- number = 1,
- year = 2006,
- pages = "93--98",
- doi = "10.1073/pnas.0503758103",
- abstract = "Mechanical folding trajectories for polyproteins
- starting from initially stretched conformations
- generated by single-molecule atomic force microscopy
- experiments [Fernandez, J. M. & Li, H. (2004) Science
- 303, 1674-1678] show that refolding, monitored by the
- end-to-end distance, occurs in distinct multiple
- stages. To clarify the molecular nature of folding
- starting from stretched conformations, we have probed
- the folding dynamics, upon force quench, for the single
- I27 domain from the muscle protein titin by using a
- C{alpha}-Go model. Upon temperature quench, collapse
- and folding of I27 are synchronous. In contrast,
- refolding from stretched initial structures not only
- increases the folding and collapse time scales but also
- decouples the two kinetic processes. The increase in
- the folding times is associated primarily with the
- stretched state to compact random coil transition.
- Surprisingly, force quench does not alter the nature of
- the refolding kinetics, but merely increases the height
- of the free-energy folding barrier. Force quench
- refolding times scale as f1.gif, where {Delta}xf
- {approx} 0.6 nm is the location of the average
- transition state along the reaction coordinate given by
- end-to-end distance. We predict that {tau}F and the
- folding mechanism can be dramatically altered by the
- initial and/or final values of force. The implications
- of our results for design and analysis of experiments
- are discussed.",
- URL = "http://www.pnas.org/cgi/content/abstract/103/1/93",
- eprint = "http://www.pnas.org/cgi/reprint/103/1/93.pdf",
-}
-
-@Article{irback05,
- author = AIrback #" and "# SMitternacht #" and "# SMohanty,
- title = "Dissecting the mechanical unfolding of ubiquitin",
- journal = PNAS,
- volume = 102,
- number = 38,
- year = 2005,
- pages = "13427--13432",
- doi = "10.1073/pnas.0501581102",
- abstract = "The unfolding behavior of ubiquitin under the
- influence of a stretching force recently was
- investigated experimentally by single-molecule
- constant-force methods. Many observed unfolding traces
- had a simple two-state character, whereas others showed
- clear evidence of intermediate states. Here, we use
- Monte Carlo simulations to investigate the
- force-induced unfolding of ubiquitin at the atomic
- level. In agreement with experimental data, we find
- that the unfolding process can occur either in a single
- step or through intermediate states. In addition to
- this randomness, we find that many quantities, such as
- the frequency of occurrence of intermediates, show a
- clear systematic dependence on the strength of the
- applied force. Despite this diversity, one common
- feature can be identified in the simulated unfolding
- events, which is the order in which the
- secondary-structure elements break. This order is the
- same in two- and three-state events and at the
- different forces studied. The observed order remains to
- be verified experimentally but appears physically
- reasonable.",
- URL = "http://www.pnas.org/cgi/content/abstract/102/38/13427",
- eprint = "http://www.pnas.org/cgi/reprint/102/38/13427.pdf",
-}
-
-@Article{sarkar04,
- author = ASarkar #" and "# RRobertson #" and "# JFernandez,
- title = "Simultaneous atomic force microscope and fluorescence
- measurements of protein unfolding using a calibrated
- evanescent wave",
- journal = PNAS,
- volume = 101,
- number = 35,
- year = 2004,
- pages = "12882--12886",
- doi = "10.1073/pnas.0403534101",
- abstract = "Fluorescence techniques for monitoring single-molecule
- dynamics in the vertical dimension currently do not
- exist. Here we use an atomic force microscope to
- calibrate the distance-dependent intensity decay of an
- evanescent wave. The measured evanescent wave transfer
- function was then used to convert the vertical motions
- of a fluorescent particle into displacement ($SD =< 1$
- nm). We demonstrate the use of the calibrated
- evanescent wave to resolve the 20.1 {+/-} 0.5-nm step
- increases in the length of the small protein ubiquitin
- during forced unfolding. The experiments that we report
- here make an important contribution to fluorescence
- microscopy by demonstrating the unambiguous optical
- tracking of a single molecule with a resolution
- comparable to that of an atomic force microscope.",
- URL = "http://www.pnas.org/cgi/content/abstract/101/35/12882",
- eprint = "http://www.pnas.org/cgi/reprint/101/35/12882.pdf",
-}
-
-@Article{bustanji03,
- author = YBustanji #" and "# CArciola #" and "# MConti #" and "#
- EMandello #" and "# LMontanaro #" and "# BSamori,
- title = "Dynamics of the interaction between a fibronectin
- molecule and a living bacterium under mechanical
- force",
- journal = PNAS,
- volume = 100,
- number = 23,
- year = 2003,
- pages = "13292--13297",
- doi = "10.1073/pnas.1735343100",
- abstract = "Fibronectin (Fn) is an important mediator of bacterial
- invasions and of persistent infections like that of
- Staphylococcus epidermis. Similar to many other types
- of cell-protein adhesion, the binding between Fn and S.
- epidermidis takes place under physiological shear
- rates. We investigated the dynamics of the interaction
- between individual living S. epidermidis cells and
- single Fn molecules under mechanical force by using the
- scanning force microscope. The mechanical strength of
- this interaction and the binding site in the Fn
- molecule were determined. The energy landscape of the
- binding/unbinding process was mapped, and the force
- spectrum and the association and dissociation rate
- constants of the binding pair were measured. The
- interaction between S. epidermidis cells and Fn
- molecules is compared with those of two other
- protein/ligand pairs known to mediate different dynamic
- states of adhesion of cells under a hydrodynamic flow:
- the firm adhesion mediated by biotin/avidin
- interactions, and the rolling adhesion, mediated by
- L-selectin/P-selectin glycoprotein ligand-1
- interactions. The inner barrier in the energy landscape
- of the Fn case characterizes a high-energy binding mode
- that can sustain larger deformations and for
- significantly longer times than the correspondent
- high-strength L-selectin/P-selectin glycoprotein
- ligand-1 binding mode. The association kinetics of the
- former interaction is much slower to settle than the
- latter. On this basis, the observations made at the
- macroscopic scale by other authors of a strong lability
- of the bacterial adhesions mediated by Fn under high
- turbulent flow are rationalized at the molecular
- level.",
- URL = "http://www.pnas.org/cgi/content/abstract/100/23/13292",
- eprint = "http://www.pnas.org/cgi/reprint/100/23/13292.pdf",
-}
-
-@Article{liu03,
- author = WLiu #" and "# VMontana #" and "# EChapman #" and "#
- UMohideen #" and "# VParpura,
- title = "Botulinum toxin type {B} micromechanosensor",
- journal = PNAS,
- volume = 100,
- number = 23,
- year = 2003,
- pages = "13621--13625",
- doi = "10.1073/pnas.2233819100",
- abstract = "Botulinum neurotoxin (BoNT) types A, B, E, and F are
- toxic to humans; early and rapid detection is essential
- for adequate medical treatment. Presently available
- tests for detection of BoNTs, although sensitive,
- require hours to days. We report a BoNT-B sensor whose
- properties allow detection of BoNT-B within minutes.
- The technique relies on the detection of an agarose
- bead detachment from the tip of a micromachined
- cantilever resulting from BoNT-B action on its
- substratum, the synaptic protein synaptobrevin 2,
- attached to the beads. The mechanical resonance
- frequency of the cantilever is monitored for the
- detection. To suspend the bead off the cantilever we
- use synaptobrevin's molecular interaction with another
- synaptic protein, syntaxin 1A, that was deposited onto
- the cantilever tip. Additionally, this bead detachment
- technique is general and can be used in any
- displacement reaction, such as in receptor-ligand
- pairs, where the introduction of one chemical leads to
- the displacement of another. The technique is of broad
- interest and will find uses outside toxicology.",
- URL = "http://www.pnas.org/cgi/content/abstract/100/23/13621",
- eprint = "http://www.pnas.org/cgi/reprint/100/23/13621.pdf",
-}
-
-@Article{oroudjev02,
- author = EOroudjev #" and "# JSoares #" and "# SArcidiacono #" and "#
- JThompson #" and "# SFossey #" and "# HHansma,
- title = "Segmented nanofibers of spider dragline silk: Atomic
- force microscopy and single-molecule force
- spectroscopy",
- journal = PNAS,
- volume = 99,
- number = 90002,
- year = 2002,
- pages = "6460--6465",
- doi = "10.1073/pnas.082526499",
- abstract = "Despite its remarkable materials properties, the
- structure of spider dragline silk has remained
- unsolved. Results from two probe microscopy techniques
- provide new insights into the structure of spider
- dragline silk. A soluble synthetic protein from
- dragline silk spontaneously forms nanofibers, as
- observed by atomic force microscopy. These nanofibers
- have a segmented substructure. The segment length and
- amino acid sequence are consistent with a slab-like
- shape for individual silk protein molecules. The height
- and width of nanofiber segments suggest a stacking
- pattern of slab-like molecules in each nanofiber
- segment. This stacking pattern produces nano-crystals
- in an amorphous matrix, as observed previously by NMR
- and x-ray diffraction of spider dragline silk. The
- possible importance of nanofiber formation to native
- silk production is discussed. Force spectra for single
- molecules of the silk protein demonstrate that this
- protein unfolds through a number of rupture events,
- indicating a modular substructure within single silk
- protein molecules. A minimal unfolding module size is
- estimated to be around 14 nm, which corresponds to the
- extended length of a single repeated module, 38 amino
- acids long. The structure of this spider silk protein
- is distinctly different from the structures of other
- proteins that have been analyzed by single-molecule
- force spectroscopy, and the force spectra show
- correspondingly novel features.",
- URL = "http://www.pnas.org/cgi/content/abstract/99/suppl_2/6460",
- eprint = "http://www.pnas.org/cgi/reprint/99/suppl_2/6460.pdf",
-}
-
-@Article{baneyx02,
- author = GBaneyx #" and "# LBaugh #" and "# VVogel,
- title = "Supramolecular Chemistry And Self-assembly Special
- Feature: Fibronectin extension and unfolding within
- cell matrix fibrils controlled by cytoskeletal
- tension",
- journal = PNAS,
- volume = 99,
- number = 8,
- year = 2002,
- pages = "5139--5143",
- doi = "10.1073/pnas.072650799",
- abstract = "Evidence is emerging that mechanical stretching can
- alter the functional states of proteins. Fibronectin
- (Fn) is a large, extracellular matrix protein that is
- assembled by cells into elastic fibrils and subjected
- to contractile forces. Assembly into fibrils coincides
- with expression of biological recognition sites that
- are buried in Fn's soluble state. To investigate how
- supramolecular assembly of Fn into fibrillar matrix
- enables cells to mechanically regulate its structure,
- we used fluorescence resonance energy transfer (FRET)
- as an indicator of Fn conformation in the fibrillar
- matrix of NIH 3T3 fibroblasts. Fn was randomly labeled
- on amine residues with donor fluorophores and
- site-specifically labeled on cysteine residues in
- modules FnIII7 and FnIII15 with acceptor fluorophores.
- Intramolecular FRET was correlated with known
- structural changes of Fn in denaturing solution, then
- applied in cell culture as an indicator of Fn
- conformation within the matrix fibrils of NIH 3T3
- fibroblasts. Based on the level of FRET, Fn in many
- fibrils was stretched by cells so that its dimer arms
- were extended and at least one FnIII module unfolded.
- When cytoskeletal tension was disrupted using
- cytochalasin D, FRET increased, indicating refolding of
- Fn within fibrils. These results suggest that
- cell-generated force is required to maintain Fn in
- partially unfolded conformations. The results support a
- model of Fn fibril elasticity based on unraveling and
- refolding of FnIII modules. We also observed variation
- of FRET between and along single fibrils, indicating
- variation in the degree of unfolding of Fn in fibrils.
- Molecular mechanisms by which mechanical force can
- alter the structure of Fn, converting tensile forces
- into biochemical cues, are discussed.",
- URL = "http://www.pnas.org/cgi/content/abstract/99/8/5139",
- eprint = "http://www.pnas.org/cgi/reprint/99/8/5139.pdf",
-}
-
-@Article{brower-toland02,
- author = BDBrowerToland #" and "# CSmith #" and "# RYeh #" and "#
- JLis #" and "# CPeterson #" and "# MWang,
- title = "From the Cover: Mechanical disruption of individual
- nucleosomes reveals a reversible multistage release of
- {DNA}",
- journal = PNAS,
- volume = 99,
- number = 4,
- year = 2002,
- pages = "1960--1965",
- doi = "10.1073/pnas.022638399",
- abstract = "The dynamic structure of individual nucleosomes was
- examined by stretching nucleosomal arrays with a
- feedback-enhanced optical trap. Forced disassembly of
- each nucleosome occurred in three stages. Analysis of
- the data using a simple worm-like chain model yields 76
- bp of DNA released from the histone core at low
- stretching force. Subsequently, 80 bp are released at
- higher forces in two stages: full extension of DNA with
- histones bound, followed by detachment of histones.
- When arrays were relaxed before the dissociated state
- was reached, nucleosomes were able to reassemble and to
- repeat the disassembly process. The kinetic parameters
- for nucleosome disassembly also have been determined.",
- URL = "http://www.pnas.org/cgi/content/abstract/99/4/1960",
- eprint = "http://www.pnas.org/cgi/reprint/99/4/1960.pdf",
-}
-
-@Article{hummer01,
- author = GHummer #" and "# ASzabo,
- title = "From the Cover: Free energy reconstruction from
- nonequilibrium single-molecule pulling experiments",
- journal = PNAS,
- volume = 98,
- number = 7,
- pages = "3658--3661",
- year = 2001,
- doi = "10.1073/pnas.071034098",
- URL = "http://www.pnas.org/cgi/content/abstract/98/7/3658",
- eprint = "http://www.pnas.org/cgi/reprint/98/7/3658.pdf",
- note = "READ",
-}
-
-@Article{talaga00,
- author = DTalaga #" and "# WLau #" and "# HRoder #" and "#
- JTang #" and "# YJia #" and "# WDeGrado #" and "#
- RHochstrasser,
- title = "Dynamics and folding of single two-stranded
- coiled-coil peptides studied by fluorescent energy
- transfer confocal microscopy",
- journal = PNAS,
- volume = 97,
- number = 24,
- pages = "13021--13026",
- year = 2000,
- doi = "10.1073/pnas.97.24.13021",
- URL = "http://www.pnas.org/cgi/content/abstract/97/24/13021",
- eprint = "http://www.pnas.org/cgi/reprint/97/24/13021.pdf",
-}
-
-@Article{gergely00,
- author = CGergely #" and "# JCVoegel #" and "# PSchaaf #" and "#
- BSenger #" and "# MMaaloum #" and "# JHorber #" and "#
- JHemmerle,
- title = "Unbinding process of adsorbed proteins under external
- stress studied by atomic force microscopy
- spectroscopy",
- journal = PNAS,
- year = 2000,
- volume = 97,
- number = 20,
- pages = "10802--10807",
- doi = "10.1073/pnas.180293097",
- URL = "http://www.pnas.org/cgi/content/abstract/97/20/10802",
- eprint = "http://www.pnas.org/cgi/reprint/97/20/10802.pdf",
-}
-
-@Article{paci00,
- author = EPaci #" and "# MKarplus,
- title = "Unfolding proteins by external forces and
- temperature: The importance of topology and
- energetics",
- journal = PNAS,
- volume = 97,
- number = 12,
- pages = "6521--6526",
- year = 2000,
- doi = "10.1073/pnas.100124597",
- URL = "http://www.pnas.org/cgi/content/abstract/97/12/6521",
- eprint = "http://www.pnas.org/cgi/reprint/97/12/6521.pdf",
-}
-
-@Article{yang00,
- author = GYang #" and "# CCecconi #" and "# WBaase #" and "#
- IVetter #" and "# WBreyer #" and "# JHaack #" and "#
- BMatthews #" and "# FDahlquist #" and "# CBustamante,
- title = "Solid-state synthesis and mechanical unfolding of
- polymers of {T4} lysozyme",
- journal = PNAS,
- volume = 97,
- number = 1,
- pages = "139--144",
- year = 2000,
- doi = "10.1073/pnas.97.1.139",
- URL = "http://www.pnas.org/cgi/content/abstract/97/1/139",
- eprint = "http://www.pnas.org/cgi/reprint/97/1/139.pdf",
-}
-
-@Article{strunz99,
- author = TStrunz #" and "# KOroszlan #" and "# RSchafer #" and "#
- HJGuntherodt,
- title = "Dynamic force spectroscopy of single {DNA} molecules",
- journal = PNAS,
- volume = 96,
- number = 20,
- pages = "11277--11282",
- year = 1999,
- doi = "10.1073/pnas.96.20.11277",
- URL = "http://www.pnas.org/cgi/content/abstract/96/20/11277",
- eprint = "http://www.pnas.org/cgi/reprint/96/20/11277.pdf",
-}
-
-@Article{carrion-vazquez99b,
- author = MCarrionVazquez #" and "# AOberhauser #" and "#
- SFowler #" and "# PMarszalek #" and "# SBroedel #" and "#
- JClarke #" and "# JFernandez,
- title = "Mechanical and chemical unfolding of a single
- protein: A comparison",
- journal = PNAS,
- volume = 96,
- number = 7,
- pages = "3694--3699",
- year = 1999,
- doi = "10.1073/pnas.96.7.3694",
- URL = "http://www.pnas.org/cgi/content/abstract/96/7/3694",
- eprint = "http://www.pnas.org/cgi/reprint/96/7/3694.pdf",
-}
-
-@Article{nevo04,
- author = RNevo #" and "# VBrumfeld #" and "# MElbaum #" and "#
- PHinterdorfer #" and "# ZReich,
- title = "Direct discrimination between models of protein
- activation by single-molecule force measurements",
- journal = BPJ,
- year = 2004,
- month = oct,
- volume = 87,
- number = 4,
- pages = "2630--2634",
- keywords = "Elasticity; Enzyme Activation; Micromanipulation; Microscopy, Atomic Force; Models, Chemical; Models, Molecular; Multiprotein Complexes; Nuclear Proteins; Physical Stimulation; Protein Binding; Stress, Mechanical; Structure-Activity Relationship; beta Karyopherins; ran GTP-Binding Protein",
- abstract = "The limitations imposed on the analyses of complex
- chemical and biological systems by ensemble averaging
- can be overcome by single-molecule experiments. Here,
- we used a single-molecule technique to discriminate
- between two generally accepted mechanisms of a key
- biological process--the activation of proteins by
- molecular effectors. The two mechanisms, namely
- induced-fit and population-shift, are normally
- difficult to discriminate by ensemble approaches. As a
- model, we focused on the interaction between the
- nuclear transport effector, RanBP1, and two related
- complexes consisting of the nuclear import receptor,
- importin beta, and the GDP- or GppNHp-bound forms of
- the small GTPase, Ran. We found that recognition by the
- effector proceeds through either an induced-fit or a
- population-shift mechanism, depending on the substrate,
- and that the two mechanisms can be differentiated by
- the data.",
- ISSN = "0006-3495",
- doi = "10.1529/biophysj.104.041889",
- URL = "http://www.biophysj.org/cgi/content/abstract/87/4/2630",
- eprint = "http://www.biophysj.org/cgi/reprint/87/4/2630.pdf",
-}
-
-@Article{nevo03,
- author = RNevo #" and "# CStroh #" and "# FKienberger #" and "#
- DKaftan #" and "# VBrumfeld #" and "# MElbaum #" and "#
- ZReich #" and "# PHinterdorfer,
- title = "A molecular switch between alternative conformational
- states in the complex of {Ran} and importin beta1",
- journal = NSB,
- year = 2003,
- month = jul,
- volume = 10,
- number = 7,
- pages = "553--557",
- keywords = "Guanosine Diphosphate; Guanosine Triphosphate; Microscopy, Atomic Force; Protein Binding; Protein Conformation; beta Karyopherins; ran GTP-Binding Protein",
- abstract = "Several million macromolecules are exchanged each
- minute between the nucleus and cytoplasm by
- receptor-mediated transport. Most of this traffic is
- controlled by the small GTPase Ran, which regulates
- assembly and disassembly of the receptor-cargo
- complexes in the appropriate cellular compartment. Here
- we applied dynamic force spectroscopy to study the
- interaction of Ran with the nuclear import receptor
- importin beta1 (impbeta) at the single-molecule level.
- We found that the complex alternates between two
- distinct conformational states of different adhesion
- strength. The application of an external mechanical
- force shifts equilibrium toward one of these states by
- decreasing the height of the interstate activation
- energy barrier. The other state can be stabilized by a
- functional Ran mutant that increases this barrier.
- These results support a model whereby functional
- control of Ran-impbeta is achieved by a population
- shift between pre-existing alternative conformations.",
- ISSN = "1072-8368",
- doi = "10.1038/nsb940",
- URL = "http://www.nature.com/nsmb/journal/v10/n7/abs/nsb940.html",
- eprint = "http://www.nature.com/nsmb/journal/v10/n7/pdf/nsb940.pdf",
-}
-
-@Article{grossman05,
- title = "Optical Tweezers Advanced Lab",
- author = "C. Grossman and A. Stout",
- numpages = "12",
- year = "2005",
- season = "Fall",
- eprint = "http://chirality.swarthmore.edu/PHYS81/OpticalTweezers.pdf",
- note = "Fairly complete overdamped PSD derivation in section
- 4.3., cites \citet{tlusty98} and \citet{bechhoefer02} for
- further details. However, Tlusty (listed as reference
- 8) doesn't contain the thermal response fn.\ derivation
- it was cited for. Also, the single sided PSD definition
- credited to reference 9 (listed as Bechhoefer) looks
- more like Press (listed as reference 10). I imagine
- Grossman and Stout mixed up their references, and meant
- to refer to \citet{bechhoefer02} and \citet{press92}
- respectively instead.",
- project = "Cantilever Calibration",
-}
-
-@Article{tlusty98,
- author = "Tsvi Tlusty and Amit Meller and Roy Bar-Ziv",
- title = "Optical Gradient Forces of Strongly Localized Fields",
- journal = PRL,
- volume = 81,
- number = 8,
- pages = "1738--1741",
- numpages = 3,
- year = 1998,
- month = aug,
- publisher = APS,
- doi = "10.1103/PhysRevLett.81.1738",
- eprint = "http://prola.aps.org/pdf/PRL/v81/i8/p1738_1",
- note = "also at
- \url{http://nanoscience.bu.edu/papers/p1738_1_Meller.pdf}.
- Cited by \citet{grossman05} for derivation of thermal
- response fn. However, I only see a referenced thermal
- energy when they list the likelyhood of a small
- partical (radius < $R_c$) escaping due to thermal
- energy, where $R_c$ is roughly $R_c \sim (k_B T /
- \alpha I_0)^(1/3)$, $\alpha$ is a dielectric scaling
- term, and $I_0$ is the maximum beam energy density. I
- imagine Grossman and Stout mixed up this reference.",
- project = "Cantilever Calibration",
-}
-
-@Article{bechhoefer02,
- author = JBechhoefer #" and Scott Wilson",
- collaboration = "",
- title = "Faster, cheaper, safer optical tweezers for the
- undergraduate laboratory",
- publisher = "AAPT",
- year = "2002",
- journal = "American Journal of Physics",
- volume = "70",
- number = "4",
- pages = "393--400",
- keywords = "student experiments; safety; radiation pressure; laser
- beam applications",
- URL = "http://link.aip.org/link/?AJP/70/393/1",
- doi = "10.1119/1.1445403",
- project = "Cantilever Calibration",
- note = "Good discussion of the effect of correlation time on
- calibration. Excellent detail on power spectrum
- derivation and thermal noise for extremely overdamped
- oscillators in Appendix A (references \citet{rief65}).
- References work on deconvolving thermal noise from
- other noise\citep{cowan98}",
-}
-
-@Book{press92,
- title = "Numerical Recipies in {C}: The Art of Scientific
- Computing",
- author = "W. Press and S. Teukolsky and W. Vetterling and B.
- Flannery",
- edition = "2",
- publisher = "Cambridge University Press",
- address = "New York",
- year = "1992",
- eprint = "http://www.nrbook.com/a/bookcpdf.php",
- note = "See sections 12.0, 12.1, 12.3, and 13.4 for a good
- introduction to Fourier transforms and power spectrum
- estimation.",
- project = "Cantilever Calibration",
-}
-
-@Book{cowan98,
- title = "Statistical Data Analysis",
- author = "Glen Cowan",
- publisher = "Oxford University Press",
- address = "New York",
- year = "1998",
- note = "Noise deconvolution in Chapter 11",
- project = "Cantilever Calibration",
-}
-
-@Book{rief65,
- title = "Fundamentals of Statistical and Thermal Physics",
- author = "Frederick Rief",
- publisher = "McGraw-Hill",
- address = "New York",
- year = "1965",
- note = "Thermal noise for SHOs, in Chapter 15, Sections 6 and
- 10.",
- project = "Cantilever Calibration",
-}
-
-@Book{thornton04,
- title = "Classical Dynamics of Particles and Systems",
- author = "S.~Thornton and J.~Marion",
- edition = "5",
- publisher = "Brooks/Cole",
- address = "Belmont, CA",
- year = "2004",
- isbn = "0-534-40896-6",
-}
-
-@Article{schlierf06,
- author = MSchlierf #" and "# MRief,
- title = "Single-molecule unfolding force distributions reveal a
- funnel-shaped energy landscape",
- journal = BPJ,
- year = "2006",
- month = feb,
- day = "15",
- volume = "90",
- number = "4",
- pages = "L33--L35",
- keywords = "Models, Molecular; Protein Folding; Proteins; Thermodynamics",
- abstract = "The protein folding process is described as diffusion
- on a high-dimensional energy landscape. Experimental
- data showing details of the underlying energy surface
- are essential to understanding folding. So far in
- single-molecule mechanical unfolding experiments a
- simplified model assuming a force-independent
- transition state has been used to extract such
- information. Here we show that this so-called Bell
- model, although fitting well to force velocity data,
- fails to reproduce full unfolding force distributions.
- We show that by applying Kramers' diffusion model, we
- were able to reconstruct a detailed funnel-like
- curvature of the underlying energy landscape and
- establish full agreement with the data. We demonstrate
- that obtaining spatially resolved details of the
- unfolding energy landscape from mechanical
- single-molecule protein unfolding experiments requires
- models that go beyond the Bell model.",
- ISSN = "0006-3495",
- doi = "10.1529/biophysj.105.077982",
- URL = "http://www.biophysj.org/cgi/content/abstract/90/4/L33",
- note = "The inspiration behind my sawtooth simulation.
- Bell model fit to $f_{unfold}(v)$, but
- Kramers model fit to unfolding distribution for a given $v$.
- Eqn.~3 in the supplement is \citet{evans99} 1999's Eqn.~2, but it is just ``[dying percent] * [surviving population] = [deaths]'' (TODO, check).
- $\nu \equiv k$ is the force/time-dependent off rate... (TODO)
- The Kramers' rate equation (second equation in the paper) is \citet{hanggi90} Eq.~4.56b (page 275).
- It is important to extract $k_0$ and $\Delta x$ using every
- available method.",
-}
-
-@Article{marko95,
- author = "John F. Marko and Eric D. Siggia",
- title = "Stretching {DNA}",
- journal = "Macromolecules",
- volume = "28",
- number = "26",
- pages = "8759--8770",
- year = "1995",
- abstract = "",
- URL = "http://pubs3.acs.org/acs/journals/doilookup?in_doi=10.1021/ma00130a008",
- affiliation = "",
- ISSN = "0024-9297",
- eprint = "http://pubs.acs.org/cgi-bin/archive.cgi/mamobx/1995/28/i26/pdf/ma00130a008.pdf",
- note = "Derivation of the Worm-like Chain interpolation
- function.",
-}
-
-% 0021-4922 is the print ISSN. The online ISSN is 1347-4065.
-@Article{dietz07,
- author = HDietz #" and "# MRief,
- title = "Detecting Molecular Fingerprints in Single Molecule
- Force Spectroscopy Using Pattern Recognition",
- journal = "Japanese Journal of Applied Physics",
- volume = "46",
- number = "8B",
- pages = "5540--5542",
- year = "2007",
- keywords = "single molecule, protein mechanics, force
- spectroscopy, AFM, pattern recognition, GFP",
- abstract = "Single molecule force spectroscopy has given
- experimental access to the mechanical properties of
- protein molecules. Typically, less than 1% of the
- experimental recordings reflect true single molecule
- events due to abundant surface and multiple-molecule
- interactions. A key issue in single molecule force
- spectroscopy is thus to identify the characteristic
- mechanical `fingerprint' of a specific protein in noisy
- data sets. Here, we present an objective pattern
- recognition algorithm that is able to identify
- fingerprints in such noisy data sets.",
- ISSN = "0021-4922",
- URL = "http://jjap.ipap.jp/link?JJAP/46/5540/",
- doi = "10.1143/JJAP.46.5540",
- note = "Automatic force curve selection. Seems a bit shoddy.
- Details later.",
-}
-
-@Article{kleiner07,
- author = "Ariel Kleiner and Eugene Shakhnovich",
- title = "The mechanical unfolding of ubiquitin through all-atom
- Monte Carlo simulation with a Go-type potential",
- journal = BPJ,
- year = "2007",
- month = mar,
- day = "15",
- volume = "92",
- number = "6",
- pages = "2054--2061",
- keywords = "Computer Simulation; Models, Chemical; Models, Molecular; Models, Statistical; Monte Carlo Method; Motion; Protein Conformation; Protein Denaturation; Protein Folding; Ubiquitin",
- abstract = "The mechanical unfolding of proteins under a
- stretching force has an important role in living
- systems and is a logical extension of the more general
- protein folding problem. Recent advances in
- experimental methodology have allowed the stretching of
- single molecules, thus rendering this process ripe for
- computational study. We use all-atom Monte Carlo
- simulation with a G?-type potential to study the
- mechanical unfolding pathway of ubiquitin. A detailed,
- robust, well-defined pathway is found, confirming
- existing results in this vein though using a different
- model. Additionally, we identify the protein's
- fundamental stabilizing secondary structure
- interactions in the presence of a stretching force and
- show that this fundamental stabilizing role does not
- persist in the absence of mechanical stress. The
- apparent success of simulation methods in studying
- ubiquitin's mechanical unfolding pathway indicates
- their potential usefulness for future study of the
- stretching of other proteins and the relationship
- between protein structure and the response to
- mechanical deformation.",
- ISSN = "0006-3495",
- doi = "10.1529/biophysj.106.081257",
- URL = "http://www.biophysj.org/cgi/content/full/92/6/2054",
- eprint = "http://www.biophysj.org/cgi/reprint/92/6/2054",
-}
-
-@Article{makarov01,
- author = "Dmitrii E. Makarov"#" and "# PHansma #" and "#"Horia
- Metiu",
- collaboration = "",
- title = "Kinetic Monte Carlo simulation of titin unfolding",
- publisher = "AIP",
- year = "2001",
- journal = "The Journal of Chemical Physics",
- volume = "114",
- number = "21",
- pages = "9663--9673",
- keywords = "proteins; hydrogen bonds; digital simulation; Monte
- Carlo methods; molecular biophysics; intramolecular
- mechanics; macromolecules; atomic force microscopy",
- URL = "http://link.aip.org/link/?JCP/114/9663/1",
- eprint = "http://hansmalab.physics.ucsb.edu/pdf/297%20-%20Makarov,%20D.E._J.Chem.Phys._2001.pdf",
- doi = "10.1063/1.1369622",
-}
-
-@Article{rief98,
- author = MRief #" and "# JFernandez #" and "# HGaub,
- title = "Elastically Coupled Two-Level Systems as a Model for
- Biopolymer Extensibility",
- journal = PRL,
- volume = 81,
- number = 21,
- pages = "4764--4767",
- numpages = 3,
- year = 1998,
- month = nov,
- doi = "10.1103/PhysRevLett.81.4764",
- url = "http://prola.aps.org/abstract/PRL/v81/i21/p4764_1",
- eprint = "http://prola.aps.org/pdf/PRL/v81/i21/p4764_1",
- publisher = APS,
- note = "Original details on mechanical unfolding analysis via Monte Carlo simulation.",
-}
-
-@Article{zinober02,
- author = "Rebecca C. Zinober and David J. Brockwell and Godfrey
- S. Beddard and Anthony W. Blake and Peter D. Olmsted
- and Sheena E. Radford and D. Alastair Smith",
- title = "Mechanically unfolding proteins: the effect of
- unfolding history and the supramolecular scaffold",
- journal = PS,
- year = 2002,
- month = dec,
- volume = 11,
- number = 12,
- pages = "2759--2765",
- keywords = "Computer Simulation; Models, Molecular; Monte Carlo Method; Protein Folding; Protein Structure, Tertiary; Proteins",
- abstract = "The mechanical resistance of a folded domain in a
- polyprotein of five mutant I27 domains (C47S, C63S
- I27)(5)is shown to depend on the unfolding history of
- the protein. This observation can be understood on the
- basis of competition between two effects, that of the
- changing number of domains attempting to unfold, and
- the progressive increase in the compliance of the
- polyprotein as domains unfold. We present Monte Carlo
- simulations that show the effect and experimental data
- that verify these observations. The results are
- confirmed using an analytical model based on transition
- state theory. The model and simulations also predict
- that the mechanical resistance of a domain depends on
- the stiffness of the surrounding scaffold that holds
- the domain in vivo, and on the length of the unfolded
- domain. Together, these additional factors that
- influence the mechanical resistance of proteins have
- important consequences for our understanding of natural
- proteins that have evolved to withstand force.",
- ISSN = "0961-8368",
- doi = "10.1110/ps.0224602",
- URL = "http://www.proteinscience.org/cgi/content/abstract/11/12/2759",
- eprint = "http://www.proteinscience.org/cgi/reprint/11/12/2759.pdf",
- note = "Introduces unfolding-order \emph{scaffold effect} on average unfolding force.",
- project = "sawtooth simulation",
-}
-
-@Article{brockwell02,
- author = "David J. Brockwell and Godfrey S. Beddard and John
- Clarkson and Rebecca C. Zinober and Anthony W. Blake
- and John Trinick and Peter D. Olmsted and D. Alastair
- Smith and Sheena E. Radford",
- title = "The effect of core destabilization on the mechanical
- resistance of {I27}",
- journal = BPJ,
- year = "2002",
- month = jul,
- volume = "83",
- number = "1",
- pages = "458--472",
- keywords = "Amino Acid Sequence; Dose-Response Relationship, Drug; Kinetics; Magnetic Resonance Spectroscopy; Models, Molecular; Molecular Sequence Data; Monte Carlo Method; Muscle Proteins; Mutation; Peptide Fragments; Protein Denaturation; Protein Folding; Protein Kinases; Protein Structure, Secondary; Protein Structure, Tertiary; Proteins; Thermodynamics",
- abstract = "It is still unclear whether mechanical unfolding
- probes the same pathways as chemical denaturation. To
- address this point, we have constructed a concatamer of
- five mutant I27 domains (denoted (I27)(5)*) and used it
- for mechanical unfolding studies. This protein consists
- of four copies of the mutant C47S, C63S I27 and a
- single copy of C63S I27. These mutations severely
- destabilize I27 (DeltaDeltaG(UN) = 8.7 and 17.9 kJ
- mol(-1) for C63S I27 and C47S, C63S I27, respectively).
- Both mutations maintain the hydrogen bond network
- between the A' and G strands postulated to be the major
- region of mechanical resistance for I27. Measuring the
- speed dependence of the force required to unfold
- (I27)(5)* in triplicate using the atomic force
- microscope allowed a reliable assessment of the
- intrinsic unfolding rate constant of the protein to be
- obtained (2.0 x 10(-3) s(-1)). The rate constant of
- unfolding measured by chemical denaturation is over
- fivefold faster (1.1 x 10(-2) s(-1)), suggesting that
- these techniques probe different unfolding pathways.
- Also, by comparing the parameters obtained from the
- mechanical unfolding of a wild-type I27 concatamer with
- that of (I27)(5)*, we show that although the observed
- forces are considerably lower, core destabilization has
- little effect on determining the mechanical sensitivity
- of this domain.",
- ISSN = "0006-3495",
- doi = "10.1016/S0006-3495(02)75182-5",
- URL = "http://www.biophysj.org/cgi/content/abstract/83/1/458",
- eprint = {http://www.biophysj.org/cgi/reprint/83/1/458.pdf},
-}
-
-@Article{hummer03,
- author = "Gerhard Hummer and Attila Szabo",
- title = "Kinetics from nonequilibrium single-molecule pulling
- experiments",
- journal = BPJ,
- year = "2003",
- month = jul,
- volume = "85",
- number = "1",
- pages = "5--15",
- keywords = "Computer Simulation; Crystallography; Energy Transfer; Kinetics; Lasers; Micromanipulation; Microscopy, Atomic Force; Models, Molecular; Molecular Conformation; Motion; Muscle Proteins; Nanotechnology; Physical Stimulation; Protein Conformation; Protein Denaturation; Protein Folding; Protein Kinases; Stress, Mechanical",
- abstract = "Mechanical forces exerted by laser tweezers or atomic
- force microscopes can be used to drive rare transitions
- in single molecules, such as unfolding of a protein or
- dissociation of a ligand. The phenomenological
- description of pulling experiments based on Bell's
- expression for the force-induced rupture rate is found
- to be inadequate when tested against computer
- simulations of a simple microscopic model of the
- dynamics. We introduce a new approach of comparable
- complexity to extract more accurate kinetic information
- about the molecular events from pulling experiments.
- Our procedure is based on the analysis of a simple
- stochastic model of pulling with a harmonic spring and
- encompasses the phenomenological approach, reducing to
- it in the appropriate limit. Our approach is tested
- against computer simulations of a multimodule titin
- model with anharmonic linkers and then an illustrative
- application is made to the forced unfolding of I27
- subunits of the protein titin. Our procedure to extract
- kinetic information from pulling experiments is simple
- to implement and should prove useful in the analysis of
- experiments on a variety of systems.",
- ISSN = "0006-3495",
- URL = "http://www.biophysj.org/cgi/content/abstract/85/1/5",
- eprint = "http://www.biophysj.org/cgi/reprint/85/1/5.pdf",
- project = "sawtooth simulation",
- note = "READ",
-}
-
-@Article{thirumalai05,
- author = DThirumalai #" and "# CHyeon,
- title = "{RNA} and Protein Folding: Common Themes and
- Variations",
- journal = "Biochemistry",
- volume = "44",
- number = "13",
- pages = "4957--4970",
- year = "2005",
- abstract = "Visualizing the navigation of an ensemble of unfolded
- molecules through the bumpy energy landscape in search
- of the native state gives a pictorial view of
- biomolecular folding. This picture, when combined with
- concepts in polymer theory, provides a unified theory
- of RNA and protein folding. Just as for proteins, the
- major folding free energy barrier for RNA scales
- sublinearly with the number of nucleotides, which
- allows us to extract the elusive prefactor for RNA
- folding. Several folding scenarios can be anticipated
- by considering variations in the energy landscape that
- depend on sequence, native topology, and external
- conditions. RNA and protein folding mechanism can be
- described by the kinetic partitioning mechanism (KPM)
- according to which a fraction () of molecules reaches
- the native state directly, whereas the remaining
- fraction gets kinetically trapped in metastable
- conformations. For two-state folders 1. Molecular
- chaperones are recruited to assist protein folding
- whenever is small. We show that the iterative annealing
- mechanism, introduced to describe chaperonin-mediated
- folding, can be generalized to understand
- protein-assisted RNA folding. The major differences
- between the folding of proteins and RNA arise in the
- early stages of folding. For RNA, folding can only
- begin after the polyelectrolyte problem is solved,
- whereas protein collapse requires burial of hydrophobic
- residues. Cross-fertilization of ideas between the two
- fields should lead to an understanding of how RNA and
- proteins solve their folding problems.",
- URL = "http://pubs3.acs.org/acs/journals/doilookup?in_doi=10.1021/bi047314+",
- affiliation = "Biophysics Program, and Department of Chemistry and
- Biochemistry, Institute for Physical Science and
- Technology, University of Maryland, College Park,
- Maryland 20742",
- ISSN = "0006-2960",
- note = "unfolding-refolding",
-}
-
-@article{schwaiger05,
- author = "Ingo Schwaiger and Michael Schleicher and Angelika A.
- Noegel and "# MRief,
- title = "The folding pathway of a fast-folding immunoglobulin
- domain revealed by single-molecule mechanical
- experiments",
- journal = "EMBO Rep",
- year = "2005",
- month = jan,
- volume = "6",
- number = "1",
- pages = "46--51",
- keywords = "Animals; Contractile Proteins; Dictyostelium; Immunoglobulins; Kinetics; Microfilament Proteins; Models, Molecular; Protein Folding; Protein Structure, Tertiary",
- abstract = "The F-actin crosslinker filamin from Dictyostelium
- discoideum (ddFLN) has a rod domain consisting of six
- structurally similar immunoglobulin domains. When
- subjected to a stretching force, domain 4 unfolds at a
- lower force than all the other domains in the chain.
- Moreover, this domain shows a stable intermediate along
- its mechanical unfolding pathway. We have developed a
- mechanical single-molecule analogue to a double-jump
- stopped-flow experiment to investigate the folding
- kinetics and pathway of this domain. We show that an
- obligatory and productive intermediate also occurs on
- the folding pathway of the domain. Identical mechanical
- properties suggest that the unfolding and refolding
- intermediates are closely related. The folding process
- can be divided into two consecutive steps: in the first
- step 60 C-terminal amino acids form an intermediate at
- the rate of 55 s(-1); and in the second step the
- remaining 40 amino acids are packed on this core at the
- rate of 179 s(-1). This division increases the overall
- folding rate of this domain by a factor of ten compared
- with all other homologous domains of ddFLN that lack
- the folding intermediate.",
- ISSN = "1469-221X",
- doi = "10.1038/sj.embor.7400317",
- url = "http://www.nature.com/embor/journal/v6/n1/index.html",
- eprint = "http://www.nature.com/embor/journal/v6/n1/pdf/7400317.pdf",
-}
-
-@Article{evans99,
- author = "E. Evans and K. Ritchie",
- title = "Strength of a weak bond connecting flexible polymer
- chains",
- journal = BPJ,
- year = "1999",
- month = may,
- volume = "76",
- number = "5",
- pages = "2439--2447",
- keywords = "Animals; Biophysics; Biopolymers; Microscopy, Atomic Force; Models, Chemical; Muscle Proteins; Protein Folding; Protein Kinases; Stochastic Processes; Stress, Mechanical; Thermodynamics",
- abstract = "Bond dissociation under steadily rising force occurs
- most frequently at a time governed by the rate of
- loading (Evans and Ritchie, 1997 Biophys. J.
- 72:1541-1555). Multiplied by the loading rate, the
- breakage time specifies the force for most frequent
- failure (called bond strength) that obeys the same
- dependence on loading rate. The spectrum of bond
- strength versus log(loading rate) provides an image of
- the energy landscape traversed in the course of
- unbonding. However, when a weak bond is connected to
- very compliant elements like long polymers, the load
- applied to the bond does not rise steadily under
- constant pulling speed. Because of nonsteady loading,
- the most frequent breakage force can differ
- significantly from that of a bond loaded at constant
- rate through stiff linkages. Using generic models for
- wormlike and freely jointed chains, we have analyzed
- the kinetic process of failure for a bond loaded by
- pulling the polymer linkages at constant speed. We find
- that when linked by either type of polymer chain, a
- bond is likely to fail at lower force under steady
- separation than through stiff linkages. Quite
- unexpectedly, a discontinuous jump can occur in bond
- strength at slow separation speed in the case of long
- polymer linkages. We demonstrate that the predictions
- of strength versus log(loading rate) can rationalize
- conflicting results obtained recently for unfolding Ig
- domains along muscle titin with different force
- techniques.",
- ISSN = "0006-3495",
-URL = {http://www.biophysj.org/cgi/content/abstract/76/5/2439},
-eprint = {http://www.biophysj.org/cgi/reprint/76/5/2439.pdf},
-note= {Develops Kramers improvement on Bell model for domain unfolding.
- Presents unfolding under variable loading rates.
- Often cited as the ``Bell-Evans'' model?
- They derive a unitless treatment, scaling force by $f_\beta$, TODO;
- time by $\tau_f$, TODO; elasiticity by compliance $c(f)$.
- The appendix has relaxation time formulas for WLC and FJC polymer models.},
- project = "sawtooth simulation",
-}
-
-@Article{evans97,
- author = "E. Evans and K. Ritchie",
- title = "Dynamic strength of molecular adhesion bonds",
- journal = BPJ,
- year = "1997",
- month = apr,
- volume = "72",
- number = "4",
- pages = "1541--1555",
- keywords = "Avidin; Biotin; Chemistry, Physical; Computer Simulation; Mathematics; Monte Carlo Method; Protein Binding",
- abstract = "In biology, molecular linkages at, within, and beneath
- cell interfaces arise mainly from weak noncovalent
- interactions. These bonds will fail under any level of
- pulling force if held for sufficient time. Thus, when
- tested with ultrasensitive force probes, we expect
- cohesive material strength and strength of adhesion at
- interfaces to be time- and loading rate-dependent
- properties. To examine what can be learned from
- measurements of bond strength, we have extended
- Kramers' theory for reaction kinetics in liquids to
- bond dissociation under force and tested the
- predictions by smart Monte Carlo (Brownian dynamics)
- simulations of bond rupture. By definition, bond
- strength is the force that produces the most frequent
- failure in repeated tests of breakage, i.e., the peak
- in the distribution of rupture forces. As verified by
- the simulations, theory shows that bond strength
- progresses through three dynamic regimes of loading
- rate. First, bond strength emerges at a critical rate
- of loading (> or = 0) at which spontaneous dissociation
- is just frequent enough to keep the distribution peak
- at zero force. In the slow-loading regime immediately
- above the critical rate, strength grows as a weak power
- of loading rate and reflects initial coupling of force
- to the bonding potential. At higher rates, there is
- crossover to a fast regime in which strength continues
- to increase as the logarithm of the loading rate over
- many decades independent of the type of attraction.
- Finally, at ultrafast loading rates approaching the
- domain of molecular dynamics simulations, the bonding
- potential is quickly overwhelmed by the rapidly
- increasing force, so that only naked frictional drag on
- the structure remains to retard separation. Hence, to
- expose the energy landscape that governs bond strength,
- molecular adhesion forces must be examined over an
- enormous span of time scales. However, a significant
- gap exists between the time domain of force
- measurements in the laboratory and the extremely fast
- scale of molecular motions. Using results from a
- simulation of biotin-avidin bonds (Izrailev, S., S.
- Stepaniants, M. Balsera, Y. Oono, and K. Schulten.
- 1997. Molecular dynamics study of unbinding of the
- avidin-biotin complex. Biophys. J., this issue), we
- describe how Brownian dynamics can help bridge the gap
- between molecular dynamics and probe tests.",
- ISSN = "0006-3495",
-URL = {http://www.biophysj.org/cgi/content/abstract/72/4/1541},
-eprint = {http://www.biophysj.org/cgi/reprint/72/4/1541.pdf},
- project = "sawtooth simulation",
-}
-
-@Article{shillcock98,
- title = {Escape from a metastable well under a time-ramped force},
- author = {Shillcock, Julian and Seifert, Udo },
- journal = {Phys. Rev. E},
- volume = {57},
- number = {6},
- pages = {7301--7304},
- numpages = {3},
- year = {1998},
- month = {Jun},
- doi = {10.1103/PhysRevE.57.7301},
- publisher = {American Physical Society},
- url = "http://link.aps.org/abstract/PRE/v57/p7301",
- eprint = "http://prola.aps.org/pdf/PRE/v57/i6/p7301_1",
- project = "sawtooth simulation",
-}
-
-@Article{hatfield99,
- title = {Dynamic Properties of an Extended Polymer in Solution},
- author = {Hatfield, John William and Quake, Stephen R.},
- journal = {Phys. Rev. Lett.},
- volume = {82},
- number = {17},
- pages = {3548--3551},
- numpages = {3},
- year = {1999},
- month = {Apr},
- doi = {10.1103/PhysRevLett.82.3548},
- url = "http://link.aps.org/abstract/PRL/v82/p3548",
- publisher = {American Physical Society},
- note = "Defines WLC and FJC models, citing textbooks.",
- project = "sawtooth simulation",
-}
-
-@Article{hanggi90,
- title = {Reaction-rate theory: fifty years after {K}ramers},
- author = {H\"anggi, Peter and Talkner, Peter and Borkovec, Michal },
- journal = RMP,
- volume = {62},
- number = {2},
- pages = {251--341},
- numpages = {90},
- year = {1990},
- month = {Apr},
- doi = {10.1103/RevModPhys.62.251},
- url = {http://prola.aps.org/abstract/RMP/v62/i2/p251_1},
- eprint = {http://www.physik.uni-augsburg.de/theo1/hanggi/Papers/112.pdf},
- publisher = {American Physical Society},
- note = "\emph{The} Kramers' theory review article. See pages 268--279 for the Kramers-specific introduction.",
- project = "sawtooth simulation",
-}
-
-% onuchic, contacting the folding funnnel with NMR, pnas 1997?
-
-@Article{onuchic1996,
- author = "J. N. Onuchic and N. D. Socci and Z. Luthey-Schulten
- and P. G. Wolynes",
- title = "Protein folding funnels: the nature of the transition
- state ensemble",
- journal = "Fold Des",
- year = "1996",
- volume = "1",
- number = "6",
- pages = "441--450",
- keywords = "Animals; Cytochrome c Group; Humans; Infant; Protein Folding",
- abstract = "BACKGROUND: Energy landscape theory predicts that the
- folding funnel for a small fast-folding alpha-helical
- protein will have a transition state half-way to the
- native state. Estimates of the position of the
- transition state along an appropriate reaction
- coordinate can be obtained from linear free energy
- relationships observed for folding and unfolding rate
- constants as a function of denaturant concentration.
- The experimental results of Huang and Oas for lambda
- repressor, Fersht and collaborators for C12, and Gray
- and collaborators for cytochrome c indicate a free
- energy barrier midway between the folded and unfolded
- regions. This barrier arises from an entropic
- bottleneck for the folding process. RESULTS: In keeping
- with the experimental results, lattice simulations
- based on the folding funnel description show that the
- transition state is not just a single conformation, but
- rather an ensemble of a relatively large number of
- configurations that can be described by specific values
- of one or a few order parameters (e.g. the fraction of
- native contacts). Analysis of this transition state or
- bottleneck region from our lattice simulations and from
- atomistic models for small alpha-helical proteins by
- Boczko and Brooks indicates a broad distribution for
- native contact participation in the transition state
- ensemble centered around 50\%. Importantly, however,
- the lattice-simulated transition state ensemble does
- include some particularly hot contacts, as seen in the
- experiments, which have been termed by others a folding
- nucleus. CONCLUSIONS: Linear free energy relations
- provide a crude spectroscopy of the transition state,
- allowing us to infer the values of a reaction
- coordinate based on the fraction of native contacts.
- This bottleneck may be thought of as a collection of
- delocalized nuclei where different native contacts will
- have different degrees of participation. The agreement
- between the experimental results and the theoretical
- predictions provides strong support for the landscape
- analysis.",
- ISSN = "1359-0278",
-}
-
-@article{socci96,
-author = {N. D. Socci and J. N. Onuchic and P. G. Wolynes},
-collaboration = {},
-title = {Diffusive dynamics of the reaction coordinate for protein folding funnels},
-publisher = {AIP},
-year = {1996},
-journal = {The Journal of Chemical Physics},
-volume = {104},
-number = {15},
-pages = {5860--5868},
- keywords = {PROTEINS; FOLDS; DIFFUSION; MONTE CARLO METHOD; SIMULATION; FREE ENERGY},
-abstract = {The quantitative description
-of model protein folding kinetics using a diffusive
-collective reaction coordinate is examined.
-Direct folding kinetics, diffusional coefficients
-and free energy profiles are determined
-from Monte Carlo simulations of a 27-mer, 3
-letter code lattice model, which corresponds
-roughly to a small helical protein. Analytic
-folding calculations, using simple diffusive rate
-theory, agree extremely well with the full simulation
-results. Folding in this system is best
-seen as a diffusive, funnel-like process.},
-url = {http://link.aip.org/link/?JCP/104/5860/1},
-doi = {10.1063/1.471317},
-eprint = {http://arxiv.org/pdf/cond-mat/9601091},
-note = {A nice introduction to some quantitative ramifications of the funnel energy landscape. There's also a bit of Kramers' theory and graph theory thrown in for good measure.},
-}
-
-
-@Article{schwaiger04,
- author = "Ingo Schwaiger and Angelika Kardinal and Michael
- Schleicher and Angelika A. Noegel and "# MRief,
- title = "A mechanical unfolding intermediate in an
- actin-crosslinking protein",
- journal = NSMB,
- year = 2004,
- month = jan,
- day = 29,
- volume = 11,
- number = 1,
- pages = "81--85",
- keywords = "Actins; Animals; Contractile Proteins; Cross-Linking Reagents; Dictyostelium; Dimerization; Microfilament Proteins; Microscopy, Atomic Force; Mutagenesis, Site-Directed; Protein Denaturation; Protein Folding; Protein Structure, Tertiary; Protozoan Proteins",
- abstract = "Many F-actin crosslinking proteins consist of two
- actin-binding domains separated by a rod domain that
- can vary considerably in length and structure. In this
- study, we used single-molecule force spectroscopy to
- investigate the mechanics of the immunoglobulin (Ig)
- rod domains of filamin from Dictyostelium discoideum
- (ddFLN). We find that one of the six Ig domains unfolds
- at lower forces than do those of all other domains and
- exhibits a stable unfolding intermediate on its
- mechanical unfolding pathway. Amino acid inserts into
- various loops of this domain lead to contour length
- changes in the single-molecule unfolding pattern. These
- changes allowed us to map the stable core of
- approximately 60 amino acids that constitutes the
- unfolding intermediate. Fast refolding in combination
- with low unfolding forces suggest a potential in vivo
- role for this domain as a mechanically extensible
- element within the ddFLN rod.",
- ISSN = "1545-9993",
- doi = "10.1038/nsmb705",
- url = "http://www.nature.com/nsmb/journal/v11/n1/full/nsmb705.html",
- eprint = "http://www.nature.com/nsmb/journal/v11/n1/pdf/nsmb705.pdf",
- note = "ddFLN unfolding with WLC params for sacrificial domains.
- Gives persistence length $p = 0.5\mbox{ nm}$ in ``high force regime'', $p = 0.9\mbox{ nm}$ in ``low force regime'', with a transition at $F = 30\mbox{ pN}$.",
- project = "sawtooth simulation",
-}
-
-@article{sheng05,
-author = {Yu-Jane Sheng and Shaoyi Jiang and Heng-Kwong Tsao},
-collaboration = {},
-title = {Forced Kramers escape in single-molecule pulling experiments},
-publisher = {AIP},
-year = {2005},
-journal = {The Journal of Chemical Physics},
-volume = {123},
-number = {9},
-eid = {091102},
-numpages = {4},
-pages = {091102},
-keywords = {molecular biophysics; bonds (chemical); proteins},
-url = {http://link.aip.org/link/?JCP/123/091102/1},
-doi = {10.1063/1.2046632},
- project = "sawtooth simulation",
-note = "Gives appropriate Einstein-S... relation for diffusion to damping",
-}
-
-@Article{bell78,
- author = "G. I. Bell",
- title = "Models for the specific adhesion of cells to cells",
- journal = SCI,
- year = "1978",
- month = may,
- day = "12",
- volume = "200",
- number = "4342",
- pages = "618--627",
- keywords = "Antigen-Antibody Reactions; Cell Adhesion; Cell Membrane; Chemistry, Physical; Electrophysiology; Enzymes; Glycoproteins; Kinetics; Ligands; Membrane Proteins; Models, Biological; Receptors, Drug",
- abstract = "A theoretical framework is proposed for the analysis
- of adhesion between cells or of cells to surfaces when
- the adhesion is mediated by reversible bonds between
- specific molecules such as antigen and antibody, lectin
- and carbohydrate, or enzyme and substrate. From a
- knowledge of the reaction rates for reactants in
- solution and of their diffusion constants both in
- solution and on membranes, it is possible to estimate
- reaction rates for membrane-bound reactants. Two models
- are developed for predicting the rate of bond formation
- between cells and are compared with experiments. The
- force required to separate two cells is shown to be
- greater than the expected electrical forces between
- cells, and of the same order of magnitude as the forces
- required to pull gangliosides and perhaps some integral
- membrane proteins out of the cell membrane.",
- ISSN = "0036-8075",
- url = "http://www.jstor.org/stable/1746930",
- note = "The Bell model and a fair bit of cell bonding background.",
- project = "sawtooth simulation",
-}
-
-@Article{Mello2004,
- author = "Cecilia C. Mello and Doug Barrick",
- title = "An experimentally determined protein folding energy
- landscape",
- journal = PNAS,
- year = "2004",
- month = sep,
- day = "28",
- volume = "101",
- number = "39",
- pages = "14102--14107",
- keywords = "Animals; Ankyrin Repeat; Circular Dichroism; Drosophila Proteins; Drosophila melanogaster; Gene Deletion; Models, Chemical; Models, Molecular; Protein Denaturation; Protein Folding; Protein Structure, Tertiary; Spectrometry, Fluorescence; Thermodynamics; Urea",
- abstract = "Energy landscapes have been used to conceptually
- describe and model protein folding but have been
- difficult to measure experimentally, in large part
- because of the myriad of partly folded protein
- conformations that cannot be isolated and
- thermodynamically characterized. Here we experimentally
- determine a detailed energy landscape for protein
- folding. We generated a series of overlapping
- constructs containing subsets of the seven ankyrin
- repeats of the Drosophila Notch receptor, a protein
- domain whose linear arrangement of modular structural
- units can be fragmented without disrupting structure.
- To a good approximation, stabilities of each construct
- can be described as a sum of energy terms associated
- with each repeat. The magnitude of each energy term
- indicates that each repeat is intrinsically unstable
- but is strongly stabilized by interactions with its
- nearest neighbors. These linear energy terms define an
- equilibrium free energy landscape, which shows an early
- free energy barrier and suggests preferred low-energy
- routes for folding.",
- ISSN = "0027-8424",
- doi = "10.1073/pnas.0403386101",
-}
-
-@Article{Bryngelson1995,
- author = "J. D. Bryngelson and J. N. Onuchic and N. D. Socci and
- P. G. Wolynes",
- title = "Funnels, pathways, and the energy landscape of protein
- folding: a synthesis",
- journal = "Proteins",
- year = "1995",
- month = mar,
- volume = "21",
- number = "3",
- pages = "167--195",
- keywords = "Amino Acid Sequence; Chemistry, Physical; Computer Simulation; Data Interpretation, Statistical; Kinetics; Models, Chemical; Molecular Sequence Data; Protein Biosynthesis; Protein Conformation; Protein Folding; Proteins; Thermodynamics",
- abstract = "The understanding, and even the description of protein
- folding is impeded by the complexity of the process.
- Much of this complexity can be described and understood
- by taking a statistical approach to the energetics of
- protein conformation, that is, to the energy landscape.
- The statistical energy landscape approach explains when
- and why unique behaviors, such as specific folding
- pathways, occur in some proteins and more generally
- explains the distinction between folding processes
- common to all sequences and those peculiar to
- individual sequences. This approach also gives new,
- quantitative insights into the interpretation of
- experiments and simulations of protein folding
- thermodynamics and kinetics. Specifically, the picture
- provides simple explanations for folding as a two-state
- first-order phase transition, for the origin of
- metastable collapsed unfolded states and for the curved
- Arrhenius plots observed in both laboratory experiments
- and discrete lattice simulations. The relation of these
- quantitative ideas to folding pathways, to
- uniexponential vs. multiexponential behavior in protein
- folding experiments and to the effect of mutations on
- folding is also discussed. The success of energy
- landscape ideas in protein structure prediction is also
- described. The use of the energy landscape approach for
- analyzing data is illustrated with a quantitative
- analysis of some recent simulations, and a qualitative
- analysis of experiments on the folding of three
- proteins. The work unifies several previously proposed
- ideas concerning the mechanism protein folding and
- delimits the regions of validity of these ideas under
- different thermodynamic conditions.",
- ISSN = "0887-3585",
- doi = "10.1002/prot.340210302",
-}
-
-@Article{Bryngelson1987,
- author = "J. D. Bryngelson and P. G. Wolynes",
- title = "Spin glasses and the statistical mechanics of protein
- folding",
- journal = PNAS,
- year = "1987",
- month = nov,
- volume = "84",
- number = "21",
- pages = "7524--7528",
- keywords = "Kinetics; Mathematics; Models, Theoretical; Protein Conformation; Proteins; Stochastic Processes",
- abstract = "The theory of spin glasses was used to study a simple
- model of protein folding. The phase diagram of the
- model was calculated, and the results of dynamics
- calculations are briefly reported. The relation of
- these results to folding experiments, the relation of
- these hypotheses to previous protein folding theories,
- and the implication of these hypotheses for protein
- folding prediction schemes are discussed.",
- ISSN = "0027-8424",
- note = "Seminal protein folding via energy landscape paper.",
-}
-
-@Article{bustamante94,
- author = CBustamante #" and J. F. Marko and E. D. Siggia and S.
- Smith",
- title = "Entropic elasticity of lambda-phage {DNA}",
- journal = SCI,
- year = 1994,
- month = sep,
- day = "09",
- volume = 265,
- number = 5178,
- pages = "1599--1600",
- keywords = "Bacteriophage lambda; DNA, Viral; Least-Squares Analysis; Thermodynamics",
- ISSN = "0036-8075",
- doi = "10.1126/science.8079175",
- url = "http://www.sciencemag.org/cgi/content/abstract/265/5178/1599",
- eprint = "http://www.sciencemag.org/cgi/reprint/265/5178/1599.pdf",
- note = "WLC interpolation formula.",
-}
-
-@article{nummela07,
-author = {Nummela, Jeremiah and Andricioaei, Ioan},
-title = {{Exact Low-Force Kinetics from High-Force Single-Molecule Unfolding Events}},
-journal = {Biophys. J.},
-volume = {93},
-number = {10},
-pages = {3373--3381},
-doi = {10.1529/biophysj.107.111658},
-year = {2007},
-abstract = {Mechanical forces play a key role in crucial cellular processes involving force-bearing biomolecules, as well as in novel single-molecule pulling experiments. We present an exact method that enables one to extrapolate, to low (or zero) forces, entire time-correlation functions and kinetic rate constants from the conformational dynamics either simulated numerically or measured experimentally at a single, relatively higher, external force. The method has twofold relevance: 1), to extrapolate the kinetics at physiological force conditions from molecular dynamics trajectories generated at higher forces that accelerate conformational transitions; and 2), to extrapolate unfolding rates from experimental force-extension single-molecule curves. The theoretical formalism, based on stochastic path integral weights of Langevin trajectories, is presented for the constant-force, constant loading rate, and constant-velocity modes of the pulling experiments. For the first relevance, applications are described for simulating the conformational isomerization of alanine dipeptide; and for the second relevance, the single-molecule pulling of RNA is considered. The ability to assign a weight to each trace in the single-molecule data also suggests a means to quantitatively compare unfolding pathways under different conditions.
-},
-URL = {http://www.biophysj.org/cgi/content/abstract/93/10/3373},
-eprint = {http://www.biophysj.org/cgi/reprint/93/10/3373.pdf}
-}
-
-@article{gompertz25,
- jstor_articletype = {primary_article},
- title = {On the Nature of the Function Expressive of the Law of Human Mortality, and on a New Mode of Determining the Value of Life Contingencies},
- author = {Gompertz, Benjamin},
- journal = {Philosophical Transactions of the Royal Society of London},
- jstor_issuetitle = {},
- volume = {115},
- number = {},
- jstor_formatteddate = {1825},
- pages = {513--583},
- url = {http://www.jstor.org/stable/107756},
- ISSN = {02610523},
- abstract = {},
- publisher = {The Royal Society},
- copyright = {Copyright \copy\ 1825 The Royal Society},
- year = {1825},
- }
-
-@Article{dudko07,
- author = "Olga K. Dudko and J{\'e}r{\^o}me Math{\'e} and Attila
- Szabo and Amit Meller and Gerhard Hummer",
- title = "Extracting kinetics from single-molecule force
- spectroscopy: nanopore unzipping of {DNA} hairpins",
- journal = BPJ,
- year = "2007",
- month = jun,
- day = "15",
- volume = "92",
- number = "12",
- pages = "4188--4195",
- keywords = "Computer Simulation;DNA;Elasticity;Mechanics;Micromanipulation;Microscopy, Atomic Force;Models, Chemical;Models, Molecular;Nanostructures;Nucleic Acid Conformation;Porosity;Stress, Mechanical",
- abstract = "Single-molecule force experiments provide powerful new
- tools to explore biomolecular interactions. Here, we
- describe a systematic procedure for extracting kinetic
- information from force-spectroscopy experiments, and
- apply it to nanopore unzipping of individual DNA
- hairpins. Two types of measurements are considered:
- unzipping at constant voltage, and unzipping at
- constant voltage-ramp speeds. We perform a global
- maximum-likelihood analysis of the experimental data at
- low-to-intermediate ramp speeds. To validate the
- theoretical models, we compare their predictions with
- two independent sets of data, collected at high ramp
- speeds and at constant voltage, by using a quantitative
- relation between the two types of measurements.
- Microscopic approaches based on Kramers theory of
- diffusive barrier crossing allow us to estimate not
- only intrinsic rates and transition state locations, as
- in the widely used phenomenological approach based on
- Bell's formula, but also free energies of activation.
- The problem of extracting unique and accurate kinetic
- parameters of a molecular transition is discussed in
- light of the apparent success of the microscopic
- theories in reproducing the experimental data.",
- ISSN = "0006-3495",
- doi = "10.1529/biophysj.106.102855",
- eprint = "http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1877759&blobtype=pdf",
-}
-
-@Article{dudko06,
- author = "Olga K. Dudko and Gerhard Hummer and Attila Szabo",
- title = "Intrinsic rates and activation free energies from
- single-molecule pulling experiments",
- journal = "Phys Rev Lett",
- year = "2006",
- month = mar,
- day = "17",
- volume = "96",
- number = "10",
- pages = "108101",
- keywords = "Biophysics;Computer Simulation;Data Interpretation, Statistical;Kinetics;Micromanipulation;Models, Chemical;Models, Molecular;Molecular Conformation;Muscle Proteins;Nucleic Acid Conformation;Protein Binding;Protein Denaturation;Protein Folding;Protein Kinases;RNA;Stress, Mechanical;Thermodynamics;Time Factors",
- abstract = "We present a unified framework for extracting kinetic
- information from single-molecule pulling experiments at
- constant force or constant pulling speed. Our procedure
- provides estimates of not only (i) the intrinsic rate
- coefficient and (ii) the location of the transition
- state but also (iii) the free energy of activation. By
- analyzing simulated data, we show that the resulting
- rates of force-induced rupture are significantly more
- reliable than those obtained by the widely used
- approach based on Bell's formula. We consider the
- uniqueness of the extracted kinetic information and
- suggest guidelines to avoid over-interpretation of
- experiments.",
- ISSN = "0031-9007",
- doi = "10.1103/PhysRevLett.96.108101",
-}
-
-@Article{wu04,
- author = "Jong-Wuu Wu and Wen-Liang Hung and Chih-Hui Tsai",
- title = "Estimation of parameters of the {G}ompertz distribution using the least squares method",
- journal = "Applied Mathematics and Computation",
- year = "2004",
- month = oct,
- day = "25",
- volume = "158",
- number = "1",
- pages = "133--147",
- keywords = "Gompertz distribution; Least squares estimate; Maximum likelihood estimate; First failure-censored; Series system",
- abstract = "The Gompertz distribution has been used to describe human mortality and establish actuarial tables. Recently, this distribution has been again studied by some authors. The maximum likelihood estimates for the parameters of the Gompertz distribution has been discussed by Garg et al. [J. R. Statist. Soc. C 19 (1970) 152]. The purpose of this paper is to propose unweighted and weighted least squares estimates for parameters of the Gompertz distribution under the complete data and the first failure-censored data (series systems; see [J. Statist. Comput. Simulat. 52 (1995) 337]). A simulation study is carried out to compare the proposed estimators and the maximum likelihood estimators. Results of the simulation studies show that the performance of the weighted least squares estimators is acceptable.",
- ISSN = "0096-3003",
- doi = "10.1016/j.amc.2003.08.086",
- url = "http://dx.doi.org/10.1016/j.amc.2003.08.086",
-}
-
-
-
-
-@Article{braverman08,
- author = "Elena Braverman and Reneeta Mamdani",
- title = "Continuous versus pulse harvesting for population
- models in constant and variable environment",
- journal = "J Math Biol",
- year = "2008",
- month = sep,
- day = "18",
- volume = "57",
- number = "3",
- pages = "413--434",
- abstract = "We consider both autonomous and nonautonomous
- population models subject to either impulsive or
- continuous harvesting. It is demonstrated in the paper
- that the impulsive strategy can be as good as the
- continuous one, but cannot outperform it. We introduce
- a model, where certain harm to the population is
- incorporated in each harvesting event, and study it for
- the logistic and the Gompertz laws of growth. In this
- case, impulsive harvesting is not only the optimal
- strategy but is the only possible one.",
- ISSN = "0303-6812",
- doi = "10.1007/s00285-008-0169-z",
- url = "http://www.springerlink.com/content/a1m23v50201m2401/",
- eprint = "http://www.springerlink.com/content/a1m23v50201m2401/fulltext.pdf",
- note = "An example of non-exponential Gomperz law.",
-}
-
-@Article{gavrilov01,
- author = "L. A. Gavrilov and N. S. Gavrilova",
- title = "The reliability theory of aging and longevity",
- journal = "J Theor Biol",
- year = "2001",
- month = dec,
- day = "21",
- volume = "213",
- number = "4",
- pages = "527--545",
- keywords = "Adult;Aged;Aging;Animals;Humans;Longevity;Middle Aged;Models, Biological;Survival Rate;Systems Theory",
- abstract = "Reliability theory is a general theory about systems
- failure. It allows researchers to predict the
- age-related failure kinetics for a system of given
- architecture (reliability structure) and given
- reliability of its components. Reliability theory
- predicts that even those systems that are entirely
- composed of non-aging elements (with a constant failure
- rate) will nevertheless deteriorate (fail more often)
- with age, if these systems are redundant in
- irreplaceable elements. Aging, therefore, is a direct
- consequence of systems redundancy. Reliability theory
- also predicts the late-life mortality deceleration with
- subsequent leveling-off, as well as the late-life
- mortality plateaus, as an inevitable consequence of
- redundancy exhaustion at extreme old ages. The theory
- explains why mortality rates increase exponentially
- with age (the Gompertz law) in many species, by taking
- into account the initial flaws (defects) in newly
- formed systems. It also explains why organisms
- ``prefer'' to die according to the Gompertz law, while
- technical devices usually fail according to the Weibull
- (power) law. Theoretical conditions are specified when
- organisms die according to the Weibull law: organisms
- should be relatively free of initial flaws and defects.
- The theory makes it possible to find a general failure
- law applicable to all adult and extreme old ages, where
- the Gompertz and the Weibull laws are just special
- cases of this more general failure law. The theory
- explains why relative differences in mortality rates of
- compared populations (within a given species) vanish
- with age, and mortality convergence is observed due to
- the exhaustion of initial differences in redundancy
- levels. Overall, reliability theory has an amazing
- predictive and explanatory power with a few, very
- general and realistic assumptions. Therefore,
- reliability theory seems to be a promising approach for
- developing a comprehensive theory of aging and
- longevity integrating mathematical methods with
- specific biological knowledge.",
- ISSN = "0022-5193",
- doi = "10.1006/jtbi.2001.2430",
- note = "An example of exponential (standard) Gomperz law.",
-}
-
-@Article{olshansky97,
- author = "S. J. Olshansky and B. A. Carnes",
- title = "Ever since {G}ompertz",
- journal = "Demography",
- year = "1997",
- month = feb,
- volume = "34",
- number = "1",
- pages = "1--15",
- keywords = "Aging;Biometry;History, 19th Century;History, 20th Century;Humans;Life Tables;Mortality;Sexual Maturation",
- abstract = "In 1825 British actuary Benjamin Gompertz made a
- simple but important observation that a law of
- geometrical progression pervades large portions of
- different tables of mortality for humans. The simple
- formula he derived describing the exponential rise in
- death rates between sexual maturity and old age is
- commonly, referred to as the Gompertz equation-a
- formula that remains a valuable tool in demography and
- in other scientific disciplines. Gompertz's observation
- of a mathematical regularity in the life table led him
- to believe in the presence of a low of mortality that
- explained why common age patterns of death exist. This
- law of mortality has captured the attention of
- scientists for the past 170 years because it was the
- first among what are now several reliable empirical
- tools for describing the dying-out process of many
- living organisms during a significant portion of their
- life spans. In this paper we review the literature on
- Gompertz's law of mortality and discuss the importance
- of his observations and insights in light of research
- on aging that has taken place since then.",
- ISSN = "0070-3370",
- note = "Hardly any actual math, but the references might be interesting.
-I'll look into them if I have the time.
-Available through several repositories.",
-url = "http://www.jstor.org/stable/2061656",
-}
-
-@Article{juckett93,
- author = "D. A. Juckett and B. Rosenberg",
- title = "Comparison of the {G}ompertz and {W}eibull functions as
- descriptors for human mortality distributions and their
- intersections",
- journal = "Mech Ageing Dev",
- year = 1993,
- month = jun,
- volume = 69,
- number = "1--2",
- pages = "1--31",
- keywords = "Adolescent;Adult;Aged;Aged, 80 and over;Aging;Biometry;Child;Child, Preschool;Data Interpretation, Statistical;Female;Humans;Infant;Infant, Newborn;Longitudinal Studies;Male;Middle Aged;Models, Biological;Models, Statistical;Mortality",
- abstract = "The Gompertz and Weibull functions are compared with
- respect to goodness-of-fit to human mortality
- distributions; ability to describe mortality curve
- intersections; and, parameter interpretation. The
- Gompertz function is shown to be a better descriptor
- for 'all-causes' of deaths and combined disease
- categories while the Weibull function is shown to be a
- better descriptor of purer, single causes-of-death. A
- modified form of the Weibull function maps directly to
- the inherent degrees of freedom of human mortality
- distributions while the Gompertz function does not.
- Intersections in the old-age tails of mortality are
- explored in the context of both functions and, in
- particular, the relationship between distribution
- intersections, and the Gompertz ln[R0] versus alpha
- regression is examined. Evidence is also presented that
- mortality intersections are fundamental to the
- survivorship form and not the rate (hazard) form.
- Finally, comparisons are made to the parameter
- estimates in recent longitudinal Gompertzian analyses
- and the probable errors in those analyses are
- discussed.",
- ISSN = "0047-6374",
- note = "Nice table of various functions associated with Gompertz and Weibull models.",
-doi = "10.1016/0047-6374(93)90068-3"
-}
-
-@Article{rief02,
- author = MRief #" and Helmut Grubm{\"u}ller",
- title = "Force spectroscopy of single biomolecules",
- journal = "Chemphyschem",
- year = "2002",
- month = mar,
- day = "12",
- volume = "3",
- number = "3",
- pages = "255--261",
- keywords = "Ligands;Microscopy, Atomic Force;Polysaccharides;Protein Denaturation;Proteins",
- abstract = "Many processes in the body are effected and regulated
- by highly specialized protein molecules: These
- molecules certainly deserve the name ``biochemical
- nanomachines''. Recent progress in single-molecule
- experiments and corresponding simulations with
- supercomputers enable us to watch these
- ``nanomachines'' at work, revealing a host of
- astounding mechanisms. Examples are the fine-tuned
- movements of the binding pocket of a receptor protein
- locking into its ligand molecule and the forced
- unfolding of titin, which acts as a molecular shock
- absorber to protect muscle cells. At present, we are
- not capable of designing such high precision machines,
- but we are beginning to understand their working
- principles and to simulate and predict their
- function.",
- ISSN = "1439-4235",
- doi = "10.1002/1439-7641(20020315)3:3<255::AID-CPHC255>3.0.CO;2-M",
- url = "http://www3.interscience.wiley.com/journal/91016383/abstract",
- note = "Nice, general review of force spectroscopy to 2002, but not much detail.",
-}
-
-@Article{raible04,
- author = "M. Raible and M. Evstigneev and P. Reimann and F. W.
- Bartels and R. Ros",
- title = "Theoretical analysis of dynamic force spectroscopy
- experiments on ligand-receptor complexes",
- journal = "J Biotechnol",
- year = "2004",
- month = aug,
- day = "26",
- volume = "112",
- number = "1-2",
- pages = "13--23",
- keywords = "Binding Sites;Computer Simulation;DNA;DNA-Binding Proteins;Elasticity;Ligands;Macromolecular Substances;Micromanipulation;Microscopy, Atomic Force;Models, Chemical;Molecular Biology;Nucleic Acid Conformation;Physical Stimulation;Protein Binding;Protein Conformation;Stress, Mechanical",
- abstract = "The forced rupture of single chemical bonds in
- biomolecular compounds (e.g. ligand-receptor systems)
- as observed in dynamic force spectroscopy experiments
- is addressed. Under the assumption that the probability
- of bond rupture depends only on the instantaneously
- acting force, a data collapse onto a single master
- curve is predicted. For rupture data obtained
- experimentally by dynamic AFM force spectroscopy of a
- ligand-receptor bond between a DNA and a regulatory
- protein we do not find such a collapse. We conclude
- that the above mentioned, generally accepted assumption
- is not satisfied and we discuss possible
- explanations.",
- ISSN = "0168-1656",
- doi = "10.1016/j.jbiotec.2004.04.017",
-}
-
-@Article{raible06,
- author = "M. Raible and M. Evstigneev and F. W. Bartels and R.
- Eckel and M. Nguyen-Duong and R. Merkel and R. Ros and
- D. Anselmetti and P. Reimann",
- title = "Theoretical analysis of single-molecule force
- spectroscopy experiments: heterogeneity of chemical
- bonds",
- journal = BPJ,
- year = "2006",
- month = jun,
- day = "01",
- volume = "90",
- number = "11",
- pages = "3851--3864",
- keywords= "Biomechanics;Microscopy, Atomic Force;Models, Molecular;Statistical Distributions;Thermodynamics",
- abstract = "We show that the standard theoretical framework in
- single-molecule force spectroscopy has to be extended
- to consistently describe the experimental findings. The
- basic amendment is to take into account heterogeneity
- of the chemical bonds via random variations of the
- force-dependent dissociation rates. This results in a
- very good agreement between theory and rupture data
- from several different experiments.",
- ISSN = "0006-3495",
- doi = "10.1529/biophysj.105.077099",
- url = "http://www.biophysj.org/cgi/content/abstract/90/11/3851",
- eprint = "http://www.biophysj.org/cgi/reprint/90/11/3851.pdf",
-}
-
-@article{szabo80,
-author = {Attila Szabo and Klaus Schulten and Zan Schulten},
-collaboration = {},
-title = {First passage time approach to diffusion controlled reactions},
-publisher = {AIP},
-year = {1980},
-journal = {The Journal of Chemical Physics},
-volume = {72},
-number = {8},
-pages = {4350--4357},
- keywords = {DIFFUSION; CHEMICAL REACTIONS; CHEMICAL REACTION KINETICS; PROBABILITY; DIFFERENTIAL EQUATIONS},
-url = {http://link.aip.org/link/?JCP/72/4350/1},
-doi = {10.1063/1.439715}
-}
-
-@Article{dudko03,
- author = "O. K. Dudko and A. E. Filippov and J. Klafter and M.
- Urbakh",
- title = "Beyond the conventional description of dynamic force
- spectroscopy of adhesion bonds",
- journal = PNAS,
- year = "2003",
- month = sep,
- day = "30",
- volume = "100",
- number = "20",
- pages = "11378--11381",
- keywords = "Spectrum Analysis;Temperature",
- abstract = "Dynamic force spectroscopy of single molecules is
- described by a model that predicts a distribution of
- rupture forces, the corresponding mean rupture force,
- and variance, which are all amenable to experimental
- tests. The distribution has a pronounced asymmetry,
- which has recently been observed experimentally. The
- mean rupture force follows a (lnV)2/3 dependence on the
- pulling velocity, V, and differs from earlier
- predictions. Interestingly, at low pulling velocities,
- a rebinding process is obtained whose signature is an
- intermittent behavior of the spring force, which delays
- the rupture. An extension to include conformational
- changes of the adhesion complex is proposed, which
- leads to the possibility of bimodal distributions of
- rupture forces.",
- ISSN = "0027-8424",
- doi = "10.1073/pnas.1534554100",
- url = "http://www.pnas.org/content/100/20/11378.abstract",
- eprint = "http://www.pnas.org/content/100/20/11378.full.pdf",
-}
-
-@Article{balsera97,
- author = "M. Balsera and S. Stepaniants and S. Izrailev and Y.
- Oono and K. Schulten",
- title = "Reconstructing potential energy functions from
- simulated force-induced unbinding processes",
- journal = BPJ,
- year = "1997",
- month = sep,
- volume = "73",
- number = "3",
- pages = "1281--1287",
- keywords = "Binding Sites;Biopolymers;Kinetics;Ligands;Microscopy, Atomic Force;Models, Chemical;Molecular Conformation;Protein Conformation;Proteins;Reproducibility of Results;Stochastic Processes;Thermodynamics",
- abstract = "One-dimensional stochastic models demonstrate that
- molecular dynamics simulations of a few nanoseconds can
- be used to reconstruct the essential features of the
- binding potential of macromolecules. This can be
- accomplished by inducing the unbinding with the help of
- external forces applied to the molecules, and
- discounting the irreversible work performed on the
- system by these forces. The fluctuation-dissipation
- theorem sets a fundamental limit on the precision with
- which the binding potential can be reconstructed by
- this method. The uncertainty in the resulting potential
- is linearly proportional to the irreversible component
- of work performed on the system during the simulation.
- These results provide an a priori estimate of the
- energy barriers observable in molecular dynamics
- simulations.",
- ISSN = "0006-3495",
- url = "http://www.biophysj.org/cgi/content/abstract/73/3/1281",
- eprint = "http://www.biophysj.org/cgi/reprint/73/3/1281.pdf",
-}
-
-@Article{izrailev97,
- author = "S. Izrailev and S. Stepaniants and M. Balsera and Y.
- Oono and K. Schulten",
- title = "Molecular dynamics study of unbinding of the
- avidin-biotin complex",
- journal = BPJ,
- year = "1997",
- month = apr,
- volume = "72",
- number = "4",
- pages = "1568--1581",
- keywords = "Avidin;Binding Sites;Biotin;Computer Simulation;Hydrogen Bonding;Mathematics;Microscopy, Atomic Force;Microspheres;Models, Molecular;Molecular Structure;Protein Binding;Protein Conformation;Protein Folding;Sepharose",
- abstract = "We report molecular dynamics simulations that induce,
- over periods of 40-500 ps, the unbinding of biotin from
- avidin by means of external harmonic forces with force
- constants close to those of AFM cantilevers. The
- applied forces are sufficiently large to reduce the
- overall binding energy enough to yield unbinding within
- the measurement time. Our study complements earlier
- work on biotin-streptavidin that employed a much larger
- harmonic force constant. The simulations reveal a
- variety of unbinding pathways, the role of key residues
- contributing to adhesion as well as the spatial range
- over which avidin binds biotin. In contrast to the
- previous studies, the calculated rupture forces exceed
- by far those observed. We demonstrate, in the framework
- of models expressed in terms of one-dimensional
- Langevin equations with a schematic binding potential,
- the associated Smoluchowski equations, and the theory
- of first passage times, that picosecond to nanosecond
- simulation of ligand unbinding requires such strong
- forces that the resulting protein-ligand motion
- proceeds far from the thermally activated regime of
- millisecond AFM experiments, and that simulated
- unbinding cannot be readily extrapolated to the
- experimentally observed rupture.",
- ISSN = "0006-3495",
- url = "http://www.biophysj.org/cgi/content/abstract/72/4/1568",
- eprint = "http://www.biophysj.org/cgi/reprint/72/4/1568.pdf",
-}
-
-@Article{heymann00,
- author = "B. Heymann and H. Grubm{\"u}ller",
- title = "Dynamic force spectroscopy of molecular adhesion
- bonds",
- journal = "Phys Rev Lett",
- year = "2000",
- month = jun,
- day = "26",
- volume = "84",
- number = "26 Pt 1",
- pages = "6126--6129",
- abstract = "Recent advances in atomic force microscopy,
- biomembrane force probe experiments, and optical
- tweezers allow one to measure the response of single
- molecules to mechanical stress with high precision.
- Such experiments, due to limited spatial resolution,
- typically access only one single force value in a
- continuous force profile that characterizes the
- molecular response along a reaction coordinate. We
- develop a theory that allows one to reconstruct force
- profiles from force spectra obtained from measurements
- at varying loading rates, without requiring increased
- resolution. We show that spectra obtained from
- measurements with different spring constants contain
- complementary information.",
- ISSN = "0031-9007",
- doi = "10.1103/PhysRevLett.84.6126",
- url = "http://prola.aps.org/abstract/PRL/v84/p6126",
- eprint = "http://prola.aps.org/pdf/PRL/v84/i26/p6126_1",
-}
-
-@Article{kosztin06,
- author = "Ioan Kosztin and Bogdan Barz and Lorant Janosi",
- title = "Calculating potentials of mean force and diffusion coefficients from nonequilibrium processes without Jarzynski's equality",
- journal = "J. Chem. Phys.",
- year = "2006",
- month = feb,
- day = "10",
- volume = "124",
- pages = "064106",
- ISSN = "0031-9007",
- doi = "10.1063/1.2166379",
- url = "http://link.aip.org/link/?JCPSA6/124/064106/1",
-}
-
-@Article{kramers40,
- author = "H.A.~Kramers",
- title = "Brownian motion in a field of force and the diffusion model of chemical reactions",
- journal = "Physica",
- year = "1940",
- month = apr,
- volume = "7",
- number = "4",
- pages = "284--304",
- ISSN = "0031-8914",
- abstract = "A particle which is caught in a potential hole and which, through the shuttling action of Brownian motion, can escape over a potential barrier yields a suitable model for elucidating the applicability of the transition state method for calculating the rate of chemical reactions.",
- doi = "10.1016/S0031-8914(40)90098-2",
- url = "http://dx.doi.org/10.1016/S0031-8914(40)90098-2",
- note = "Seminal paper on thermally activated barrier crossings.",
-}
-
-@Book{vanKampen07,
- title = "Stochastic Processes in Physics and Chemistry",
- author = "van Kampen, N.G.",
- edition = "3",
- publisher = "Elsevier, North-Holland Personal Library",
- address = "Amsterdam",
- year = "2007",
- note = "",
- project = "sawtooth simulation",
-}
-
-@Article{marszalek99,
- author = PMarszalek #" and "# HLu #" and "# HLi #" and "#
- MCarrionVazquez #" and "# AOberhauser #" and K. Schulten
- and "# JFernandez,
- title = "Mechanical unfolding intermediates in titin modules",
- journal = NAT,
- year = 1999,
- month = nov,
- day = 04,
- volume = 402,
- number = 6757,
- pages = "100--103",
- keywords = "Biomechanics;Computer Simulation;Humans;Hydrogen Bonding;Microscopy, Atomic Force;Models, Molecular;Muscle Proteins;Myocardium;Protein Folding;Protein Kinases;Recombinant Proteins",
- abstract = "The modular protein titin, which is responsible for
- the passive elasticity of muscle, is subjected to
- stretching forces. Previous work on the experimental
- elongation of single titin molecules has suggested that
- force causes consecutive unfolding of each domain in an
- all-or-none fashion. To avoid problems associated with
- the heterogeneity of the modular, naturally occurring
- titin, we engineered single proteins to have multiple
- copies of single immunoglobulin domains of human
- cardiac titin. Here we report the elongation of these
- molecules using the atomic force microscope. We find an
- abrupt extension of each domain by approximately 7 A
- before the first unfolding event. This fast initial
- extension before a full unfolding event produces a
- reversible 'unfolding intermediate' Steered molecular
- dynamics simulations show that the rupture of a pair of
- hydrogen bonds near the amino terminus of the protein
- domain causes an extension of about 6 A, which is in
- good agreement with our observations. Disruption of
- these hydrogen bonds by site-directed mutagenesis
- eliminates the unfolding intermediate. The unfolding
- intermediate extends titin domains by approximately
- 15\% of their slack length, and is therefore likely to
- be an important previously unrecognized component of
- titin elasticity.",
- ISSN = "0028-0836",
- doi = "10.1038/47083",
- url = "http://www.nature.com/nature/journal/v402/n6757/abs/402100a0.html",
- eprint = "http://www.nature.com/nature/journal/v402/n6757/pdf/402100a0.pdf",
-}
-
-@Article{fujii02,
- author = "Tadashi Fujii and Yu-Long Sun and Kai-Nan An and
- Zong-Ping Luo",
- title = "Mechanical properties of single hyaluronan
- molecules",
- journal = "J Biomech",
- year = "2002",
- month = apr,
- volume = "35",
- number = "4",
- pages = "527--531",
- keywords = "Biomechanics;Cross-Linking Reagents;Elasticity;Extracellular Matrix;Humans;Hyaluronic Acid;Lasers;Microspheres;Nanotechnology",
- abstract = "Hyaluronan (HA) is a major component of the
- extracellular matrix. It plays an important role in the
- mechanical functions of the extracellular matrix and
- stabilization of cells. Currently, its mechanical
- properties have been investigated only at the gross
- level. In this study, the mechanical properties of
- single HA molecules were directly measured with an
- optical tweezer technique, yielding a persistence
- length of 4.5 +/- 1.2 nm. This information may help us
- to understand the mechanical roles in the extracellular
- matrix infrastructure, cell attachment, and to design
- tissue engineering and drug delivery systems where the
- mechanical functions of HA are essential.",
- ISSN = "0021-9290",
-}
-
-@Article{delpech01,
- author = "B. Delpech and M. N. Courel and C. Maingonnat and C.
- Chauzy and R. Sesbo{\"u}{\'e} and G. Pratesi",
- title = "Hyaluronan digestion and synthesis in an experimental
- model of metastatic tumour",
- journal = "Histochem J",
- year = "2001",
- month = sep # "/" # oct,
- volume = "33",
- number = "9-10",
- pages = "553--558",
- keywords = "Animals;Culture Media;Humans;Hyaluronic Acid;Hyaluronoglucosaminidase;Mice;Mice, Nude;Neoplasm Metastasis;Neoplasm Transplantation;Neoplasms, Experimental;Tumor Cells, Cultured",
- abstract = "To approach the question of hyaluronan catabolism in
- tumours, we have selected the cancer cell line H460M, a
- highly metastatic cell line in the nude mouse. H460M
- cells release hyaluronidase in culture media at a high
- rate of 57 pU/cell/h, without producing hyaluronan.
- Hyaluronidase was measured in the H460M cell culture
- medium at the optimum pH 3.8, and was not found above
- pH 4.5, with the enzyme-linked sorbent assay technique
- and zymography. Tritiated hyaluronan was digested at pH
- 3.8 by cells or cell membranes as shown by gel
- permeation chromatography, but no activity was recorded
- at pH 7 with this technique. Hyaluronan was digested in
- culture medium by tumour slices, prepared from tumours
- developed in nude mice grafted with H460M cells,
- showing that hyaluronan could be digested in complex
- tissue at physiological pH. Culture of tumour slices
- with tritiated acetate resulted in the accumulation
- within 2 days of radioactive macromolecules in the
- culture medium. The radioactive macromolecular material
- was mostly digested by Streptomyces hyaluronidase,
- showing that hyaluronan was its main component and that
- hyaluronan synthesis occurred together with its
- digestion. These results demonstrate that the
- membrane-associated hyaluronidase of H460M cells can
- act in vivo, and that hyaluronan, which is synthesised
- by the tumour stroma, can be made soluble and reduced
- to a smaller size by tumour cells before being
- internalised and further digested.",
- ISSN = "0018-2214",
-}
-
-@Article{lu98,
- author = "H. Lu and B. Isralewitz and A. Krammer and V. Vogel
- and K. Schulten",
- title = "Unfolding of titin immunoglobulin domains by steered
- molecular dynamics simulation",
- journal = BPJ,
- year = 1998,
- month = aug,
- volume = 75,
- number = 2,
- pages = "662--671",
- keywords = "Amino Acid Sequence;Animals;Computer Simulation;Glutamic Acid;Immunoglobulins;Lysine;Macromolecular Substances;Models, Molecular;Molecular Sequence Data;Muscle Proteins;Myocardium;Proline;Protein Denaturation;Protein Folding;Protein Kinases;Protein Structure, Secondary;Sequence Alignment;Sequence Homology, Amino Acid;Valine",
- abstract = "Titin, a 1-microm-long protein found in striated
- muscle myofibrils, possesses unique elastic and
- extensibility properties in its I-band region, which is
- largely composed of a PEVK region (70\% proline,
- glutamic acid, valine, and lysine residue) and
- seven-strand beta-sandwich immunoglobulin-like (Ig)
- domains. The behavior of titin as a multistage entropic
- spring has been shown in atomic force microscope and
- optical tweezer experiments to partially depend on the
- reversible unfolding of individual Ig domains. We
- performed steered molecular dynamics simulations to
- stretch single titin Ig domains in solution with
- pulling speeds of 0.5 and 1.0 A/ps. Resulting
- force-extension profiles exhibit a single dominant peak
- for each Ig domain unfolding, consistent with the
- experimentally observed sequential, as opposed to
- concerted, unfolding of Ig domains under external
- stretching forces. This force peak can be attributed to
- an initial burst of backbone hydrogen bonds, which
- takes place between antiparallel beta-strands A and B
- and between parallel beta-strands A' and G. Additional
- features of the simulations, including the position of
- the force peak and relative unfolding resistance of
- different Ig domains, can be related to experimental
- observations.",
- ISSN = "0006-3495",
- doi = "10.1016/S0006-3495(98)77556-3",
- url = "http://www.cell.com/biophysj/abstract/S0006-3495(98)77556-3",
- eprint = "http://download.cell.com/biophysj/pdf/PIIS0006349598775563.pdf",
-}
-
-@Article{lu99,
- author = "H. Lu and K. Schulten",
- title = "Steered molecular dynamics simulations of
- force-induced protein domain unfolding",
- journal = PROT,
- year = 1999,
- month = jun,
- day = "01",
- volume = 35,
- number = 4,
- pages = "453--463",
- keywords = "Computer Simulation;Fibronectins;Hydrogen Bonding;Microscopy, Atomic Force;Models, Molecular;Protein Denaturation",
- abstract = "Steered molecular dynamics (SMD), a computer
- simulation method for studying force-induced reactions
- in biopolymers, has been applied to investigate the
- response of protein domains to stretching apart of
- their terminal ends. The simulations mimic atomic force
- microscopy and optical tweezer experiments, but proceed
- on much shorter time scales. The simulations on
- different domains for 0.6 nanosecond each reveal two
- types of protein responses: the first type, arising in
- certain beta-sandwich domains, exhibits nanosecond
- unfolding only after a force above 1,500 pN is applied;
- the second type, arising in a wider class of protein
- domain structures, requires significantly weaker forces
- for nanosecond unfolding. In the first case, strong
- forces are needed to concertedly break a set of
- interstrand hydrogen bonds which protect the domains
- against unfolding through stretching; in the second
- case, stretching breaks backbone hydrogen bonds one by
- one, and does not require strong forces for this
- purpose. Stretching of beta-sandwich (immunoglobulin)
- domains has been investigated further revealing a
- specific relationship between response to mechanical
- strain and the architecture of beta-sandwich domains.",
- ISSN = "0887-3585",
- doi = "10.1002/(SICI)1097-0134(19990601)35:4<453::AID-PROT9>3.0.CO;2-M",
- url = "http://www3.interscience.wiley.com/journal/65000328/abstract",
- eprint = "http://www3.interscience.wiley.com/cgi-bin/fulltext/65000328/PDFSTART",
-}
-
-@Article{krammer99,
- author = "A. Krammer and H. Lu and B. Isralewitz and K. Schulten
- and V. Vogel",
- title = "Forced unfolding of the fibronectin type {III} module
- reveals a tensile molecular recognition switch",
- journal = PNAS,
- year = "1999",
- month = feb,
- day = "16",
- volume = "96",
- number = "4",
- pages = "1351--1356",
- keywords = "Amino Acid Sequence;Binding Sites;Computer Simulation;Crystallography, X-Ray;Disulfides;Fibronectins;Hydrogen Bonding;Integrins;Models, Molecular;Oligopeptides;Protein Conformation;Protein Denaturation;Protein Folding;Protein Structure, Secondary;Protein Structure, Tertiary;Software;Tensile Strength",
- abstract = "The 10th type III module of fibronectin possesses a
- beta-sandwich structure consisting of seven
- beta-strands (A-G) that are arranged in two
- antiparallel sheets. It mediates cell adhesion to
- surfaces via its integrin binding motif, Arg78, Gly79,
- and Asp80 (RGD), which is placed at the apex of the
- loop connecting beta-strands F and G. Steered molecular
- dynamics simulations in which tension is applied to the
- protein's terminal ends reveal that the beta-strand G
- is the first to break away from the module on forced
- unfolding whereas the remaining fold maintains its
- structural integrity. The separation of strand G from
- the remaining fold results in a gradual shortening of
- the distance between the apex of the RGD-containing
- loop and the module surface, which potentially reduces
- the loop's accessibility to surface-bound integrins.
- The shortening is followed by a straightening of the
- RGD-loop from a tight beta-turn into a linear
- conformation, which suggests a further decrease of
- affinity and selectivity to integrins. The RGD-loop
- therefore is located strategically to undergo strong
- conformational changes in the early stretching stages
- of the module and thus constitutes a mechanosensitive
- control of ligand recognition.",
- ISSN = "0027-8424",
-}
-
-@Article{socci99,
- author = "N. D. Socci and J. N. Onuchic and P. G. Wolynes",
- title = "Stretching lattice models of protein folding",
- journal = PNAS,
- year = "1999",
- month = mar,
- day = "02",
- volume = "96",
- number = "5",
- pages = "2031--2035",
- keywords = "Amino Acid Sequence;Drug Stability;Kinetics;Models, Theoretical;Molecular Sequence Data;Peptides;Protein Denaturation;Protein Folding",
- abstract = "A new class of experiments that probe folding of
- individual protein domains uses mechanical stretching
- to cause the transition. We show how stretching forces
- can be incorporated in lattice models of folding. For
- fast folding proteins, the analysis suggests a complex
- relation between the force dependence and the reaction
- coordinate for folding.",
- ISSN = "0027-8424",
-}
-
-@Article{paci99,
- author = "E. Paci and M. Karplus",
- title = "Forced unfolding of fibronectin type 3 modules: an
- analysis by biased molecular dynamics simulations",
- journal = JMB,
- year = "1999",
- month = may,
- day = "07",
- volume = "288",
- number = "3",
- pages = "441--459",
- keywords = "Dimerization;Fibronectins;Humans;Hydrogen Bonding;Microscopy, Atomic Force;Protein Denaturation;Protein Folding",
- abstract = "Titin, an important constituent of vertebrate muscles,
- is a protein of the order of a micrometer in length in
- the folded state. Atomic force microscopy and laser
- tweezer experiments have been used to stretch titin
- molecules to more than ten times their folded lengths.
- To explain the observed relation between force and
- extension, it has been suggested that the
- immunoglobulin and fibronectin domains unfold one at a
- time in an all-or-none fashion. We use molecular
- dynamics simulations to study the forced unfolding of
- two different fibronectin type 3 domains (the ninth,
- 9Fn3, and the tenth, 10Fn3, from human fibronectin) and
- of their heterodimer of known structure. An external
- biasing potential on the N to C distance is employed
- and the protein is treated in the polar hydrogen
- representation with an implicit solvation model. The
- latter provides an adiabatic solvent response, which is
- important for the nanosecond unfolding simulation
- method used here. A series of simulations is performed
- for each system to obtain meaningful results. The two
- different fibronectin domains are shown to unfold in
- the same way along two possible pathways. These involve
- the partial separation of the ``beta-sandwich'', an
- essential structural element, and the unfolding of the
- individual sheets in a stepwise fashion. The biasing
- potential results are confirmed by constant force
- unfolding simulations. For the two connected domains,
- there is complete unfolding of one domain (9Fn3) before
- major unfolding of the second domain (10Fn3).
- Comparison of different models for the potential energy
- function demonstrates that the dominant cohesive
- element in both proteins is due to the attractive van
- der Waals interactions; electrostatic interactions play
- a structural role but appear to make only a small
- contribution to the stabilization of the domains, in
- agreement with other studies of beta-sheet stability.
- The unfolding forces found in the simulations are of
- the order of those observed experimentally, even though
- the speed of the former is more than six orders of
- magnitude greater than that used in the latter.",
- ISSN = "0022-2836",
- doi = "10.1006/jmbi.1999.2670",
-}
-
-@Article{lu00a,
- author = "H. Lu and A. Krammer and B. Isralewitz and V. Vogel
- and K. Schulten",
- title = "Computer modeling of force-induced titin domain
- unfolding",
- journal = "Adv Exp Med Biol",
- year = "2000",
- volume = "481",
- pages = "143--60",
- keywords = "Amino Acid Sequence;Animals;Computer Simulation;Elasticity;Fibronectins;Humans;Hydrogen Bonding;Immunoglobulins;Models, Molecular;Muscle Proteins;Muscle, Skeletal;Myofibrils;Protein Conformation;Protein Denaturation;Protein Kinases;Software",
- abstract = "Titin, a 1 micron long protein found in striated
- muscle myofibrils, possesses unique elastic and
- extensibility properties, and is largely composed of a
- PEVK region and beta-sandwich immunoglobulin (Ig) and
- fibronectin type III (FnIII) domains. The extensibility
- behavior of titin has been shown in atomic force
- microscope and optical tweezer experiments to partially
- depend on the reversible unfolding of individual Ig and
- FnIII domains. We performed steered molecular dynamics
- simulations to stretch single titin Ig domains in
- solution with pulling speeds of 0.1-1.0 A/ps, and FnIII
- domains with a pulling speed of 0.5 A/ps. Resulting
- force-extension profiles exhibit a single dominant peak
- for each domain unfolding, consistent with the
- experimentally observed sequential, as opposed to
- concerted, unfolding of Ig and FnIII domains under
- external stretching forces. The force peaks can be
- attributed to an initial burst of a set of backbone
- hydrogen bonds connected to the domains' terminal
- beta-strands. Constant force stretching simulations,
- applying 500-1000 pN of force, were performed on Ig
- domains. The resulting domain extensions are halted at
- an initial extension of 10 A until the set of all six
- hydrogen bonds connecting terminal beta-strands break
- simultaneously. This behavior is accounted for by a
- barrier separating folded and unfolded states, the
- shape of which is consistent with AFM and chemical
- denaturation data.",
- ISSN = "0065-2598",
- note = "discussion in journal on pages 161--2",
-}
-
-@Article{lu00b,
- author = "H. Lu and K. Schulten",
- title = "The key event in force-induced unfolding of Titin's
- immunoglobulin domains",
- journal = BPJ,
- year = "2000",
- month = jul,
- volume = "79",
- number = "1",
- pages = "51--65",
- keywords = "Amino Acid Sequence;Computer Simulation;Double Bind Interaction;Hydrogen Bonding;Immunoglobulins;Microscopy, Atomic Force;Models, Chemical;Models, Molecular;Molecular Sequence Data;Muscle Proteins;Protein Folding;Protein Kinases;Protein Structure, Tertiary;Stress, Mechanical;Water",
- abstract = "Steered molecular dynamics simulation of force-induced
- titin immunoglobulin domain I27 unfolding led to the
- discovery of a significant potential energy barrier at
- an extension of approximately 14 A on the unfolding
- pathway that protects the domain against stretching.
- Previous simulations showed that this barrier is due to
- the concurrent breaking of six interstrand hydrogen
- bonds (H-bonds) between beta-strands A' and G that is
- preceded by the breaking of two to three hydrogen bonds
- between strands A and B, the latter leading to an
- unfolding intermediate. The simulation results are
- supported by Angstrom-resolution atomic force
- microscopy data. Here we perform a structural and
- energetic analysis of the H-bonds breaking. It is
- confirmed that H-bonds between strands A and B break
- rapidly. However, the breaking of the H-bond between
- strands A' and G needs to be assisted by fluctuations
- of water molecules. In nanosecond simulations, water
- molecules are found to repeatedly interact with the
- protein backbone atoms, weakening individual
- interstrand H-bonds until all six A'-G H-bonds break
- simultaneously under the influence of external
- stretching forces. Only when those bonds are broken can
- the generic unfolding take place, which involves
- hydrophobic interactions of the protein core and exerts
- weaker resistance against stretching than the key
- event.",
- ISSN = "0006-3495",
-}
-
-@Article{kreuzer01,
- author = "H. J. Kreuzer and S. H. Payne",
- title = "Stretching a macromolecule in an atomic force
- microscope: statistical mechanical analysis",
- journal = "Phys Rev E Stat Nonlin Soft Matter Phys",
- year = "2001",
- month = feb,
- day = "23",
- volume = "63",
- number = "2 Pt 1",
- pages = "021906",
- keywords = "Biophysics;Macromolecular Substances;Microscopy, Atomic Force;Models, Statistical;Models, Theoretical;Statistics as Topic",
- abstract = "We formulate the proper statistical mechanics to
- describe the stretching of a macromolecule under a
- force provided by the cantilever of an atomic force
- microscope. In the limit of a soft cantilever the
- generalized ensemble of the coupled molecule/cantilever
- system reduces to the Gibbs ensemble for an isolated
- molecule subject to a constant force in which the
- extension is fluctuating. For a stiff cantilever we
- obtain the Helmholtz ensemble for an isolated molecule
- held at a fixed extension with the force fluctuating.
- Numerical examples are given for poly (ethylene glycol)
- chains.",
- ISSN = "1539-3755",
- url = "http://www.biophysj.org/cgi/content/abstract/80/6/2505",
- eprint = "http://www.biophysj.org/cgi/reprint/80/6/2505.pdf",
-}
-
-@Article{kellermayer97,
- author = "M. S. Kellermayer and S. B. Smith and H. L. Granzier"
- #" and "# CBustamante,
- title = "Folding-unfolding transitions in single titin
- molecules characterized with laser tweezers",
- journal = SCI,
- year = 1997,
- month = may,
- day = 16,
- volume = 276,
- number = 5315,
- pages = "1112--1116",
- keywords = "Amino Acid Sequence;Elasticity;Entropy;Immunoglobulins;Lasers;Models, Chemical;Muscle Contraction;Muscle Proteins;Muscle Relaxation;Muscle, Skeletal;Protein Denaturation;Protein Folding;Protein Kinases;Stress, Mechanical",
- abstract = "Titin, a giant filamentous polypeptide, is believed to
- play a fundamental role in maintaining sarcomeric
- structural integrity and developing what is known as
- passive force in muscle. Measurements of the force
- required to stretch a single molecule revealed that
- titin behaves as a highly nonlinear entropic spring.
- The molecule unfolds in a high-force transition
- beginning at 20 to 30 piconewtons and refolds in a
- low-force transition at approximately 2.5 piconewtons.
- A fraction of the molecule (5 to 40 percent) remains
- permanently unfolded, behaving as a wormlike chain with
- a persistence length (a measure of the chain's bending
- rigidity) of 20 angstroms. Force hysteresis arises from
- a difference between the unfolding and refolding
- kinetics of the molecule relative to the stretch and
- release rates in the experiments, respectively. Scaling
- the molecular data up to sarcomeric dimensions
- reproduced many features of the passive force versus
- extension curve of muscle fibers.",
- ISSN = "0036-8075",
-}
-
-@Article{linke98a,
- author = WLinke #" and M. R. Stockmeier and M. Ivemeyer and
- H. Hosser and P. Mundel",
- title = "Characterizing titin's {I}-band {Ig} domain region as an
- entropic spring",
- journal = JCS,
- year = 1998,
- month = jun,
- volume = "111 (Pt 11)",
- pages = "1567--1574",
- keywords = "Animals;Elasticity;Immunoglobulins;Male;Muscle Proteins;Muscle, Skeletal;Protein Kinases;Rats;Rats, Wistar;Structure-Activity Relationship",
- abstract = "The poly-immunoglobulin domain region of titin,
- located within the elastic section of this giant muscle
- protein, determines the extensibility of relaxed
- myofibrils mainly at shorter physiological lengths. To
- elucidate this region's contribution to titin
- elasticity, we measured the elastic properties of the
- N-terminal I-band Ig region by using
- immunofluorescence/immunoelectron microscopy and
- myofibril mechanics and tried to simulate the results
- with a model of entropic polymer elasticity. Rat psoas
- myofibrils were stained with titin-specific antibodies
- flanking the Ig region at the N terminus and C
- terminus, respectively, to record the extension
- behaviour of that titin segment. The segment's
- end-to-end length increased mainly at small stretch,
- reaching approximately 90\% of the native contour
- length of the Ig region at a sarcomere length of 2.8
- microm. At this extension, the average force per single
- titin molecule, deduced from the steady-state passive
- length-tension relation of myofibrils, was
- approximately 5 or 2.5 pN, depending on whether we
- assumed a number of 3 or 6 titins per half thick
- filament. When the force-extension curve constructed
- for the Ig region was simulated by the wormlike chain
- model, best fits were obtained for a persistence
- length, a measure of the chain's bending rigidity, of
- 21 or 42 nm (for 3 or 6 titins/half thick filament),
- which correctly reproduced the curve for sarcomere
- lengths up to 3.4 microm. Systematic deviations between
- data and fits above that length indicated that forces
- of >30 pN per titin strand may induce unfolding of Ig
- modules. We conclude that stretches of at least 5-6 Ig
- domains, perhaps coinciding with known super repeat
- patterns of these titin modules in the I-band, may
- represent the unitary lengths of the wormlike chain.
- The poly-Ig regions might thus act as compliant
- entropic springs that determine the minute levels of
- passive tension at low extensions of a muscle fiber.",
- ISSN = "0021-9533",
- doi = "",
- url = "http://jcs.biologists.org/cgi/content/abstract/111/11/1567",
- eprint = "http://jcs.biologists.org/cgi/reprint/111/11/1567",
-}
-
-@Article{linke98b,
- author = WLinke #" and M. Ivemeyer and P. Mundel and M. R.
- Stockmeier and B. Kolmerer",
- title = "Nature of {PEVK}-titin elasticity in skeletal
- muscle",
- journal = PNAS,
- year = "1998",
- month = jul,
- day = "07",
- volume = "95",
- number = "14",
- pages = "8052--8057",
- keywords = "Animals;Elasticity;Fluorescent Antibody Technique;Male;Microscopy, Immunoelectron;Muscle Proteins;Muscle, Skeletal;Protein Kinases;Rats;Rats, Wistar;Stress, Mechanical",
- abstract = "A unique sequence within the giant titin molecule, the
- PEVK domain, has been suggested to greatly contribute
- to passive force development of relaxed skeletal muscle
- during stretch. To explore the nature of PEVK
- elasticity, we used titin-specific antibodies to stain
- both ends of the PEVK region in rat psoas myofibrils
- and determined the region's force-extension relation by
- combining immunofluorescence and immunoelectron
- microscopy with isolated myofibril mechanics. We then
- tried to fit the results with recent models of polymer
- elasticity. The PEVK segment elongated substantially at
- sarcomere lengths above 2.4 micro(m) and reached its
- estimated contour length at approximately 3.5 micro(m).
- In immunofluorescently labeled sarcomeres stretched and
- released repeatedly above 3 micro(m), reversible PEVK
- lengthening could be readily visualized. At extensions
- near the contour length, the average force per titin
- molecule was calculated to be approximately 45 pN.
- Attempts to fit the force-extension curve of the PEVK
- segment with a standard wormlike chain model of
- entropic elasticity were successful only for low to
- moderate extensions. In contrast, the experimental data
- also could be correctly fitted at high extensions with
- a modified wormlike chain model that incorporates
- enthalpic elasticity. Enthalpic contributions are
- likely to arise from electrostatic stiffening, as
- evidenced by the ionic-strength dependency of
- titin-based myofibril stiffness; at high stretch,
- hydrophobic effects also might become relevant. Thus,
- at physiological muscle lengths, the PEVK region does
- not function as a pure entropic spring. Rather, PEVK
- elasticity may have both entropic and enthalpic origins
- characterizable by a polymer persistence length and a
- stretch modulus.",
- ISSN = "0027-8424",
-}
-
-@Article{smith96,
- author = "S. B. Smith and Y. Cui and "# CBustamante,
- title = "Overstretching {B}-{DNA}: the elastic response of
- individual double-stranded and single-stranded {DNA}
- molecules",
- journal = SCI,
- year = 1996,
- month = feb,
- day = 09,
- volume = 271,
- number = 5250,
- pages = "795--799",
- keywords = "Base Composition;Chemistry, Physical;DNA;DNA, Single-Stranded;Elasticity;Nucleic Acid Conformation;Osmolar Concentration;Thermodynamics",
- abstract = "Single molecules of double-stranded DNA (dsDNA) were
- stretched with force-measuring laser tweezers. Under a
- longitudinal stress of approximately 65 piconewtons
- (pN), dsDNA molecules in aqueous buffer undergo a
- highly cooperative transition into a stable form with
- 5.8 angstroms rise per base pair, that is, 70\% longer
- than B form dsDNA. When the stress was relaxed below 65
- pN, the molecules rapidly and reversibly contracted to
- their normal contour lengths. This transition was
- affected by changes in the ionic strength of the medium
- and the water activity or by cross-linking of the two
- strands of dsDNA. Individual molecules of
- single-stranded DNA were also stretched giving a
- persistence length of 7.5 angstroms and a stretch
- modulus of 800 pN. The overstretched form may play a
- significant role in the energetics of DNA
- recombination.",
- ISSN = "0036-8075",
-}
-
-@Article{klimov99,
- author = DKlimov #" and "# DThirumalai,
- title = "Stretching single-domain proteins: phase diagram and
- kinetics of force-induced unfolding",
- journal = PNAS,
- year = "1999",
- month = may,
- day = "25",
- volume = "96",
- number = "11",
- pages = "6166--6170",
- keywords = "Amino Acid Sequence;Kinetics;Models, Chemical;Protein Denaturation;Protein Folding;Proteins;Thermodynamics;Time Factors",
- abstract = "Single-molecule force spectroscopy reveals unfolding
- of domains in titin on stretching. We provide a
- theoretical framework for these experiments by
- computing the phase diagrams for force-induced
- unfolding of single-domain proteins using lattice
- models. The results show that two-state folders (at
- zero force) unravel cooperatively, whereas stretching
- of non-two-state folders occurs through intermediates.
- The stretching rates of individual molecules show great
- variations reflecting the heterogeneity of
- force-induced unfolding pathways. The approach to the
- stretched state occurs in a stepwise ``quantized''
- manner. Unfolding dynamics and forces required to
- stretch proteins depend sensitively on topology. The
- unfolding rates increase exponentially with force f
- till an optimum value, which is determined by the
- barrier to unfolding when f = 0. A mapping of these
- results to proteins shows qualitative agreement with
- force-induced unfolding of Ig-like domains in titin. We
- show that single-molecule force spectroscopy can be
- used to map the folding free energy landscape of
- proteins in the absence of denaturants.",
- ISSN = "0027-8424",
-}
-
-@Article{cornish07,
- author = "Peter V. Cornish and Taekjip Ha",
- title = "A survey of single-molecule techniques in chemical
- biology",
- journal = "ACS Chem Biol",
- year = "2007",
- month = jan,
- day = "23",
- volume = "2",
- number = "1",
- pages = "53--61",
- keywords = "Animals;Data Collection;Humans;Microscopy, Atomic Force;Microscopy, Fluorescence;Molecular Biology",
- abstract = "Single-molecule methods have revolutionized scientific
- research by rendering the investigation of
- once-inaccessible biological processes amenable to
- scientific inquiry. Several of the more established
- techniques will be emphasized in this Review, including
- single-molecule fluorescence microscopy, optical
- tweezers, and atomic force microscopy, which have been
- applied to many diverse biological processes. Serving
- as a taste of all the exciting research currently
- underway, recent examples will be discussed of
- translocation of RNA polymerase, myosin VI walking,
- protein folding, and enzyme activity. We will end by
- providing an assessment of what the future holds,
- including techniques that are currently in
- development.",
- ISSN = "1554-8937",
- doi = "10.1021/cb600342a",
-}
-
-@Article{rief97a,
- author = MRief #" and "# FOesterhelt #" and Heymann and "# HGaub,
- title = "Single Molecule Force Spectroscopy on Polysaccharides
- by Atomic Force Microscopy",
- journal = SCI,
- year = 1997,
- month = feb,
- day = 28,
- volume = 275,
- number = 5304,
- pages = "1295--1297",
- abstract = "Recent developments in piconewton instrumentation
- allow the manipulation of single molecules and
- measurements of intermolecular as well as
- intramolecular forces. Dextran filaments linked to a
- gold surface were probed with the atomic force
- microscope tip by vertical stretching. At low forces
- the deformation of dextran was found to be dominated by
- entropic forces and can be described by the Langevin
- function with a 6 angstrom Kuhn length. At elevated
- forces the strand elongation was governed by a twist of
- bond angles. At higher forces the dextran filaments
- underwent a distinct conformational change. The polymer
- stiffened and the segment elasticity was dominated by
- the bending of bond angles. The conformational change
- was found to be reversible and was corroborated by
- molecular dynamics calculations.",
- ISSN = "1095-9203",
- doi = "10.1126/science.275.5304.1295",
- url = "http://www.sciencemag.org/cgi/content/abstract/275/5304/1295",
- eprint = "http://www.sciencemag.org/cgi/reprint/275/5304/1295.pdf",
-}
-
-@Article{bustamante08,
- author = CBustamante,
- title = "In singulo Biochemistry: When Less Is More",
- journal = ARBC,
- year = 2008,
- volume = 77,
- pages = "45--50",
- abstract = "It has been over one-and-a-half decades since methods
- of single-molecule detection and manipulation were
- first introduced in biochemical research. Since then,
- the application of these methods to an expanding
- variety of problems has grown at a vertiginous pace.
- While initially many of these experiments led more to
- confirmatory results than to new discoveries, today
- single-molecule methods are often the methods of choice
- to establish new mechanism-based results in biochemical
- research. Throughout this process, improvements in the
- sensitivity, versatility, and both spatial and temporal
- resolution of these techniques has occurred hand in
- hand with their applications. We discuss here some of
- the advantages of single-molecule methods over their
- bulk counterparts and argue that these advantages
- should help establish them as essential tools in the
- technical arsenal of the modern biochemist.",
- ISSN = "0066-4154",
- doi = "10.1146/annurev.biochem.012108.120952",
- url = "http://arjournals.annualreviews.org/doi/abs/10.1146/annurev.biochem.012108.120952",
- eprint = "http://arjournals.annualreviews.org/doi/pdf/10.1146/annurev.biochem.012108.120952",
-}
-
-@Article{borgia08,
- author = " Borgia and Williams and Clarke",
- title = "Single-Molecule Studies of Protein Folding",
- journal = ARBC,
- year = 2008,
- month = jul,
- day = "07",
- volume = 77,
- pages = "101--125",
- abstract = "Although protein-folding studies began several decades
- ago, it is only recently that the tools to analyze
- protein folding at the single-molecule level have been
- developed. Advances in single-molecule fluorescence and
- force spectroscopy techniques allow investigation of
- the folding and dynamics of single protein molecules,
- both at equilibrium and as they fold and unfold. The
- experiments are far from simple, however, both in
- execution and in interpretation of the results. In this
- review, we discuss some of the highlights of the work
- so far and concentrate on cases where comparisons with
- the classical experiments can be made. We conclude
- that, although there have been relatively few startling
- insights from single-molecule studies, the rapid
- progress that has been made suggests that these
- experiments have significant potential to advance our
- understanding of protein folding. In particular, new
- techniques offer the possibility to explore regions of
- the energy landscape that are inaccessible to classical
- ensemble measurements and, perhaps, to observe rare
- events undetectable by other means.",
- ISSN = "0066-4154",
- doi = "10.1146/annurev.biochem.77.060706.093102",
- url = "http://arjournals.annualreviews.org/doi/abs/10.1146/annurev.biochem.77.060706.093102",
- eprint = "http://arjournals.annualreviews.org/doi/pdf/10.1146/annurev.biochem.77.060706.093102",
-}
-
-@Article{linke08,
- author = WLinke #" and Anika Gr{\"u}tzner",
- title = "Pulling single molecules of titin by {AFM}--recent
- advances and physiological implications",
- journal = "Pflugers Arch",
- year = "2008",
- month = apr,
- day = "06",
- volume = "456",
- number = "1",
- pages = "101--115",
- abstract = "Perturbation of a protein away from its native state
- by mechanical stress is a physiological process
- immanent to many cells. The mechanical stability and
- conformational diversity of proteins under force
- therefore are important parameters in nature.
- Molecular-level investigations of ``mechanical
- proteins'' have enjoyed major breakthroughs over the
- last decade, a development to which atomic force
- microscopy (AFM) force spectroscopy has been
- instrumental. The giant muscle protein titin continues
- to be a paradigm model in this field. In this paper, we
- review how single-molecule mechanical measurements of
- titin using AFM have served to elucidate key aspects of
- protein unfolding-refolding and mechanisms by which
- biomolecular elasticity is attained. We outline recent
- work combining protein engineering and AFM force
- spectroscopy to establish the mechanical behavior of
- titin domains using molecular ``fingerprinting.''
- Furthermore, we summarize AFM force-extension data
- demonstrating different mechanical stabilities of
- distinct molecular-spring elements in titin, compare
- AFM force-extension to novel force-ramp/force-clamp
- studies, and elaborate on exciting new results showing
- that AFM force clamp captures the unfolding and
- refolding trajectory of single mechanical proteins.
- Along the way, we discuss the physiological
- implications of the findings, not least with respect to
- muscle mechanics. These studies help us understand how
- proteins respond to forces in cells and how
- mechanosensing and mechanosignaling events may proceed
- in vivo.",
- ISSN = "0031-6768",
- doi = "10.1007/s00424-007-0389-x",
-}
-
-@Article{law03,
- author = "Richard Law and George Liao and Sandy Harper and
- Guoliang Yang and David W. Speicher and Dennis E.
- Discher",
- title = "Pathway shifts and thermal softening in
- temperature-coupled forced unfolding of spectrin
- domains",
- journal = BPJ,
- year = "2003",
- month = nov,
- volume = "85",
- number = "5",
- pages = "3286--3293",
- keywords = "Circular Dichroism;Elasticity;Heat;Microscopy, Atomic Force;Physical Stimulation;Protein Conformation;Protein Denaturation;Protein Folding;Protein Structure, Tertiary;Spectrin;Stress, Mechanical;Temperature",
- abstract = "Pathways of unfolding a protein depend in principle on
- the perturbation-whether it is temperature, denaturant,
- or even forced extension. Widely-shared, helical-bundle
- spectrin repeats are known to melt at temperatures as
- low as 40-45 degrees C and are also known to unfold via
- multiple pathways as single molecules in atomic force
- microscopy. Given the varied roles of spectrin family
- proteins in cell deformability, we sought to determine
- the coupled effects of temperature on forced unfolding.
- Bimodal distributions of unfolding intervals are seen
- at all temperatures for the four-repeat beta(1-4)
- spectrin-an alpha-actinin homolog. The major unfolding
- length corresponds to unfolding of a single repeat, and
- a minor peak at twice the length corresponds to tandem
- repeats. Increasing temperature shows fewer tandem
- events but has no effect on unfolding intervals. As T
- approaches T(m), however, mean unfolding forces in
- atomic force microscopy also decrease; and circular
- dichroism studies demonstrate a nearly proportional
- decrease of helical content in solution. The results
- imply a thermal softening of a helical linker between
- repeats which otherwise propagates a helix-to-coil
- transition to adjacent repeats. In sum, structural
- changes with temperature correlate with both
- single-molecule unfolding forces and shifts in
- unfolding pathways.",
- ISSN = "0006-3495",
-}
-
-@Article{smith92,
- author = "S. B. Smith and L. Finzi and "# CBustamante,
- title = "Direct mechanical measurements of the elasticity of
- single {DNA} molecules by using magnetic beads",
- journal = SCI,
- year = 1992,
- month = nov,
- day = 13,
- volume = 258,
- number = 5085,
- pages = "1122--1126",
- keywords = "Chemistry, Physical;Cisplatin;DNA;Elasticity;Ethidium;Glass;Indoles;Intercalating Agents;Magnetics;Mathematics;Microspheres",
- abstract = "Single DNA molecules were chemically attached by one
- end to a glass surface and by their other end to a
- magnetic bead. Equilibrium positions of the beads were
- observed in an optical microscope while the beads were
- acted on by known magnetic and hydrodynamic forces.
- Extension versus force curves were obtained for
- individual DNA molecules at three different salt
- concentrations with forces between 10(-14) and 10(-11)
- newtons. Deviations from the force curves predicted by
- the freely jointed chain model suggest that DNA has
- significant local curvature in solution. Ethidium
- bromide and 4',6-diamidino-2-phenylindole had little
- effect on the elastic response of the molecules, but
- their extent of intercalation was directly measured.
- Conversely, the effect of bend-inducing
- cis-diamminedichloroplatinum (II) was large and
- supports the hypothesis of natural curvature in DNA.",
- ISSN = "0036-8075",
- doi = "10.1126/science.1439819",
- url = "http://www.sciencemag.org/cgi/content/abstract/258/5085/1122",
- eprint = "http://www.sciencemag.org/cgi/reprint/258/5085/1122.pdf",
-}
-
-@Article{strick96,
- author = "T. R. Strick and J. F. Allemand and D. Bensimon and A.
- Bensimon and V. Croquette",
- title = "The elasticity of a single supercoiled {DNA}
- molecule",
- journal = SCI,
- year = 1996,
- month = mar,
- day = 29,
- volume = 271,
- number = 5257,
- pages = "1835--1837",
- keywords = "Bacteriophage lambda;DNA, Superhelical;DNA, Viral;Elasticity;Magnetics;Nucleic Acid Conformation;Temperature",
- abstract = "Single linear DNA molecules were bound at multiple
- sites at one extremity to a treated glass cover slip
- and at the other to a magnetic bead. The DNA was
- therefore torsionally constrained. A magnetic field was
- used to rotate the beads and thus to coil and pull the
- DNA. The stretching force was determined by analysis of
- the Brownian fluctuations of the bead. Here the elastic
- behavior of individual lambda DNA molecules over- and
- underwound by up to 500 turns was studied. A sharp
- transition was discovered from a low to a high
- extension state at a force of approximately 0.45
- piconewtons for underwound molecules and at a force of
- approximately 3 piconewtons for overwound ones. These
- transitions, probably reflecting the formation of
- alternative structures in stretched coiled DNA
- molecules, might be relevant for DNA transcription and
- replication.",
- ISSN = "0036-8075",
-}
-
-@Article{allemand03,
- author = "Jean-Fran\c{c}ois Allemand and David Bensimon and
- Vincent Croquette",
- title = "Stretching {DNA} and {RNA} to probe their interactions
- with proteins",
- journal = "Curr Opin Struct Biol",
- year = "2003",
- month = jun,
- volume = "13",
- number = "3",
- pages = "266--274",
- keywords = "DNA;DNA-Binding Proteins;Isomerases;Micromanipulation;Microscopy, Atomic Force;Nucleic Acid Conformation;Nucleotidyltransferases",
- abstract = "When interacting with a single stretched DNA, many
- proteins modify its end-to-end distance. This distance
- can be monitored in real time using various
- micromanipulation techniques that were initially used
- to determine the elastic properties of bare nucleic
- acids and their mechanically induced structural
- transitions. These methods are currently being applied
- to the study of DNA enzymes such as DNA and RNA
- polymerases, topoisomerases and structural proteins
- such as RecA. They permit the measurement of the
- probability distributions of the rate, processivity,
- on-time, affinity and efficiency for a large variety of
- DNA-based molecular motors.",
- ISSN = "0959-440X",
-}
-
-@Article{rief99,
- author = MRief #" and H. Clausen-Schaumann and "# HGaub,
- title = "Sequence-dependent mechanics of single {DNA}
- molecules",
- journal = NSB,
- year = 1999,
- month = apr,
- volume = 6,
- number = 4,
- pages = "346--349",
- keywords = "Bacteriophage lambda;Base Pairing;DNA;DNA, Single-Stranded;DNA, Viral;Gold;Mechanics;Microscopy, Atomic Force;Nucleotides;Spectrum Analysis;Thermodynamics",
- abstract = "Atomic force microscope-based single-molecule force
- spectroscopy was employed to measure sequence-dependent
- mechanical properties of DNA by stretching individual
- DNA double strands attached between a gold surface and
- an AFM tip. We discovered that in lambda-phage DNA the
- previously reported B-S transition, where 'S'
- represents an overstretched conformation, at 65 pN is
- followed by a nonequilibrium melting transition at 150
- pN. During this transition the DNA is split into single
- strands that fully recombine upon relaxation. The
- sequence dependence was investigated in comparative
- studies with poly(dG-dC) and poly(dA-dT) DNA. Both the
- B-S and the melting transition occur at significantly
- lower forces in poly(dA-dT) compared to poly(dG-dC). We
- made use of the melting transition to prepare single
- poly(dG-dC) and poly(dA-dT) DNA strands that upon
- relaxation reannealed into hairpins as a result of
- their self-complementary sequence. The unzipping of
- these hairpins directly revealed the base
- pair-unbinding forces for G-C to be 20 +/- 3 pN and for
- A-T to be 9 +/- 3 pN.",
- ISSN = "1072-8368",
- doi = "10.1038/7582",
- url = "http://www.nature.com/nsmb/journal/v6/n4/abs/nsb0499_346.html",
- eprint = "http://www.nature.com/nsmb/journal/v6/n4/pdf/nsb0499_346.pdf",
-}
-
-@article{levy02,
- author= RLevy #" and "# MMaaloum,
- title="Measuring the spring constant of atomic force microscope
- cantilevers: thermal fluctuations and other methods",
- journal=NANOTECH,
- volume=13,
- number=1,
- pages="33--37",
- year=2002,
- abstract={Knowledge of the interaction forces between surfaces
- gained using an atomic force microscope (AFM) is
- crucial in a variety of industrial and scientific
- applications and necessitates a precise knowledge of
- the cantilever spring constant. Many methods have
- been devised to experimentally determine the spring
- constants of AFM cantilevers. The thermal
- fluctuation method is elegant but requires a
- theoretical model of the bending modes. For a
- rectangular cantilever, this model is available
- (Butt and Jaschke). Detailed thermal fluctuation
- measurements of a series of AFM cantilever beams
- have been performed in order to test the validity
- and accuracy of the recent theoretical models. The
- spring constant of rectangular cantilevers can also
- be determined easily with the method of Sader and
- White. We found very good agreement between the two
- methods. In the case of the V-shaped cantilever, we
- have shown that the thermal fluctuation method is a
- valid and accurate approach to the evaluation of the
- spring constant. A comparison between this method
- and those of Sader-Neumeister and of Ducker has been
- established. In some cases, we found disagreement
- between these two methods; the effect of
- non-conservation of material properties over all
- cantilevers from a single chip is qualitatively
- invoked.},
- url="http://stacks.iop.org/0957-4484/13/33",
- doi="10.1088/0957-4484/13/1/307",
- project = "Cantilever Calibration",
- note = "Good review of thermal calibration to 2002, but not much on
- the derviation of the Lorentzian fit.",
-}
-
-@Article{chyan04,
- author = "Chia-Lin Chyan and Fan-Chi Lin and Haibo Peng and
- Jian-Min Yuan and Chung-Hung Chang and Sheng-Hsien Lin
- and "# GYang,
- title = "Reversible mechanical unfolding of single ubiquitin
- molecules",
- journal = BPJ,
- year = 2004,
- month = dec,
- day = 10,
- volume = 87,
- number = 6,
- pages = "3995--4006",
- keywords = "Computer Simulation;Elasticity;Mechanics;Micromanipulation;Microscopy, Atomic Force;Models, Chemical;Models, Molecular;Protein Conformation;Protein Denaturation;Protein Folding;Stress, Mechanical;Structure-Activity Relationship;Ubiquitin",
- abstract = "Single-molecule manipulation techniques have enabled
- the characterization of the unfolding and refolding
- process of individual protein molecules, using
- mechanical forces to initiate the unfolding transition.
- Experimental and computational results following this
- approach have shed new light on the mechanisms of the
- mechanical functions of proteins involved in several
- cellular processes, as well as revealed new information
- on the protein folding/unfolding free-energy
- landscapes. To investigate how protein molecules of
- different folds respond to a stretching force, and to
- elucidate the effects of solution conditions on the
- mechanical stability of a protein, we synthesized
- polymers of the protein ubiquitin and characterized the
- force-induced unfolding and refolding of individual
- ubiquitin molecules using an
- atomic-force-microscope-based single-molecule
- manipulation technique. The ubiquitin molecule was
- highly resistant to a stretching force, and the
- mechanical unfolding process was reversible. A model
- calculation based on the hydrogen-bonding pattern in
- the native structure was performed to explain the
- origin of this high mechanical stability. Furthermore,
- pH effects were studied and it was found that the
- forces required to unfold the protein remained constant
- within a pH range around the neutral value, and forces
- decreased as the solution pH was lowered to more acidic
- values.",
- ISSN = "0006-3495",
- doi = "10.1529/biophysj.104.042754",
- url = "http://www.cell.com/biophysj/abstract/S0006-3495(04)73864-3",
- eprint = "http://download.cell.com/biophysj/pdf/PIIS0006349504738643.pdf",
-}
-% TODO: preceding url seems dead...
-
-@Article{carrion-vazquez03,
- author = MCarrionVazquez #" and "# HLi #" and "# HLu #" and "#
- PMarszalek #" and "# AOberhauser #" and "# JFernandez,
- title = "The mechanical stability of ubiquitin is linkage
- dependent",
- journal = NSB,
- year = "2003",
- month = sep,
- day = "17",
- volume = "10",
- number = "9",
- pages = "738--743",
- keywords = "Humans;Hydrogen Bonding;Kinetics;Lysine;Microscopy, Atomic Force;Models, Molecular;Polyubiquitin;Protein Binding;Protein Folding;Protein Structure, Tertiary;Ubiquitin",
- abstract = "Ubiquitin chains are formed through the action of a
- set of enzymes that covalently link ubiquitin either
- through peptide bonds or through isopeptide bonds
- between their C terminus and any of four lysine
- residues. These naturally occurring polyproteins allow
- one to study the mechanical stability of a protein,
- when force is applied through different linkages. Here
- we used single-molecule force spectroscopy techniques
- to examine the mechanical stability of N-C-linked and
- Lys48-C-linked ubiquitin chains. We combined these
- experiments with steered molecular dynamics (SMD)
- simulations and found that the mechanical stability and
- unfolding pathway of ubiquitin strongly depend on the
- linkage through which the mechanical force is applied
- to the protein. Hence, a protein that is otherwise very
- stable may be easily unfolded by a relatively weak
- mechanical force applied through the right linkage.
- This may be a widespread mechanism in biological
- systems.",
- ISSN = "1072-8368",
- doi = "10.1038/nsb965",
- url = "http://www.nature.com/nsmb/journal/v10/n9/abs/nsb965.html",
- eprint = "http://www.nature.com/nsmb/journal/v10/n9/pdf/nsb965.pdf",
-}
-
-@Article{dicola05,
- key = "diCola05",
- author = EDCola #" and "#"Thomas A. Waigh and John Trinick
- and Larissa Tskhovrebova and Ahmed Houmeida and Wim
- Pyckhout-Hintzen and Charles Dewhurst",
- title = "Persistence length of titin from rabbit skeletal
- muscles measured with scattering and microrheology
- techniques",
- journal = BPJ,
- year = "2005",
- month = jun,
- day = "25",
- volume = "88",
- number = "6",
- pages = "4095--4106",
- keywords = "Animals;Biophysics;Elasticity;Light;Muscle Proteins;Muscle, Skeletal;Neutrons;Protein Conformation;Protein Kinases;Rabbits;Rheology;Scattering, Radiation;Temperature",
- abstract = "The persistence length of titin from rabbit skeletal
- muscles was measured using a combination of static and
- dynamic light scattering, and neutron small angle
- scattering. Values of persistence length in the range
- 9-16 nm were found for titin-II, which corresponds to
- mainly physiologically inelastic A-band part of the
- protein, and for a proteolytic fragment with 100-nm
- contour length from the physiologically elastic I-band
- part. The ratio of the hydrodynamic radius to the
- static radius of gyration indicates that the proteins
- obey Gaussian statistics typical of a flexible polymer
- in a -solvent. Furthermore, measurements of the
- flexibility as a function of temperature demonstrate
- that titin-II and the I-band titin fragment experience
- a similar denaturation process; unfolding begins at 318
- K and proceeds in two stages: an initial gradual 50\%
- change in persistence length is followed by a sharp
- unwinding transition at 338 K. Complementary
- microrheology (video particle tracking) measurements
- indicate that the viscoelasticity in dilute solution
- behaves according to the Flory/Fox model, providing a
- value of the radius of gyration for titin-II (63 +/- 1
- nm) in agreement with static light scattering and small
- angle neutron scattering results.",
- ISSN = "0006-3495",
- doi = "10.1529/biophysj.104.054908",
- url = "http://www.cell.com/biophysj/retrieve/pii/S0006349505734603",
- eprint = "http://download.cell.com/biophysj/pdf/PIIS0006349505734603.pdf",
-}
-
-@Article{tshiprut08,
- author = "Z. Tshiprut and J. Klafter and M. Urbakh",
- title = "Single-molecule pulling experiments: when the
- stiffness of the pulling device matters",
- journal = BPJ,
- year = "2008",
- month = sep,
- day = "15",
- volume = "95",
- number = "6",
- pages = "L42--L44",
- abstract = "Using Langevin modeling, we investigate the role of
- the experimental setup on the unbinding forces measured
- in single-molecule pulling experiments. We demonstrate
- that the stiffness of the pulling device, K(eff), may
- influence the unbinding forces through its effect on
- the barrier heights for both unbinding and rebinding
- processes. Under realistic conditions the effect of
- K(eff) on the rebinding barrier is shown to play the
- most important role. This results in a significant
- increase of the mean unbinding force with the stiffness
- for a given loading rate. Thus, in contrast to the
- phenomenological Bell model, we find that the loading
- rate (the multiplicative value K(eff)V, V being the
- pulling velocity) is not the only control parameter
- that determines the mean unbinding force. If interested
- in intrinsic properties of a molecular system, we
- recommend probing the system in the parameter range
- corresponding to a weak spring and relatively high
- loading rates where rebinding is negligible.",
- ISSN = "1542-0086",
- doi = "10.1529/biophysj.108.141580",
- eprint = "http://www.biophysj.org/cgi/reprint/95/6/L42.pdf",
- note = "Cites \citet{dudko03} for Kramers' description of
- irreversible rupture, and claims it is required to
- explain the deviations in $\avg{F}$ at the same loading
- rate. Proposes Moese equation as an example
- potential. Cites \citet{walton08} for experimental
- evidence of $\avg{F}$ increasing with linker stiffness.",
-}
-
-@Article{walton08,
- author = "Emily B. Walton and Sunyoung Lee and Krystyn J. {Van
- Vliet}",
- title = "Extending {B}ell's model: how force transducer stiffness
- alters measured unbinding forces and kinetics of
- molecular complexes",
- journal = BPJ,
- year = "2008",
- month = apr,
- day = "01",
- volume = "94",
- number = "7",
- pages = "2621--2630",
- keywords = "Biotin;Computer Simulation;Elasticity;Kinetics;Mechanotransduction, Cellular;Models, Chemical;Models, Molecular;Molecular Motor Proteins;Motion;Streptavidin;Stress, Mechanical;Transducers",
- abstract = "Forced unbinding of complementary macromolecules such
- as ligand-receptor complexes can reveal energetic and
- kinetic details governing physiological processes
- ranging from cellular adhesion to drug metabolism.
- Although molecular-level experiments have enabled
- sampling of individual ligand-receptor complex
- dissociation events, disparities in measured unbinding
- force F(R) among these methods lead to marked variation
- in inferred binding energetics and kinetics at
- equilibrium. These discrepancies are documented for
- even the ubiquitous ligand-receptor pair,
- biotin-streptavidin. We investigated these disparities
- and examined atomic-level unbinding trajectories via
- steered molecular dynamics simulations, as well as via
- molecular force spectroscopy experiments on
- biotin-streptavidin. In addition to the well-known
- loading rate dependence of F(R) predicted by Bell's
- model, we find that experimentally accessible
- parameters such as the effective stiffness of the force
- transducer k can significantly perturb the energy
- landscape and the apparent unbinding force of the
- complex for sufficiently stiff force transducers.
- Additionally, at least 20\% variation in unbinding
- force can be attributed to minute differences in
- initial atomic positions among energetically and
- structurally comparable complexes. For force
- transducers typical of molecular force spectroscopy
- experiments and atomistic simulations, this energy
- barrier perturbation results in extrapolated energetic
- and kinetic parameters of the complex that depend
- strongly on k. We present a model that explicitly
- includes the effect of k on apparent unbinding force of
- the ligand-receptor complex, and demonstrate that this
- correction enables prediction of unbinding distances
- and dissociation rates that are decoupled from the
- stiffness of actual or simulated molecular linkers.",
- ISSN = "1542-0086",
- doi = "10.1529/biophysj.107.114454",
- note = "Some detailed estimates at U(x).",
-}
-
-@Article{Ganchev2008,
- author = "Dragomir N. Ganchev and Nathan J. Cobb and Krystyna
- Surewicz and Witold K. Surewicz",
- title = "Nanomechanical properties of human prion protein
- amyloid as probed by force spectroscopy",
- journal = BPJ,
- year = "2008",
- month = sep,
- day = "15",
- volume = "95",
- number = "6",
- pages = "2909--2915",
- abstract = "Amyloids are associated with a number of protein
- misfolding disorders, including prion diseases. In this
- study, we used single-molecule force spectroscopy to
- characterize the nanomechanical properties and
- molecular structure of amyloid fibrils formed by human
- prion protein PrP90-231. Force-extension curves
- obtained by specific attachment of a gold-covered
- atomic force microscope tip to engineered Cys residues
- could be described by the worm-like chain model for
- entropic elasticity of a polymer chain, with the size
- of the N-terminal segment that could be stretched
- entropically depending on the tip attachment site. The
- data presented here provide direct information about
- the forces required to extract an individual monomer
- from the core of the PrP90-231 amyloid, and indicate
- that the beta-sheet core of this amyloid starts at
- residue approximately 164-169. The latter finding has
- important implications for the ongoing debate regarding
- the structure of PrP amyloid.",
- ISSN = "1542-0086",
- doi = "10.1529/biophysj.108.133108",
-}
-
-@Article{Lois2008,
- author = "Gregg Lois and Jerzy Blawzdziewicz and Corey S.
- O'Hern",
- title = "Reliable protein folding on complex energy landscapes:
- the free energy reaction path",
- journal = BPJ,
- year = "2008",
- month = sep,
- day = "15",
- volume = "95",
- number = "6",
- pages = "2692--2701",
- abstract = "A theoretical framework is developed to study the
- dynamics of protein folding. The key insight is that
- the search for the native protein conformation is
- influenced by the rate r at which external parameters,
- such as temperature, chemical denaturant, or pH, are
- adjusted to induce folding. A theory based on this
- insight predicts that 1), proteins with complex energy
- landscapes can fold reliably to their native state; 2),
- reliable folding can occur as an equilibrium or
- out-of-equilibrium process; and 3), reliable folding
- only occurs when the rate r is below a limiting value,
- which can be calculated from measurements of the free
- energy. We test these predictions against numerical
- simulations of model proteins with a single energy
- scale.",
- ISSN = "1542-0086",
- doi = "10.1529/biophysj.108.133132",
-}
-
-@article{walton86,
- author={Alan J Walton},
- title={The Abbe theory of imaging: an alternative derivation of the resolution limit},
- journal={European Journal of Physics},
- volume={7},
- number={1},
- pages={62--63},
- url={http://stacks.iop.org/0143-0807/7/62},
- year={1986}
-}
-
-@Article{evans01,
- author = "E. Evans",
- title = "Probing the relation between force--lifetime--and
- chemistry in single molecular bonds",
- journal = "Annu Rev Biophys Biomol Struct",
- year = "2001",
- volume = "30",
- pages = "105--128",
- keywords = "Biophysics;Kinetics;Microscopy, Atomic Force;Models, Chemical;Protein Binding;Spectrum Analysis;Time Factors",
- abstract = "On laboratory time scales, the energy landscape of a
- weak bond along a dissociation pathway is fully
- explored through Brownian-thermal excitations, and
- energy barriers become encoded in a dissociation time
- that varies with applied force. Probed with ramps of
- force over an enormous range of rates (force/time),
- this kinetic profile is transformed into a dynamic
- spectrum of bond rupture force as a function of loading
- rate. On a logarithmic scale in loading rate, the force
- spectrum provides an easy-to-read map of the prominent
- energy barriers traversed along the force-driven
- pathway and exposes the differences in energy between
- barriers. In this way, the method of dynamic force
- spectroscopy (DFS) is being used to probe the complex
- relation between force-lifetime-and chemistry in single
- molecular bonds. Most important, DFS probes the inner
- world of molecular interactions to reveal barriers that
- are difficult or impossible to detect in assays of near
- equilibrium dissociation but that determine bond
- lifetime and strength under rapid detachment. To use an
- ultrasensitive force probe as a spectroscopic tool, we
- need to understand the physics of bond dissociation
- under force, the impact of experimental technique on
- the measurement of detachment force (bond strength),
- the consequences of complex interactions in
- macromolecular bonds, and effects of multiply-bonded
- attachments.",
- ISSN = "1056-8700",
- doi = "10.1146/annurev.biophys.30.1.105",
- url = "http://arjournals.annualreviews.org/doi/abs/10.1146%2Fannurev.biophys.30.1.105",
-}
-@Article{berk91,
- author = "D. Berk and E. Evans",
- title = "Detachment of agglutinin-bonded red blood cells.
- {III}. Mechanical analysis for large contact areas",
- journal = BPJ,
- year = "1991",
- month = apr,
- volume = "59",
- number = "4",
- pages = "861--872",
- keywords = "Cell Adhesion;Erythrocyte Membrane;Erythrocytes;Hemagglutination;Hemagglutinins;Humans;Kinetics;Mathematics;Models, Biological;Pressure",
- abstract = "An experimental method and analysis are introduced
- which provide direct quantitation of the strength of
- adhesive contact for large agglutinin-bonded regions
- between macroscopically smooth membrane capsules (e.g.,
- red blood cells). The approach yields intrinsic
- properties for separation of adherent regions
- independent of mechanical deformation of the membrane
- capsules during detachment. Conceptually, the
- micromechanical method involves one rigid test-capsule
- surface (in the form of a perfect sphere) held fixed by
- a micropipette and a second deformable capsule
- maneuvered with another micropipette to force contact
- with the test capsule. Only the test capsule is bound
- with agglutinin so that the maximum number of
- cross-bridges can be formed without steric
- interference. Following formation of a large adhesion
- region by mechanical impingement, the deformable
- capsule is detached from the rigid capsule surface by
- progressive aspiration into the micropipette. For the
- particular case modeled here, the deformable capsule is
- assumed to be a red blood cell which is preswollen by
- slight osmotic hydration before the test. The caliber
- of the detachment pipette is chosen so that the capsule
- will form a smooth cylindrical ``piston'' inside the
- pipette as it is aspirated. Because of the high
- flexibility of the membrane, the capsule naturally
- seals against the tube wall by pressurization even
- though it does not adhere to the glass. This
- arrangement maintains perfect axial symmetry and
- prevents the membrane from folding or buckling. Hence,
- it is possible to rigorously analyze the mechanics of
- deformation of the cell body to obtain the crucial
- ``transducer'' relation between pipette suction force
- and the membrane tension applied directly at the
- perimeter of the adhesive contact. Further, the
- geometry of the cell throughout the detachment process
- is predicted which provides accurate specification of
- the contact angle theta c between surfaces at the
- perimeter of the contact. A full analysis of red cell
- capsules during detachment has been carried out;
- however, it is shown that the shear rigidity of the red
- cell membrane can often be neglected so that the red
- cell can be treated as if it were an underfilled lipid
- bilayer vesicle. From the analysis, the mechanical
- leverage factor (1-cos theta c) and the membrane
- tension at the contact perimeter are determined to
- provide a complete description of the local mechanics
- of membrane separation as functions of large-scale
- experimental variables (e.g., suction force, contact
- diameter, overall cell length).(ABSTRACT TRUNCATED AT
- 400 WORDS)",
- ISSN = "0006-3495",
-}
-
-@Article{evans91b,
- author = "E. Evans and D. Berk and A. Leung and N. Mohandas",
- title = "Detachment of agglutinin-bonded red blood cells. {II}.
- Mechanical energies to separate large contact areas",
- journal = BPJ,
- year = "1991",
- month = apr,
- volume = "59",
- number = "4",
- pages = "849--860",
- keywords = "Animals;Antibodies, Monoclonal;Cell Adhesion;Erythrocyte Membrane;Erythrocytes;Helix (Snails);Hemagglutination;Hemagglutinins;Humans;Immune Sera;Kinetics;Lectins;Mathematics",
- abstract = "As detailed in a companion paper (Berk, D., and E.
- Evans. 1991. Biophys. J. 59:861-872), a method was
- developed to quantitate the strength of adhesion
- between agglutinin-bonded membranes without ambiguity
- due to mechanical compliance of the cell body. The
- experimental method and analysis were formulated around
- controlled assembly and detachment of a pair of
- macroscopically smooth red blood cell surfaces. The
- approach provides precise measurement of the membrane
- tension applied at the perimeter of an adhesive contact
- and the contact angle theta c between membrane surfaces
- which defines the mechanical leverage factor (1-cos
- theta c) important in the definition of the work to
- separate a unit area of contact. Here, the method was
- applied to adhesion and detachment of red cells bound
- together by different monoclonal antibodies to red cell
- membrane glycophorin and the snail-helix
- pomatia-lectin. For these tests, one of the two red
- cells was chemically prefixed in the form of a smooth
- sphere then equilibrated with the agglutinin before the
- adhesion-detachment procedure. The other cell was not
- exposed to the agglutinin until it was forced into
- contact with the rigid cell surface by mechanical
- impingement. Large regions of agglutinin bonding were
- produced by impingement but no spontaneous spreading
- was observed beyond the forced contact. Measurements of
- suction force to detach the deformable cell yielded
- consistent behavior for all of the agglutinins: i.e.,
- the strength of adhesion increased progressively with
- reduction in contact diameter throughout detachment.
- This tension-contact diameter behavior was not altered
- over a ten-fold range of separation rates. In special
- cases, contacts separated smoothly after critical
- tensions were reached; these were the highest values
- attained for tension. Based on measurements reported in
- another paper (Evans et al. 1991. Biophys. J.
- 59:838-848) of the forces required to rupture
- molecular-point attachments, the density of
- cross-bridges was estimated with the assumption that
- the tension was proportional to the discrete rupture
- force x the number of attachments per unit length.
- These estimates showed that only a small fraction of
- agglutinin formed cross-bridges at initial assembly and
- increased progressively with separation. When critical
- tension levels were reached, it appeared that nearly
- all local agglutinin was involved as cross-bridges.
- Because one cell surface was chemically fixed, receptor
- accumulation was unlikely; thus, microscopic
- ``roughness'' and steric repulsion probably modulated
- formation of cross-bridges on initial contact.(ABSTRACT
- TRUNCATED AT 400 WORDS)",
- ISSN = "0006-3495",
-}
-
-@Article{evans91a,
- author = "E. Evans and D. Berk and A. Leung",
- title = "Detachment of agglutinin-bonded red blood cells. {I}.
- Forces to rupture molecular-point attachments",
- journal = BPJ,
- year = "1991",
- month = apr,
- volume = "59",
- number = "4",
- pages = "838--848",
- keywords = "ABO Blood-Group System;Animals;Antibodies, Monoclonal;Erythrocyte Deformability;Erythrocyte Membrane;Erythrocytes;Glycophorin;Helix (Snails);Hemagglutinins;Humans;Immune Sera;Lectins;Mathematics;Models, Biological",
- abstract = "A simple micromechanical method has been developed to
- measure the rupture strength of a molecular-point
- attachment (focal bond) between two macroscopically
- smooth membrane capsules. In the procedure, one capsule
- is prepared with a low density coverage of adhesion
- molecules, formed as a stiff sphere, and held at fixed
- position by a micropipette. The second capsule without
- adhesion molecules is pressurized into a spherical
- shape with low suction by another pipette. This capsule
- is maneuvered to initiate point contact at the pole
- opposite the stiff capsule which leads to formation of
- a few (or even one) molecular attachments. Then, the
- deformable capsule is slowly withdrawn by displacement
- of the pipette. Analysis shows that the end-to-end
- extension of the capsule provides a direct measure of
- the force at the point contact and, therefore, the
- rupture strength when detachment occurs. The range for
- point forces accessible to this technique depends on
- the elastic moduli of the membrane, membrane tension,
- and the size of the capsule. For biological and
- synthetic vesicle membranes, the range of force lies
- between 10(-7)-10(-5) dyn (10(-12)-10(-10) N) which is
- 100-fold less than presently measurable by Atomic Force
- Microscopy! Here, the approach was used to study the
- forces required to rupture microscopic attachments
- between red blood cells formed by a monoclonal antibody
- to red cell membrane glycophorin, anti-A serum, and a
- lectin from the snail-helix pomatia. Failure of the
- attachments appeared to be a stochastic function of the
- magnitude and duration of the detachment force. We have
- correlated the statistical behavior observed for
- rupture with a random process model for failure of
- small numbers of molecular attachments. The surprising
- outcome of the measurements and analysis was that the
- forces deduced for short-time failure of 1-2 molecular
- attachments were nearly the same for all of the
- agglutinin, i.e., 1-2 x 10(-6) dyn. Hence,
- microfluorometric tests were carried out to determine
- if labeled agglutinins and/or labeled surface molecules
- were transferred between surfaces after separation of
- large areas of adhesive contact. The results showed
- that the attachments failed because receptors were
- extracted from the membrane.",
- ISSN = "0006-3495",
-}
-
-@article{brochard-wyart99,
- author={F. Brochard-Wyart and A. Buguin and P. G. de Gennes},
- title="Dynamics of taut {DNA} chains",
- journal={EPL (Europhysics Letters)},
- volume={47},
- number={2},
- pages={171--174},
- year={1999},
- abstract={We discuss the dynamics of stretched DNA chains, subjected to a tension force f, in a "taut" regime where ph = flp0/kBT $>$ 1 (lp0 being the unperturbed persistence length). We deal with two variables: the local transverse displacements u, and the longitudinal position of a monomer u[?]. The variables u and u[?] follow two distinct Rouse equations, with diffusion coefficients D[?] = f/e (where e is the solvent viscosity) and D[?] = 4ph1/2D[?]. We apply these ideas to a discussion of various transient regimes.},
- url={http://stacks.iop.org/0295-5075/47/171},
- eprint = "http://www.iop.org/EJ/article/0295-5075/47/2/171/epl_47_2_171.pdf",
- note = "Theory for weakly bending relaxation modes in WLCs and FJCs.",
-}
-
-@article{Watanabe2005,
- author={Hiroshi Watanabe and Tadashi Inoue},
- title={Conformational dynamics of Rouse chains during creep/recovery processes: a review},
- journal=JPCM,
- volume={17},
- number={19},
- pages={R607--R636},
- year={2005},
- abstract={The Rouse model is a well-established model for non-entangled polymer chains and also serves as a fundamental model for entangled chains. The dynamic behaviour of this model under strain-controlled conditions has been fully analysed in the literature. However, despite the importance of the Rouse model, no analysis has been made so far of the orientational anisotropy of the Rouse eigenmodes during the stress-controlled, creep and recovery processes. For completeness of the analysis of the model, the Rouse equation of motion is solved to calculate this anisotropy for monodisperse chains and their binary blends during the creep/recovery processes. The calculation is simple and straightforward, but the result is intriguing in the sense that each Rouse eigenmode during these processes has a distribution in the retardation times. This behaviour, reflecting the interplay/correlation among the Rouse eigenmodes of different orders (and for different chains in the blends) under the constant stress condition, is quite different from the behaviour under rate-controlled flow (where each eigenmode exhibits retardation/relaxation associated with a single characteristic time). Furthermore, the calculation indicates that the Rouse chains exhibit affine deformation on sudden imposition/removal of the stress and the magnitude of this deformation is inversely proportional to the number of bond vectors per chain. In relation to these results, a difference between the creep and relaxation properties is also discussed for chains obeying multiple relaxation mechanisms (Rouse and reptation mechanisms).},
- url={http://stacks.iop.org/0953-8984/17/R607},
- eprint = "http://www.iop.org/EJ/article/0953-8984/17/19/R01/cm5_19_R01.pdf",
- doi = "10.1088/0953-8984/17/19/R01",
- note = "Middly-detailed Rouse model review.",
-}
-
-@article{Kroy07,
- author={Klaus Kroy and Jens Glaser},
- title={The glassy wormlike chain},
- journal={New Journal of Physics},
- volume={9},
- number={11},
- pages={416},
- year={2007},
- abstract={We introduce a new model for the dynamics of a wormlike chain (WLC) in an environment that gives rise to a rough free energy landscape, which we name the glassy WLC. It is obtained from the common WLC by an exponential stretching of the relaxation spectrum of its long-wavelength eigenmodes, controlled by a single parameter \\boldsymbol{\\cal E} . Predictions for pertinent observables such as the dynamic structure factor and the microrheological susceptibility exhibit the characteristics of soft glassy rheology and compare favourably with experimental data for reconstituted cytoskeletal networks and live cells. We speculate about the possible microscopic origin of the stretching, implications for the nonlinear rheology, and the potential physiological significance of our results.},
- url={http://stacks.iop.org/1367-2630/9/416},
- eprint = "http://www.iop.org/EJ/article/1367-2630/9/11/416/njp7_11_416.pdf",
- doi = "10.1088/1367-2630/9/11/416",
- note = "Has short section on WLC relaxation time in the weakly bending limit.",
-}
-
-@Article{schlierf04,
- author = MSchlierf #" and "# HLi #" and "# JFernandez,
- title = "The unfolding kinetics of ubiquitin captured with
- single-molecule force-clamp techniques",
- journal = PNAS,
- year = 2004,
- month = may,
- day = 11,
- volume = 101,
- number = 19,
- pages = "7299--7304",
- keywords = "Kinetics;Microscopy, Atomic Force;Probability;Ubiquitin",
- abstract = "We use single-molecule force spectroscopy to study the
- kinetics of unfolding of the small protein ubiquitin.
- Upon a step increase in the stretching force, a
- ubiquitin polyprotein extends in discrete steps of 20.3
- +/- 0.9 nm marking each unfolding event. An average of
- the time course of these unfolding events was well
- described by a single exponential, which is a necessary
- condition for a memoryless Markovian process. Similar
- ensemble averages done at different forces showed that
- the unfolding rate was exponentially dependent on the
- stretching force. Stretching a ubiquitin polyprotein
- with a force that increased at a constant rate
- (force-ramp) directly measured the distribution of
- unfolding forces. This distribution was accurately
- reproduced by the simple kinetics of an all-or-none
- unfolding process. Our force-clamp experiments directly
- demonstrate that an ensemble average of ubiquitin
- unfolding events is well described by a two-state
- Markovian process that obeys the Arrhenius equation.
- However, at the single-molecule level, deviant behavior
- that is not well represented in the ensemble average is
- readily observed. Our experiments make an important
- addition to protein spectroscopy by demonstrating an
- unambiguous method of analysis of the kinetics of
- protein unfolding by a stretching force.",
- ISSN = "0027-8424",
- doi = "10.1073/pnas.0400033101",
- URL = "http://www.pnas.org/cgi/content/abstract/101/19/7299",
- eprint = "http://www.pnas.org/cgi/reprint/101/19/7299.pdf",
-}
-
-@Article{li03,
- author = HLi #" and "# JFernandez,
- title = "Mechanical design of the first proximal Ig domain of
- human cardiac titin revealed by single molecule force
- spectroscopy",
- journal = JMB,
- year = "2003",
- month = nov,
- day = "14",
- volume = "334",
- number = "1",
- pages = "75--86",
- keywords = "Amino Acid Sequence;Disulfides;Humans;Immunoglobulins;Models, Molecular;Molecular Sequence Data;Muscle Proteins;Myocardium;Protein Denaturation;Protein Engineering;Protein Kinases;Protein Structure, Tertiary;Spectrum Analysis",
- abstract = "The elastic I-band part of muscle protein titin
- contains two tandem immunoglobulin (Ig) domain regions
- of distinct mechanical properties. Until recently, the
- only known structure was that of the I27 module of the
- distal region, whose mechanical properties have been
- reported in detail. Recently, the structure of the
- first proximal domain, I1, has been resolved at 2.1A.
- In addition to the characteristic beta-sandwich
- structure of all titin Ig domains, the crystal
- structure of I1 showed an internal disulfide bridge
- that was proposed to modulate its mechanical
- extensibility in vivo. Here, we use single molecule
- force spectroscopy and protein engineering to examine
- the mechanical architecture of this domain. In contrast
- to the predictions made from the X-ray crystal
- structure, we find that the formation of a disulfide
- bridge in I1 is a relatively rare event in solution,
- even under oxidative conditions. Furthermore, our
- studies of the mechanical stability of I1 modules
- engineered with point mutations reveal significant
- differences between the mechanical unfolding of the I1
- and I27 modules. Our study illustrates the varying
- mechanical architectures of the titin Ig modules.",
- ISSN = "0022-2836",
- doi = "10.1016/j.jmb.2003.09.036",
-}
-
-@Article{li05,
- author = "Lewyn Li"#" and "# HHuang #" and "# CBadilla #"
- and "# JFernandez,
- title = "Mechanical unfolding intermediates observed by
- single-molecule force spectroscopy in a fibronectin
- type {III} module",
- journal = JMB,
- year = "2005",
- month = jan,
- day = "28",
- volume = "345",
- number = "4",
- pages = "817--826",
- keywords = "Fibronectins;Kinetics;Microscopy, Atomic Force;Models, Molecular;Mutagenesis, Site-Directed;Protein Denaturation;Protein Folding;Protein Structure, Tertiary;Recombinant Fusion Proteins",
- abstract = "Domain 10 of type III fibronectin (10FNIII) is known
- to play a pivotal role in the mechanical interactions
- between cell surface integrins and the extracellular
- matrix. Recent molecular dynamics simulations have
- predicted that 10FNIII, when exposed to a stretching
- force, unfolds along two pathways, each with a
- distinct, mechanically stable intermediate. Here, we
- use single-molecule force spectroscopy combined with
- protein engineering to test these predictions by
- probing the mechanical unfolding pathway of 10FNIII.
- Stretching single polyproteins containing the 10FNIII
- module resulted in sawtooth patterns where 10FNIII was
- seen unfolding in two consecutive steps. The native
- state unfolded at 100(+/-20) pN, elongating (10)FNIII
- by 12(+/-2) nm and reaching a clearly marked
- intermediate that unfolded at 50(+/-20) pN. Unfolding
- of the intermediate completed the elongation of the
- molecule by extending another 19(+/-2) nm.
- Site-directed mutagenesis of residues in the A and B
- beta-strands (E9P and L19P) resulted in sawtooth
- patterns with all-or-none unfolding events that
- elongated the molecule by 19(+/-2) nm. In contrast,
- mutating residues in the G beta-strand gave results
- that were dependent on amino acid position. The
- mutation I88P in the middle of the G beta-strand
- resulted in native like unfolding sawtooth patterns
- showing an intact intermediate state. The mutation
- Y92P, which is near the end of G beta-strand, produced
- sawtooth patterns with all-or-none unfolding events
- that lengthened the molecule by 17(+/-2) nm. These
- results are consistent with the view that 10FNIII can
- unfold in two different ways. Along one pathway, the
- detachment of the A and B beta-strands from the body of
- the folded module constitute the first unfolding event,
- followed by the unfolding of the remaining
- beta-sandwich structure. Along the second pathway, the
- detachment of the G beta-strands is involved in the
- first unfolding event. These results are in excellent
- agreement with the sequence of events predicted by
- molecular dynamics simulations of the 10FNIII module.",
- ISSN = "0022-2836",
- doi = "10.1016/j.jmb.2004.11.021",
-}
-
-@Article{brockwell03,
- author = "David J. Brockwell and Emanuele Paci and Rebecca C.
- Zinober and Godfrey S. Beddard and Peter D. Olmsted and
- D. Alastair Smith and Richard N. Perham and Sheena E.
- Radford",
- title = "Pulling geometry defines the mechanical resistance of
- a beta-sheet protein",
- journal = NSB,
- year = "2003",
- month = sep,
- day = "17",
- volume = "10",
- number = "9",
- pages = "731--737",
- keywords = "Anisotropy;Escherichia coli;Kinetics;Models, Molecular;Monte Carlo Method;Protein Folding;Protein Structure, Secondary;Protein Structure, Tertiary;Proteins;Software;Temperature;Thermodynamics",
- abstract = "Proteins show diverse responses when placed under
- mechanical stress. The molecular origins of their
- differing mechanical resistance are still unclear,
- although the orientation of secondary structural
- elements relative to the applied force vector is
- thought to have an important function. Here, by using a
- method of protein immobilization that allows force to
- be applied to the same all-beta protein, E2lip3, in two
- different directions, we show that the energy landscape
- for mechanical unfolding is markedly anisotropic. These
- results, in combination with molecular dynamics (MD)
- simulations, reveal that the unfolding pathway depends
- on the pulling geometry and is associated with
- unfolding forces that differ by an order of magnitude.
- Thus, the mechanical resistance of a protein is not
- dictated solely by amino acid sequence, topology or
- unfolding rate constant, but depends critically on the
- direction of the applied extension.",
- ISSN = "1072-8368",
- doi = "10.1038/nsb968",
- url = "http://www.nature.com/nsmb/journal/v10/n9/abs/nsb968.html",
- eprint = "http://www.nature.com/nsmb/journal/v10/n9/pdf/nsb968.pdf",
- note = "Another scaffold effect paper. TODO: details",
-}
-
-@article{friddle08,
-author = {Friddle, Raymond W. and Podsiadlo, Paul and Artyukhin, Alexander B. and Noy, Aleksandr},
-title = {Near-Equilibrium Chemical Force Microscopy},
-journal = {The Journal of Physical Chemistry C},
-volume = {112},
-number = {13},
-pages = {4986--4990},
-year = {2008},
-doi = {10.1021/jp7095967},
-URL = {http://pubs.acs.org/doi/abs/10.1021/jp7095967},
-eprint = {http://pubs.acs.org/doi/pdf/10.1021/jp7095967}
-}
-
-@article{kaplan58,
- title = {Nonparametric Estimation from Incomplete Observations},
- author = {Kaplan, E. L. and Meier, Paul},
- journal = {Journal of the American Statistical Association},
- volume = {53},
- number = {282},
- pages = {457--481},
- url = {http://www.jstor.org/stable/2281868},
- ISSN = {01621459},
- abstract = {},
- year = {1958},
- month = {jun},
- publisher = {American Statistical Association},
- copyright = {Copyright \copy\ 1958 American Statistical Association},
-}
-
-@article{kellermayer03,
-title = "Mechanics and structure of titin oligomers explored with atomic force microscopy",
-journal = "Biochimica et Biophysica Acta (BBA) - Bioenergetics",
-volume = "1604",
-number = "2",
-pages = "105--114",
-year = "2003",
-note = "",
-issn = "0005-2728",
-doi = "10.1016/S0005-2728(03)00029-X",
-url = "http://dx.doi.org/10.1016/S0005-2728(03)00029-X",
-author = "Mikl\'os S. Z. Kellermayer"#" and "# CBustamante #" and "#"Henk L. Granzier",
- keywords = "Titin;Wormlike chain;Unfolding;Elasticity;AFM;Molecular force spectroscopy",
-abstract = "
-Titin is a giant polypeptide that spans half of the striated muscle sarcomere and generates passive force upon stretch. To explore the elastic response and structure of single molecules and oligomers of titin, we carried out molecular force spectroscopy and atomic force microscopy (AFM) on purified full-length skeletal-muscle titin. From the force data, apparent persistence lengths as long as ~1.5 nm were obtained for the single, unfolded titin molecule. Furthermore, data suggest that titin molecules may globally associate into oligomers which mechanically behave as independent wormlike chains (WLCs). Consistent with this, AFM of surface-adsorbed titin molecules revealed the presence of oligomers. Although oligomers may form globally via head-to-head association of titin, the constituent molecules otherwise appear independent from each other along their contour. Based on the global association but local independence of titin molecules, we discuss a mechanical model of the sarcomere in which titin molecules with different contour lengths, corresponding to different isoforms, are held in a lattice. The net force response of aligned titin molecules is determined by the persistence length of the tandemly arranged, different WLC components of the individual molecules, the ratio of their overall contour lengths, and by domain unfolding events. Biased domain unfolding in mechanically selected constituent molecules may serve as a compensatory mechanism for contour- and persistence-length differences. Variation in the ratio and contour length of the component chains may provide mechanisms for the fine-tuning of the sarcomeric passive force response."
-}
-
-@article{ryckaert77,
-title = "Numerical integration of the cartesian equations of motion of a system with constraints: molecular dynamics of n-alkanes",
-journal = "Journal of Computational Physics",
-volume = "23",
-number = "3",
-pages = "327--341",
-year = "1977",
-issn = "0021-9991",
-doi = "10.1016/0021-9991(77)90098-5",
-url = "http://dx.doi.org/10.1016/0021-9991(77)90098-5",
-author = "Jean-Paul Ryckaert and Giovanni Ciccotti and Herman J. C. Berendsen",
-abstract = "
-A numerical algorithm integrating the 3N Cartesian equations of motion of a system of N points subject to holonomic constraints is formulated. The relations of constraint remain perfectly fulfilled at each step of the trajectory despite the approximate character of numerical integration. The method is applied to a molecular dynamics simulation of a liquid of 64 n-butane molecules and compared to a simulation using generalized coordinates. The method should be useful for molecular dynamics calculations on large molecules with internal degrees of freedom.",
-note = "Entry-level explaination of MD with rigid constraints. Explicit Verlet integrator example."
-}
-
-@article{ciccotti86,
-title = "Molecular dynamics simulation of rigid molecules",
-journal = "Computer Physics reports",
-volume = "4",
-number = "6",
-pages = "346--392",
-year = "1986",
-issn = "0167-7977",
-doi = "10.1016/0167-7977(86)90022-5",
-url = "http://dx.doi.org/10.1016/0167-7977(86)90022-5",
-author = "G. Ciccotti and J. P. Ryckaert",
-note = "I haven't read this, but it looks like a nice review of MD with constraints."
-}
-
-@Article{forde02,
- author = "Nancy R. Forde and David Izhaky and Glenna R. Woodcock
- and Gijs J. L. Wuite and "# CBustamante,
- title = "Using mechanical force to probe the mechanism of
- pausing and arrest during continuous elongation by
- Escherichia coli {RNA} polymerase",
- journal = PNAS,
- year = 2002,
- month = sep,
- day = 03,
- volume = 99,
- number = 18,
- pages = "11682--11687",
- keywords = "DNA-Directed RNA Polymerases;Escherichia coli;Kinetics;Transcription, Genetic",
- abstract = "Escherichia coli RNA polymerase translocates along the
- DNA discontinuously during the elongation phase of
- transcription, spending proportionally more time at
- some template positions, known as pause and arrest
- sites, than at others. Current models of elongation
- suggest that the enzyme backtracks at these locations,
- but the dynamics are unresolved. Here, we study the
- role of lateral displacement in pausing and arrest by
- applying force to individually transcribing molecules.
- We find that an assisting mechanical force does not
- alter the translocation rate of the enzyme, but does
- reduce the efficiency of both pausing and arrest.
- Moreover, arrested molecules cannot be rescued by
- force, suggesting that arrest occurs by a bipartite
- mechanism: the enzyme backtracks along the DNA followed
- by a conformational change of the ternary complex (RNA
- polymerase, DNA and transcript), which cannot be
- reversed mechanically.",
- ISSN = "0027-8424",
- doi = "10.1073/pnas.142417799",
- url = "http://www.pnas.org/content/99/18/11682",
- eprint = "http://www.pnas.org/cgi/reprint/99/18/11682.pdf",
-}
-
-@Article{merkel99,
- author = "R. Merkel and P. Nassoy and A. Leung and K. Ritchie
- and E. Evans",
- title = "Energy landscapes of receptor-ligand bonds explored
- with dynamic force spectroscopy",
- journal = NAT,
- year = 1999,
- month = jan,
- day = "07",
- volume = 397,
- number = 6714,
- pages = "50--53",
- keywords = "Biotin;Microscopy, Atomic Force;Protein Binding;Streptavidin",
- abstract = "Atomic force microscopy (AFM) has been used to measure
- the strength of bonds between biological receptor
- molecules and their ligands. But for weak noncovalent
- bonds, a dynamic spectrum of bond strengths is
- predicted as the loading rate is altered, with the
- measured strength being governed by the prominent
- barriers traversed in the energy landscape along the
- force-driven bond-dissociation pathway. In other words,
- the pioneering early AFM measurements represent only a
- single point in a continuous spectrum of bond
- strengths, because theory predicts that these will
- depend on the rate at which the load is applied. Here
- we report the strength spectra for the bonds between
- streptavidin (or avidin) and biotins-the prototype of
- receptor-ligand interactions used in earlier AFM
- studies, and which have been modelled by molecular
- dynamics. We have probed bond formation over six orders
- of magnitude in loading rate, and find that the bond
- survival time diminished from about 1 min to 0.001 s
- with increasing loading rate over this range. The bond
- strength, meanwhile, increased from about 5 pN to 170
- pN. Thus, although they are among the strongest
- noncovalent linkages in biology (affinity of 10(13) to
- 10(15) M(-1)), these bonds in fact appear strong or
- weak depending on how fast they are loaded. We are also
- able to relate the activation barriers derived from our
- strength spectra to the shape of the energy landscape
- derived from simulations of the biotin-avidin
- complex.",
- ISSN = "0028-0836",
- doi = "10.1038/16219",
- url = "http://www.nature.com/nature/journal/v397/n6714/full/397050a0.html",
-}
-
-@Article{fernandez04,
- author = JFernandez #" and "# HLi,
- title = "Force-clamp spectroscopy monitors the folding
- trajectory of a single protein",
- journal = SCI,
- year = 2004,
- month = mar,
- day = 12,
- volume = 303,
- number = 5664,
- pages = "1674--1678",
- keywords = "Chemistry, Physical;Microscopy, Atomic Force;Physicochemical Phenomena;Polyubiquitin;Protein Conformation;Protein Denaturation;Protein Folding;Protein Structure, Secondary;Time Factors;Ubiquitin",
- abstract = "We used force-clamp atomic force microscopy to measure
- the end-to-end length of the small protein ubiquitin
- during its folding reaction at the single-molecule
- level. Ubiquitin was first unfolded and extended at a
- high force, then the stretching force was quenched and
- protein folding was observed. The folding trajectories
- were continuous and marked by several distinct stages.
- The time taken to fold was dependent on the contour
- length of the unfolded protein and the stretching force
- applied during folding. The folding collapse was marked
- by large fluctuations in the end-to-end length of the
- protein, but these fluctuations vanished upon the final
- folding contraction. These direct observations of the
- complete folding trajectory of a protein provide a
- benchmark to determine the physical basis of the
- folding reaction.",
- ISSN = "1095-9203",
- doi = "10.1126/science.1092497",
- url = "http://www.sciencemag.org/cgi/content/abstract/303/5664/1674",
- eprint = "http://www.sciencemag.org/cgi/reprint/303/5664/1674.pdf",
-}
-
-@Article{jollymore09,
- author = "Ashlee Jollymore and Claire Lethias and "# QPeng #" and
- Yi Cao and "# HLi,
- title = "Nanomechanical properties of tenascin-{X} revealed by
- single-molecule force spectroscopy",
- journal = JMB,
- year = 2009,
- month = jan,
- day = 30,
- volume = 385,
- number = 4,
- pages = "1277--1286",
- keywords = "Animals;Biomechanics;Cattle;Fibronectins;Kinetics;Microscopy, Atomic Force;Protein Folding;Protein Structure, Tertiary;Spectrum Analysis;Tenascin",
- abstract = "Tenascin-X is an extracellular matrix protein and
- binds a variety of molecules in extracellular matrix
- and on cell membrane. Tenascin-X plays important roles
- in regulating the structure and mechanical properties
- of connective tissues. Using single-molecule atomic
- force microscopy, we have investigated the mechanical
- properties of bovine tenascin-X in detail. Our results
- indicated that tenascin-X is an elastic protein and the
- fibronectin type III (FnIII) domains can unfold under a
- stretching force and refold to regain their mechanical
- stability upon the removal of the stretching force. All
- the 30 FnIII domains of tenascin-X show similar
- mechanical stability, mechanical unfolding kinetics,
- and contour length increment upon domain unfolding,
- despite their large sequence diversity. In contrast to
- the homogeneity in their mechanical unfolding
- behaviors, FnIII domains fold at different rates. Using
- the 10th FnIII domain of tenascin-X (TNXfn10) as a
- model system, we constructed a polyprotein chimera
- composed of alternating TNXfn10 and GB1 domains and
- used atomic force microscopy to confirm that the
- mechanical properties of TNXfn10 are consistent with
- those of the FnIII domains of tenascin-X. These results
- lay the foundation to further study the mechanical
- properties of individual FnIII domains and establish
- the relationship between point mutations and mechanical
- phenotypic effect on tenascin-X. Moreover, our results
- provided the opportunity to compare the mechanical
- properties and design of different forms of tenascins.
- The comparison between tenascin-X and tenascin-C
- revealed interesting common as well as distinguishing
- features for mechanical unfolding and folding of
- tenascin-C and tenascin-X and will open up new avenues
- to investigate the mechanical functions and
- architectural design of different forms of tenascins.",
- ISSN = "1089-8638",
- doi = "10.1016/j.jmb.2008.11.038",
- url = "http://dx.doi.org/10.1016/j.jmb.2008.11.038",
-}
-
-@Article{carrion-vazquez00,
- author = MCarrionVazquez #" and "# AOberhauser #" and T. E.
- Fisher and "# PMarszalek #" and "# HLi #" and "# JFernandez,
- title = "Mechanical design of proteins studied by
- single-molecule force spectroscopy and protein
- engineering",
- journal = PBPMB,
- year = 2000,
- volume = 74,
- number = "1-2",
- pages = "63--91",
- keywords = "Elasticity;Hydrogen Bonding;Microscopy, Atomic Force;Protein Denaturation;Protein Engineering;Protein Folding;Recombinant Proteins;Signal Processing, Computer-Assisted",
- abstract = "Mechanical unfolding and refolding may regulate the
- molecular elasticity of modular proteins with
- mechanical functions. The development of the atomic
- force microscopy (AFM) has recently enabled the dynamic
- measurement of these processes at the single-molecule
- level. Protein engineering techniques allow the
- construction of homomeric polyproteins for the precise
- analysis of the mechanical unfolding of single domains.
- alpha-Helical domains are mechanically compliant,
- whereas beta-sandwich domains, particularly those that
- resist unfolding with backbone hydrogen bonds between
- strands perpendicular to the applied force, are more
- stable and appear frequently in proteins subject to
- mechanical forces. The mechanical stability of a domain
- seems to be determined by its hydrogen bonding pattern
- and is correlated with its kinetic stability rather
- than its thermodynamic stability. Force spectroscopy
- using AFM promises to elucidate the dynamic mechanical
- properties of a wide variety of proteins at the single
- molecule level and provide an important complement to
- other structural and dynamic techniques (e.g., X-ray
- crystallography, NMR spectroscopy, patch-clamp).",
- ISSN = "0079-6107",
- url = "http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1302160",
- eprint = "http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1302160&blobtype=pdf",
-}
-
-@Article{sims09,
- author = "Gregory E. Sims and Se-Ran Jun and Guohong A. Wu and
- Sung-Hou Kim",
- title = "Alignment-free genome comparison with feature
- frequency profiles ({FFP}) and optimal resolutions",
- journal = PNAS,
- year = 2009,
- month = feb,
- day = 24,
- volume = 106,
- number = 8,
- pages = "2677--2682",
- keywords = "Genome;Introns;Phylogeny",
- abstract = "For comparison of whole-genome (genic + nongenic)
- sequences, multiple sequence alignment of a few
- selected genes is not appropriate. One approach is to
- use an alignment-free method in which feature (or
- l-mer) frequency profiles (FFP) of whole genomes are
- used for comparison-a variation of a text or book
- comparison method, using word frequency profiles. In
- this approach it is critical to identify the optimal
- resolution range of l-mers for the given set of genomes
- compared. The optimum FFP method is applicable for
- comparing whole genomes or large genomic regions even
- when there are no common genes with high homology. We
- outline the method in 3 stages: (i) We first show how
- the optimal resolution range can be determined with
- English books which have been transformed into long
- character strings by removing all punctuation and
- spaces. (ii) Next, we test the robustness of the
- optimized FFP method at the nucleotide level, using a
- mutation model with a wide range of base substitutions
- and rearrangements. (iii) Finally, to illustrate the
- utility of the method, phylogenies are reconstructed
- from concatenated mammalian intronic genomes; the FFP
- derived intronic genome topologies for each l within
- the optimal range are all very similar. The topology
- agrees with the established mammalian phylogeny
- revealing that intron regions contain a similar level
- of phylogenic signal as do coding regions.",
- ISSN = "1091-6490",
- doi = "10.1073/pnas.0813249106",
- url = "http://www.pnas.org/content/106/8/2677",
- eprint = "http://www.pnas.org/cgi/reprint/106/31/12826",
-}
-
-@Article{lin91,
- author = "Jianhua Lin",
- title = "Divergence measures based on the {S}hannon entropy",
- journal = "IEEE Transactions on Information Theory",
- year = "1991",
- month = jan,
- volume = "37",
- number = "1",
- pages = "145--151",
- keywords = "divergence;dissimilarity measure;discrimintation information;entropy;probability of error bounds",
- abstract = "A novel class of information-theoretic divergence
- measures based on the Shannon entropy is
- introduced. Unlike the well-known Kullback
- divergences, the new measures do not require the
- condition of absolute continuity to be satisfied by
- the probability distributions involved. More
- importantly, their close relationship with the
- variational distance and the probability of
- misclassification error are established in terms of
- bounds. These bounds are crucial in many
- applications of divergence measures. The measures
- are also well characterized by the properties of
- nonnegativity, finiteness, semiboundedness, and
- boundedness.",
- ISSN = "0018-9448",
- doi = "10.1109/18.61115",
- url = "http://ieeexplore.ieee.org/xpl/freeabs_all.jsp?isnumber=2227&arnumber=61115&count=35&index=9",
-}
-
-@Article{granzier97,
- author = "H. Granzier and M. Kellermayer and M. Helmes and K.
- Trombit{\'a}s",
- title = "Titin elasticity and mechanism of passive force
- development in rat cardiac myocytes probed by
- thin-filament extraction",
- journal = BPJ,
- year = 1997,
- month = oct,
- volume = 73,
- number = 4,
- pages = "2043--2053",
- keywords = "Amino Acid Sequence;Animals;Biomechanics;Biophysical Phenomena;Biophysics;Cell Fractionation;Elasticity;Gelsolin;Microscopy, Immunoelectron;Models, Cardiovascular;Molecular Structure;Muscle Proteins;Myocardial Contraction;Myocardium;Protein Kinases;Rats;Sarcomeres",
- abstract = "Titin (also known as connectin) is a giant filamentous
- protein whose elastic properties greatly contribute to
- the passive force in muscle. In the sarcomere, the
- elastic I-band segment of titin may interact with the
- thin filaments, possibly affecting the molecule's
- elastic behavior. Indeed, several studies have
- indicated that interactions between titin and actin
- occur in vitro and may occur in the sarcomere as well.
- To explore the properties of titin alone, one must
- first eliminate the modulating effect of the thin
- filaments by selectively removing them. In the present
- work, thin filaments were selectively removed from the
- cardiac myocyte by using a gelsolin fragment. Partial
- extraction left behind approximately 100-nm-long thin
- filaments protruding from the Z-line, whereas the rest
- of the I-band became devoid of thin filaments, exposing
- titin. By applying a much more extensive gelsolin
- treatment, we also removed the remaining short thin
- filaments near the Z-line. After extraction, the
- extensibility of titin was studied by using
- immunoelectron microscopy, and the passive
- force-sarcomere length relation was determined by using
- mechanical techniques. Titin's regional extensibility
- was not detectably affected by partial thin-filament
- extraction. Passive force, on the other hand, was
- reduced at sarcomere lengths longer than approximately
- 2.1 microm, with a 33 +/- 9\% reduction at 2.6 microm.
- After a complete extraction, the slack sarcomere length
- was reduced to approximately 1.7 microm. The segment of
- titin near the Z-line, which is otherwise inextensible,
- collapsed toward the Z-line in sarcomeres shorter than
- approximately 2.0 microm, but it was extended in
- sarcomeres longer than approximately 2.3 microm.
- Passive force became elevated at sarcomere lengths
- between approximately 1.7 and approximately 2.1 microm,
- but was reduced at sarcomere lengths of >2.3 microm.
- These changes can be accounted for by modeling titin as
- two wormlike chains in series, one of which increases
- its contour length by recruitment of the titin segment
- near the Z-line into the elastic pool.",
- ISSN = "0006-3495",
- doi = "10.1016/S0006-3495(97)78234-1",
- url = "http://www.cell.com/biophysj/retrieve/pii/S0006349597782341",
-}
-
-@article{verdier70,
- author = "Peter H. Verdier",
- collaboration = "",
- title = "Relaxation Behavior of the Freely Jointed Chain",
- publisher = AIP,
- year = 1970,
- journal = JCP,
- volume = 52,
- number = 11,
- pages = "5512--5517",
- doi = "10.1063/1.1672818",
- url = "http://link.aip.org/link/?JCP/52/5512/1",
-}
-
-@article{roters96,
- author="Andreas Roters and Diethelm Johannsmann",
- title="Distance-dependent noise measurements in scanning force microscopy",
- journal= JPCM,
- volume=8,
- number=41,
- pages="7561-7577",
- year=1996,
- abstract="The changes in the thermal noise spectrum of a
- scanning-force-microscope cantilever upon approach of the tip to
- the sample were used to investigate the interactions between the
- cantilever and the sample. The investigation of thermal noise is
- the natural choice for dynamic measurements with little
- disturbance of the sample. In particular, the small amplitudes
- involved ensure linear dynamic response. It is possible to
- discriminate between viscous coupling, elastic coupling and
- changes in the effective mass. The technique is versatile in terms
- of substrates and environments. Hydrodynamic long-range
- interactions depending on the sample, the geometry and the ambient
- medium are observed. The dependence of hydrodynamic interaction on
- various parameters such as the viscosity and the density of the
- medium is described. For sufficiently soft surfaces, the method is
- sensitive to viscoelastic properties of the surface. For example,
- the viscous coupling to the surface is strongly increased when the
- surface is covered with a swollen `polymer brush'.",
- doi = "10.1088/0953-8984",
- url = "http://stacks.iop.org/0953-8984/8/7561",
- eprint = "http://www.iop.org/EJ/article/0953-8984/8/41/006/c64103.pdf",
- project = "Cantilever Calibration",
- note = "They actually write down Lagrangian formula and give a decent
- derivation of PSD, but don't show or work out the integrals.",
-}
-
-@Article{staple08,
- author = "Douglas B. Staple and Stephen H. Payne and Andrew L.
- C. Reddin and Hans J{\"u}rgen Kreuzer",
- title = "Model for stretching and unfolding the giant
- multidomain muscle protein using single-molecule force
- spectroscopy.",
- journal = PRL,
- year = 2008,
- month = dec,
- day = 12,
- volume = 101,
- number = 24,
- pages = 248301,
- keywords = "Kinetics;Microscopy, Atomic Force;Models, Chemical;Muscle Proteins;Protein Conformation;Protein Folding;Protein Kinases;Protein Structure, Tertiary;Thermodynamics",
- abstract = "Single-molecule manipulation has allowed the forced
- unfolding of multidomain proteins. Here we outline a
- theory that not only explains these experiments but
- also points out a number of difficulties in their
- interpretation and makes suggestions for further
- experiments. For titin we reproduce force-extension
- curves, the dependence of break force on pulling speed,
- and break-force distributions and also validate two
- common experimental views: Unfolding titin Ig domains
- can be explained as stepwise increases in contour
- length, and increasing force peaks in native Ig
- sequences represent a hierarchy of bond strengths. Our
- theory is valid for essentially any molecule that can
- be unfolded in atomic force microscopy; as a further
- example, we present force-extension curves for the
- unfolding of RNA hairpins.",
- ISSN = "0031-9007",
- doi = "10.1103/PhysRevLett.101.248301",
- url = "http://dx.doi.org/10.1103/PhysRevLett.101.248301",
-}
-
-@Misc{NIST:gumbel,
- key = "NIST:gumbel",
- author="{NIST/SEMATECH}",
- title="e-Handbook of Statistical Methods: Extreme Value Type {I}
- Distribution",
- year=2009,
- month=oct,
- day=9,
- url = "http://www.itl.nist.gov/div898/handbook/eda/section3/eda366g.htm",
-}
-
-@Article{janshoff00,
- author = "Andreas Janshoff and Marcus Neitzert and York Oberd{\"o}rfer and Harald Fuchs",
- title = "Force Spectroscopy of Molecular Systems-Single
- Molecule Spectroscopy of Polymers and Biomolecules.",
- journal = ACIEE,
- year = 2000,
- month = sep,
- day = 15,
- volume = 39,
- number = 18,
- pages = "3212--3237",
- abstract = "How do molecules interact with each other? What
- happens if a neurotransmitter binds to a
- ligand-operated ion channel? How do antibodies
- recognize their antigens? Molecular recognition events
- play a pivotal role in nature: in enzymatic catalysis
- and during the replication and transcription of the
- genome; it is also important for the cohesion of
- cellular structures and in numerous metabolic reactions
- that molecules interact with each other in a specific
- manner. Conventional methods such as calorimetry
- provide very precise values of binding enthalpies;
- these are, however, average values obtained from a
- large ensemble of molecules without knowledge of the
- dynamics of the molecular recognition event. Which
- forces occur when a single molecular couple meets and
- forms a bond? Since the development of the scanning
- force microscope and force spectroscopy a couple of
- years ago, tools have now become available for
- measuring the forces between interfaces with high
- precision-starting from colloidal forces to the
- interaction of single molecules. The manipulation of
- individual molecules using force spectroscopy is also
- possible. In this way, the mechanical properties on a
- molecular scale are measurable. The study of single
- molecules is not an exclusive domain of force
- spectroscopy; it can also be performed with a surface
- force apparatus, laser tweezers, or the micropipette
- technique. Regardless of these techniques, force
- spectroscopy has been proven as an extraordinary
- versatile tool. The intention of this review article is
- to present a critical evaluation of the actual
- development of static force spectroscopy. The article
- mainly focuses on experiments dealing with inter- and
- intramolecular forces-starting with ``simple''
- electrostatic forces, then ligand-receptor systems, and
- finally the stretching of individual molecules.",
- ISSN = "1521-3773",
- doi = "10.1002/1521-3773(20000915)39:18<3212::AID-ANIE3212>3.0.CO;2-X",
- url = "http://dx.doi.org/10.1002/1521-3773(20000915)39:18<3212::AID-ANIE3212>3.0.CO;2-X",
- eprint = "",
-}
-@Article{Best2008a,
- author = "Robert B. Best and Gerhard Hummer",
- title = "Protein folding kinetics under force from molecular
- simulation.",
- journal = "J Am Chem Soc",
- year = "2008",
- month = mar,
- day = "26",
- volume = "130",
- number = "12",
- pages = "3706--3707",
- keywords = "Computer Simulation;Kinetics;Models, Chemical;Protein Folding;Stress, Mechanical;Ubiquitin",
- abstract = "Despite a large number of studies on the mechanical
- unfolding of proteins, there are still relatively few
- successful attempts to refold proteins in the presence
- of a stretching force. We explore refolding kinetics
- under force using simulations of a coarse-grained model
- of ubiquitin. The effects of force on the folding
- kinetics can be fitted by a one-dimensional Kramers
- theory of diffusive barrier crossing, resulting in
- physically meaningful parameters for the height and
- location of the folding activation barrier. By
- comparing parameters obtained from pulling in different
- directions, we find that the unfolded state plays a
- dominant role in the refolding kinetics. Our findings
- explain why refolding becomes very slow at even
- moderate pulling forces and suggest how it could be
- practically observed in experiments at higher forces.",
- ISSN = "1520-5126",
- doi = "10.1021/ja0762691",
-}
-
-@Article{Best2008b,
- author = "Robert B. Best and Emanuele Paci and Gerhard Hummer
- and Olga K. Dudko",
- title = "Pulling direction as a reaction coordinate for the
- mechanical unfolding of single molecules.",
- journal = "J Phys Chem B",
- year = "2008",
- month = may,
- day = "15",
- volume = "112",
- number = "19",
- pages = "5968--5976",
- keywords = "Computer Simulation;Kinetics;Models, Molecular;Protein Folding;Protein Structure, Tertiary;Time Factors;Ubiquitin",
- abstract = "The folding and unfolding kinetics of single
- molecules, such as proteins or nucleic acids, can be
- explored by mechanical pulling experiments. Determining
- intrinsic kinetic information, at zero stretching
- force, usually requires an extrapolation by fitting a
- theoretical model. Here, we apply a recent theoretical
- approach describing molecular rupture in the presence
- of force to unfolding kinetic data obtained from
- coarse-grained simulations of ubiquitin. Unfolding
- rates calculated from simulations over a broad range of
- stretching forces, for different pulling directions,
- reveal a remarkable ``turnover'' from a
- force-independent process at low force to a
- force-dependent process at high force, akin to the
- ``roll-over'' in unfolding rates sometimes seen in
- studies using chemical denaturant. While such a
- turnover in rates is unexpected in one dimension, we
- demonstrate that it can occur for dynamics in just two
- dimensions. We relate the turnover to the quality of
- the pulling direction as a reaction coordinate for the
- intrinsic folding mechanism. A novel pulling direction,
- designed to be the most relevant to the intrinsic
- folding pathway, results in the smallest turnover. Our
- results are in accord with protein engineering
- experiments and simulations which indicate that the
- unfolding mechanism at high force can differ from the
- intrinsic mechanism. The apparent similarity between
- extrapolated and intrinsic rates in experiments,
- unexpected for different unfolding barriers, can be
- explained if the turnover occurs at low forces.",
- ISSN = "1520-6106",
- doi = "10.1021/jp075955j",
-}
-
-@article{butt95,
- author=HJButt #" and "# MJaschke,
- title="Calculation of thermal noise in atomic force microscopy",
- journal=NANOTECH,
- volume=6,
- number=1,
- pages="1--7",
- year=1995,
- abstract={Thermal fluctuations of the cantilever are a fundamental
- source of noise in atomic force microscopy. We
- calculated thermal noise using the equipartition
- theorem and considering all possible vibration modes
- of the cantilever. The measurable amplitude of
- thermal noise depends on the temperature, the spring
- constant K of the cantilever and on the method by
- which the cantilever defletion is detected. If the
- deflection is measured directly, e.g. with an
- interferometer or a scanning tunneling microscope,
- the thermal noise of a cantilever with a free end
- can be calculated from square root kT/K. If the end
- of the cantilever is supported by a hard surface no
- thermal fluctuations of the deflection are
- possible. If the optical lever technique is applied
- to measure the deflection, the thermal noise of a
- cantilever with a free end is square root
- 4kT/3K. When the cantilever is supported thermal
- noise decreases to square root kT/3K, but it does
- not vanish.},
- url="http://stacks.iop.org/0957-4484/6/1",
- doi="10.1088/0957-4484/6/1/001",
- project = "Cantilever Calibration",
- note = "Corrections to basic $kx^2 = kB T$ due to higher order modes
- in rectangular cantilevers.",
-}
-
-@article{florin95,
-author = ELFlorin #" and "# MRief #" and "# HLehmann #" and "# MLudwig
- #" and "# CDornmair #" and "# VMoy #" and "# HGaub,
-title = "Sensing specific molecular interactions with the atomic force
- microscope",
-journal = BIOSENSE,
-volume = 10,
-number = "9--10",
-pages = "895--901",
-year = 1995,
-issn = "0956-5663",
-abstract = "One of the unique features of the atomic force microscope
- (AFM) is its capacity to measure interactions
- between tip and sample with high sensitivity and
- unparal leled spatial resolution. Since the
- development of methods for the functionaliza tion of
- the tips, the versatility of the AFM has been
- expanded to experiments wh ere specific molecular
- interactions are measured. For illustration, we
- present m easurements of the interaction between
- complementary strands of DNA. A necessary
- prerequisite for the quantitative analysis of the
- interaction force is knowledg e of the spring
- constant of the cantilevers. Here, we compare
- different techniqu es that allow for the in situ
- measurement of the absolute value of the spring co
- nstant of cantilevers.",
-doi = "10.1016/0956-5663(95)99227-C",
-url = "http://www.sciencedirect.com/science/article/B6TFC-3XY2HK9-G/2/6f4e9f67e9a1e14c8bbcc478e5360682",
- project = "Cantilever Calibration",
- note = "Good review of calibration to 1995, with experimental
- comparison between resonance-shift,
- reference-spring, and thermal methods.",
-}
-
-@article{ohler07,
-author = BOhler,
-title = "Cantilever spring constant calibration using laser Doppler vibrometry",
-publisher = AIP,
-year = 2007,
-journal = RSI,
-volume = 78,
-number = 6,
-eid = 063701,
-numpages = 5,
-pages = 063701,
- keywords = {calibration; vibration measurement; measurement by laser beam; Doppler measurement; measurement uncertainty; atomic force microscopy},
-url = {http://link.aip.org/link/?RSI/78/063701/1},
-doi = {10.1063/1.2743272},
- project = "Cantilever Calibration",
- note = "Excellent review of thermal calibration to 2007, but nothing
- in the way of derivations. Compares thermal tune
- and Sader method with laser Doppler vibrometry.",
-}
-
-@Article{stark01,
- author = RStark #" and "# TDrobek #" and "# WHeckl,
- title = "Thermomechanical noise of a free v-shaped cantilever
- for atomic-force microscopy.",
- journal = ULTRAMIC,
- year = 2001,
- month = jan,
- volume = 86,
- number = "1--2",
- pages = "207--215",
- abstract = "We have calculated the thermal noise of a v-shaped AFM
- cantilever (Microlever, Type E, Thermomicroscopes) by
- means of a finite element analysis. The modal shapes of
- the first 10 eigenmodes are displayed as well as the
- numerical constants, which are needed for the
- calibration using the thermal noise method. In the
- first eigenmode, values for the thermomechanical noise
- of the z-displacement at 22 degrees C temperature of
- square root of u2(1) = A/square root of c(cant) and the
- photodiode signal (normal-force) of S2(1) = A/square
- root of c(cant) were obtained. The results also
- indicate a systematic deviation ofthe spectral density
- of the thermomechanical noise of v-shaped cantilevers
- as compared to rectangular beam-shaped cantilevers.",
- ISSN = "0304-3991",
- doi = "http://dx.doi.org/10.1016/S0304-3991(00)00077-2",
- project = "Cantilever Calibration",
- note = "Higher mode adjustments for v-shaped cantilevers from simulation.",
-}
-
-@Article{hutter05,
- author = JHutter,
- title = "Comment on tilt of atomic force microscope
- cantilevers: effect on spring constant and adhesion
- measurements.",
- journal = "Langmuir",
- year = "2005",
- month = mar,
- day = "15",
- volume = "21",
- number = "6",
- pages = "2630--2632",
- ISSN = "0743-7463",
- doi = "10.1021/la047670t",
- project = "Cantilever Calibration",
- note = "Tilted cantilever corrections (not needed? see Ohler/VEECO note)",
-}
-
-@article{jones05,
-author = "R.E. Jones and D.P. Hart",
-title = "Force interactions between substrates and {SPM} cantilevers
- immersed in fluids",
-journal = "Tribology International",
-volume = 38,
-number = 3,
-pages = "355--361",
-year = 2005,
-issn = "0301-679X",
-keywords = "AFM;Liquid;Hydrodynamic;Lubrication",
-abstract = "With the availability of equipment used in Scanning Probe
- Microscopy (SPM), researchers have been able to probe the local
- fluid-substrate force interactions with resolutions of pN using a
- variety of SPM cantilevers. When using such methods, it is essential
- to differentiate between contributions to the net force on the
- cantilever. Specifically, the interaction between the cantilever,
- substrate and fluid, quantified while generating force curves, are
- discussed and compared with theoretical models for squeeze-film
- effects and drag on the SPM cantilevers. In addition we have
- demonstrated a simple method for utilizing the system as a
- micro-viscometer, independently measuring the viscosity of the
- lubricant for each test.",
-doi = "DOI: 10.1016/j.triboint.2004.08.016",
-url = "http://www.sciencedirect.com/science/article/B6V57-4DN9K7J-1/2/fef91ac022594c2c6a701376d83ecd31",
-}
-
-@Article {halvorsen2010,
-author = "Ken Halvorsen and Wesley P. Wong",
-title = "Massively parallel single-molecule manipulation using centrifugal force",
-journal = "arXiv",
-year = 2009,
-abstract = {Precise manipulation of single molecules has already led
- to remarkable insights in physics, chemistry, biology and
- medicine. However, widespread adoption of single-molecule techniques
- has been impeded by equipment cost and the laborious nature of
- making measurements one molecule at a time. We have solved these
- issues with a new approach: massively parallel single-molecule force
- measurements using centrifugal force. This approach is realized in a
- novel instrument that we call the Centrifuge Force Microscope (CFM),
- in which objects in an orbiting sample are subjected to a
- calibration-free, macroscopically uniform force-field while their
- micro-to-nanoscopic motions are observed. We demonstrate
- high-throughput single-molecule force spectroscopy with this
- technique by performing thousands of rupture experiments in
- parallel, characterizing force-dependent unbinding kinetics of an
- antibody-antigen pair in minutes rather than days. Additionally, we
- verify the force accuracy of the instrument by measuring the
- well-established DNA overstretching transition at 66 $\pm$ 3
- pN. With significant benefits in efficiency, cost, simplicity, and
- versatility, "single-molecule centrifugation" has the potential to
- revolutionize single-molecule experimentation, and open access to a
- wider range of researchers and experimental systems.},
-url = "http://arxiv.org/abs/0912.5370",
-}
-
-@Article{wolfsberg01,
- author = "T. G. Wolfsberg and J. McEntyre and G. D. Schuler",
- title = "Guide to the draft human genome.",
- journal = NAT,
- year = 2001,
- month = feb,
- day = 15,
- volume = 409,
- number = 6822,
- pages = "824--826",
- keywords = "Amino Acid Sequence;Chromosome Mapping;Computational Biology;Genes;Genetic Variation;Genome, Human;Human Genome Project;Humans;Internet;Molecular Sequence Data;Sequence Analysis, DNA",
- abstract = "There are a number of ways to investigate the
- structure, function and evolution of the human genome.
- These include examining the morphology of normal and
- abnormal chromosomes, constructing maps of genomic
- landmarks, following the genetic transmission of
- phenotypes and DNA sequence variations, and
- characterizing thousands of individual genes. To this
- list we can now add the elucidation of the genomic DNA
- sequence, albeit at 'working draft' accuracy. The
- current challenge is to weave together these disparate
- types of data to produce the information infrastructure
- needed to support the next generation of biomedical
- research. Here we provide an overview of the different
- sources of information about the human genome and how
- modern information technology, in particular the
- internet, allows us to link them together.",
- ISSN = "0028-0836",
- doi = "10.1038/35057000",
- url = "http://www.nature.com/nature/journal/v409/n6822/full/409824a0.html",
- eprint = "http://www.nature.com/nature/journal/v409/n6822/pdf/409824a0.pdf",
-}
-
-@Article{mcpherson01,
- author = "J. D. McPherson and M. Marra and L. Hillier and R. H.
- Waterston and A. Chinwalla and J. Wallis and M. Sekhon
- and K. Wylie and E. R. Mardis and R. K. Wilson and R.
- Fulton and T. A. Kucaba and C. Wagner-McPherson and W.
- B. Barbazuk and S. G. Gregory and S. J. Humphray and L.
- French and R. S. Evans and G. Bethel and A. Whittaker
- and J. L. Holden and O. T. McCann and A. Dunham and C.
- Soderlund and C. E. Scott and D. R. Bentley and G.
- Schuler and H. C. Chen and W. Jang and E. D. Green and
- J. R. Idol and V. V. Maduro and K. T. Montgomery and E.
- Lee and A. Miller and S. Emerling and Kucherlapati and
- R. Gibbs and S. Scherer and J. H. Gorrell and E.
- Sodergren and K. Clerc-Blankenburg and P. Tabor and S.
- Naylor and D. Garcia and P. J. de Jong and J. J.
- Catanese and N. Nowak and K. Osoegawa and S. Qin and L.
- Rowen and A. Madan and M. Dors and L. Hood and B. Trask
- and C. Friedman and H. Massa and V. G. Cheung and I. R.
- Kirsch and T. Reid and R. Yonescu and J. Weissenbach
- and T. Bruls and R. Heilig and E. Branscomb and A.
- Olsen and N. Doggett and J. F. Cheng and T. Hawkins and
- R. M. Myers and J. Shang and L. Ramirez and J. Schmutz
- and O. Velasquez and K. Dixon and N. E. Stone and D. R.
- Cox and D. Haussler and W. J. Kent and T. Furey and S.
- Rogic and S. Kennedy and S. Jones and A. Rosenthal and
- G. Wen and M. Schilhabel and G. Gloeckner and G.
- Nyakatura and R. Siebert and B. Schlegelberger and J.
- Korenberg and X. N. Chen and A. Fujiyama and M. Hattori
- and A. Toyoda and T. Yada and H. S. Park and Y. Sakaki
- and N. Shimizu and S. Asakawa and K. Kawasaki and T.
- Sasaki and A. Shintani and A. Shimizu and K. Shibuya
- and J. Kudoh and S. Minoshima and J. Ramser and P.
- Seranski and C. Hoff and A. Poustka and R. Reinhardt
- and H. Lehrach",
- title = "A physical map of the human genome.",
- journal = NAT,
- year = 2001,
- month = feb,
- day = 15,
- volume = 409,
- number = 6822,
- pages = "934--941",
- keywords = "Chromosomes, Artificial, Bacterial;Cloning, Molecular;Contig Mapping;DNA Fingerprinting;Gene Duplication;Genome, Human;Humans;In Situ Hybridization, Fluorescence;Repetitive Sequences, Nucleic Acid",
- abstract = "The human genome is by far the largest genome to be
- sequenced, and its size and complexity present many
- challenges for sequence assembly. The International
- Human Genome Sequencing Consortium constructed a map of
- the whole genome to enable the selection of clones for
- sequencing and for the accurate assembly of the genome
- sequence. Here we report the construction of the
- whole-genome bacterial artificial chromosome (BAC) map
- and its integration with previous landmark maps and
- information from mapping efforts focused on specific
- chromosomal regions. We also describe the integration
- of sequence data with the map.",
- ISSN = "0028-0836",
- doi = "10.1038/35057157",
- url = "http://www.nature.com/nature/journal/v409/n6822/full/409934a0.html",
- eprint = "http://www.nature.com/nature/journal/v409/n6822/pdf/409934a0.pdf",
-}
-
-@Article{venter01,
-author = "Venter, J. C. and Adams, M. D. and Myers, E. W. and Li,
- P. W. and Mural, R. J. and Sutton, G. G. and Smith, H. O. and
- Yandell, M. and Evans, C. A. and Holt, R. A. and Gocayne, J. D. and
- Amanatides, P. and Ballew, R. M. and Huson, D. H. and Wortman,
- J. R. and Zhang, Q. and Kodira, C. D. and Zheng, X. H. and Chen,
- L. and Skupski, M. and Subramanian, G. and Thomas, P. D. and Zhang,
- J. and Gabor Miklos, G. L. and Nelson, C. and Broder, S. and Clark,
- A. G. and Nadeau, J. and McKusick, V. A. and Zinder, N. and Levine,
- A. J. and Roberts, R. J. and Simon, M. and Slayman, C. and
- Hunkapiller, M. and Bolanos, R. and Delcher, A. and Dew, I. and
- Fasulo, D. and Flanigan, M. and Florea, L. and Halpern, A. and
- Hannenhalli, S. and Kravitz, S. and Levy, S. and Mobarry, C. and
- Reinert, K. and Remington, K. and Abu-Threideh, J. and Beasley,
- E. and Biddick, K. and Bonazzi, V. and Brandon, R. and Cargill,
- M. and Chandramouliswaran, I. and Charlab, R. and Chaturvedi, K. and
- Deng, Z. and Di Francesco, V. and Dunn, P. and Eilbeck, K. and
- Evangelista, C. and Gabrielian, A. E. and Gan, W. and Ge, W. and
- Gong, F. and Gu, Z. and Guan, P. and Heiman, T. J. and Higgins,
- M. E. and Ji, R. R. and Ke, Z. and Ketchum, K. A. and Lai, Z. and
- Lei, Y. and Li, Z. and Li, J. and Liang, Y. and Lin, X. and Lu,
- F. and Merkulov, G. V. and Milshina, N. and Moore, H. M. and Naik,
- A. K. and Narayan, V. A. and Neelam, B. and Nusskern, D. and Rusch,
- D. B. and Salzberg, S. and Shao, W. and Shue, B. and Sun, J. and
- Wang, Z. and Wang, A. and Wang, X. and Wang, J. and Wei, M. and
- Wides, R. and Xiao, C. and Yan, C. and Yao, A. and Ye, J. and Zhan,
- M. and Zhang, W. and Zhang, H. and Zhao, Q. and Zheng, L. and
- Zhong, F. and Zhong, W. and Zhu, S. and Zhao, S. and Gilbert,
- D. and Baumhueter, S. and Spier, G. and Carter, C. and Cravchik,
- A. and Woodage, T. and Ali, F. and An, H. and Awe, A. and Baldwin,
- D. and Baden, H. and Barnstead, M. and Barrow, I. and Beeson,
- K. and Busam, D. and Carver, A. and Center, A. and Cheng, M. L. and
- Curry, L. and Danaher, S. and Davenport, L. and Desilets, R. and
- Dietz, S. and Dodson, K. and Doup, L. and Ferriera, S. and Garg,
- N. and Gluecksmann, A. and Hart, B. and Haynes, J. and Haynes,
- C. and Heiner, C. and Hladun, S. and Hostin, D. and Houck, J. and
- Howland, T. and Ibegwam, C. and Johnson, J. and Kalush, F. and
- Kline, L. and Koduru, S. and Love, A. and Mann, F. and May, D. and
- McCawley, S. and McIntosh, T. and McMullen, I. and Moy, M. and Moy,
- L. and Murphy, B. and Nelson, K. and Pfannkoch, C. and Pratts,
- E. and Puri, V. and Qureshi, H. and Reardon, M. and Rodriguez,
- R. and Rogers, Y. H. and Romblad, D. and Ruhfel, B. and Scott,
- R. and Sitter, C. and Smallwood, M. and Stewart, E. and Strong,
- R. and Suh, E. and Thomas, R. and Tint, N. N. and Tse, S. and Vech,
- C. and Wang, G. and Wetter, J. and Williams, S. and Williams,
- M. and Windsor, S. and Winn-Deen, E. and Wolfe, K. and Zaveri,
- J. and Zaveri, K. and Abril, J. F. and Guig{\'o}, R. and Campbell,
- M. J. and Sjolander, K. V. and Karlak, B. and Kejariwal, A. and Mi,
- H. and Lazareva, B. and Hatton, T. and Narechania, A. and Diemer,
- K. and Muruganujan, A. and Guo, N. and Sato, S. and Bafna, V. and
- Istrail, S. and Lippert, R. and Schwartz, R. and Walenz, B. and
- Yooseph, S. and Allen, D. and Basu, A. and Baxendale, J. and Blick,
- L. and Caminha, M. and Carnes-Stine, J. and Caulk, P. and Chiang,
- Y. H. and Coyne, M. and Dahlke, C. and Mays, A. and Dombroski,
- M. and Donnelly, M. and Ely, D. and Esparham, S. and Fosler, C. and
- Gire, H. and Glanowski, S. and Glasser, K. and Glodek, A. and
- Gorokhov, M. and Graham, K. and Gropman, B. and Harris, M. and Heil,
- J. and Henderson, S. and Hoover, J. and Jennings, D. and Jordan,
- C. and Jordan, J. and Kasha, J. and Kagan, L. and Kraft, C. and
- Levitsky, A. and Lewis, M. and Liu, X. and Lopez, J. and Ma, D. and
- Majoros, W. and McDaniel, J. and Murphy, S. and Newman, M. and
- Nguyen, T. and Nguyen, N. and Nodell, M. and Pan, S. and Peck,
- J. and Peterson, M. and Rowe, W. and Sanders, R. and Scott, J. and
- Simpson, M. and Smith, T. and Sprague, A. and Stockwell, T. and
- Turner, R. and Venter, E. and Wang, M. and Wen, M. and Wu, D. and
- Wu, M. and Xia, A. and Zandieh, A. and Zhu, X.",
-title="The sequence of the human genome.",
-journal=SCI,
-year=2001,
-month="Feb",
-day=16,
-volume=291,
-number=5507,
-pages="1304--1351",
- keywords = "Algorithms;Animals;Chromosome Banding;Chromosome Mapping;Chromosomes, Artificial, Bacterial;Computational Biology;Consensus Sequence;CpG Islands;DNA, Intergenic;Databases, Factual;Evolution, Molecular;Exons;Female;Gene Duplication;Genes;Genetic Variation;Genome, Human;Human Genome Project;Humans;Introns;Male;Phenotype;Physical Chromosome Mapping;Polymorphism, Single Nucleotide;Proteins;Pseudogenes;Repetitive Sequences, Nucleic Acid;Retroelements;Sequence Analysis, DNA;Species Specificity",
-abstract="A 2.91-billion base pair (bp) consensus sequence of the
-euchromatic portion of the human genome was generated by the
-whole-genome shotgun sequencing method. The 14.8-billion bp DNA
-sequence was generated over 9 months from 27,271,853 high-quality
-sequence reads (5.11-fold coverage of the genome) from both ends of
-plasmid clones made from the DNA of five individuals. Two assembly
-strategies-a whole-genome assembly and a regional chromosome
-assembly-were used, each combining sequence data from Celera and the
-publicly funded genome effort. The public data were shredded into
-550-bp segments to create a 2.9-fold coverage of those genome regions
-that had been sequenced, without including biases inherent in the
-cloning and assembly procedure used by the publicly funded group. This
-brought the effective coverage in the assemblies to eightfold,
-reducing the number and size of gaps in the final assembly over what
-would be obtained with 5.11-fold coverage. The two assembly strategies
-yielded very similar results that largely agree with independent
-mapping data. The assemblies effectively cover the euchromatic regions
-of the human chromosomes. More than 90\% of the genome is in scaffold
-assemblies of 100,000 bp or more, and 25\% of the genome is in
-scaffolds of 10 million bp or larger. Analysis of the genome sequence
-revealed 26,588 protein-encoding transcripts for which there was
-strong corroborating evidence and an additional approximately 12,000
-computationally derived genes with mouse matches or other weak
-supporting evidence. Although gene-dense clusters are obvious, almost
-half the genes are dispersed in low G+C sequence separated by large
-tracts of apparently noncoding sequence. Only 1.1\% of the genome is
-spanned by exons, whereas 24\% is in introns, with 75\% of the genome
-being intergenic DNA. Duplications of segmental blocks, ranging in
-size up to chromosomal lengths, are abundant throughout the genome and
-reveal a complex evolutionary history. Comparative genomic analysis
-indicates vertebrate expansions of genes associated with neuronal
-function, with tissue-specific developmental regulation, and with the
-hemostasis and immune systems. DNA sequence comparisons between the
-consensus sequence and publicly funded genome data provided locations
-of 2.1 million single-nucleotide polymorphisms (SNPs). A random pair
-of human haploid genomes differed at a rate of 1 bp per 1250 on
-average, but there was marked heterogeneity in the level of
-polymorphism across the genome. Less than 1\% of all SNPs resulted in
-variation in proteins, but the task of determining which SNPs have
-functional consequences remains an open challenge.",
-issn="0036-8075",
-doi="10.1126/science.1058040",
-url="http://www.sciencemag.org/cgi/content/short/291/5507/1304",
-eprint="http://www.sciencemag.org/cgi/content/pdf/291/5507/1304",
-}
-
-@Article{claverie01,
- author = "J. M. Claverie",
- title = "Gene number. What if there are only 30,000 human
- genes?",
- journal = SCI,
- year = 2001,
- month = feb,
- day = 16,
- volume = 291,
- number = 5507,
- pages = "1255--1257",
- keywords = "Animals;Computational Biology;Drug Industry;Expressed Sequence Tags;Gene Expression;Gene Expression Regulation;Genes;Genetic Techniques;Genome, Human;Genomics;Human Genome Project;Humans;Models, Genetic;Polymorphism, Single Nucleotide;Proteins;RNA, Messenger",
- ISSN = "0036-8075",
- url = "http://www.sciencemag.org/cgi/content/full/291/5507/1255",
-}
-
-@Article{collins03,
- author = "Francis S. Collins and Michael Morgan and Aristides
- Patrinos",
- title = "The Human Genome Project: lessons from large-scale
- biology.",
- journal = SCI,
- year = 2003,
- month = apr,
- day = 11,
- volume = 300,
- number = 5617,
- pages = "286--290",
- keywords = "Access to Information;Computational Biology;Databases, Nucleic Acid;Genome, Human;Genomics;Government Agencies;History, 20th Century;Human Genome Project;Humans;International Cooperation;National Institutes of Health (U.S.);Private Sector;Public Policy;Public Sector;Publishing;Quality Control;Sequence Analysis, DNA;United States",
- ISSN = "1095-9203",
- doi = "10.1126/science.1084564",
- url = "http://www.sciencemag.org/cgi/content/summary/300/5617/277",
- eprint = "http://www.sciencemag.org/cgi/reprint/300/5617/286.pdf",
- note = "See also: \href{http://www.ornl.gov/sci/techresources/Human_Genome/project/journals/journals.shtml}{Landmark HPG Papers}",
-}
-
-@Article{levinthal68,
- author = "Levinthal, Cyrus",
- title = "Are there pathways for protein folding?",
- journal = JCPPCB,
- volume = 65,
- number = 1,
- pages = "44--45",
- year = 1968,
- eprint = "http://www.biochem.wisc.edu/courses/biochem704/Reading/Levinthal1968.pdf",
- note = "\emph{Not} Levinthal's paradox.",
-}
-
-@Inproceedings{levinthal69,
- author = "Levinthal, Cyrus",
- title = "How to Fold Graciously.",
- booktitle = "Mossbauer Spectroscopy in Biological Systems",
- year = 1969,
- editor = {Debrunner, P. and Tsibris, J.C.M. and M\"unck, E.},
- pages = "22--24",
- address = "Allerton House, Monticello, IL",
- publisher = "University of Illinois Press, Urbana",
- url = "http://www-miller.ch.cam.ac.uk/levinthal/levinthal.html"
-}
-
-@Article{zwanzig92,
- author = "R. Zwanzig and A. Szabo and B. Bagchi",
- title = "Levinthal's paradox.",
- journal = PNAS,
- year = 1992,
- month = jan,
- day = 01,
- volume = 89,
- number = 1,
- pages = "20--22",
- keywords = "Mathematics;Models, Theoretical;Protein Conformation;Proteins",
- abstract = "Levinthal's paradox is that finding the native folded
- state of a protein by a random search among all
- possible configurations can take an enormously long
- time. Yet proteins can fold in seconds or less.
- Mathematical analysis of a simple model shows that a
- small and physically reasonable energy bias against
- locally unfavorable configurations, of the order of a
- few kT, can reduce Levinthal's time to a biologically
- significant size.",
- ISSN = "0027-8424",
- url = "http://www.ncbi.nlm.nih.gov/pmc/articles/PMC48166/",
- eprint = "http://www.ncbi.nlm.nih.gov/pmc/articles/PMC48166/pdf/pnas01075-0036.pdf",
-}
-
-@Article{freitag97,
- author = "S. Freitag and I. Le Trong and L. Klumb and P. S.
- Stayton and R. E. Stenkamp",
- title = "Structural studies of the streptavidin binding loop.",
- journal = PS,
- year = 1997,
- month = jun,
- volume = 6,
- number = 6,
- pages = "1157--1166",
- keywords = "Allosteric Regulation;Bacterial Proteins;Binding Sites;Biotin;Crystallography, X-Ray;Hydrogen Bonding;Ligands;Models, Molecular;Molecular Conformation;Streptavidin;Tryptophan",
- abstract = "The streptavidin-biotin complex provides the basis for
- many important biotechnological applications and is an
- interesting model system for studying high-affinity
- protein-ligand interactions. We report here
- crystallographic studies elucidating the conformation
- of the flexible binding loop of streptavidin (residues
- 45 to 52) in the unbound and bound forms. The crystal
- structures of unbound streptavidin have been determined
- in two monoclinic crystal forms. The binding loop
- generally adopts an open conformation in the unbound
- species. In one subunit of one crystal form, the
- flexible loop adopts the closed conformation and an
- analysis of packing interactions suggests that
- protein-protein contacts stabilize the closed loop
- conformation. In the other crystal form all loops adopt
- an open conformation. Co-crystallization of
- streptavidin and biotin resulted in two additional,
- different crystal forms, with ligand bound in all four
- binding sites of the first crystal form and biotin
- bound in only two subunits in a second. The major
- change associated with binding of biotin is the closure
- of the surface loop incorporating residues 45 to 52.
- Residues 49 to 52 display a 3(10) helical conformation
- in unbound subunits of our structures as opposed to the
- disordered loops observed in other structure
- determinations of streptavidin. In addition, the open
- conformation is stabilized by a beta-sheet hydrogen
- bond between residues 45 and 52, which cannot occur in
- the closed conformation. The 3(10) helix is observed in
- nearly all unbound subunits of both the co-crystallized
- and ligand-free structures. An analysis of the
- temperature factors of the binding loop regions
- suggests that the mobility of the closed loops in the
- complexed structures is lower than in the open loops of
- the ligand-free structures. The two biotin bound
- subunits in the tetramer found in the MONO-b1 crystal
- form are those that contribute Trp 120 across their
- respective binding pockets, suggesting a structural
- link between these binding sites in the tetramer.
- However, there are no obvious signatures of binding
- site communication observed upon ligand binding, such
- as quaternary structure changes or shifts in the region
- of Trp 120. These studies demonstrate that while
- crystallographic packing interactions can stabilize
- both the open and closed forms of the flexible loop, in
- their absence the loop is open in the unbound state and
- closed in the presence of biotin. If present in
- solution, the helical structure in the open loop
- conformation could moderate the entropic penalty
- associated with biotin binding by contributing an
- order-to-disorder component to the loop closure.",
- ISSN = "0961-8368",
- doi = "10.1002/pro.5560060604",
- note ="\href{http://www.rcsb.org/pdb/explore.do?structureId=1SWE}{PDB ID: 1SWE},
- DOI: \href{http://dx.doi.org/10.2210/pdb1swe/pdb}{10.2210/pdb1swe/pdb}.",
-}
-
-
-@Article{improta96,
- author = "S. Improta and A. S. Politou and A. Pastore",
- title = "Immunoglobulin-like modules from titin {I}-band:
- extensible components of muscle elasticity.",
- journal = STR,
- year = 1996,
- month = mar,
- day = 15,
- volume = 4,
- number = 3,
- pages = "323--337",
- keywords = "Amino Acid Sequence;Immunoglobulins;Magnetic Resonance Spectroscopy;Models, Molecular;Molecular Sequence Data;Molecular Structure;Muscle Proteins;Protein Kinases;Protein Structure, Secondary;Protein Structure, Tertiary;Sequence Alignment",
- abstract = "BACKGROUND. The giant muscle protein titin forms a
- filament which spans half of the sarcomere and
- performs, along its length, quite diverse functions.
- The region of titin located in the sarcomere I-band is
- believed to play a major role in extensibility and
- passive elasticity of muscle. In the I-band, the titin
- sequence consists mostly of repetitive motifs of tandem
- immunoglobulin-like (Ig) modules intercalated by a
- potentially non-globular region. The highly repetitive
- titin architecture suggests that the molecular basis of
- its mechanical properties be approached through the
- characterization of the isolated components of the
- I-band and their interfaces. In the present paper, we
- report on the structure determination in solution of a
- representative Ig module from the I-band (I27) as
- solved by NMR techniques. RESULTS. The structure of I27
- consists of a beta sandwich formed by two four-stranded
- sheets (named ABED and A'GFC). This fold belongs to the
- intermediate frame (I frame) of the immunoglobulin
- superfamily. Comparison of I27 with another titin
- module from the region located in the M-line (M5) shows
- that two loops (between the B and C and the F and G
- strands) are shorter in I27, conferring a less
- elongated appearance to this structure. Such a feature
- is specific to the Ig domains in the I-band and might
- therefore be related to the functions of the protein in
- this region. The structure of tandem Ig domains as
- modeled from I27 suggests the presence of hinge regions
- connecting contiguous modules. CONCLUSIONS. We suggest
- that titin Ig domains in the I-band function as
- extensible components of muscle elasticity by
- stretching the hinge regions.",
- ISSN = "0969-2126",
- doi = "10.1016/S0969-2126(96)00036-6",
- note ="\href{http://www.rcsb.org/pdb/explore.do?structureId=1TIT}{PDB ID: 1TIT},
- DOI: \href{http://dx.doi.org/10.2210/pdb1tit/pdb}{10.2210/pdb1tit/pdb}.",
-}
-
-@Article{uniprot10,
- key = "uniprot10",
- title = "The Universal Protein Resource (UniProt) in 2010.",
- author = "The UniProt Consortium",
- journal = NAR,
- year = 2010,
- month = jan,
- day = 20,
- volume = 38,
- number = "Database issue",
- pages = "D142--D148",
- keywords = "Algorithms;Animals;Computational Biology;Databases, Nucleic Acid;Databases, Protein;Europe;Genome, Fungal;Genome, Viral;Humans;Information Storage and Retrieval;Internet;Protein Isoforms;Proteome;Proteomics;Software",
- abstract = "The primary mission of UniProt is to support
- biological research by maintaining a stable,
- comprehensive, fully classified, richly and accurately
- annotated protein sequence knowledgebase, with
- extensive cross-references and querying interfaces
- freely accessible to the scientific community. UniProt
- is produced by the UniProt Consortium which consists of
- groups from the European Bioinformatics Institute
- (EBI), the Swiss Institute of Bioinformatics (SIB) and
- the Protein Information Resource (PIR). UniProt is
- comprised of four major components, each optimized for
- different uses: the UniProt Archive, the UniProt
- Knowledgebase, the UniProt Reference Clusters and the
- UniProt Metagenomic and Environmental Sequence
- Database. UniProt is updated and distributed every 3
- weeks and can be accessed online for searches or
- download at http://www.uniprot.org.",
- ISSN = "1362-4962",
- doi = "10.1093/nar/gkp846",
- url = "http://nar.oxfordjournals.org/cgi/content/abstract/38/suppl_1/D142",
-}
-
-@Misc{uniprot:STRAV,
- key = "uniprot:STRAV",
- url = "http://www.uniprot.org/uniprot/P22629",
-}
-@article{alon90,
-author = "Ronen Alon and Edward A. Bayer and Meir Wilchek",
-title = "Streptavidin contains an {RYD} sequence which mimics the
- {RGD} receptor domain of fibronectin",
-journal = BCBPRC,
-year = 1990,
-month = aug,
-day = 16,
-volume = 170,
-number = 3,
-pages = "1236--1241",
- keywords = "Amino Acid Sequence;Animals;Bacterial Proteins;Binding Sites;Cell Line;Cell Membrane;Cricetinae;Fibronectins;Molecular Sequence Data;Streptavidin",
- abstract = "Streptavidin binds at low levels and high affinity to
- cell surfaces, the cause of which can be traced to the
- occurrence of a sequence containing RYD (Arg-Tyr-Asp)
- in the protein molecule. This binding is enhanced in
- the presence of biotin. Cell-bound streptavidin can be
- displaced by fibronectin, as well as by RGD- and
- RYD-containing peptides. In addition, streptavidin can
- displace fibronectin from cell surfaces. The RYD
- sequence of streptavidin thus mimics RGD (Arg-Gly-Asp),
- the universal recognition domain present in fibronectin
- and other adhesion-related molecules. The observed
- adhesion to cells has no relevance to biotin-binding
- since the RYD sequence is not part of the
- biotin-binding site of streptavidin. Since the use of
- streptavidin in avidin-biotin technology is based on
- its biotin-binding properties, researchers are hereby
- warned against its indiscriminate use in histochemical
- and cytochemical studies.",
- ISSN = "0006-291X",
-doi = "DOI: 10.1016/0006-291X(90)90526-S",
-url = "http://www.sciencedirect.com/science/article/B6WBK-4F5M7K3-3C/2/c94b612e06efc8534ee24bb1da889811",
- note = "Biological role of streptavidin.",
-}
-
-@Article{dill97,
- author = "K. A. Dill and H. S. Chan",
- title = "From Levinthal to pathways to funnels.",
- journal = NSB,
- year = 1997,
- month = jan,
- volume = 4,
- number = 1,
- pages = "10--19",
- keywords = "Kinetics;Models, Chemical;Protein Folding",
- abstract = "While the classical view of protein folding kinetics
- relies on phenomenological models, and regards folding
- intermediates in a structural way, the new view
- emphasizes the ensemble nature of protein
- conformations. Although folding has sometimes been
- regarded as a linear sequence of events, the new view
- sees folding as parallel microscopic multi-pathway
- diffusion-like processes. While the classical view
- invoked pathways to solve the problem of searching for
- the needle in the haystack, the pathway idea was then
- seen as conflicting with Anfinsen's experiments showing
- that folding is pathway-independent (Levinthal's
- paradox). In contrast, the new view sees no inherent
- paradox because it eliminates the pathway idea: folding
- can funnel to a single stable state by multiple routes
- in conformational space. The general energy landscape
- picture provides a conceptual framework for
- understanding both two-state and multi-state folding
- kinetics. Better tests of these ideas will come when
- new experiments become available for measuring not just
- averages of structural observables, but also
- correlations among their fluctuations. At that point we
- hope to learn much more about the real shapes of
- protein folding landscapes.",
- ISSN = "1072-8368",
- doi = "10.1038/nsb0197-10",
- url = "http://www.nature.com/nsmb/journal/v4/n1/abs/nsb0197-10.html",
- eprint = "http://www.nature.com/nsmb/journal/v4/n1/pdf/nsb0197-10.pdf",
- note = "Pretty folding funnel figures.",
-}
-
-@Article{bedard08,
- author = "Sabrina B{\'e}dard and Mallela M. G. Krishna and
- Leland Mayne and S. Walter Englander",
- title = "Protein folding: independent unrelated pathways or
- predetermined pathway with optional errors.",
- journal = PNAS,
- year = 2008,
- month = may,
- day = 20,
- volume = 105,
- number = 20,
- pages = "7182--7187",
- keywords = "Biochemistry;Guanidine;Kinetics;Micrococcal Nuclease;Models, Biological;Models, Chemical;Models, Theoretical;Protein Conformation;Protein Denaturation;Protein Folding;Protein Structure, Secondary;Proteins;Proteomics;Reproducibility of Results;Thermodynamics",
- abstract = "The observation of heterogeneous protein folding
- kinetics has been widely interpreted in terms of
- multiple independent unrelated pathways (IUP model),
- both experimentally and in theoretical calculations.
- However, direct structural information on folding
- intermediates and their properties now indicates that
- all of a protein population folds through essentially
- the same stepwise pathway, determined by cooperative
- native-like foldon units and the way that the foldons
- fit together in the native protein. It is essential to
- decide between these fundamentally different folding
- mechanisms. This article shows, contrary to previous
- supposition, that the heterogeneous folding kinetics
- observed for the staphylococcal nuclease protein
- (SNase) does not require alternative parallel pathways.
- SNase folding kinetics can be fit equally well by a
- single predetermined pathway that allows for optional
- misfolding errors, which are known to occur
- ubiquitously in protein folding. Structural, kinetic,
- and thermodynamic information for the folding
- intermediates and pathways of many proteins is
- consistent with the predetermined pathway-optional
- error (PPOE) model but contrary to the properties
- implied in IUP models.",
- ISSN = "1091-6490",
- doi = "10.1073/pnas.0801864105",
- url = "http://www.pnas.org/content/105/20/7182.full",
- eprint = "http://www.pnas.org/content/105/20/7182.full.pdf",
-}
-
-@Article{puchner08,
- author = EPuchner #" and "# GFranzen #" and "# MGautel #" and "# HGaub,
- title = "Comparing proteins by their unfolding pattern.",
- journal = BPJ,
- year = 2008,
- month = jul,
- volume = 95,
- number = 1,
- pages = "426--434",
- keywords = "Algorithms;Computer Simulation;Microscopy, Atomic Force;Models, Chemical;Models, Molecular;Protein Denaturation;Protein Folding;Proteins",
- abstract = "Single molecule force spectroscopy has evolved into an
- important and extremely powerful technique for
- investigating the folding potentials of biomolecules.
- Mechanical tension is applied to individual molecules,
- and the subsequent, often stepwise unfolding is
- recorded in force extension traces. However, because
- the energy barriers of the folding potentials are often
- close to the thermal energy, both the extensions and
- the forces at which these barriers are overcome are
- subject to marked fluctuations. Therefore, force
- extension traces are an inadequate representation
- despite widespread use particularly when large
- populations of proteins need to be compared and
- analyzed. We show in this article that contour length,
- which is independent of fluctuations and alterable
- experimental parameters, is a more appropriate variable
- than extension. By transforming force extension traces
- into contour length space, histograms are obtained that
- directly represent the energy barriers. In contrast to
- force extension traces, such barrier position
- histograms can be averaged to investigate details of
- the unfolding potential. The cross-superposition of
- barrier position histograms allows us to detect and
- visualize the order of unfolding events. We show with
- this approach that in contrast to the sequential
- unfolding of bacteriorhodopsin, two main steps in the
- unfolding of the enzyme titin kinase are independent of
- each other. The potential of this new method for
- accurate and automated analysis of force spectroscopy
- data and for novel automated screening techniques is
- shown with bacteriorhodopsin and with protein
- constructs containing GFP and titin kinase.",
- ISSN = "1542-0086",
- doi = "10.1529/biophysj.108.129999",
- url = "http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2426622/",
- eprint = "http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2426622/pdf/426.pdf",
-}
-
-@Misc{codata-boltzmann,
- key="codata-boltzmann",
- crossref = "codata06",
- url = "http://physics.nist.gov/cgi-bin/cuu/Value?k",
-}
-
-@Article{codata06,
- key="codata06",
- title = "{CODATA} recommended values of the fundamental physical constants: 2006",
- author = "Mohr, Peter J. and Taylor, Barry N. and Newell, David B.",
- journal = RMP,
- volume = 80,
- number = 2,
- pages = "633--730",
- numpages = 97,
- year = 2008,
- month = jun,
- doi = "10.1103/RevModPhys.80.633",
- publisher = APS,
-}
-
-@article{king10,
-author = WKing #" and "# MSu #" and "# GYang,
-title = "{M}onte {C}arlo simulation of mechanical unfolding of
- proteins based on a simple two-state model",
-journal = IJBMM,
-volume = 46,
-number = 2,
-pages = "159--166",
-year = 2010,
-issn = "0141-8130",
-keywords = "Atomic force microscopy;Mechanical unfolding;Monte Carlo simulation;Worm-like chain;Single molecule methods",
-abstract = "Single molecule methods are becoming routine biophysical
- techniques for studying biological macromolecules. In mechanical
- unfolding of proteins, an externally applied force is used to induce
- the unfolding of individual protein molecules. Such experiments have
- revealed novel information that has significantly enhanced our
- understanding of the function and folding mechanisms of several
- types of proteins. To obtain information on the unfolding kinetics
- and the free energy landscape of the protein molecule from
- mechanical unfolding data, a Monte Carlo simulation based on a
- simple two-state kinetic model is often used. In this paper, we
- provide a detailed description of the procedure to perform such
- simulations and discuss the approximations and assumptions
- involved. We show that the appearance of the force versus extension
- curves from mechanical unfolding of proteins is affected by a
- variety of experimental parameters, such as the length of the
- protein polymer and the force constant of the cantilever. We also
- analyze the errors associated with different methods of data pooling
- and present a quantitative measure of how well the simulation
- results fit experimental data. These findings will be helpful in
- experimental design, artifact identification, and data analysis for
- single molecule studies of various proteins using the mechanical
- unfolding method.",
-doi = "10.1016/j.ijbiomac.2009.12.001",
-url = "http://www.sciencedirect.com/science/article/B6T7J-4XWMND2-1/2/7ef768562b4157fc201d450553e5de5e",
-}
-
-@Article{metropolis87,
- author = "Nicholas Metropolis",
- title = "The Beginning of the Monte Carlo Method",
- journal = "Los Alamos Science",
- volume = 15,
- pages = "125--130",
- year = 1987,
- publisher = "Los Alamos National Laboratory",
- url = "http://library.lanl.gov/cgi-bin/getfile?15-12.pdf",
-}
-
-@Book{noy08,
- editor = ANoy,
- title = "Handbook of Molecular Force Spectroscopy",
- publisher = SPRINGER,
- year = 2008,
- ISBN="978-0-387-49987-1",
- note="The first book about force spectroscopy. Discusses the scaffold effect in section 8.4.1.",
+@string{AAPT = "AAPT"}
+@string{ACSChemBiol = "ACS Chem Biol"}
+@string{AIP = "AIP"}
+@string{DAbramavicius = "Abramavicius, Darius"}
+@string{JFAbril = "Abril, J. F."}
+@string{JAbu-Threideh = "Abu-Threideh, J."}
+@string{MDAdams = "Adams, M. D."}
+@string{AdvExpMedBiol = "Adv Exp Med Biol"}
+@string{SAinavarapu = "Ainavarapu, Sri Rama Koti"}
+@string{FAli = "Ali, F."}
+@string{JFAllemand = "Allemand, J. F."}
+@string{JFAllemandX = "Allemand, Jean-Fran\c{c}ois"}
+@string{DAllen = "Allen, D."}
+@string{MAllen = "Allen, Mark D."}
+@string{RAlon = "Alon, Ronen"}
+@string{PAmanatides = "Amanatides, P."}
+@string{AmericanJournalofPhysics = "American Journal of Physics"}
+@string{APS = "American Physical Society"}
+@string{AmericanStatisticalAssociation = "American Statistical Association"}
+@string{HAn = "An, H."}
+@string{KNAn = "An, Kai-Nan"}
+@string{IAndricioaei = "Andricioaei, Ioan"}
+@string{MAngelikaANoegelandRief = "Angelika A. Noegel andRief, Matthias"}
+@string{ACIEE = "Angew. Chem. Int. Ed. Engl."}
+@string{AnnuRevBiophysBiomolStruct = "Annu Rev Biophys Biomol Struct"}
+@string{ARBC = "Annual Review of Biochemistry"}
+@string{DAnselmetti = "Anselmetti, D."}
+@string{AppliedMathematicsandComputation = "Applied Mathematics and Computation"}
+@string{SArcidiacono = "Arcidiacono, S"}
+@string{CArciola = "Arciola, Carla Renata"}
+@string{ABArtyukhin = "Artyukhin, Alexander B."}
+@string{SAsakawa = "Asakawa, S."}
+@string{AAwe = "Awe, A."}
+@string{WBaase = "Baase, Walter A."}
+@string{HBaden = "Baden, H."}
+@string{CBadilla = "Badilla, Carmen L."}
+@string{JMBadilla = "Badilla, Carmen L.andFernandez, Julio M."}
+@string{VBafna = "Bafna, V."}
+@string{BBagchi = "Bagchi, B."}
+@string{MBalamurali = "Balamurali, M. M."}
+@string{DBaldwin = "Baldwin, D."}
+@string{RMBallew = "Ballew, R. M."}
+@string{MBalsera = "Balsera, M."}
+@string{GBaneyx = "Baneyx, Gretchen"}
+@string{RBar-Ziv = "Bar-Ziv, Roy"}
+@string{WBBarbazuk = "Barbazuk, W. B."}
+@string{MBarnstead = "Barnstead, M."}
+@string{DBarrick = "Barrick, Doug"}
+@string{IBarrow = "Barrow, I."}
+@string{FWBartels = "Bartels, F. W."}
+@string{BBarz = "Barz, Bogdan"}
+@string{TBasche = "Basche, Th."}
+@string{ABasu = "Basu, A."}
+@string{LBaugh = "Baugh, Loren"}
+@string{SBaumhueter = "Baumhueter, S."}
+@string{JBaxendale = "Baxendale, J."}
+@string{EABayer = "Bayer, Edward A."}
+@string{EBeasley = "Beasley, E."}
+@string{JBechhoefer = "Bechhoefer, John"}
+@string{JSWBechhoefer = "Bechhoefer, Johnand Scott Wilson"}
+@string{GSBeddard = "Beddard, Godfrey S."}
+@string{KBeeson = "Beeson, K."}
+@string{GIBell = "Bell, G. I."}
+@string{VBenes = "Benes, Vladimir"}
+@string{ABensimon = "Bensimon, A."}
+@string{DBensimon = "Bensimon, D."}
+@string{DBensimonX = "Bensimon, David"}
+@string{DRBentley = "Bentley, D. R."}
+@string{HJCBerendsen = "Berendsen, Herman J. C."}
+@string{DBerk = "Berk, D."}
+@string{FBerkemeier = "Berkemeier, Felix"}
+@string{BBerne = "Berne, Bruce J."}
+@string{MBertz = "Bertz, Morten"}
+@string{RBest = "Best, Robert B."}
+@string{GBethel = "Bethel, G."}
+@string{NBhasin = "Bhasin, Nishant"}
+@string{KBiddick = "Biddick, K."}
+@string{KBillings = "Billings, Kate S."}
+@string{BCBPRC = "Biochemical and Biophysical Research Communications"}
+@string{Biochemistry = "Biochemistry"}
+@string{BiochimicaetBiophysicaActaBBA-Bioenergetics = "Biochimica et Biophysica Acta (BBA) - Bioenergetics"}
+@string{BPJ = "Biophys. J."}
+@string{BIOSENSE = "Biosensors and Bioelectronics"}
+@string{JBirchler = "Birchler, James A."}
+@string{AWBlake = "Blake, Anthony W."}
+@string{JBlawzdziewicz = "Blawzdziewicz, Jerzy"}
+@string{LBlick = "Blick, L."}
+@string{RBolanos = "Bolanos, R."}
+@string{VBonazzi = "Bonazzi, V."}
+@string{Borgia = "Borgia"}
+@string{MBorkovec = "Borkovec, Michal"}
+@string{RBrandon = "Brandon, R."}
+@string{EBranscomb = "Branscomb, E."}
+@string{EBraverman = "Braverman, Elena"}
+@string{WBreyer = "Breyer, Wendy A."}
+@string{FBrochard-Wyart = "Brochard-Wyart, F."}
+@string{DJBrockwell = "Brockwell, David J."}
+@string{SBroder = "Broder, S."}
+@string{SBroedel = "Broedel, Sheldon E."}
+@string{BrooksCole = "Brooks/Cole"}
+@string{BDBrowerToland = "Brower-Toland, Brent D."}
+@string{TBruls = "Bruls, T."}
+@string{VBrumfeld = "Brumfeld, Vlad"}
+@string{JDBryngelson = "Bryngelson, J. D."}
+@string{ABuguin = "Buguin, A."}
+@string{BBullard = "Bullard, Belinda"}
+@string{DBusam = "Busam, D."}
+@string{CBustamante = "Bustamante, Carlos"}
+@string{CJFMBustamante = "Bustamante, Carlosand J. F. Marko"}
+@string{YBustanji = "Bustanji, Yasser"}
+@string{HJButt = {Butt, Hans-J\"urgen}}
+@string{SBedard = "B{\'e}dard, Sabrina"}
+@string{CambridgeUniversityPress = "Cambridge University Press"}
+@string{MCaminha = "Caminha, M."}
+@string{ICampbell = "Campbell, Iain D."}
+@string{MJCampbell = "Campbell, M. J."}
+@string{YCao = "Cao, Yi"}
+@string{MCargill = "Cargill, M."}
+@string{PCarl = "Carl, Philippe"}
+@string{BACarnes = "Carnes, B. A."}
+@string{JCarnes-Stine = "Carnes-Stine, J."}
+@string{MCarrionVazquez = "Carrion-Vazquez, Mariano"}
+@string{CCarter = "Carter, C."}
+@string{ACarver = "Carver, A."}
+@string{JJCatanese = "Catanese, J. J."}
+@string{PCaulk = "Caulk, P."}
+@string{CCecconi = "Cecconi, Ciro"}
+@string{ACenter = "Center, A."}
+@string{HSChan = "Chan, H. S."}
+@string{IChandramouliswaran = "Chandramouliswaran, I."}
+@string{CHChang = "Chang, Chung-Hung"}
+@string{EChapman = "Chapman, Edwin R."}
+@string{RCharlab = "Charlab, R."}
+@string{KChaturvedi = "Chaturvedi, K."}
+@string{CChauzy = "Chauzy, C."}
+@string{Chemphyschem = "Chemphyschem"}
+@string{HCChen = "Chen, H. C."}
+@string{LChen = "Chen, L."}
+@string{XNChen = "Chen, X. N."}
+@string{JFCheng = "Cheng, J. F."}
+@string{MLCheng = "Cheng, M. L."}
+@string{VGCheung = "Cheung, V. G."}
+@string{YHChiang = "Chiang, Y. H."}
+@string{AChinwalla = "Chinwalla, A."}
+@string{JChoy = "Choy, Jason"}
+@string{CLChyan = "Chyan, Chia-Lin"}
+@string{GCiccottiX = "Ciccotti, G."}
+@string{GCiccotti = "Ciccotti, Giovanni"}
+@string{HClaireLethiasandPeng = "Claire Lethias andPeng, Qingand Yi Cao andLi, Hongbin"}
+@string{AGClark = "Clark, A. G."}
+@string{Clarke = "Clarke"}
+@string{JClarke = "Clarke, Jane"}
+@string{JClarkson = "Clarkson, John"}
+@string{JMClaverie = "Claverie, J. M."}
+@string{KClerc-Blankenburg = "Clerc-Blankenburg, K."}
+@string{NJCobb = "Cobb, Nathan J."}
+@string{FSCollins = "Collins, Francis S."}
+@string{ComputerPhysicsreports = "Computer Physics reports"}
+@string{TUPConsortium = "Consortium, The UniProt"}
+@string{MConti = "Conti, Matteo"}
+@string{PVCornish = "Cornish, Peter V."}
+@string{MNCourel = "Courel, M. N."}
+@string{GCowan = "Cowan, Glen"}
+@string{DRCox = "Cox, D. R."}
+@string{MCoyne = "Coyne, M."}
+@string{DCraig = "Craig, David"}
+@string{ACravchik = "Cravchik, A."}
+@string{VCroquette = "Croquette, V."}
+@string{VCroquetteX = "Croquette, Vincent"}
+@string{CurrOpinStructBiol = "Curr Opin Struct Biol"}
+@string{LCurry = "Curry, L."}
+@string{CDahlke = "Dahlke, C."}
+@string{FDahlquist = "Dahlquist, Frederick W."}
+@string{SDanaher = "Danaher, S."}
+@string{LDavenport = "Davenport, L."}
+@string{WDeGrado = "DeGrado, William F."}
+@string{PDebrunner = "Debrunner, P."}
+@string{ADelcher = "Delcher, A."}
+@string{BDelpech = "Delpech, B."}
+@string{Demography = "Demography"}
+@string{ZDeng = "Deng, Z."}
+@string{RDesilets = "Desilets, R."}
+@string{IDew = "Dew, I."}
+@string{CDewhurst = "Dewhurst, Charles"}
+@string{VDiFrancesco = "Di Francesco, V."}
+@string{KDiemer = "Diemer, K."}
+@string{HDietz = "Dietz, Hendrik"}
+@string{CDietz = "Dietz, HendrikandHyeon, Changbong"}
+@string{SDietz = "Dietz, S."}
+@string{KADill = "Dill, K. A."}
+@string{RDima = "Dima, Ruxandra I."}
+@string{DDischer = "Discher, Dennis E."}
+@string{KDixon = "Dixon, K."}
+@string{KDodson = "Dodson, K."}
+@string{NDoggett = "Doggett, N."}
+@string{MDombroski = "Dombroski, M."}
+@string{MDonnelly = "Donnelly, M."}
+@string{CDornmair = "Dornmair, C."}
+@string{MDors = "Dors, M."}
+@string{LDougan = "Dougan, Lorna"}
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+@string{RNPerham = "Perham, Richard N."}
+@string{OPerisic = "Perisic, Ognjen"}
+@string{CPeterson = "Peterson, Craig L."}
+@string{MPeterson = "Peterson, M."}
+@string{CPfannkoch = "Pfannkoch, C."}
+@string{PflugersArch = "Pflugers Arch"}
+@string{PhilosophicalTransactionsoftheRoyalSocietyofLondon = "Philosophical Transactions of the Royal Society of London"}
+@string{PhysRevEStatNonlinSoftMatterPhys = "Phys Rev E Stat Nonlin Soft Matter Phys"}
+@string{PhysRevLett = "Phys Rev Lett"}
+@string{PhysRevE = "Phys. Rev. E"}
+@string{PRL = "Phys. Rev. Lett."}
+@string{Physica = "Physica"}
+@string{PPodsiadlo = "Podsiadlo, Paul"}
+@string{ASPolitou = "Politou, A. S."}
+@string{APoustka = "Poustka, A."}
+@string{GPratesi = "Pratesi, G."}
+@string{EPratts = "Pratts, E."}
+@string{WPress = "Press, W."}
+@string{PNAS = "Proceedings of the National Academy of Sciences USA"}
+@string{PBPMB = "Progress in Biophysics and Molecular Biology"}
+@string{PS = "Protein Sci."}
+@string{PROT = "Proteins"}
+@string{EPuchner = "Puchner, Elias M."}
+@string{VPuri = "Puri, V."}
+@string{WPyckhout-Hintzen = "Pyckhout-Hintzen, Wim"}
+@string{SQin = "Qin, S."}
+@string{SRQuake = "Quake, Stephen R."}
+@string{HQureshi = "Qureshi, H."}
+@string{SERadford = "Radford, Sheena E."}
+@string{MRaible = "Raible, M."}
+@string{LRamirez = "Ramirez, L."}
+@string{JRamser = "Ramser, J."}
+@string{LRandles = "Randles, Lucy G."}
+@string{MReardon = "Reardon, M."}
+@string{ALCReddin = "Reddin, Andrew L. C."}
+@string{SRedick = "Redick, Sambra D."}
+@string{ZReich = "Reich, Ziv"}
+@string{TReid = "Reid, T."}
+@string{PReimann = "Reimann, P."}
+@string{KReinert = "Reinert, K."}
+@string{RReinhardt = "Reinhardt, R."}
+@string{KRemington = "Remington, K."}
+@string{RMP = "Rev. Mod. Phys."}
+@string{RSI = "Review of Scientific Instruments"}
+@string{FRief = "Rief, Frederick"}
+@string{MRief = "Rief, Matthias"}
+@string{HERief = "Rief, Matthiasand H. Clausen-Schaumann andGaub, Hermann E."}
+@string{MHGRief = {Rief, Matthiasand Helmut Grubm{\"u}ller}}
+@string{KRitchie = "Ritchie, K."}
+@string{RJRoberts = "Roberts, R. J."}
+@string{RRobertson = "Robertson, Ragan B."}
+@string{HRoder = "Roder, Heinrich"}
+@string{RRodriguez = "Rodriguez, R."}
+@string{YHRogers = "Rogers, Y. H."}
+@string{SRogic = "Rogic, S."}
+@string{DRomblad = "Romblad, D."}
+@string{RRos = "Ros, R."}
+@string{BRosenberg = "Rosenberg, B."}
+@string{ARosenthal = "Rosenthal, A."}
+@string{ARoters = "Roters, Andreas"}
+@string{WRowe = "Rowe, W."}
+@string{LRowen = "Rowen, L."}
+@string{BRuhfel = "Ruhfel, B."}
+@string{DBRusch = "Rusch, D. B."}
+@string{JPRyckaertX = "Ryckaert, J. P."}
+@string{JPRyckaert = "Ryckaert, Jean-Paul"}
+@string{YSakaki = "Sakaki, Y."}
+@string{SSalzberg = "Salzberg, S."}
+@string{BSamori = "Samori, Bruno"}
+@string{RSanders = "Sanders, R."}
+@string{ASarkar = "Sarkar, Atom"}
+@string{TSasaki = "Sasaki, T."}
+@string{SSato = "Sato, S."}
+@string{TSato = "Sato, Takehiro"}
+@string{PSchaaf = "Schaaf, P."}
+@string{RSchafer = "Schafer, Rolf"}
+@string{NScherer = "Scherer, Norbert F."}
+@string{SScherer = "Scherer, S."}
+@string{MSchilhabel = "Schilhabel, M."}
+@string{BSchlegelberger = "Schlegelberger, B."}
+@string{MSchleicher = "Schleicher, Michael"}
+@string{MSchlierf = "Schlierf, Michael"}
+@string{JSchmutz = "Schmutz, J."}
+@string{GSchuler = "Schuler, G."}
+@string{GDSchuler = "Schuler, G. D."}
+@string{KSchultenX = "Schulten, K."}
+@string{KSchulten = "Schulten, Klaus"}
+@string{ZSchulten = "Schulten, Zan"}
+@string{ISchwaiger = "Schwaiger, Ingo"}
+@string{RSchwartz = "Schwartz, R."}
+@string{SCI = "Science"}
+@string{CEScott = "Scott, C. E."}
+@string{JScott = "Scott, J."}
+@string{RScott = "Scott, R."}
+@string{USeifert = "Seifert, Udo"}
+@string{MSekhon = "Sekhon, M."}
+@string{BSenger = "Senger, B."}
+@string{PSeranski = "Seranski, P."}
+@string{RSesboue = {Sesbo{\"u}{\'e}, R.}}
+@string{EShakhnovich = "Shakhnovich, Eugene"}
+@string{JShang = "Shang, J."}
+@string{WShao = "Shao, W."}
+@string{DSharma = "Sharma, Deepak"}
+@string{YJSheng = "Sheng, Yu-Jane"}
+@string{GSheng-HsienLinandYang = "Sheng-Hsien Lin andYang, Guoliang"}
+@string{KShibuya = "Shibuya, K."}
+@string{JShillcock = "Shillcock, Julian"}
+@string{AShimizu = "Shimizu, A."}
+@string{NShimizu = "Shimizu, N."}
+@string{AShintani = "Shintani, A."}
+@string{BShue = "Shue, B."}
+@string{RSiebert = "Siebert, R."}
+@string{EDSiggiaX = "Siggia, E. D."}
+@string{EDSiggia = "Siggia, Eric D."}
+@string{MSimon = "Simon, M."}
+@string{MSimpson = "Simpson, M."}
+@string{GESims = "Sims, Gregory E."}
+@string{CSitter = "Sitter, C."}
+@string{KVSjolander = "Sjolander, K. V."}
+@string{MSkupski = "Skupski, M."}
+@string{CSlayman = "Slayman, C."}
+@string{MSmallwood = "Smallwood, M."}
+@string{CSmith = "Smith, Corey L."}
+@string{DASmith = "Smith, D. Alastair"}
+@string{HOSmith = "Smith, H. O."}
+@string{SSmith = "Smith, S."}
+@string{SBSmith = "Smith, S. B."}
+@string{TSmith = "Smith, T."}
+@string{JSoares = "Soares, J."}
+@string{NDSocci = "Socci, N. D."}
+@string{ESodergren = "Sodergren, E."}
+@string{CSoderlund = "Soderlund, C."}
+@string{DSpeicher = "Speicher, David W."}
+@string{GSpier = "Spier, G."}
+@string{ASprague = "Sprague, A."}
+@string{SPRINGER = "Springer Science + Business Media, LLC"}
+@string{DBStaple = "Staple, Douglas B."}
+@string{RStark = "Stark, R. W."}
+@string{PSStayton = "Stayton, P. S."}
+@string{REStenkamp = "Stenkamp, R. E."}
+@string{SStepaniants = "Stepaniants, S."}
+@string{EStewart = "Stewart, E."}
+@string{MRStockmeier = "Stockmeier, M. R."}
+@string{TStockwell = "Stockwell, T."}
+@string{NEStone = "Stone, N. E."}
+@string{AStout = "Stout, A."}
+@string{TRStrick = "Strick, T. R."}
+@string{CStroh = "Stroh, Cordula"}
+@string{RStrong = "Strong, R."}
+@string{STR = "Structure"}
+@string{TStrunz = "Strunz, Torsten"}
+@string{MSu = "Su, Meihong"}
+@string{GSubramanian = "Subramanian, G."}
+@string{ESuh = "Suh, E."}
+@string{JSun = "Sun, J."}
+@string{YLSun = "Sun, Yu-Long"}
+@string{KSurewicz = "Surewicz, Krystyna"}
+@string{WKSurewicz = "Surewicz, Witold K."}
+@string{GGSutton = "Sutton, G. G."}
+@string{ASzaboX = "Szabo, A."}
+@string{ASzabo = "Szabo, Attila"}
+@string{PTabor = "Tabor, P."}
+@string{DTalaga = "Talaga, David S."}
+@string{PTalkner = "Talkner, Peter"}
+@string{JTang = "Tang, Jianyong"}
+@string{BNTaylor = "Taylor, Barry N."}
+@string{STeukolsky = "Teukolsky, S."}
+@string{JCP = "The Journal of Chemical Physics"}
+@string{TheJournalofPhysicalChemistryC = "The Journal of Physical Chemistry C"}
+@string{TheRoyalSociety = "The Royal Society"}
+@string{DThirumalai = "Thirumalai, Devarajan"}
+@string{PDThomas = "Thomas, P. D."}
+@string{RThomas = "Thomas, R."}
+@string{JThompson = "Thompson, J. B."}
+@string{SThornton = "Thornton, S."}
+@string{NNTint = "Tint, N. N."}
+@string{TTlusty = "Tlusty, Tsvi"}
+@string{JTocaHerrera = "Toca-Herrera, Jose L."}
+@string{AToyoda = "Toyoda, A."}
+@string{BTrask = "Trask, B."}
+@string{TribologyInternational = "Tribology International"}
+@string{JTrinick = "Trinick, John"}
+@string{KTrombitas = "Trombit{\'a}s, K."}
+@string{ILTrong = "Trong, I. Le"}
+@string{CHTsai = "Tsai, Chih-Hui"}
+@string{HKTsao = "Tsao, Heng-Kwong"}
+@string{STse = "Tse, S."}
+@string{ZTshiprut = "Tshiprut, Z."}
+@string{JCMTsibris = "Tsibris, J.C.M."}
+@string{LTskhovrebova = "Tskhovrebova, Larissa"}
+@string{RTurner = "Turner, R."}
+@string{ULTRAMIC = "Ultramicroscopy"}
+@string{UniversityofIllinoisPressUrbana = "University of Illinois Press, Urbana"}
+@string{MUrbakh = "Urbakh, M."}
+@string{CVech = "Vech, C."}
+@string{OVelasquez = "Velasquez, O."}
+@string{EVenter = "Venter, E."}
+@string{JCVenter = "Venter, J. C."}
+@string{PHVerdier = "Verdier, Peter H."}
+@string{IVetter = "Vetter, Ingrid R."}
+@string{WVetterling = "Vetterling, W."}
+@string{JCVoegel = "Voegel, J.-C."}
+@string{VVogelX = "Vogel, V."}
+@string{VVogel = "Vogel, Viola"}
+@string{CWagner-McPherson = "Wagner-McPherson, C."}
+@string{TAWaigh = "Waigh, Thomas A."}
+@string{BWalenz = "Walenz, B."}
+@string{JWallis = "Wallis, J."}
+@string{KWalther = "Walther, Kirstin A."}
+@string{AJWalton = "Walton, Alan J"}
+@string{EBWalton = "Walton, Emily B."}
+@string{AWang = "Wang, A."}
+@string{GWang = "Wang, G."}
+@string{JWang = "Wang, J."}
+@string{MWangX = "Wang, M."}
+@string{MWang = "Wang, Michelle D."}
+@string{XWang = "Wang, X."}
+@string{ZWang = "Wang, Z."}
+@string{HWatanabe = "Watanabe, Hiroshi"}
+@string{KWatanabe = "Watanabe, Kaori"}
+@string{RHWaterston = "Waterston, R. H."}
+@string{MWei = "Wei, M."}
+@string{JWeissenbach = "Weissenbach, J."}
+@string{GWen = "Wen, G."}
+@string{MWen = "Wen, M."}
+@string{JWetter = "Wetter, J."}
+@string{AWhittaker = "Whittaker, A."}
+@string{RWides = "Wides, R."}
+@string{AWiita = "Wiita, Arun P."}
+@string{MWilchek = "Wilchek, Meir"}
+@string{AWilcox = "Wilcox, Alexander J."}
+@string{Williams = "Williams"}
+@string{MWilliams = "Williams, M."}
+@string{SWilliams = "Williams, S."}
+@string{RKWilson = "Wilson, R. K."}
+@string{SWindsor = "Windsor, S."}
+@string{EWinn-Deen = "Winn-Deen, E."}
+@string{CWitt = "Witt, Christian"}
+@string{KWolfe = "Wolfe, K."}
+@string{TGWolfsberg = "Wolfsberg, T. G."}
+@string{PGWolynes = "Wolynes, P. G."}
+@string{WPWong = "Wong, Wesley P."}
+@string{TWoodage = "Woodage, T."}
+@string{GRWoodcock = "Woodcock, Glenna R."}
+@string{JRWortman = "Wortman, J. R."}
+@string{DWu = "Wu, D."}
+@string{GAWu = "Wu, Guohong A."}
+@string{JWWu = "Wu, Jong-Wuu"}
+@string{MWu = "Wu, M."}
+@string{YWu = "Wu, Yiming"}
+@string{KWylie = "Wylie, K."}
+@string{AXia = "Xia, A."}
+@string{CXiao = "Xiao, C."}
+@string{CYCuiandBustamante = "Y. Cui andBustamante, Carlos"}
+@string{TYada = "Yada, T."}
+@string{CYan = "Yan, C."}
+@string{MYandell = "Yandell, M."}
+@string{GYang = "Yang, Guoliang"}
+@string{YYang = "Yang, Yao"}
+@string{AYao = "Yao, A."}
+@string{JYe = "Ye, J."}
+@string{RYeh = "Yeh, Richard C."}
+@string{RYonescu = "Yonescu, R."}
+@string{SYooseph = "Yooseph, S."}
+@string{WYu = "Yu, Weichang"}
+@string{JMYuan = "Yuan, Jian-Min"}
+@string{AZandieh = "Zandieh, A."}
+@string{JZaveri = "Zaveri, J."}
+@string{KZaveri = "Zaveri, K."}
+@string{MZhan = "Zhan, M."}
+@string{HZhang = "Zhang, H."}
+@string{JZhang = "Zhang, J."}
+@string{QZhang = "Zhang, Q."}
+@string{WZhang = "Zhang, W."}
+@string{JZhao = "Zhao, Jason Ming"}
+@string{QZhao = "Zhao, Q."}
+@string{SZhao = "Zhao, S."}
+@string{LZheng = "Zheng, L."}
+@string{XHZheng = "Zheng, X. H."}
+@string{FZhong = "Zhong, F."}
+@string{WZhong = "Zhong, W."}
+@string{SZhu = "Zhu, S."}
+@string{XZhu = "Zhu, X."}
+@string{WZhuang = "Zhuang, Wei"}
+@string{NZinder = "Zinder, N."}
+@string{RCZinober = "Zinober, Rebecca C."}
+@string{RZwanzig = "Zwanzig, R."}
+@string{arXiv = "arXiv"}
+@string{PGdeGennes = "de Gennes, P. G."}
+@string{PJdeJong = "de Jong, P. J."}
+@string{NGvanKampen = "van Kampen, N.G."}
+@string{NISTSEMATECH = "{NIST/SEMATECH}"}
+@string{KJVanVliet = "{Van Vliet}, Krystyn J."}
+@string{EDCola = "{\uppercase{d}}i Cola, Emanuela"}
+
+@misc { NIST:gumbel,
+ author = NISTSEMATECH,
+ key = "NIST:gumbel",
+ title = "e-Handbook of Statistical Methods: Extreme Value Type {I}
+ Distribution",
+ year = 2009,
+ month = oct,
+ day = 9,
+ url = "http://www.itl.nist.gov/div898/handbook/eda/section3/eda366g.htm"
+}
+
+@article { allemand03,
+ author = JFAllemandX #" and "# DBensimonX #" and "# VCroquetteX,
+ title = "Stretching {DNA} and {RNA} to probe their interactions with
+ proteins",
+ year = 2003,
+ month = jun,
+ journal = CurrOpinStructBiol,
+ volume = 13,
+ number = 3,
+ pages = "266--274",
+ issn = "0959-440X",
+ keywords = "DNA;DNA-Binding
+ Proteins;Isomerases;Micromanipulation;Microscopy, Atomic Force;Nucleic
+ Acid Conformation;Nucleotidyltransferases",
+ abstract = "When interacting with a single stretched DNA, many proteins
+ modify its end-to-end distance. This distance can be monitored in real
+ time using various micromanipulation techniques that were initially
+ used to determine the elastic properties of bare nucleic acids and
+ their mechanically induced structural transitions. These methods are
+ currently being applied to the study of DNA enzymes such as DNA and RNA
+ polymerases, topoisomerases and structural proteins such as RecA. They
+ permit the measurement of the probability distributions of the rate,
+ processivity, on-time, affinity and efficiency for a large variety of
+ DNA-based molecular motors."
+}
+
+@article { alon90,
+ author = RAlon #" and "# EABayer #" and "# MWilchek,
+ title = "Streptavidin contains an {RYD} sequence which mimics the {RGD}
+ receptor domain of fibronectin",
+ year = 1990,
+ month = aug,
+ day = 16,
+ journal = BCBPRC,
+ volume = 170,
+ number = 3,
+ pages = "1236--1241",
+ issn = "0006-291X",
+ doi = "DOI: 10.1016/0006-291X(90)90526-S",
+ url = "http://www.sciencedirect.com/science/article/B6WBK-
+ 4F5M7K3-3C/2/c94b612e06efc8534ee24bb1da889811",
+ keywords = "Amino Acid Sequence;Animals;Bacterial Proteins;Binding
+ Sites;Cell Line;Cell Membrane;Cricetinae;Fibronectins;Molecular
+ Sequence Data;Streptavidin",
+ abstract = "Streptavidin binds at low levels and high affinity to cell
+ surfaces, the cause of which can be traced to the occurrence of a
+ sequence containing RYD (Arg-Tyr-Asp) in the protein molecule. This
+ binding is enhanced in the presence of biotin. Cell-bound streptavidin
+ can be displaced by fibronectin, as well as by RGD- and RYD-containing
+ peptides. In addition, streptavidin can displace fibronectin from cell
+ surfaces. The RYD sequence of streptavidin thus mimics RGD (Arg-Gly-
+ Asp), the universal recognition domain present in fibronectin and other
+ adhesion-related molecules. The observed adhesion to cells has no
+ relevance to biotin-binding since the RYD sequence is not part of the
+ biotin-binding site of streptavidin. Since the use of streptavidin in
+ avidin-biotin technology is based on its biotin-binding properties,
+ researchers are hereby warned against its indiscriminate use in
+ histochemical and cytochemical studies.",
+ note = "Biological role of streptavidin."
+}
+
+@article { balsera97,
+ author = MBalsera #" and "# SStepaniants #" and "# SIzrailev #" and "#
+ YOono #" and "# KSchultenX,
+ title = "Reconstructing potential energy functions from simulated force-
+ induced unbinding processes",
+ year = 1997,
+ month = sep,
+ journal = BPJ,
+ volume = 73,
+ number = 3,
+ pages = "1281--1287",
+ issn = "0006-3495",
+ eprint = "http://www.biophysj.org/cgi/reprint/73/3/1281.pdf",
+ url = "http://www.biophysj.org/cgi/content/abstract/73/3/1281",
+ keywords = "Binding Sites;Biopolymers;Kinetics;Ligands;Microscopy, Atomic
+ Force;Models, Chemical;Molecular Conformation;Protein
+ Conformation;Proteins;Reproducibility of Results;Stochastic
+ Processes;Thermodynamics",
+ abstract = "One-dimensional stochastic models demonstrate that molecular
+ dynamics simulations of a few nanoseconds can be used to reconstruct
+ the essential features of the binding potential of macromolecules. This
+ can be accomplished by inducing the unbinding with the help of external
+ forces applied to the molecules, and discounting the irreversible work
+ performed on the system by these forces. The fluctuation-dissipation
+ theorem sets a fundamental limit on the precision with which the
+ binding potential can be reconstructed by this method. The uncertainty
+ in the resulting potential is linearly proportional to the irreversible
+ component of work performed on the system during the simulation. These
+ results provide an a priori estimate of the energy barriers observable
+ in molecular dynamics simulations."
+}
+
+@article { baneyx02,
+ author = GBaneyx #" and "# LBaugh #" and "# VVogel,
+ title = "Supramolecular Chemistry And Self-assembly Special Feature:
+ Fibronectin extension and unfolding within cell matrix fibrils
+ controlled by cytoskeletal tension",
+ year = 2002,
+ journal = PNAS,
+ volume = 99,
+ number = 8,
+ pages = "5139--5143",
+ doi = "10.1073/pnas.072650799",
+ eprint = "http://www.pnas.org/cgi/reprint/99/8/5139.pdf",
+ url = "http://www.pnas.org/cgi/content/abstract/99/8/5139",
+ abstract = "Evidence is emerging that mechanical stretching can alter the
+ functional states of proteins. Fibronectin (Fn) is a large,
+ extracellular matrix protein that is assembled by cells into elastic
+ fibrils and subjected to contractile forces. Assembly into fibrils
+ coincides with expression of biological recognition sites that are
+ buried in Fn's soluble state. To investigate how supramolecular
+ assembly of Fn into fibrillar matrix enables cells to mechanically
+ regulate its structure, we used fluorescence resonance energy transfer
+ (FRET) as an indicator of Fn conformation in the fibrillar matrix of
+ NIH 3T3 fibroblasts. Fn was randomly labeled on amine residues with
+ donor fluorophores and site-specifically labeled on cysteine residues
+ in modules FnIII7 and FnIII15 with acceptor fluorophores.
+ Intramolecular FRET was correlated with known structural changes of Fn
+ in denaturing solution, then applied in cell culture as an indicator of
+ Fn conformation within the matrix fibrils of NIH 3T3 fibroblasts. Based
+ on the level of FRET, Fn in many fibrils was stretched by cells so that
+ its dimer arms were extended and at least one FnIII module unfolded.
+ When cytoskeletal tension was disrupted using cytochalasin D, FRET
+ increased, indicating refolding of Fn within fibrils. These results
+ suggest that cell-generated force is required to maintain Fn in
+ partially unfolded conformations. The results support a model of Fn
+ fibril elasticity based on unraveling and refolding of FnIII modules.
+ We also observed variation of FRET between and along single fibrils,
+ indicating variation in the degree of unfolding of Fn in fibrils.
+ Molecular mechanisms by which mechanical force can alter the structure
+ of Fn, converting tensile forces into biochemical cues, are discussed."
+}
+
+@article { basche01,
+ author = TBasche #" and "# SNie #" and "# JFernandez,
+ title = "Single molecules",
+ year = 2001,
+ journal = PNAS,
+ volume = 98,
+ number = 19,
+ pages = "10527--10528",
+ doi = "10.1073/pnas.191365898",
+ eprint = "http://www.pnas.org/cgi/reprint/98/19/10527.pdf",
+ url = "http://www.pnas.org/cgi/content/abstract/98/19/10527",
+ note = "Mini summary of single-molecule techniques and look to future.
+ Focuses on AFM, but mentions others."
+}
+
+@article { bechhoefer02,
+ author = JSWBechhoefer,
+ title = "Faster, cheaper, safer optical tweezers for the undergraduate
+ laboratory",
+ collaboration = "",
+ year = 2002,
+ journal = AmericanJournalofPhysics,
+ volume = 70,
+ number = 4,
+ pages = "393--400",
+ publisher = AAPT,
+ doi = "10.1119/1.1445403",
+ url = "http://link.aip.org/link/?AJP/70/393/1",
+ keywords = "student experiments; safety; radiation pressure; laser beam
+ applications",
+ note = "Good discussion of the effect of correlation time on calibration.
+ Excellent detail on power spectrum derivation and thermal noise for
+ extremely overdamped oscillators in Appendix A (references
+ \citet{rief65}). References work on deconvolving thermal noise from
+ other noise\citep{cowan98}",
+ project = "Cantilever Calibration"
+}
+
+@article { bedard08,
+ author = SBedard #" and "# MMGKrishna #" and "# LMayne #" and "#
+ SWEnglander,
+ title = "Protein folding: independent unrelated pathways or predetermined
+ pathway with optional errors.",
+ year = 2008,
+ month = may,
+ day = 20,
+ journal = PNAS,
+ volume = 105,
+ number = 20,
+ pages = "7182--7187",
+ issn = "1091-6490",
+ doi = "10.1073/pnas.0801864105",
+ eprint = "http://www.pnas.org/content/105/20/7182.full.pdf",
+ url = "http://www.pnas.org/content/105/20/7182.full",
+ keywords = "Biochemistry;Guanidine;Kinetics;Micrococcal Nuclease;Models,
+ Biological;Models, Chemical;Models, Theoretical;Protein
+ Conformation;Protein Denaturation;Protein Folding;Protein Structure,
+ Secondary;Proteins;Proteomics;Reproducibility of
+ Results;Thermodynamics",
+ abstract = "The observation of heterogeneous protein folding kinetics has
+ been widely interpreted in terms of multiple independent unrelated
+ pathways (IUP model), both experimentally and in theoretical
+ calculations. However, direct structural information on folding
+ intermediates and their properties now indicates that all of a protein
+ population folds through essentially the same stepwise pathway,
+ determined by cooperative native-like foldon units and the way that the
+ foldons fit together in the native protein. It is essential to decide
+ between these fundamentally different folding mechanisms. This article
+ shows, contrary to previous supposition, that the heterogeneous folding
+ kinetics observed for the staphylococcal nuclease protein (SNase) does
+ not require alternative parallel pathways. SNase folding kinetics can
+ be fit equally well by a single predetermined pathway that allows for
+ optional misfolding errors, which are known to occur ubiquitously in
+ protein folding. Structural, kinetic, and thermodynamic information for
+ the folding intermediates and pathways of many proteins is consistent
+ with the predetermined pathway-optional error (PPOE) model but contrary
+ to the properties implied in IUP models."
+}
+
+@article { bell78,
+ author = GIBell,
+ title = "Models for the specific adhesion of cells to cells",
+ year = 1978,
+ month = may,
+ day = 12,
+ journal = SCI,
+ volume = 200,
+ number = 4342,
+ pages = "618--627",
+ issn = "0036-8075",
+ url = "http://www.jstor.org/stable/1746930",
+ keywords = "Antigen-Antibody Reactions; Cell Adhesion; Cell Membrane;
+ Chemistry, Physical; Electrophysiology; Enzymes; Glycoproteins;
+ Kinetics; Ligands; Membrane Proteins; Models, Biological; Receptors,
+ Drug",
+ abstract = "A theoretical framework is proposed for the analysis of
+ adhesion between cells or of cells to surfaces when the adhesion is
+ mediated by reversible bonds between specific molecules such as antigen
+ and antibody, lectin and carbohydrate, or enzyme and substrate. From a
+ knowledge of the reaction rates for reactants in solution and of their
+ diffusion constants both in solution and on membranes, it is possible
+ to estimate reaction rates for membrane-bound reactants. Two models are
+ developed for predicting the rate of bond formation between cells and
+ are compared with experiments. The force required to separate two cells
+ is shown to be greater than the expected electrical forces between
+ cells, and of the same order of magnitude as the forces required to
+ pull gangliosides and perhaps some integral membrane proteins out of
+ the cell membrane.",
+ note = "The Bell model and a fair bit of cell bonding background.",
+ project = "sawtooth simulation"
+}
+
+@article { berk91,
+ author = DBerk #" and "# EEvans,
+ title = "Detachment of agglutinin-bonded red blood cells. {III}. Mechanical
+ analysis for large contact areas",
+ year = 1991,
+ month = apr,
+ journal = BPJ,
+ volume = 59,
+ number = 4,
+ pages = "861--872",
+ issn = "0006-3495",
+ keywords = "Cell Adhesion;Erythrocyte Membrane;Erythrocytes;Hemagglutinatio
+ n;Hemagglutinins;Humans;Kinetics;Mathematics;Models,
+ Biological;Pressure",
+ abstract = "An experimental method and analysis are introduced which
+ provide direct quantitation of the strength of adhesive contact for
+ large agglutinin-bonded regions between macroscopically smooth membrane
+ capsules (e.g., red blood cells). The approach yields intrinsic
+ properties for separation of adherent regions independent of mechanical
+ deformation of the membrane capsules during detachment. Conceptually,
+ the micromechanical method involves one rigid test-capsule surface (in
+ the form of a perfect sphere) held fixed by a micropipette and a second
+ deformable capsule maneuvered with another micropipette to force
+ contact with the test capsule. Only the test capsule is bound with
+ agglutinin so that the maximum number of cross-bridges can be formed
+ without steric interference. Following formation of a large adhesion
+ region by mechanical impingement, the deformable capsule is detached
+ from the rigid capsule surface by progressive aspiration into the
+ micropipette. For the particular case modeled here, the deformable
+ capsule is assumed to be a red blood cell which is preswollen by slight
+ osmotic hydration before the test. The caliber of the detachment
+ pipette is chosen so that the capsule will form a smooth cylindrical
+ ``piston'' inside the pipette as it is aspirated. Because of the high
+ flexibility of the membrane, the capsule naturally seals against the
+ tube wall by pressurization even though it does not adhere to the
+ glass. This arrangement maintains perfect axial symmetry and prevents
+ the membrane from folding or buckling. Hence, it is possible to
+ rigorously analyze the mechanics of deformation of the cell body to
+ obtain the crucial ``transducer'' relation between pipette suction
+ force and the membrane tension applied directly at the perimeter of the
+ adhesive contact. Further, the geometry of the cell throughout the
+ detachment process is predicted which provides accurate specification
+ of the contact angle theta c between surfaces at the perimeter of the
+ contact. A full analysis of red cell capsules during detachment has
+ been carried out; however, it is shown that the shear rigidity of the
+ red cell membrane can often be neglected so that the red cell can be
+ treated as if it were an underfilled lipid bilayer vesicle. From the
+ analysis, the mechanical leverage factor (1-cos theta c) and the
+ membrane tension at the contact perimeter are determined to provide a
+ complete description of the local mechanics of membrane separation as
+ functions of large-scale experimental variables (e.g., suction force,
+ contact diameter, overall cell length).(ABSTRACT TRUNCATED AT 400
+ WORDS)"
+}
+
+@article { best02,
+ author = RBest #" and "# SFowler #" and "# JTocaHerrera #" and "# JClarke,
+ title = "A simple method for probing the mechanical unfolding pathway of
+ proteins in detail",
+ year = 2002,
+ journal = PNAS,
+ volume = 99,
+ number = 19,
+ pages = "12143--12148",
+ doi = "10.1073/pnas.192351899",
+ eprint = "http://www.pnas.org/cgi/reprint/99/19/12143.pdf",
+ url = "http://www.pnas.org/cgi/content/abstract/99/19/12143",
+ abstract = "Atomic force microscopy is an exciting new single-molecule
+ technique to add to the toolbox of protein (un)folding methods.
+ However, detailed analysis of the unfolding of proteins on application
+ of force has, to date, relied on protein molecular dynamics simulations
+ or a qualitative interpretation of mutant data. Here we describe how
+ protein engineering {Phi} value analysis can be adapted to characterize
+ the transition states for mechanical unfolding of proteins. Single-
+ molecule studies also have an advantage over bulk experiments, in that
+ partial {Phi} values arising from partial structure in the transition
+ state can be clearly distinguished from those averaged over alternate
+ pathways. We show that unfolding rate constants derived in the standard
+ way by using Monte Carlo simulations are not reliable because of the
+ errors involved. However, it is possible to circumvent these problems,
+ providing the unfolding mechanism is not changed by mutation, either by
+ a modification of the Monte Carlo procedure or by comparing mutant and
+ wild-type data directly. The applicability of the method is tested on
+ simulated data sets and experimental data for mutants of titin I27.",
+ note = "Points out order-of-magnitude errors in $k_{u0}$ estimation from
+ fitting Monte Carlo simulations."
+}
+
+@article { best08a,
+ author = RBest #" and "# GHummer,
+ title = "Protein folding kinetics under force from molecular simulation.",
+ year = 2008,
+ month = mar,
+ day = 26,
+ journal = JAmChemSoc,
+ volume = 130,
+ number = 12,
+ pages = "3706--3707",
+ issn = "1520-5126",
+ doi = "10.1021/ja0762691",
+ keywords = "Computer Simulation;Kinetics;Models, Chemical;Protein
+ Folding;Stress, Mechanical;Ubiquitin",
+ abstract = "Despite a large number of studies on the mechanical unfolding
+ of proteins, there are still relatively few successful attempts to
+ refold proteins in the presence of a stretching force. We explore
+ refolding kinetics under force using simulations of a coarse-grained
+ model of ubiquitin. The effects of force on the folding kinetics can be
+ fitted by a one-dimensional Kramers theory of diffusive barrier
+ crossing, resulting in physically meaningful parameters for the height
+ and location of the folding activation barrier. By comparing parameters
+ obtained from pulling in different directions, we find that the
+ unfolded state plays a dominant role in the refolding kinetics. Our
+ findings explain why refolding becomes very slow at even moderate
+ pulling forces and suggest how it could be practically observed in
+ experiments at higher forces."
+}
+
+@article { best08b,
+ author = RBest #" and "# EPaci #" and "# GHummer #" and "# OKDudkoX,
+ title = "Pulling direction as a reaction coordinate for the mechanical
+ unfolding of single molecules.",
+ year = 2008,
+ month = may,
+ day = 15,
+ journal = JPhysChemB,
+ volume = 112,
+ number = 19,
+ pages = "5968--5976",
+ issn = "1520-6106",
+ doi = "10.1021/jp075955j",
+ keywords = "Computer Simulation;Kinetics;Models, Molecular;Protein
+ Folding;Protein Structure, Tertiary;Time Factors;Ubiquitin",
+ abstract = "The folding and unfolding kinetics of single molecules, such as
+ proteins or nucleic acids, can be explored by mechanical pulling
+ experiments. Determining intrinsic kinetic information, at zero
+ stretching force, usually requires an extrapolation by fitting a
+ theoretical model. Here, we apply a recent theoretical approach
+ describing molecular rupture in the presence of force to unfolding
+ kinetic data obtained from coarse-grained simulations of ubiquitin.
+ Unfolding rates calculated from simulations over a broad range of
+ stretching forces, for different pulling directions, reveal a
+ remarkable ``turnover'' from a force-independent process at low force
+ to a force-dependent process at high force, akin to the ``roll-over''
+ in unfolding rates sometimes seen in studies using chemical denaturant.
+ While such a turnover in rates is unexpected in one dimension, we
+ demonstrate that it can occur for dynamics in just two dimensions. We
+ relate the turnover to the quality of the pulling direction as a
+ reaction coordinate for the intrinsic folding mechanism. A novel
+ pulling direction, designed to be the most relevant to the intrinsic
+ folding pathway, results in the smallest turnover. Our results are in
+ accord with protein engineering experiments and simulations which
+ indicate that the unfolding mechanism at high force can differ from the
+ intrinsic mechanism. The apparent similarity between extrapolated and
+ intrinsic rates in experiments, unexpected for different unfolding
+ barriers, can be explained if the turnover occurs at low forces."
+}
+
+@article { borgia08,
+ author = Borgia #" and "# Williams #" and "# Clarke,
+ title = "Single-Molecule Studies of Protein Folding",
+ year = 2008,
+ month = jul,
+ day = 07,
+ journal = ARBC,
+ volume = 77,
+ pages = "101--125",
+ issn = "0066-4154",
+ doi = "10.1146/annurev.biochem.77.060706.093102",
+ eprint = "http://arjournals.annualreviews.org/doi/pdf/10.1146/annurev.bioch
+ em.77.060706.093102",
+ url = "http://arjournals.annualreviews.org/doi/abs/10.1146/annurev.biochem.
+ 77.060706.093102",
+ abstract = "Although protein-folding studies began several decades ago, it
+ is only recently that the tools to analyze protein folding at the
+ single-molecule level have been developed. Advances in single-molecule
+ fluorescence and force spectroscopy techniques allow investigation of
+ the folding and dynamics of single protein molecules, both at
+ equilibrium and as they fold and unfold. The experiments are far from
+ simple, however, both in execution and in interpretation of the
+ results. In this review, we discuss some of the highlights of the work
+ so far and concentrate on cases where comparisons with the classical
+ experiments can be made. We conclude that, although there have been
+ relatively few startling insights from single-molecule studies, the
+ rapid progress that has been made suggests that these experiments have
+ significant potential to advance our understanding of protein folding.
+ In particular, new techniques offer the possibility to explore regions
+ of the energy landscape that are inaccessible to classical ensemble
+ measurements and, perhaps, to observe rare events undetectable by other
+ means."
+}
+
+@article { braverman08,
+ author = EBraverman #" and "# RMamdani,
+ title = "Continuous versus pulse harvesting for population models in
+ constant and variable environment",
+ year = 2008,
+ month = sep,
+ day = 18,
+ journal = JMathBiol,
+ volume = 57,
+ number = 3,
+ pages = "413--434",
+ issn = "0303-6812",
+ doi = "10.1007/s00285-008-0169-z",
+ eprint =
+ "http://www.springerlink.com/content/a1m23v50201m2401/fulltext.pdf",
+ url = "http://www.springerlink.com/content/a1m23v50201m2401/",
+ abstract = "We consider both autonomous and nonautonomous population models
+ subject to either impulsive or continuous harvesting. It is
+ demonstrated in the paper that the impulsive strategy can be as good as
+ the continuous one, but cannot outperform it. We introduce a model,
+ where certain harm to the population is incorporated in each harvesting
+ event, and study it for the logistic and the Gompertz laws of growth.
+ In this case, impulsive harvesting is not only the optimal strategy but
+ is the only possible one.",
+ note = "An example of non-exponential Gomperz law."
+}
+
+@article { brochard-wyart99,
+ author = FBrochard-Wyart #" and "# ABuguin #" and "# PGdeGennes,
+ title = "Dynamics of taut {DNA} chains",
+ year = 1999,
+ journal = EPLEurophysicsLetters,
+ volume = 47,
+ number = 2,
+ pages = "171--174",
+ eprint =
+ "http://www.iop.org/EJ/article/0295-5075/47/2/171/epl_47_2_171.pdf",
+ url = "http://stacks.iop.org/0295-5075/47/171",
+ abstract = {We discuss the dynamics of stretched DNA chains, subjected to a
+ tension force f, in a "taut" regime where ph = flp0/kBT $>$ 1 (lp0
+ being the unperturbed persistence length). We deal with two variables:
+ the local transverse displacements u, and the longitudinal position of
+ a monomer u[?]. The variables u and u[?] follow two distinct Rouse
+ equations, with diffusion coefficients D[?] = f/e (where e is the
+ solvent viscosity) and D[?] = 4ph1/2D[?]. We apply these ideas to a
+ discussion of various transient regimes.},
+ note = "Theory for weakly bending relaxation modes in WLCs and FJCs."
+}
+
+@article { brockwell02,
+ author = DJBrockwell #" and "# GSBeddard #" and "# JClarkson #" and "#
+ RCZinober #" and "# AWBlake #" and "# JTrinick #" and "# PDOlmsted #"
+ and "# DASmith #" and "# SERadford,
+ title = "The effect of core destabilization on the mechanical resistance of
+ {I27}",
+ year = 2002,
+ month = jul,
+ journal = BPJ,
+ volume = 83,
+ number = 1,
+ pages = "458--472",
+ issn = "0006-3495",
+ doi = "10.1016/S0006-3495(02)75182-5",
+ eprint = "http://www.biophysj.org/cgi/reprint/83/1/458.pdf",
+ url = "http://www.biophysj.org/cgi/content/abstract/83/1/458",
+ keywords = "Amino Acid Sequence; Dose-Response Relationship, Drug;
+ Kinetics; Magnetic Resonance Spectroscopy; Models, Molecular; Molecular
+ Sequence Data; Monte Carlo Method; Muscle Proteins; Mutation; Peptide
+ Fragments; Protein Denaturation; Protein Folding; Protein Kinases;
+ Protein Structure, Secondary; Protein Structure, Tertiary; Proteins;
+ Thermodynamics",
+ abstract = "It is still unclear whether mechanical unfolding probes the
+ same pathways as chemical denaturation. To address this point, we have
+ constructed a concatamer of five mutant I27 domains (denoted (I27)(5)*)
+ and used it for mechanical unfolding studies. This protein consists of
+ four copies of the mutant C47S, C63S I27 and a single copy of C63S I27.
+ These mutations severely destabilize I27 (DeltaDeltaG(UN) = 8.7 and
+ 17.9 kJ mol(-1) for C63S I27 and C47S, C63S I27, respectively). Both
+ mutations maintain the hydrogen bond network between the A' and G
+ strands postulated to be the major region of mechanical resistance for
+ I27. Measuring the speed dependence of the force required to unfold
+ (I27)(5)* in triplicate using the atomic force microscope allowed a
+ reliable assessment of the intrinsic unfolding rate constant of the
+ protein to be obtained (2.0 x 10(-3) s(-1)). The rate constant of
+ unfolding measured by chemical denaturation is over fivefold faster
+ (1.1 x 10(-2) s(-1)), suggesting that these techniques probe different
+ unfolding pathways. Also, by comparing the parameters obtained from the
+ mechanical unfolding of a wild-type I27 concatamer with that of
+ (I27)(5)*, we show that although the observed forces are considerably
+ lower, core destabilization has little effect on determining the
+ mechanical sensitivity of this domain."
+}
+
+@article { brockwell03,
+ author = DJBrockwell #" and "# EPaci #" and "# RCZinober #" and "#
+ GSBeddard #" and "# PDOlmsted #" and "# DASmith #" and "# RNPerham #"
+ and "# SERadford,
+ title = "Pulling geometry defines the mechanical resistance of a beta-sheet
+ protein",
+ year = 2003,
+ month = sep,
+ day = 17,
+ journal = NSB,
+ volume = 10,
+ number = 9,
+ pages = "731--737",
+ issn = "1072-8368",
+ doi = "10.1038/nsb968",
+ eprint = "http://www.nature.com/nsmb/journal/v10/n9/pdf/nsb968.pdf",
+ url = "http://www.nature.com/nsmb/journal/v10/n9/abs/nsb968.html",
+ keywords = "Anisotropy;Escherichia coli;Kinetics;Models, Molecular;Monte
+ Carlo Method;Protein Folding;Protein Structure, Secondary;Protein
+ Structure, Tertiary;Proteins;Software;Temperature;Thermodynamics",
+ abstract = "Proteins show diverse responses when placed under mechanical
+ stress. The molecular origins of their differing mechanical resistance
+ are still unclear, although the orientation of secondary structural
+ elements relative to the applied force vector is thought to have an
+ important function. Here, by using a method of protein immobilization
+ that allows force to be applied to the same all-beta protein, E2lip3,
+ in two different directions, we show that the energy landscape for
+ mechanical unfolding is markedly anisotropic. These results, in
+ combination with molecular dynamics (MD) simulations, reveal that the
+ unfolding pathway depends on the pulling geometry and is associated
+ with unfolding forces that differ by an order of magnitude. Thus, the
+ mechanical resistance of a protein is not dictated solely by amino acid
+ sequence, topology or unfolding rate constant, but depends critically
+ on the direction of the applied extension.",
+ note = "Another scaffold effect paper. TODO: details"
+}
+
+@article { brower-toland02,
+ author = BDBrowerToland #" and "# CSmith #" and "# RYeh #" and "# JLis #"
+ and "# CPeterson #" and "# MWang,
+ title = "From the Cover: Mechanical disruption of individual nucleosomes
+ reveals a reversible multistage release of {DNA}",
+ year = 2002,
+ journal = PNAS,
+ volume = 99,
+ number = 4,
+ pages = "1960--1965",
+ doi = "10.1073/pnas.022638399",
+ eprint = "http://www.pnas.org/cgi/reprint/99/4/1960.pdf",
+ url = "http://www.pnas.org/cgi/content/abstract/99/4/1960",
+ abstract = "The dynamic structure of individual nucleosomes was examined by
+ stretching nucleosomal arrays with a feedback-enhanced optical trap.
+ Forced disassembly of each nucleosome occurred in three stages.
+ Analysis of the data using a simple worm-like chain model yields 76 bp
+ of DNA released from the histone core at low stretching force.
+ Subsequently, 80 bp are released at higher forces in two stages: full
+ extension of DNA with histones bound, followed by detachment of
+ histones. When arrays were relaxed before the dissociated state was
+ reached, nucleosomes were able to reassemble and to repeat the
+ disassembly process. The kinetic parameters for nucleosome disassembly
+ also have been determined."
+}
+
+@article { bryngelson87,
+ author = JDBryngelson #" and "# PGWolynes,
+ title = "Spin glasses and the statistical mechanics of protein folding",
+ year = 1987,
+ month = nov,
+ journal = PNAS,
+ volume = 84,
+ number = 21,
+ pages = "7524--7528",
+ issn = "0027-8424",
+ keywords = "Kinetics; Mathematics; Models, Theoretical; Protein
+ Conformation; Proteins; Stochastic Processes",
+ abstract = "The theory of spin glasses was used to study a simple model of
+ protein folding. The phase diagram of the model was calculated, and the
+ results of dynamics calculations are briefly reported. The relation of
+ these results to folding experiments, the relation of these hypotheses
+ to previous protein folding theories, and the implication of these
+ hypotheses for protein folding prediction schemes are discussed.",
+ note = "Seminal protein folding via energy landscape paper."
+}
+
+@article { bryngelson95,
+ author = JDBryngelson #" and "# JNOnuchic #" and "# NDSocci #" and "#
+ PGWolynes,
+ title = "Funnels, pathways, and the energy landscape of protein folding: a
+ synthesis",
+ year = 1995,
+ month = mar,
+ journal = PROT,
+ volume = 21,
+ number = 3,
+ pages = "167--195",
+ issn = "0887-3585",
+ doi = "10.1002/prot.340210302",
+ keywords = "Amino Acid Sequence; Chemistry, Physical; Computer Simulation;
+ Data Interpretation, Statistical; Kinetics; Models, Chemical; Molecular
+ Sequence Data; Protein Biosynthesis; Protein Conformation; Protein
+ Folding; Proteins; Thermodynamics",
+ abstract = "The understanding, and even the description of protein folding
+ is impeded by the complexity of the process. Much of this complexity
+ can be described and understood by taking a statistical approach to the
+ energetics of protein conformation, that is, to the energy landscape.
+ The statistical energy landscape approach explains when and why unique
+ behaviors, such as specific folding pathways, occur in some proteins
+ and more generally explains the distinction between folding processes
+ common to all sequences and those peculiar to individual sequences.
+ This approach also gives new, quantitative insights into the
+ interpretation of experiments and simulations of protein folding
+ thermodynamics and kinetics. Specifically, the picture provides simple
+ explanations for folding as a two-state first-order phase transition,
+ for the origin of metastable collapsed unfolded states and for the
+ curved Arrhenius plots observed in both laboratory experiments and
+ discrete lattice simulations. The relation of these quantitative ideas
+ to folding pathways, to uniexponential vs. multiexponential behavior in
+ protein folding experiments and to the effect of mutations on folding
+ is also discussed. The success of energy landscape ideas in protein
+ structure prediction is also described. The use of the energy landscape
+ approach for analyzing data is illustrated with a quantitative analysis
+ of some recent simulations, and a qualitative analysis of experiments
+ on the folding of three proteins. The work unifies several previously
+ proposed ideas concerning the mechanism protein folding and delimits
+ the regions of validity of these ideas under different thermodynamic
+ conditions."
+}
+
+@article { bullard06,
+ author = BBullard #" and "# TGarcia #" and "# VBenes #" and "# MLeake #"
+ and "# WLinke #" and "# AOberhauser,
+ title = "The molecular elasticity of the insect flight muscle proteins
+ projectin and kettin",
+ year = 2006,
+ journal = PNAS,
+ volume = 103,
+ number = 12,
+ pages = "4451--4456",
+ doi = "10.1073/pnas.0509016103",
+ eprint = "http://www.pnas.org/cgi/reprint/103/12/4451.pdf",
+ url = "http://www.pnas.org/cgi/content/abstract/103/12/4451",
+ abstract = "Projectin and kettin are titin-like proteins mainly responsible
+ for the high passive stiffness of insect indirect flight muscles, which
+ is needed to generate oscillatory work during flight. Here we report
+ the mechanical properties of kettin and projectin by single-molecule
+ force spectroscopy. Force-extension and force-clamp curves obtained
+ from Lethocerus projectin and Drosophila recombinant projectin or
+ kettin fragments revealed that fibronectin type III domains in
+ projectin are mechanically weaker (unfolding force, Fu {approx} 50-150
+ pN) than Ig-domains (Fu {approx} 150-250 pN). Among Ig domains in
+ Sls/kettin, the domains near the N terminus are less stable than those
+ near the C terminus. Projectin domains refolded very fast [85% at 15
+ s-1 (25{degrees}C)] and even under high forces (15-30 pN). Temperature
+ affected the unfolding forces with a Q10 of 1.3, whereas the refolding
+ speed had a Q10 of 2-3, probably reflecting the cooperative nature of
+ the folding mechanism. High bending rigidities of projectin and kettin
+ indicated that straightening the proteins requires low forces. Our
+ results suggest that titin-like proteins in indirect flight muscles
+ could function according to a folding-based-spring mechanism."
+}
+
+@article { bustamante08,
+ author = CBustamante,
+ title = "In singulo Biochemistry: When Less Is More",
+ year = 2008,
+ journal = ARBC,
+ volume = 77,
+ pages = "45--50",
+ issn = "0066-4154",
+ doi = "10.1146/annurev.biochem.012108.120952",
+ eprint = "http://arjournals.annualreviews.org/doi/pdf/10.1146/annurev.bioch
+ em.012108.120952",
+ url = "http://arjournals.annualreviews.org/doi/abs/10.1146/annurev.biochem.
+ 012108.120952",
+ abstract = "It has been over one-and-a-half decades since methods of
+ single-molecule detection and manipulation were first introduced in
+ biochemical research. Since then, the application of these methods to
+ an expanding variety of problems has grown at a vertiginous pace. While
+ initially many of these experiments led more to confirmatory results
+ than to new discoveries, today single-molecule methods are often the
+ methods of choice to establish new mechanism-based results in
+ biochemical research. Throughout this process, improvements in the
+ sensitivity, versatility, and both spatial and temporal resolution of
+ these techniques has occurred hand in hand with their applications. We
+ discuss here some of the advantages of single-molecule methods over
+ their bulk counterparts and argue that these advantages should help
+ establish them as essential tools in the technical arsenal of the
+ modern biochemist."
+}
+
+@article { bustamante94,
+ author = CJFMBustamante #" and "# EDSiggiaX #" and "# SSmith,
+ title = "Entropic elasticity of lambda-phage {DNA}",
+ year = 1994,
+ month = sep,
+ day = 09,
+ journal = SCI,
+ volume = 265,
+ number = 5178,
+ pages = "1599--1600",
+ issn = "0036-8075",
+ doi = "10.1126/science.8079175",
+ eprint = "http://www.sciencemag.org/cgi/reprint/265/5178/1599.pdf",
+ url = "http://www.sciencemag.org/cgi/content/abstract/265/5178/1599",
+ keywords = "Bacteriophage lambda; DNA, Viral; Least-Squares Analysis;
+ Thermodynamics",
+ note = "WLC interpolation formula."
+}
+
+@article { bustanji03,
+ author = YBustanji #" and "# CArciola #" and "# MConti #" and "# EMandello
+ #" and "# LMontanaro #" and "# BSamori,
+ title = "Dynamics of the interaction between a fibronectin molecule and a
+ living bacterium under mechanical force",
+ year = 2003,
+ journal = PNAS,
+ volume = 100,
+ number = 23,
+ pages = "13292--13297",
+ doi = "10.1073/pnas.1735343100",
+ eprint = "http://www.pnas.org/cgi/reprint/100/23/13292.pdf",
+ url = "http://www.pnas.org/cgi/content/abstract/100/23/13292",
+ abstract = "Fibronectin (Fn) is an important mediator of bacterial
+ invasions and of persistent infections like that of Staphylococcus
+ epidermis. Similar to many other types of cell-protein adhesion, the
+ binding between Fn and S. epidermidis takes place under physiological
+ shear rates. We investigated the dynamics of the interaction between
+ individual living S. epidermidis cells and single Fn molecules under
+ mechanical force by using the scanning force microscope. The mechanical
+ strength of this interaction and the binding site in the Fn molecule
+ were determined. The energy landscape of the binding/unbinding process
+ was mapped, and the force spectrum and the association and dissociation
+ rate constants of the binding pair were measured. The interaction
+ between S. epidermidis cells and Fn molecules is compared with those of
+ two other protein/ligand pairs known to mediate different dynamic
+ states of adhesion of cells under a hydrodynamic flow: the firm
+ adhesion mediated by biotin/avidin interactions, and the rolling
+ adhesion, mediated by L-selectin/P-selectin glycoprotein ligand-1
+ interactions. The inner barrier in the energy landscape of the Fn case
+ characterizes a high-energy binding mode that can sustain larger
+ deformations and for significantly longer times than the correspondent
+ high-strength L-selectin/P-selectin glycoprotein ligand-1 binding mode.
+ The association kinetics of the former interaction is much slower to
+ settle than the latter. On this basis, the observations made at the
+ macroscopic scale by other authors of a strong lability of the
+ bacterial adhesions mediated by Fn under high turbulent flow are
+ rationalized at the molecular level."
+}
+
+@article { butt95,
+ author = HJButt #" and "# MJaschke,
+ title = "Calculation of thermal noise in atomic force microscopy",
+ year = 1995,
+ journal = NANOTECH,
+ volume = 6,
+ number = 1,
+ pages = "1--7",
+ doi = "10.1088/0957-4484/6/1/001",
+ url = "http://stacks.iop.org/0957-4484/6/1",
+ abstract = "Thermal fluctuations of the cantilever are a fundamental source
+ of noise in atomic force microscopy. We calculated thermal noise using
+ the equipartition theorem and considering all possible vibration modes
+ of the cantilever. The measurable amplitude of thermal noise depends on
+ the temperature, the spring constant K of the cantilever and on the
+ method by which the cantilever defletion is detected. If the deflection
+ is measured directly, e.g. with an interferometer or a scanning
+ tunneling microscope, the thermal noise of a cantilever with a free end
+ can be calculated from square root kT/K. If the end of the cantilever
+ is supported by a hard surface no thermal fluctuations of the
+ deflection are possible. If the optical lever technique is applied to
+ measure the deflection, the thermal noise of a cantilever with a free
+ end is square root 4kT/3K. When the cantilever is supported thermal
+ noise decreases to square root kT/3K, but it does not vanish.",
+ note = "Corrections to basic $kx^2 = kB T$ due to higher order modes in
+ rectangular cantilevers.",
+ project = "Cantilever Calibration"
+}
+
+@article { cao07,
+ author = YCao #" and "# MBalamurali #" and "# DSharma #" and "# HLi,
+ title = "A functional single-molecule binding assay via force spectroscopy",
+ year = 2007,
+ journal = PNAS,
+ volume = 104,
+ number = 40,
+ pages = "15677--15681",
+ doi = "10.1073/pnas.0705367104",
+ eprint = "http://www.pnas.org/cgi/reprint/104/40/15677.pdf",
+ url = "http://www.pnas.org/cgi/content/abstract/104/40/15677",
+ abstract = "Protein-ligand interactions, including protein-protein
+ interactions, are ubiquitously essential in biological processes and
+ also have important applications in biotechnology. A wide range of
+ methodologies have been developed for quantitative analysis of protein-
+ ligand interactions. However, most of them do not report direct
+ functional/structural consequence of ligand binding. Instead they only
+ detect the change of physical properties, such as fluorescence and
+ refractive index, because of the colocalization of protein and ligand,
+ and are susceptible to false positives. Thus, important information
+ about the functional state of proteinligand complexes cannot be
+ obtained directly. Here we report a functional single-molecule binding
+ assay that uses force spectroscopy to directly probe the functional
+ consequence of ligand binding and report the functional state of
+ protein-ligand complexes. As a proof of principle, we used protein G
+ and the Fc fragment of IgG as a model system in this study. Binding of
+ Fc to protein G does not induce major structural changes in protein G
+ but results in significant enhancement of its mechanical stability.
+ Using mechanical stability of protein G as an intrinsic functional
+ reporter, we directly distinguished and quantified Fc-bound and Fc-free
+ forms of protein G on a single-molecule basis and accurately determined
+ their dissociation constant. This single-molecule functional binding
+ assay is label-free, nearly background-free, and can detect functional
+ heterogeneity, if any, among proteinligand interactions. This
+ methodology opens up avenues for studying protein-ligand interactions
+ in a functional context, and we anticipate that it will find broad
+ application in diverse protein-ligand systems."
+}
+
+@article { carl01,
+ author = PCarl #" and "# CKwok #" and "# GManderson #" and "# DSpeicher #"
+ and "# DDischer,
+ title = "Forced unfolding modulated by disulfide bonds in the Ig domains of
+ a cell adhesion molecule",
+ year = 2001,
+ journal = PNAS,
+ volume = 98,
+ number = 4,
+ pages = "1565--1570",
+ doi = "10.1073/pnas.031409698",
+ eprint = "http://www.pnas.org/cgi/reprint/98/4/1565.pdf",
+ url = "http://www.pnas.org/cgi/content/abstract/98/4/1565",
+ abstract = ""
+}
+
+@article { carrion-vazquez00,
+ author = MCarrionVazquez #" and "# PEOberhauser #" and "# HLi #" and "#
+ JFernandez,
+ title = "Mechanical design of proteins studied by single-molecule force
+ spectroscopy and protein engineering",
+ year = 2000,
+ journal = PBPMB,
+ volume = 74,
+ number = "1-2",
+ pages = "63--91",
+ issn = "0079-6107",
+ eprint = "http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1302160&blo
+ btype=pdf",
+ url = "http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1302160",
+ keywords = "Elasticity;Hydrogen Bonding;Microscopy, Atomic Force;Protein
+ Denaturation;Protein Engineering;Protein Folding;Recombinant
+ Proteins;Signal Processing, Computer-Assisted",
+ abstract = "Mechanical unfolding and refolding may regulate the molecular
+ elasticity of modular proteins with mechanical functions. The
+ development of the atomic force microscopy (AFM) has recently enabled
+ the dynamic measurement of these processes at the single-molecule
+ level. Protein engineering techniques allow the construction of
+ homomeric polyproteins for the precise analysis of the mechanical
+ unfolding of single domains. alpha-Helical domains are mechanically
+ compliant, whereas beta-sandwich domains, particularly those that
+ resist unfolding with backbone hydrogen bonds between strands
+ perpendicular to the applied force, are more stable and appear
+ frequently in proteins subject to mechanical forces. The mechanical
+ stability of a domain seems to be determined by its hydrogen bonding
+ pattern and is correlated with its kinetic stability rather than its
+ thermodynamic stability. Force spectroscopy using AFM promises to
+ elucidate the dynamic mechanical properties of a wide variety of
+ proteins at the single molecule level and provide an important
+ complement to other structural and dynamic techniques (e.g., X-ray
+ crystallography, NMR spectroscopy, patch-clamp)."
+}
+
+@article { carrion-vazquez03,
+ author = MCarrionVazquez #" and "# HLi #" and "# HLu #" and "# PMarszalek
+ #" and "# AOberhauser #" and "# JFernandez,
+ title = "The mechanical stability of ubiquitin is linkage dependent",
+ year = 2003,
+ month = sep,
+ day = 17,
+ journal = NSB,
+ volume = 10,
+ number = 9,
+ pages = "738--743",
+ issn = "1072-8368",
+ doi = "10.1038/nsb965",
+ eprint = "http://www.nature.com/nsmb/journal/v10/n9/pdf/nsb965.pdf",
+ url = "http://www.nature.com/nsmb/journal/v10/n9/abs/nsb965.html",
+ keywords = "Humans;Hydrogen Bonding;Kinetics;Lysine;Microscopy, Atomic
+ Force;Models, Molecular;Polyubiquitin;Protein Binding;Protein
+ Folding;Protein Structure, Tertiary;Ubiquitin",
+ abstract = "Ubiquitin chains are formed through the action of a set of
+ enzymes that covalently link ubiquitin either through peptide bonds or
+ through isopeptide bonds between their C terminus and any of four
+ lysine residues. These naturally occurring polyproteins allow one to
+ study the mechanical stability of a protein, when force is applied
+ through different linkages. Here we used single-molecule force
+ spectroscopy techniques to examine the mechanical stability of
+ N-C-linked and Lys48-C-linked ubiquitin chains. We combined these
+ experiments with steered molecular dynamics (SMD) simulations and found
+ that the mechanical stability and unfolding pathway of ubiquitin
+ strongly depend on the linkage through which the mechanical force is
+ applied to the protein. Hence, a protein that is otherwise very stable
+ may be easily unfolded by a relatively weak mechanical force applied
+ through the right linkage. This may be a widespread mechanism in
+ biological systems."
+}
+
+@article { carrion-vazquez99a,
+ author = MCarrionVazquez #" and "# AFMarszalek #" and "# JFernandez,
+ title = "Atomic force microscopy captures length phenotypes in single
+ proteins",
+ year = 1999,
+ journal = PNAS,
+ volume = 96,
+ number = 20,
+ pages = "11288--11292",
+ doi = "10.1073/pnas.96.20.11288",
+ eprint = "http://www.pnas.org/cgi/reprint/96/20/11288.pdf",
+ url = "http://www.pnas.org/cgi/content/abstract/96/20/11288",
+ abstract = ""
+}
+
+@article { carrion-vazquez99b,
+ author = MCarrionVazquez #" and "# AOberhauser #" and "# SFowler #" and "#
+ PMarszalek #" and "# SBroedel #" and "# JClarke #" and "# JFernandez,
+ title = "Mechanical and chemical unfolding of a single protein: A
+ comparison",
+ year = 1999,
+ journal = PNAS,
+ volume = 96,
+ number = 7,
+ pages = "3694--3699",
+ doi = "10.1073/pnas.96.7.3694",
+ eprint = "http://www.pnas.org/cgi/reprint/96/7/3694.pdf",
+ url = "http://www.pnas.org/cgi/content/abstract/96/7/3694"
+}
+
+@article { chyan04,
+ author = CLChyan #" and "# FCLin #" and "# HPeng #" and "# JMYuan #" and "#
+ CHChang #" and "# GSheng-HsienLinandYang,
+ title = "Reversible mechanical unfolding of single ubiquitin molecules",
+ year = 2004,
+ month = dec,
+ day = 10,
+ journal = BPJ,
+ volume = 87,
+ number = 6,
+ pages = "3995--4006",
+ issn = "0006-3495",
+ doi = "10.1529/biophysj.104.042754",
+ eprint = "http://download.cell.com/biophysj/pdf/PIIS0006349504738643.pdf",
+ url = "http://www.cell.com/biophysj/abstract/S0006-3495(04)73864-3",
+ keywords = "Computer
+ Simulation;Elasticity;Mechanics;Micromanipulation;Microscopy, Atomic
+ Force;Models, Chemical;Models, Molecular;Protein Conformation;Protein
+ Denaturation;Protein Folding;Stress, Mechanical;Structure-Activity
+ Relationship;Ubiquitin",
+ abstract = "Single-molecule manipulation techniques have enabled the
+ characterization of the unfolding and refolding process of individual
+ protein molecules, using mechanical forces to initiate the unfolding
+ transition. Experimental and computational results following this
+ approach have shed new light on the mechanisms of the mechanical
+ functions of proteins involved in several cellular processes, as well
+ as revealed new information on the protein folding/unfolding free-
+ energy landscapes. To investigate how protein molecules of different
+ folds respond to a stretching force, and to elucidate the effects of
+ solution conditions on the mechanical stability of a protein, we
+ synthesized polymers of the protein ubiquitin and characterized the
+ force-induced unfolding and refolding of individual ubiquitin molecules
+ using an atomic-force-microscope-based single-molecule manipulation
+ technique. The ubiquitin molecule was highly resistant to a stretching
+ force, and the mechanical unfolding process was reversible. A model
+ calculation based on the hydrogen-bonding pattern in the native
+ structure was performed to explain the origin of this high mechanical
+ stability. Furthermore, pH effects were studied and it was found that
+ the forces required to unfold the protein remained constant within a pH
+ range around the neutral value, and forces decreased as the solution pH
+ was lowered to more acidic values."
+}
+
+@article { ciccotti86,
+ author = GCiccottiX #" and "# JPRyckaertX,
+ title = "Molecular dynamics simulation of rigid molecules",
+ year = 1986,
+ journal = ComputerPhysicsreports,
+ volume = 4,
+ number = 6,
+ pages = "346--392",
+ issn = "0167-7977",
+ doi = "10.1016/0167-7977(86)90022-5",
+ url = "http://dx.doi.org/10.1016/0167-7977(86)90022-5",
+ note = "I haven't read this, but it looks like a nice review of MD with
+ constraints."
+}
+
+@article { claverie01,
+ author = JMClaverie,
+ title = "Gene number. What if there are only 30,000 human genes?",
+ year = 2001,
+ month = feb,
+ day = 16,
+ journal = SCI,
+ volume = 291,
+ number = 5507,
+ pages = "1255--1257",
+ issn = "0036-8075",
+ url = "http://www.sciencemag.org/cgi/content/full/291/5507/1255",
+ keywords = "Animals;Computational Biology;Drug Industry;Expressed Sequence
+ Tags;Gene Expression;Gene Expression Regulation;Genes;Genetic
+ Techniques;Genome, Human;Genomics;Human Genome Project;Humans;Models,
+ Genetic;Polymorphism, Single Nucleotide;Proteins;RNA, Messenger"
+}
+
+@misc { codata-boltzmann,
+ key = "codata-boltzmann",
+ crossref = "codata06",
+ url = "http://physics.nist.gov/cgi-bin/cuu/Value?k"
+}
+
+@article { codata06,
+ author = PJMohr #" and "# BNTaylor #" and "# DBNewell,
+ key = "codata06",
+ title = "{CODATA} recommended values of the fundamental physical constants:
+ 2006",
+ year = 2008,
+ month = jun,
+ journal = RMP,
+ volume = 80,
+ number = 2,
+ pages = "633--730",
+ numpages = 97,
+ publisher = APS,
+ doi = "10.1103/RevModPhys.80.633"
+}
+
+@article { collins03,
+ author = FSCollins #" and "# MMorgan #" and "# APatrinos,
+ title = "The Human Genome Project: lessons from large-scale biology.",
+ year = 2003,
+ month = apr,
+ day = 11,
+ journal = SCI,
+ volume = 300,
+ number = 5617,
+ pages = "286--290",
+ issn = "1095-9203",
+ doi = "10.1126/science.1084564",
+ eprint = "http://www.sciencemag.org/cgi/reprint/300/5617/286.pdf",
+ url = "http://www.sciencemag.org/cgi/content/summary/300/5617/277",
+ keywords = "Access to Information;Computational Biology;Databases, Nucleic
+ Acid;Genome, Human;Genomics;Government Agencies;History, 20th
+ Century;Human Genome Project;Humans;International Cooperation;National
+ Institutes of Health (U.S.);Private Sector;Public Policy;Public
+ Sector;Publishing;Quality Control;Sequence Analysis, DNA;United States",
+ note = "See also: \href{http://www.ornl.gov/sci/techresources/Human_Genome/
+ project/journals/journals.shtml}{Landmark HPG Papers}"
+}
+
+@article { cornish07,
+ author = PVCornish #" and "# THa,
+ title = "A survey of single-molecule techniques in chemical biology",
+ year = 2007,
+ month = jan,
+ day = 23,
+ journal = ACSChemBiol,
+ volume = 2,
+ number = 1,
+ pages = "53--61",
+ issn = "1554-8937",
+ doi = "10.1021/cb600342a",
+ keywords = "Animals;Data Collection;Humans;Microscopy, Atomic
+ Force;Microscopy, Fluorescence;Molecular Biology",
+ abstract = "Single-molecule methods have revolutionized scientific research
+ by rendering the investigation of once-inaccessible biological
+ processes amenable to scientific inquiry. Several of the more
+ established techniques will be emphasized in this Review, including
+ single-molecule fluorescence microscopy, optical tweezers, and atomic
+ force microscopy, which have been applied to many diverse biological
+ processes. Serving as a taste of all the exciting research currently
+ underway, recent examples will be discussed of translocation of RNA
+ polymerase, myosin VI walking, protein folding, and enzyme activity. We
+ will end by providing an assessment of what the future holds, including
+ techniques that are currently in development."
+}
+
+@book { cowan98,
+ author = GCowan,
+ title = "Statistical Data Analysis",
+ year = 1998,
+ publisher = OxfordUniversityPress,
+ address = "New York",
+ note = "Noise deconvolution in Chapter 11",
+ project = "Cantilever Calibration"
+}
+
+@article { craig01,
+ author = DCraig #" and "# AKrammer #" and "# KSchulten #" and "# VVogel,
+ title = "Comparison of the early stages of forced unfolding for fibronectin
+ type {III} modules",
+ year = 2001,
+ journal = PNAS,
+ volume = 98,
+ number = 10,
+ pages = "5590--5595",
+ doi = "10.1073/pnas.101582198",
+ eprint = "http://www.pnas.org/cgi/reprint/98/10/5590.pdf",
+ url = "http://www.pnas.org/cgi/content/abstract/98/10/5590",
+ abstract = ""
+}
+
+@article { delpech01,
+ author = BDelpech #" and "# MNCourel #" and "# CMaingonnat #" and "#
+ CChauzy #" and "# RSesboue #" and "# GPratesi,
+ title = "Hyaluronan digestion and synthesis in an experimental model of
+ metastatic tumour",
+ year = 2001,
+ month = "September/October",
+ journal = HistochemJ,
+ volume = 33,
+ number = "9-10",
+ pages = "553--558",
+ issn = "0018-2214",
+ keywords = "Animals;Culture Media;Humans;Hyaluronic
+ Acid;Hyaluronoglucosaminidase;Mice;Mice, Nude;Neoplasm
+ Metastasis;Neoplasm Transplantation;Neoplasms, Experimental;Tumor
+ Cells, Cultured",
+ abstract = "To approach the question of hyaluronan catabolism in tumours,
+ we have selected the cancer cell line H460M, a highly metastatic cell
+ line in the nude mouse. H460M cells release hyaluronidase in culture
+ media at a high rate of 57 pU/cell/h, without producing hyaluronan.
+ Hyaluronidase was measured in the H460M cell culture medium at the
+ optimum pH 3.8, and was not found above pH 4.5, with the enzyme-linked
+ sorbent assay technique and zymography. Tritiated hyaluronan was
+ digested at pH 3.8 by cells or cell membranes as shown by gel
+ permeation chromatography, but no activity was recorded at pH 7 with
+ this technique. Hyaluronan was digested in culture medium by tumour
+ slices, prepared from tumours developed in nude mice grafted with H460M
+ cells, showing that hyaluronan could be digested in complex tissue at
+ physiological pH. Culture of tumour slices with tritiated acetate
+ resulted in the accumulation within 2 days of radioactive
+ macromolecules in the culture medium. The radioactive macromolecular
+ material was mostly digested by Streptomyces hyaluronidase, showing
+ that hyaluronan was its main component and that hyaluronan synthesis
+ occurred together with its digestion. These results demonstrate that
+ the membrane-associated hyaluronidase of H460M cells can act in vivo,
+ and that hyaluronan, which is synthesised by the tumour stroma, can be
+ made soluble and reduced to a smaller size by tumour cells before being
+ internalised and further digested."
+}
+
+@article { diCola05,
+ author = EDCola #" and "# TAWaigh #" and "# JTrinick #" and "#
+ LTskhovrebova #" and "# AHoumeida #" and "# WPyckhout-Hintzen #" and "#
+ CDewhurst,
+ key = "diCola05",
+ title = "Persistence length of titin from rabbit skeletal muscles measured
+ with scattering and microrheology techniques",
+ year = 2005,
+ month = jun,
+ day = 25,
+ journal = BPJ,
+ volume = 88,
+ number = 6,
+ pages = "4095--4106",
+ issn = "0006-3495",
+ doi = "10.1529/biophysj.104.054908",
+ eprint = "http://download.cell.com/biophysj/pdf/PIIS0006349505734603.pdf",
+ url = "http://www.cell.com/biophysj/retrieve/pii/S0006349505734603",
+ keywords = "Animals;Biophysics;Elasticity;Light;Muscle Proteins;Muscle,
+ Skeletal;Neutrons;Protein Conformation;Protein
+ Kinases;Rabbits;Rheology;Scattering, Radiation;Temperature",
+ abstract = "The persistence length of titin from rabbit skeletal muscles
+ was measured using a combination of static and dynamic light
+ scattering, and neutron small angle scattering. Values of persistence
+ length in the range 9-16 nm were found for titin-II, which corresponds
+ to mainly physiologically inelastic A-band part of the protein, and for
+ a proteolytic fragment with 100-nm contour length from the
+ physiologically elastic I-band part. The ratio of the hydrodynamic
+ radius to the static radius of gyration indicates that the proteins
+ obey Gaussian statistics typical of a flexible polymer in a -solvent.
+ Furthermore, measurements of the flexibility as a function of
+ temperature demonstrate that titin-II and the I-band titin fragment
+ experience a similar denaturation process; unfolding begins at 318 K
+ and proceeds in two stages: an initial gradual 50\% change in
+ persistence length is followed by a sharp unwinding transition at 338
+ K. Complementary microrheology (video particle tracking) measurements
+ indicate that the viscoelasticity in dilute solution behaves according
+ to the Flory/Fox model, providing a value of the radius of gyration for
+ titin-II (63 +/- 1 nm) in agreement with static light scattering and
+ small angle neutron scattering results."
+}
+
+@article { dietz04,
+ author = HDietz #" and "# MRief,
+ title = "Exploring the energy landscape of {GFP} by single-molecule
+ mechanical experiments",
+ year = 2004,
+ journal = PNAS,
+ volume = 101,
+ number = 46,
+ pages = "16192--16197",
+ doi = "10.1073/pnas.0404549101",
+ eprint = "http://www.pnas.org/cgi/reprint/101/46/16192.pdf",
+ url = "http://www.pnas.org/cgi/content/abstract/101/46/16192",
+ abstract = "We use single-molecule force spectroscopy to drive single GFP
+ molecules from the native state through their complex energy landscape
+ into the completely unfolded state. Unlike many smaller proteins,
+ mechanical GFP unfolding proceeds by means of two subsequent
+ intermediate states. The transition from the native state to the first
+ intermediate state occurs near thermal equilibrium at {approx}35 pN and
+ is characterized by detachment of a seven-residue N-terminal
+ {alpha}-helix from the beta barrel. We measure the equilibrium free
+ energy cost associated with this transition as 22 kBT. Detachment of
+ this small {alpha}-helix completely destabilizes GFP thermodynamically
+ even though the {beta}-barrel is still intact and can bear load.
+ Mechanical stability of the protein on the millisecond timescale,
+ however, is determined by the activation barrier of unfolding the
+ {beta}-barrel out of this thermodynamically unstable intermediate
+ state. High bandwidth, time-resolved measurements of the cantilever
+ relaxation phase upon unfolding of the {beta}-barrel revealed a second
+ metastable mechanical intermediate with one complete {beta}-strand
+ detached from the barrel. Quantitative analysis of force distributions
+ and lifetimes lead to a detailed picture of the complex mechanical
+ unfolding pathway through a rough energy landscape.",
+ note = "Nice energy-landscape-to-one-dimension compression graphic.
+ Unfolding Green Flourescent Protein (GFP) towards using it as an
+ embedded force probe.",
+ project = "Energy landscape roughness"
+}
+
+@article { dietz06a,
+ author = HDietz #" and "# FBerkemeier #" and "# MBertz #" and "# MRief,
+ title = "Anisotropic deformation response of single protein molecules",
+ year = 2006,
+ journal = PNAS,
+ volume = 103,
+ number = 34,
+ pages = "12724--12728",
+ doi = "10.1073/pnas.0602995103",
+ eprint = "http://www.pnas.org/cgi/reprint/103/34/12724.pdf",
+ url = "http://www.pnas.org/cgi/content/abstract/103/34/12724",
+ abstract = "Single-molecule methods have given experimental access to the
+ mechanical properties of single protein molecules. So far, access has
+ been limited to mostly one spatial direction of force application.
+ Here, we report single-molecule experiments that explore the mechanical
+ properties of a folded protein structure in precisely controlled
+ directions by applying force to selected amino acid pairs. We
+ investigated the deformation response of GFP in five selected
+ directions. We found fracture forces widely varying from 100 pN up to
+ 600 pN. We show that straining the GFP structure in one of the five
+ directions induces partial fracture of the protein into a half-folded
+ intermediate structure. From potential widths we estimated directional
+ spring constants of the GFP structure and found values ranging from 1
+ N/m up to 17 N/m. Our results show that classical continuum mechanics
+ and simple mechanistic models fail to describe the complex mechanics of
+ the GFP protein structure and offer insights into the mechanical design
+ of protein materials."
+}
+
+@article { dietz06b,
+ author = HDietz #" and "# MRief,
+ title = "Protein structure by mechanical triangulation",
+ year = 2006,
+ journal = PNAS,
+ volume = 103,
+ number = 5,
+ pages = "1244--1247",
+ doi = "10.1073/pnas.0509217103",
+ eprint = "http://www.pnas.org/cgi/reprint/103/5/1244.pdf",
+ url = "http://www.pnas.org/cgi/content/abstract/103/5/1244",
+ abstract = "Knowledge of protein structure is essential to understand
+ protein function. High-resolution protein structure has so far been the
+ domain of ensemble methods. Here, we develop a simple single-molecule
+ technique to measure spatial position of selected residues within a
+ folded and functional protein structure in solution. Construction and
+ mechanical unfolding of cysteine-engineered polyproteins with
+ controlled linkage topology allows measuring intramolecular distance
+ with angstrom precision. We demonstrate the potential of this technique
+ by determining the position of three residues in the structure of green
+ fluorescent protein (GFP). Our results perfectly agree with the GFP
+ crystal structure. Mechanical triangulation can find many applications
+ where current bulk structural methods fail."
+}
+
+@article { dietz07,
+ author = HDietz #" and "# MRief,
+ title = "Detecting Molecular Fingerprints in Single Molecule Force
+ Spectroscopy Using Pattern Recognition",
+ year = 2007,
+ journal = JapaneseJournalofAppliedPhysics,
+ volume = 46,
+ number = "8B",
+ pages = "5540--5542",
+ issn = "0021-4922",
+ doi = "10.1143/JJAP.46.5540",
+ url = "http://jjap.ipap.jp/link?JJAP/46/5540/",
+ keywords = "single molecule, protein mechanics, force spectroscopy, AFM,
+ pattern recognition, GFP",
+ abstract = "Single molecule force spectroscopy has given experimental
+ access to the mechanical properties of protein molecules. Typically,
+ less than 1% of the experimental recordings reflect true single
+ molecule events due to abundant surface and multiple-molecule
+ interactions. A key issue in single molecule force spectroscopy is thus
+ to identify the characteristic mechanical `fingerprint' of a specific
+ protein in noisy data sets. Here, we present an objective pattern
+ recognition algorithm that is able to identify fingerprints in such
+ noisy data sets.",
+ note = "Automatic force curve selection. Seems a bit shoddy. Details
+ later."
+}
+
+@article { dill97,
+ author = KADill #" and "# HSChan,
+ title = "From Levinthal to pathways to funnels.",
+ year = 1997,
+ month = jan,
+ journal = NSB,
+ volume = 4,
+ number = 1,
+ pages = "10--19",
+ issn = "1072-8368",
+ doi = "10.1038/nsb0197-10",
+ eprint = "http://www.nature.com/nsmb/journal/v4/n1/pdf/nsb0197-10.pdf",
+ url = "http://www.nature.com/nsmb/journal/v4/n1/abs/nsb0197-10.html",
+ keywords = "Kinetics;Models, Chemical;Protein Folding",
+ abstract = "While the classical view of protein folding kinetics relies on
+ phenomenological models, and regards folding intermediates in a
+ structural way, the new view emphasizes the ensemble nature of protein
+ conformations. Although folding has sometimes been regarded as a linear
+ sequence of events, the new view sees folding as parallel microscopic
+ multi-pathway diffusion-like processes. While the classical view
+ invoked pathways to solve the problem of searching for the needle in
+ the haystack, the pathway idea was then seen as conflicting with
+ Anfinsen's experiments showing that folding is pathway-independent
+ (Levinthal's paradox). In contrast, the new view sees no inherent
+ paradox because it eliminates the pathway idea: folding can funnel to a
+ single stable state by multiple routes in conformational space. The
+ general energy landscape picture provides a conceptual framework for
+ understanding both two-state and multi-state folding kinetics. Better
+ tests of these ideas will come when new experiments become available
+ for measuring not just averages of structural observables, but also
+ correlations among their fluctuations. At that point we hope to learn
+ much more about the real shapes of protein folding landscapes.",
+ note = "Pretty folding funnel figures."
+}
+
+@article { discher06,
+ author = DDischer #" and "# NBhasin #" and "# CJohnson,
+ title = "Covalent chemistry on distended proteins",
+ year = 2006,
+ journal = PNAS,
+ volume = 103,
+ number = 20,
+ pages = "7533--7534",
+ doi = "10.1073/pnas.0602388103",
+ eprint = "http://www.pnas.org/cgi/reprint/103/20/7533.pdf",
+ url = "http://www.pnas.org/cgi/content/abstract/103/20/7533.pdf"
+}
+
+@article { dudko03,
+ author = OKDudko #" and "# AEFilippov #" and "# JKlafter #" and "# MUrbakh,
+ title = "Beyond the conventional description of dynamic force spectroscopy
+ of adhesion bonds",
+ year = 2003,
+ month = sep,
+ day = 30,
+ journal = PNAS,
+ volume = 100,
+ number = 20,
+ pages = "11378--11381",
+ issn = "0027-8424",
+ doi = "10.1073/pnas.1534554100",
+ eprint = "http://www.pnas.org/content/100/20/11378.full.pdf",
+ url = "http://www.pnas.org/content/100/20/11378.abstract",
+ keywords = "Spectrum Analysis;Temperature",
+ abstract = "Dynamic force spectroscopy of single molecules is described by
+ a model that predicts a distribution of rupture forces, the
+ corresponding mean rupture force, and variance, which are all amenable
+ to experimental tests. The distribution has a pronounced asymmetry,
+ which has recently been observed experimentally. The mean rupture force
+ follows a (lnV)2/3 dependence on the pulling velocity, V, and differs
+ from earlier predictions. Interestingly, at low pulling velocities, a
+ rebinding process is obtained whose signature is an intermittent
+ behavior of the spring force, which delays the rupture. An extension to
+ include conformational changes of the adhesion complex is proposed,
+ which leads to the possibility of bimodal distributions of rupture
+ forces."
+}
+
+@article { dudko06,
+ author = OKDudkoX #" and "# GHummer #" and "# ASzabo,
+ title = "Intrinsic rates and activation free energies from single-molecule
+ pulling experiments",
+ year = 2006,
+ month = mar,
+ day = 17,
+ journal = PhysRevLett,
+ volume = 96,
+ number = 10,
+ pages = 108101,
+ issn = "0031-9007",
+ doi = "10.1103/PhysRevLett.96.108101",
+ keywords = "Biophysics;Computer Simulation;Data Interpretation,
+ Statistical;Kinetics;Micromanipulation;Models, Chemical;Models,
+ Molecular;Molecular Conformation;Muscle Proteins;Nucleic Acid
+ Conformation;Protein Binding;Protein Denaturation;Protein
+ Folding;Protein Kinases;RNA;Stress, Mechanical;Thermodynamics;Time
+ Factors",
+ abstract = "We present a unified framework for extracting kinetic
+ information from single-molecule pulling experiments at constant force
+ or constant pulling speed. Our procedure provides estimates of not only
+ (i) the intrinsic rate coefficient and (ii) the location of the
+ transition state but also (iii) the free energy of activation. By
+ analyzing simulated data, we show that the resulting rates of force-
+ induced rupture are significantly more reliable than those obtained by
+ the widely used approach based on Bell's formula. We consider the
+ uniqueness of the extracted kinetic information and suggest guidelines
+ to avoid over-interpretation of experiments."
+}
+
+@article { dudko07,
+ author = OKDudkoX #" and "# JMathe #" and "# ASzabo #" and "# AMeller #"
+ and "# GHummer,
+ title = "Extracting kinetics from single-molecule force spectroscopy:
+ nanopore unzipping of {DNA} hairpins",
+ year = 2007,
+ month = jun,
+ day = 15,
+ journal = BPJ,
+ volume = 92,
+ number = 12,
+ pages = "4188--4195",
+ issn = "0006-3495",
+ doi = "10.1529/biophysj.106.102855",
+ eprint = "http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1877759&blo
+ btype=pdf",
+ keywords = "Computer
+ Simulation;DNA;Elasticity;Mechanics;Micromanipulation;Microscopy,
+ Atomic Force;Models, Chemical;Models, Molecular;Nanostructures;Nucleic
+ Acid Conformation;Porosity;Stress, Mechanical",
+ abstract = "Single-molecule force experiments provide powerful new tools to
+ explore biomolecular interactions. Here, we describe a systematic
+ procedure for extracting kinetic information from force-spectroscopy
+ experiments, and apply it to nanopore unzipping of individual DNA
+ hairpins. Two types of measurements are considered: unzipping at
+ constant voltage, and unzipping at constant voltage-ramp speeds. We
+ perform a global maximum-likelihood analysis of the experimental data
+ at low-to-intermediate ramp speeds. To validate the theoretical models,
+ we compare their predictions with two independent sets of data,
+ collected at high ramp speeds and at constant voltage, by using a
+ quantitative relation between the two types of measurements.
+ Microscopic approaches based on Kramers theory of diffusive barrier
+ crossing allow us to estimate not only intrinsic rates and transition
+ state locations, as in the widely used phenomenological approach based
+ on Bell's formula, but also free energies of activation. The problem of
+ extracting unique and accurate kinetic parameters of a molecular
+ transition is discussed in light of the apparent success of the
+ microscopic theories in reproducing the experimental data."
+}
+
+@article { evans01,
+ author = EEvans,
+ title = "Probing the relation between force--lifetime--and chemistry in
+ single molecular bonds",
+ year = 2001,
+ journal = AnnuRevBiophysBiomolStruct,
+ volume = 30,
+ pages = "105--128",
+ issn = "1056-8700",
+ doi = "10.1146/annurev.biophys.30.1.105",
+ url = "http://arjournals.annualreviews.org/doi/abs/10.1146%2Fannurev.biophy
+ s.30.1.105",
+ keywords = "Biophysics;Kinetics;Microscopy, Atomic Force;Models,
+ Chemical;Protein Binding;Spectrum Analysis;Time Factors",
+ abstract = "On laboratory time scales, the energy landscape of a weak bond
+ along a dissociation pathway is fully explored through Brownian-thermal
+ excitations, and energy barriers become encoded in a dissociation time
+ that varies with applied force. Probed with ramps of force over an
+ enormous range of rates (force/time), this kinetic profile is
+ transformed into a dynamic spectrum of bond rupture force as a function
+ of loading rate. On a logarithmic scale in loading rate, the force
+ spectrum provides an easy-to-read map of the prominent energy barriers
+ traversed along the force-driven pathway and exposes the differences in
+ energy between barriers. In this way, the method of dynamic force
+ spectroscopy (DFS) is being used to probe the complex relation between
+ force-lifetime-and chemistry in single molecular bonds. Most important,
+ DFS probes the inner world of molecular interactions to reveal barriers
+ that are difficult or impossible to detect in assays of near
+ equilibrium dissociation but that determine bond lifetime and strength
+ under rapid detachment. To use an ultrasensitive force probe as a
+ spectroscopic tool, we need to understand the physics of bond
+ dissociation under force, the impact of experimental technique on the
+ measurement of detachment force (bond strength), the consequences of
+ complex interactions in macromolecular bonds, and effects of multiply-
+ bonded attachments."
+}
+
+@article { evans91a,
+ author = EEvans #" and "# DBerk #" and "# ALeung,
+ title = "Detachment of agglutinin-bonded red blood cells. {I}. Forces to
+ rupture molecular-point attachments",
+ year = 1991,
+ month = apr,
+ journal = BPJ,
+ volume = 59,
+ number = 4,
+ pages = "838--848",
+ issn = "0006-3495",
+ keywords = "ABO Blood-Group System;Animals;Antibodies,
+ Monoclonal;Erythrocyte Deformability;Erythrocyte
+ Membrane;Erythrocytes;Glycophorin;Helix
+ (Snails);Hemagglutinins;Humans;Immune Sera;Lectins;Mathematics;Models,
+ Biological",
+ abstract = "A simple micromechanical method has been developed to measure
+ the rupture strength of a molecular-point attachment (focal bond)
+ between two macroscopically smooth membrane capsules. In the procedure,
+ one capsule is prepared with a low density coverage of adhesion
+ molecules, formed as a stiff sphere, and held at fixed position by a
+ micropipette. The second capsule without adhesion molecules is
+ pressurized into a spherical shape with low suction by another pipette.
+ This capsule is maneuvered to initiate point contact at the pole
+ opposite the stiff capsule which leads to formation of a few (or even
+ one) molecular attachments. Then, the deformable capsule is slowly
+ withdrawn by displacement of the pipette. Analysis shows that the end-
+ to-end extension of the capsule provides a direct measure of the force
+ at the point contact and, therefore, the rupture strength when
+ detachment occurs. The range for point forces accessible to this
+ technique depends on the elastic moduli of the membrane, membrane
+ tension, and the size of the capsule. For biological and synthetic
+ vesicle membranes, the range of force lies between 10(-7)-10(-5) dyn
+ (10(-12)-10(-10) N) which is 100-fold less than presently measurable by
+ Atomic Force Microscopy! Here, the approach was used to study the
+ forces required to rupture microscopic attachments between red blood
+ cells formed by a monoclonal antibody to red cell membrane glycophorin,
+ anti-A serum, and a lectin from the snail-helix pomatia. Failure of the
+ attachments appeared to be a stochastic function of the magnitude and
+ duration of the detachment force. We have correlated the statistical
+ behavior observed for rupture with a random process model for failure
+ of small numbers of molecular attachments. The surprising outcome of
+ the measurements and analysis was that the forces deduced for short-
+ time failure of 1-2 molecular attachments were nearly the same for all
+ of the agglutinin, i.e., 1-2 x 10(-6) dyn. Hence, microfluorometric
+ tests were carried out to determine if labeled agglutinins and/or
+ labeled surface molecules were transferred between surfaces after
+ separation of large areas of adhesive contact. The results showed that
+ the attachments failed because receptors were extracted from the
+ membrane."
+}
+
+@article { evans91b,
+ author = EEvans #" and "# DBerk #" and "# ALeung #" and "# NMohandas,
+ title = "Detachment of agglutinin-bonded red blood cells. {II}. Mechanical
+ energies to separate large contact areas",
+ year = 1991,
+ month = apr,
+ journal = BPJ,
+ volume = 59,
+ number = 4,
+ pages = "849--860",
+ issn = "0006-3495",
+ keywords = "Animals;Antibodies, Monoclonal;Cell Adhesion;Erythrocyte
+ Membrane;Erythrocytes;Helix
+ (Snails);Hemagglutination;Hemagglutinins;Humans;Immune
+ Sera;Kinetics;Lectins;Mathematics",
+ abstract = "As detailed in a companion paper (Berk, D., and E. Evans. 1991.
+ Biophys. J. 59:861-872), a method was developed to quantitate the
+ strength of adhesion between agglutinin-bonded membranes without
+ ambiguity due to mechanical compliance of the cell body. The
+ experimental method and analysis were formulated around controlled
+ assembly and detachment of a pair of macroscopically smooth red blood
+ cell surfaces. The approach provides precise measurement of the
+ membrane tension applied at the perimeter of an adhesive contact and
+ the contact angle theta c between membrane surfaces which defines the
+ mechanical leverage factor (1-cos theta c) important in the definition
+ of the work to separate a unit area of contact. Here, the method was
+ applied to adhesion and detachment of red cells bound together by
+ different monoclonal antibodies to red cell membrane glycophorin and
+ the snail-helix pomatia-lectin. For these tests, one of the two red
+ cells was chemically prefixed in the form of a smooth sphere then
+ equilibrated with the agglutinin before the adhesion-detachment
+ procedure. The other cell was not exposed to the agglutinin until it
+ was forced into contact with the rigid cell surface by mechanical
+ impingement. Large regions of agglutinin bonding were produced by
+ impingement but no spontaneous spreading was observed beyond the forced
+ contact. Measurements of suction force to detach the deformable cell
+ yielded consistent behavior for all of the agglutinins: i.e., the
+ strength of adhesion increased progressively with reduction in contact
+ diameter throughout detachment. This tension-contact diameter behavior
+ was not altered over a ten-fold range of separation rates. In special
+ cases, contacts separated smoothly after critical tensions were
+ reached; these were the highest values attained for tension. Based on
+ measurements reported in another paper (Evans et al. 1991. Biophys. J.
+ 59:838-848) of the forces required to rupture molecular-point
+ attachments, the density of cross-bridges was estimated with the
+ assumption that the tension was proportional to the discrete rupture
+ force x the number of attachments per unit length. These estimates
+ showed that only a small fraction of agglutinin formed cross-bridges at
+ initial assembly and increased progressively with separation. When
+ critical tension levels were reached, it appeared that nearly all local
+ agglutinin was involved as cross-bridges. Because one cell surface was
+ chemically fixed, receptor accumulation was unlikely; thus, microscopic
+ ``roughness'' and steric repulsion probably modulated formation of
+ cross-bridges on initial contact.(ABSTRACT TRUNCATED AT 400 WORDS)"
+}
+
+@article { evans97,
+ author = EEvans #" and "# KRitchie,
+ title = "Dynamic strength of molecular adhesion bonds",
+ year = 1997,
+ month = apr,
+ journal = BPJ,
+ volume = 72,
+ number = 4,
+ pages = "1541--1555",
+ issn = "0006-3495",
+ eprint = "http://www.biophysj.org/cgi/reprint/72/4/1541.pdf",
+ url = "http://www.biophysj.org/cgi/content/abstract/72/4/1541",
+ keywords = "Avidin; Biotin; Chemistry, Physical; Computer Simulation;
+ Mathematics; Monte Carlo Method; Protein Binding",
+ abstract = "In biology, molecular linkages at, within, and beneath cell
+ interfaces arise mainly from weak noncovalent interactions. These bonds
+ will fail under any level of pulling force if held for sufficient time.
+ Thus, when tested with ultrasensitive force probes, we expect cohesive
+ material strength and strength of adhesion at interfaces to be time-
+ and loading rate-dependent properties. To examine what can be learned
+ from measurements of bond strength, we have extended Kramers' theory
+ for reaction kinetics in liquids to bond dissociation under force and
+ tested the predictions by smart Monte Carlo (Brownian dynamics)
+ simulations of bond rupture. By definition, bond strength is the force
+ that produces the most frequent failure in repeated tests of breakage,
+ i.e., the peak in the distribution of rupture forces. As verified by
+ the simulations, theory shows that bond strength progresses through
+ three dynamic regimes of loading rate. First, bond strength emerges at
+ a critical rate of loading (> or = 0) at which spontaneous dissociation
+ is just frequent enough to keep the distribution peak at zero force. In
+ the slow-loading regime immediately above the critical rate, strength
+ grows as a weak power of loading rate and reflects initial coupling of
+ force to the bonding potential. At higher rates, there is crossover to
+ a fast regime in which strength continues to increase as the logarithm
+ of the loading rate over many decades independent of the type of
+ attraction. Finally, at ultrafast loading rates approaching the domain
+ of molecular dynamics simulations, the bonding potential is quickly
+ overwhelmed by the rapidly increasing force, so that only naked
+ frictional drag on the structure remains to retard separation. Hence,
+ to expose the energy landscape that governs bond strength, molecular
+ adhesion forces must be examined over an enormous span of time scales.
+ However, a significant gap exists between the time domain of force
+ measurements in the laboratory and the extremely fast scale of
+ molecular motions. Using results from a simulation of biotin-avidin
+ bonds (Izrailev, S., S. Stepaniants, M. Balsera, Y. Oono, and K.
+ Schulten. 1997. Molecular dynamics study of unbinding of the avidin-
+ biotin complex. Biophys. J., this issue), we describe how Brownian
+ dynamics can help bridge the gap between molecular dynamics and probe
+ tests.",
+ project = "sawtooth simulation"
+}
+
+@article { evans99,
+ author = EEvans #" and "# KRitchie,
+ title = "Strength of a weak bond connecting flexible polymer chains",
+ year = 1999,
+ month = may,
+ journal = BPJ,
+ volume = 76,
+ number = 5,
+ pages = "2439--2447",
+ issn = "0006-3495",
+ eprint = "http://www.biophysj.org/cgi/reprint/76/5/2439.pdf",
+ url = "http://www.biophysj.org/cgi/content/abstract/76/5/2439",
+ keywords = "Animals; Biophysics; Biopolymers; Microscopy, Atomic Force;
+ Models, Chemical; Muscle Proteins; Protein Folding; Protein Kinases;
+ Stochastic Processes; Stress, Mechanical; Thermodynamics",
+ abstract = "Bond dissociation under steadily rising force occurs most
+ frequently at a time governed by the rate of loading (Evans and
+ Ritchie, 1997 Biophys. J. 72:1541-1555). Multiplied by the loading
+ rate, the breakage time specifies the force for most frequent failure
+ (called bond strength) that obeys the same dependence on loading rate.
+ The spectrum of bond strength versus log(loading rate) provides an
+ image of the energy landscape traversed in the course of unbonding.
+ However, when a weak bond is connected to very compliant elements like
+ long polymers, the load applied to the bond does not rise steadily
+ under constant pulling speed. Because of nonsteady loading, the most
+ frequent breakage force can differ significantly from that of a bond
+ loaded at constant rate through stiff linkages. Using generic models
+ for wormlike and freely jointed chains, we have analyzed the kinetic
+ process of failure for a bond loaded by pulling the polymer linkages at
+ constant speed. We find that when linked by either type of polymer
+ chain, a bond is likely to fail at lower force under steady separation
+ than through stiff linkages. Quite unexpectedly, a discontinuous jump
+ can occur in bond strength at slow separation speed in the case of long
+ polymer linkages. We demonstrate that the predictions of strength
+ versus log(loading rate) can rationalize conflicting results obtained
+ recently for unfolding Ig domains along muscle titin with different
+ force techniques.",
+ note = "Develops Kramers improvement on Bell model for domain unfolding.
+ Presents unfolding under variable loading rates. Often cited as the
+ ``Bell-Evans'' model? They derive a unitless treatment, scaling force
+ by $f_\beta$, TODO; time by $\tau_f$, TODO; elasiticity by compliance
+ $c(f)$. The appendix has relaxation time formulas for WLC and FJC
+ polymer models.",
+ project = "sawtooth simulation"
+}
+
+@article { fernandez04,
+ author = JFernandez #" and "# HLi,
+ title = "Force-clamp spectroscopy monitors the folding trajectory of a
+ single protein",
+ year = 2004,
+ month = mar,
+ day = 12,
+ journal = SCI,
+ volume = 303,
+ number = 5664,
+ pages = "1674--1678",
+ issn = "1095-9203",
+ doi = "10.1126/science.1092497",
+ eprint = "http://www.sciencemag.org/cgi/reprint/303/5664/1674.pdf",
+ url = "http://www.sciencemag.org/cgi/content/abstract/303/5664/1674",
+ keywords = "Chemistry, Physical;Microscopy, Atomic Force;Physicochemical
+ Phenomena;Polyubiquitin;Protein Conformation;Protein
+ Denaturation;Protein Folding;Protein Structure, Secondary;Time
+ Factors;Ubiquitin",
+ abstract = "We used force-clamp atomic force microscopy to measure the end-
+ to-end length of the small protein ubiquitin during its folding
+ reaction at the single-molecule level. Ubiquitin was first unfolded and
+ extended at a high force, then the stretching force was quenched and
+ protein folding was observed. The folding trajectories were continuous
+ and marked by several distinct stages. The time taken to fold was
+ dependent on the contour length of the unfolded protein and the
+ stretching force applied during folding. The folding collapse was
+ marked by large fluctuations in the end-to-end length of the protein,
+ but these fluctuations vanished upon the final folding contraction.
+ These direct observations of the complete folding trajectory of a
+ protein provide a benchmark to determine the physical basis of the
+ folding reaction."
+}
+
+@article { florin95,
+ author = ELFlorin #" and "# MRief #" and "# HLehmann #" and "# MLudwig #"
+ and "# CDornmair #" and "# VMoy #" and "# HGaub,
+ title = "Sensing specific molecular interactions with the atomic force
+ microscope",
+ year = 1995,
+ journal = BIOSENSE,
+ volume = 10,
+ number = "9--10",
+ pages = "895--901",
+ issn = "0956-5663",
+ doi = "10.1016/0956-5663(95)99227-C",
+ url = "http://www.sciencedirect.com/science/article/B6TFC-
+ 3XY2HK9-G/2/6f4e9f67e9a1e14c8bbcc478e5360682",
+ abstract = "One of the unique features of the atomic force microscope (AFM)
+ is its capacity to measure interactions between tip and sample with
+ high sensitivity and unparal leled spatial resolution. Since the
+ development of methods for the functionaliza tion of the tips, the
+ versatility of the AFM has been expanded to experiments wh ere specific
+ molecular interactions are measured. For illustration, we present m
+ easurements of the interaction between complementary strands of DNA. A
+ necessary prerequisite for the quantitative analysis of the interaction
+ force is knowledg e of the spring constant of the cantilevers. Here, we
+ compare different techniqu es that allow for the in situ measurement of
+ the absolute value of the spring co nstant of cantilevers.",
+ note = "Good review of calibration to 1995, with experimental comparison
+ between resonance-shift, reference-spring, and thermal methods.",
+ project = "Cantilever Calibration"
+}
+
+@article { forde02,
+ author = NRForde #" and "# DIzhaky #" and "# GRWoodcock #" and "#
+ CGijsJLWuiteandBustamante,
+ title = "Using mechanical force to probe the mechanism of pausing and
+ arrest during continuous elongation by Escherichia coli {RNA}
+ polymerase",
+ year = 2002,
+ month = sep,
+ day = 03,
+ journal = PNAS,
+ volume = 99,
+ number = 18,
+ pages = "11682--11687",
+ issn = "0027-8424",
+ doi = "10.1073/pnas.142417799",
+ eprint = "http://www.pnas.org/cgi/reprint/99/18/11682.pdf",
+ url = "http://www.pnas.org/content/99/18/11682",
+ keywords = "DNA-Directed RNA Polymerases;Escherichia
+ coli;Kinetics;Transcription, Genetic",
+ abstract = "Escherichia coli RNA polymerase translocates along the DNA
+ discontinuously during the elongation phase of transcription, spending
+ proportionally more time at some template positions, known as pause and
+ arrest sites, than at others. Current models of elongation suggest that
+ the enzyme backtracks at these locations, but the dynamics are
+ unresolved. Here, we study the role of lateral displacement in pausing
+ and arrest by applying force to individually transcribing molecules. We
+ find that an assisting mechanical force does not alter the
+ translocation rate of the enzyme, but does reduce the efficiency of
+ both pausing and arrest. Moreover, arrested molecules cannot be rescued
+ by force, suggesting that arrest occurs by a bipartite mechanism: the
+ enzyme backtracks along the DNA followed by a conformational change of
+ the ternary complex (RNA polymerase, DNA and transcript), which cannot
+ be reversed mechanically."
+}
+
+@article { freitag97,
+ author = SFreitag #" and "# ILTrong #" and "# LKlumb #" and "# PSStayton #"
+ and "# REStenkamp,
+ title = "Structural studies of the streptavidin binding loop.",
+ year = 1997,
+ month = jun,
+ journal = PS,
+ volume = 6,
+ number = 6,
+ pages = "1157--1166",
+ issn = "0961-8368",
+ doi = "10.1002/pro.5560060604",
+ keywords = "Allosteric Regulation;Bacterial Proteins;Binding
+ Sites;Biotin;Crystallography, X-Ray;Hydrogen Bonding;Ligands;Models,
+ Molecular;Molecular Conformation;Streptavidin;Tryptophan",
+ abstract = "The streptavidin-biotin complex provides the basis for many
+ important biotechnological applications and is an interesting model
+ system for studying high-affinity protein-ligand interactions. We
+ report here crystallographic studies elucidating the conformation of
+ the flexible binding loop of streptavidin (residues 45 to 52) in the
+ unbound and bound forms. The crystal structures of unbound streptavidin
+ have been determined in two monoclinic crystal forms. The binding loop
+ generally adopts an open conformation in the unbound species. In one
+ subunit of one crystal form, the flexible loop adopts the closed
+ conformation and an analysis of packing interactions suggests that
+ protein-protein contacts stabilize the closed loop conformation. In the
+ other crystal form all loops adopt an open conformation. Co-
+ crystallization of streptavidin and biotin resulted in two additional,
+ different crystal forms, with ligand bound in all four binding sites of
+ the first crystal form and biotin bound in only two subunits in a
+ second. The major change associated with binding of biotin is the
+ closure of the surface loop incorporating residues 45 to 52. Residues
+ 49 to 52 display a 3(10) helical conformation in unbound subunits of
+ our structures as opposed to the disordered loops observed in other
+ structure determinations of streptavidin. In addition, the open
+ conformation is stabilized by a beta-sheet hydrogen bond between
+ residues 45 and 52, which cannot occur in the closed conformation. The
+ 3(10) helix is observed in nearly all unbound subunits of both the co-
+ crystallized and ligand-free structures. An analysis of the temperature
+ factors of the binding loop regions suggests that the mobility of the
+ closed loops in the complexed structures is lower than in the open
+ loops of the ligand-free structures. The two biotin bound subunits in
+ the tetramer found in the MONO-b1 crystal form are those that
+ contribute Trp 120 across their respective binding pockets, suggesting
+ a structural link between these binding sites in the tetramer. However,
+ there are no obvious signatures of binding site communication observed
+ upon ligand binding, such as quaternary structure changes or shifts in
+ the region of Trp 120. These studies demonstrate that while
+ crystallographic packing interactions can stabilize both the open and
+ closed forms of the flexible loop, in their absence the loop is open in
+ the unbound state and closed in the presence of biotin. If present in
+ solution, the helical structure in the open loop conformation could
+ moderate the entropic penalty associated with biotin binding by
+ contributing an order-to-disorder component to the loop closure.",
+ note = "\href{http://www.rcsb.org/pdb/explore.do?structureId=1SWE}{PDB ID:
+ 1SWE}, DOI:
+ \href{http://dx.doi.org/10.2210/pdb1swe/pdb}{10.2210/pdb1swe/pdb}."
+}
+
+@article { friddle08,
+ author = RWFriddle #" and "# PPodsiadlo #" and "# ABArtyukhin #" and "#
+ ANoy,
+ title = "Near-Equilibrium Chemical Force Microscopy",
+ year = 2008,
+ journal = TheJournalofPhysicalChemistryC,
+ volume = 112,
+ number = 13,
+ pages = "4986--4990",
+ doi = "10.1021/jp7095967",
+ eprint = "http://pubs.acs.org/doi/pdf/10.1021/jp7095967",
+ url = "http://pubs.acs.org/doi/abs/10.1021/jp7095967"
+}
+
+@article { fujii02,
+ author = TFujii #" and "# YLSun #" and "# KNAn #" and "# ZPLuo,
+ title = "Mechanical properties of single hyaluronan molecules",
+ year = 2002,
+ month = apr,
+ journal = JBiomech,
+ volume = 35,
+ number = 4,
+ pages = "527--531",
+ issn = "0021-9290",
+ keywords = "Biomechanics;Cross-Linking Reagents;Elasticity;Extracellular
+ Matrix;Humans;Hyaluronic Acid;Lasers;Microspheres;Nanotechnology",
+ abstract = "Hyaluronan (HA) is a major component of the extracellular
+ matrix. It plays an important role in the mechanical functions of the
+ extracellular matrix and stabilization of cells. Currently, its
+ mechanical properties have been investigated only at the gross level.
+ In this study, the mechanical properties of single HA molecules were
+ directly measured with an optical tweezer technique, yielding a
+ persistence length of 4.5 +/- 1.2 nm. This information may help us to
+ understand the mechanical roles in the extracellular matrix
+ infrastructure, cell attachment, and to design tissue engineering and
+ drug delivery systems where the mechanical functions of HA are
+ essential."
+}
+
+@article { ganchev08,
+ author = DNGanchev #" and "# NJCobb #" and "# KSurewicz #" and "#
+ WKSurewicz,
+ title = "Nanomechanical properties of human prion protein amyloid as probed
+ by force spectroscopy",
+ year = 2008,
+ month = sep,
+ day = 15,
+ journal = BPJ,
+ volume = 95,
+ number = 6,
+ pages = "2909--2915",
+ issn = "1542-0086",
+ doi = "10.1529/biophysj.108.133108",
+ abstract = "Amyloids are associated with a number of protein misfolding
+ disorders, including prion diseases. In this study, we used single-
+ molecule force spectroscopy to characterize the nanomechanical
+ properties and molecular structure of amyloid fibrils formed by human
+ prion protein PrP90-231. Force-extension curves obtained by specific
+ attachment of a gold-covered atomic force microscope tip to engineered
+ Cys residues could be described by the worm-like chain model for
+ entropic elasticity of a polymer chain, with the size of the N-terminal
+ segment that could be stretched entropically depending on the tip
+ attachment site. The data presented here provide direct information
+ about the forces required to extract an individual monomer from the
+ core of the PrP90-231 amyloid, and indicate that the beta-sheet core of
+ this amyloid starts at residue approximately 164-169. The latter
+ finding has important implications for the ongoing debate regarding the
+ structure of PrP amyloid."
+}
+
+@article { gao03,
+ author = MGao #" and "# DCraig #" and "# OLequin #" and "# ICampbell #" and
+ "# VVogel #" and "# KSchulten,
+ title = "Structure and functional significance of mechanically unfolded
+ fibronectin type {III1} intermediates",
+ year = 2003,
+ journal = PNAS,
+ volume = 100,
+ number = 25,
+ pages = "14784--14789",
+ doi = "10.1073/pnas.2334390100",
+ eprint = "http://www.pnas.org/cgi/reprint/100/25/14784.pdf",
+ url = "http://www.pnas.org/cgi/content/abstract/100/25/14784",
+ abstract = "Fibronectin (FN) forms fibrillar networks coupling cells to the
+ extracellular matrix. The formation of FN fibrils, fibrillogenesis, is
+ a tightly regulated process involving the exposure of cryptic binding
+ sites in individual FN type III (FN-III) repeats presumably exposed by
+ mechanical tension. The FN-III1 module has been previously proposed to
+ contain such cryptic sites that promote the assembly of extracellular
+ matrix FN fibrils. We have combined NMR and steered molecular dynamics
+ simulations to study the structure and mechanical unfolding pathway of
+ FN-III1. This study finds that FN-III1 consists of a {beta}-sandwich
+ structure that unfolds to a mechanically stable intermediate about four
+ times the length of the native folded state. Considering previous
+ experimental findings, our studies provide a structural model by which
+ mechanical stretching of FN-III1 may induce fibrillogenesis through
+ this partially unfolded intermediate."
+}
+
+@article { gavrilov01,
+ author = LAGavrilov #" and "# NSGavrilova,
+ title = "The reliability theory of aging and longevity",
+ year = 2001,
+ month = dec,
+ day = 21,
+ journal = JTheorBiol,
+ volume = 213,
+ number = 4,
+ pages = "527--545",
+ issn = "0022-5193",
+ doi = "10.1006/jtbi.2001.2430",
+ keywords = "Adult;Aged;Aging;Animals;Humans;Longevity;Middle Aged;Models,
+ Biological;Survival Rate;Systems Theory",
+ abstract = "Reliability theory is a general theory about systems failure.
+ It allows researchers to predict the age-related failure kinetics for a
+ system of given architecture (reliability structure) and given
+ reliability of its components. Reliability theory predicts that even
+ those systems that are entirely composed of non-aging elements (with a
+ constant failure rate) will nevertheless deteriorate (fail more often)
+ with age, if these systems are redundant in irreplaceable elements.
+ Aging, therefore, is a direct consequence of systems redundancy.
+ Reliability theory also predicts the late-life mortality deceleration
+ with subsequent leveling-off, as well as the late-life mortality
+ plateaus, as an inevitable consequence of redundancy exhaustion at
+ extreme old ages. The theory explains why mortality rates increase
+ exponentially with age (the Gompertz law) in many species, by taking
+ into account the initial flaws (defects) in newly formed systems. It
+ also explains why organisms ``prefer'' to die according to the Gompertz
+ law, while technical devices usually fail according to the Weibull
+ (power) law. Theoretical conditions are specified when organisms die
+ according to the Weibull law: organisms should be relatively free of
+ initial flaws and defects. The theory makes it possible to find a
+ general failure law applicable to all adult and extreme old ages, where
+ the Gompertz and the Weibull laws are just special cases of this more
+ general failure law. The theory explains why relative differences in
+ mortality rates of compared populations (within a given species) vanish
+ with age, and mortality convergence is observed due to the exhaustion
+ of initial differences in redundancy levels. Overall, reliability
+ theory has an amazing predictive and explanatory power with a few, very
+ general and realistic assumptions. Therefore, reliability theory seems
+ to be a promising approach for developing a comprehensive theory of
+ aging and longevity integrating mathematical methods with specific
+ biological knowledge.",
+ note = "An example of exponential (standard) Gomperz law."
+}
+
+@article { gergely00,
+ author = CGergely #" and "# JCVoegel #" and "# PSchaaf #" and "# BSenger #"
+ and "# MMaaloum #" and "# JHorber #" and "# JHemmerle,
+ title = "Unbinding process of adsorbed proteins under external stress
+ studied by atomic force microscopy spectroscopy",
+ year = 2000,
+ journal = PNAS,
+ volume = 97,
+ number = 20,
+ pages = "10802--10807",
+ doi = "10.1073/pnas.180293097",
+ eprint = "http://www.pnas.org/cgi/reprint/97/20/10802.pdf",
+ url = "http://www.pnas.org/cgi/content/abstract/97/20/10802"
+}
+
+@article { gompertz25,
+ author = BGompertz,
+ title = "On the Nature of the Function Expressive of the Law of Human
+ Mortality, and on a New Mode of Determining the Value of Life
+ Contingencies",
+ year = 1825,
+ journal = PhilosophicalTransactionsoftheRoyalSocietyofLondon,
+ volume = 115,
+ number = "",
+ pages = "513--583",
+ issn = 02610523,
+ publisher = TheRoyalSociety,
+ copyright = "Copyright \copy\ 1825 The Royal Society",
+ url = "http://www.jstor.org/stable/107756",
+ abstract = "",
+ jstor_articletype = "primary_article",
+ jstor_formatteddate = 1825,
+ jstor_issuetitle = ""
+}
+
+@article { granzier97,
+ author = HGranzierX #" and "# MKellermayer #" and "# MHelmes #" and "#
+ KTrombitas,
+ title = "Titin elasticity and mechanism of passive force development in rat
+ cardiac myocytes probed by thin-filament extraction",
+ year = 1997,
+ month = oct,
+ journal = BPJ,
+ volume = 73,
+ number = 4,
+ pages = "2043--2053",
+ issn = "0006-3495",
+ doi = "10.1016/S0006-3495(97)78234-1",
+ url = "http://www.cell.com/biophysj/retrieve/pii/S0006349597782341",
+ keywords = "Amino Acid Sequence;Animals;Biomechanics;Biophysical
+ Phenomena;Biophysics;Cell Fractionation;Elasticity;Gelsolin;Microscopy,
+ Immunoelectron;Models, Cardiovascular;Molecular Structure;Muscle
+ Proteins;Myocardial Contraction;Myocardium;Protein
+ Kinases;Rats;Sarcomeres",
+ abstract = "Titin (also known as connectin) is a giant filamentous protein
+ whose elastic properties greatly contribute to the passive force in
+ muscle. In the sarcomere, the elastic I-band segment of titin may
+ interact with the thin filaments, possibly affecting the molecule's
+ elastic behavior. Indeed, several studies have indicated that
+ interactions between titin and actin occur in vitro and may occur in
+ the sarcomere as well. To explore the properties of titin alone, one
+ must first eliminate the modulating effect of the thin filaments by
+ selectively removing them. In the present work, thin filaments were
+ selectively removed from the cardiac myocyte by using a gelsolin
+ fragment. Partial extraction left behind approximately 100-nm-long thin
+ filaments protruding from the Z-line, whereas the rest of the I-band
+ became devoid of thin filaments, exposing titin. By applying a much
+ more extensive gelsolin treatment, we also removed the remaining short
+ thin filaments near the Z-line. After extraction, the extensibility of
+ titin was studied by using immunoelectron microscopy, and the passive
+ force-sarcomere length relation was determined by using mechanical
+ techniques. Titin's regional extensibility was not detectably affected
+ by partial thin-filament extraction. Passive force, on the other hand,
+ was reduced at sarcomere lengths longer than approximately 2.1 microm,
+ with a 33 +/- 9\% reduction at 2.6 microm. After a complete extraction,
+ the slack sarcomere length was reduced to approximately 1.7 microm. The
+ segment of titin near the Z-line, which is otherwise inextensible,
+ collapsed toward the Z-line in sarcomeres shorter than approximately
+ 2.0 microm, but it was extended in sarcomeres longer than approximately
+ 2.3 microm. Passive force became elevated at sarcomere lengths between
+ approximately 1.7 and approximately 2.1 microm, but was reduced at
+ sarcomere lengths of >2.3 microm. These changes can be accounted for by
+ modeling titin as two wormlike chains in series, one of which increases
+ its contour length by recruitment of the titin segment near the Z-line
+ into the elastic pool."
+}
+
+@article { grossman05,
+ author = CGrossman #" and "# AStout,
+ title = "Optical Tweezers Advanced Lab",
+ year = 2005,
+ season = "Fall",
+ numpages = 12,
+ eprint = "http://chirality.swarthmore.edu/PHYS81/OpticalTweezers.pdf",
+ note = "Fairly complete overdamped PSD derivation in section 4.3., cites
+ \citet{tlusty98} and \citet{bechhoefer02} for further details. However,
+ Tlusty (listed as reference 8) doesn't contain the thermal response
+ fn.\ derivation it was cited for. Also, the single sided PSD definition
+ credited to reference 9 (listed as Bechhoefer) looks more like Press
+ (listed as reference 10). I imagine Grossman and Stout mixed up their
+ references, and meant to refer to \citet{bechhoefer02} and
+ \citet{press92} respectively instead.",
+ project = "Cantilever Calibration"
+}
+
+@article { halvorsen09,
+ author = KHalvorsen #" and "# WPWong,
+ title = "Massively parallel single-molecule manipulation using centrifugal
+ force",
+ year = 2009,
+ journal = arXiv,
+ url = "http://arxiv.org/abs/0912.5370",
+ abstract = {Precise manipulation of single molecules has already led to
+ remarkable insights in physics, chemistry, biology and medicine.
+ However, widespread adoption of single-molecule techniques has been
+ impeded by equipment cost and the laborious nature of making
+ measurements one molecule at a time. We have solved these issues with a
+ new approach: massively parallel single-molecule force measurements
+ using centrifugal force. This approach is realized in a novel
+ instrument that we call the Centrifuge Force Microscope (CFM), in which
+ objects in an orbiting sample are subjected to a calibration-free,
+ macroscopically uniform force-field while their micro-to-nanoscopic
+ motions are observed. We demonstrate high-throughput single-molecule
+ force spectroscopy with this technique by performing thousands of
+ rupture experiments in parallel, characterizing force-dependent
+ unbinding kinetics of an antibody-antigen pair in minutes rather than
+ days. Additionally, we verify the force accuracy of the instrument by
+ measuring the well-established DNA overstretching transition at 66
+ $\pm$ 3 pN. With significant benefits in efficiency, cost, simplicity,
+ and versatility, "single-molecule centrifugation" has the potential to
+ revolutionize single-molecule experimentation, and open access to a
+ wider range of researchers and experimental systems.}
+}
+
+@article { hanggi90,
+ author = PHanggi #" and "# PTalkner #" and "# MBorkovec,
+ title = "Reaction-rate theory: fifty years after {K}ramers",
+ year = 1990,
+ month = "Apr",
+ journal = RMP,
+ volume = 62,
+ number = 2,
+ pages = "251--341",
+ numpages = 90,
+ publisher = APS,
+ doi = "10.1103/RevModPhys.62.251",
+ eprint = "http://www.physik.uni-augsburg.de/theo1/hanggi/Papers/112.pdf",
+ url = "http://prola.aps.org/abstract/RMP/v62/i2/p251_1",
+ note = "\emph{The} Kramers' theory review article. See pages 268--279 for
+ the Kramers-specific introduction.",
+ project = "sawtooth simulation"
+}
+
+@article { hatfield99,
+ author = JWHatfield #" and "# SRQuake,
+ title = "Dynamic Properties of an Extended Polymer in Solution",
+ year = 1999,
+ month = "Apr",
+ journal = PRL,
+ volume = 82,
+ number = 17,
+ pages = "3548--3551",
+ numpages = 3,
+ publisher = APS,
+ doi = "10.1103/PhysRevLett.82.3548",
+ url = "http://link.aps.org/abstract/PRL/v82/p3548",
+ note = "Defines WLC and FJC models, citing textbooks.",
+ project = "sawtooth simulation"
+}
+
+@article { heymann00,
+ author = BHeymann #" and "# HGrubmuller,
+ title = "Dynamic force spectroscopy of molecular adhesion bonds",
+ year = 2000,
+ month = jun,
+ day = 26,
+ journal = PhysRevLett,
+ volume = 84,
+ number = "26 Pt 1",
+ pages = "6126--6129",
+ issn = "0031-9007",
+ doi = "10.1103/PhysRevLett.84.6126",
+ eprint = "http://prola.aps.org/pdf/PRL/v84/i26/p6126_1",
+ url = "http://prola.aps.org/abstract/PRL/v84/p6126",
+ abstract = "Recent advances in atomic force microscopy, biomembrane force
+ probe experiments, and optical tweezers allow one to measure the
+ response of single molecules to mechanical stress with high precision.
+ Such experiments, due to limited spatial resolution, typically access
+ only one single force value in a continuous force profile that
+ characterizes the molecular response along a reaction coordinate. We
+ develop a theory that allows one to reconstruct force profiles from
+ force spectra obtained from measurements at varying loading rates,
+ without requiring increased resolution. We show that spectra obtained
+ from measurements with different spring constants contain complementary
+ information."
+}
+
+@article { hummer01,
+ author = GHummer #" and "# ASzabo,
+ title = "From the Cover: Free energy reconstruction from nonequilibrium
+ single-molecule pulling experiments",
+ year = 2001,
+ journal = PNAS,
+ volume = 98,
+ number = 7,
+ pages = "3658--3661",
+ doi = "10.1073/pnas.071034098",
+ eprint = "http://www.pnas.org/cgi/reprint/98/7/3658.pdf",
+ url = "http://www.pnas.org/cgi/content/abstract/98/7/3658",
+ note = "READ"
+}
+
+@article { hummer03,
+ author = GHummer #" and "# ASzabo,
+ title = "Kinetics from nonequilibrium single-molecule pulling experiments",
+ year = 2003,
+ month = jul,
+ journal = BPJ,
+ volume = 85,
+ number = 1,
+ pages = "5--15",
+ issn = "0006-3495",
+ eprint = "http://www.biophysj.org/cgi/reprint/85/1/5.pdf",
+ url = "http://www.biophysj.org/cgi/content/abstract/85/1/5",
+ keywords = "Computer Simulation; Crystallography; Energy Transfer;
+ Kinetics; Lasers; Micromanipulation; Microscopy, Atomic Force; Models,
+ Molecular; Molecular Conformation; Motion; Muscle Proteins;
+ Nanotechnology; Physical Stimulation; Protein Conformation; Protein
+ Denaturation; Protein Folding; Protein Kinases; Stress, Mechanical",
+ abstract = "Mechanical forces exerted by laser tweezers or atomic force
+ microscopes can be used to drive rare transitions in single molecules,
+ such as unfolding of a protein or dissociation of a ligand. The
+ phenomenological description of pulling experiments based on Bell's
+ expression for the force-induced rupture rate is found to be inadequate
+ when tested against computer simulations of a simple microscopic model
+ of the dynamics. We introduce a new approach of comparable complexity
+ to extract more accurate kinetic information about the molecular events
+ from pulling experiments. Our procedure is based on the analysis of a
+ simple stochastic model of pulling with a harmonic spring and
+ encompasses the phenomenological approach, reducing to it in the
+ appropriate limit. Our approach is tested against computer simulations
+ of a multimodule titin model with anharmonic linkers and then an
+ illustrative application is made to the forced unfolding of I27
+ subunits of the protein titin. Our procedure to extract kinetic
+ information from pulling experiments is simple to implement and should
+ prove useful in the analysis of experiments on a variety of systems.",
+ note = "READ",
+ project = "sawtooth simulation"
+}
+
+@article { hutter05,
+ author = JHutter,
+ title = "Comment on tilt of atomic force microscope cantilevers: effect on
+ spring constant and adhesion measurements.",
+ year = 2005,
+ month = mar,
+ day = 15,
+ journal = LANG,
+ volume = 21,
+ number = 6,
+ pages = "2630--2632",
+ issn = "0743-7463",
+ doi = "10.1021/la047670t",
+ note = "Tilted cantilever corrections (not needed? see Ohler/VEECO note)",
+ project = "Cantilever Calibration"
+}
+
+@article { hutter93,
+ author = JHutter #" and "# JBechhoefer,
+ title = "Calibration of atomic-force microscope tips",
+ collaboration = "",
+ year = 1993,
+ journal = RSI,
+ volume = 64,
+ number = 7,
+ pages = "1868--1873",
+ publisher = AIP,
+ doi = "10.1063/1.1143970",
+ url = "http://link.aip.org/link/?RSI/64/1868/1",
+ keywords = "ATOMIC FORCE MICROSCOPY; CALIBRATION; QUALITY FACTOR; PROBES;
+ RESONANCE; SILICON NITRIDES; MICA; VAN DER WAALS FORCES",
+ note = "Original equipartition-based calibration method (thermal
+ calibration).",
+ project = "Cantilever Calibration"
+}
+
+@article { hyeon03,
+ author = CHyeon #" and "# DThirumalai,
+ title = "Can energy landscape roughness of proteins and {RNA} be measured
+ by using mechanical unfolding experiments?",
+ year = 2003,
+ month = sep,
+ day = 02,
+ journal = PNAS,
+ volume = 100,
+ number = 18,
+ pages = "10249--10253",
+ issn = "0027-8424",
+ doi = "10.1073/pnas.1833310100",
+ eprint = "http://www.pnas.org/cgi/reprint/100/18/10249.pdf",
+ url = "http://www.pnas.org/cgi/content/abstract/100/18/10249",
+ keywords = "Protein Folding; Proteins; RNA; Temperature; Thermodynamics",
+ abstract = "By considering temperature effects on the mechanical unfolding
+ rates of proteins and RNA, whose energy landscape is rugged, the
+ question posed in the title is answered in the affirmative. Adopting a
+ theory by Zwanzig [Zwanzig, R. (1988) Proc. Natl. Acad. Sci. USA 85,
+ 2029-2030], we show that, because of roughness characterized by an
+ energy scale epsilon, the unfolding rate at constant force is retarded.
+ Similarly, in nonequilibrium experiments done at constant loading
+ rates, the most probable unfolding force increases because of energy
+ landscape roughness. The effects are dramatic at low temperatures. Our
+ analysis suggests that, by using temperature as a variable in
+ mechanical unfolding experiments of proteins and RNA, the ruggedness
+ energy scale epsilon, can be directly measured.",
+ note = "Derives the major theory behind my thesis. The Kramers rate
+ equation is \citet{hanggi90} Eq.~4.56c (page 275).",
+ project = "Energy Landscape Roughness"
+}
+
+@article { improta96,
+ author = SImprota #" and "# ASPolitou #" and "# APastore,
+ title = "Immunoglobulin-like modules from titin {I}-band: extensible
+ components of muscle elasticity.",
+ year = 1996,
+ month = mar,
+ day = 15,
+ journal = STR,
+ volume = 4,
+ number = 3,
+ pages = "323--337",
+ issn = "0969-2126",
+ doi = "10.1016/S0969-2126(96)00036-6",
+ keywords = "Amino Acid Sequence;Immunoglobulins;Magnetic Resonance
+ Spectroscopy;Models, Molecular;Molecular Sequence Data;Molecular
+ Structure;Muscle Proteins;Protein Kinases;Protein Structure,
+ Secondary;Protein Structure, Tertiary;Sequence Alignment",
+ abstract = "BACKGROUND. The giant muscle protein titin forms a filament
+ which spans half of the sarcomere and performs, along its length, quite
+ diverse functions. The region of titin located in the sarcomere I-band
+ is believed to play a major role in extensibility and passive
+ elasticity of muscle. In the I-band, the titin sequence consists mostly
+ of repetitive motifs of tandem immunoglobulin-like (Ig) modules
+ intercalated by a potentially non-globular region. The highly
+ repetitive titin architecture suggests that the molecular basis of its
+ mechanical properties be approached through the characterization of the
+ isolated components of the I-band and their interfaces. In the present
+ paper, we report on the structure determination in solution of a
+ representative Ig module from the I-band (I27) as solved by NMR
+ techniques. RESULTS. The structure of I27 consists of a beta sandwich
+ formed by two four-stranded sheets (named ABED and A'GFC). This fold
+ belongs to the intermediate frame (I frame) of the immunoglobulin
+ superfamily. Comparison of I27 with another titin module from the
+ region located in the M-line (M5) shows that two loops (between the B
+ and C and the F and G strands) are shorter in I27, conferring a less
+ elongated appearance to this structure. Such a feature is specific to
+ the Ig domains in the I-band and might therefore be related to the
+ functions of the protein in this region. The structure of tandem Ig
+ domains as modeled from I27 suggests the presence of hinge regions
+ connecting contiguous modules. CONCLUSIONS. We suggest that titin Ig
+ domains in the I-band function as extensible components of muscle
+ elasticity by stretching the hinge regions.",
+ note = "\href{http://www.rcsb.org/pdb/explore.do?structureId=1TIT}{PDB ID:
+ 1TIT}, DOI:
+ \href{http://dx.doi.org/10.2210/pdb1tit/pdb}{10.2210/pdb1tit/pdb}."
+}
+
+@article { irback05,
+ author = AIrback #" and "# SMitternacht #" and "# SMohanty,
+ title = "Dissecting the mechanical unfolding of ubiquitin",
+ year = 2005,
+ journal = PNAS,
+ volume = 102,
+ number = 38,
+ pages = "13427--13432",
+ doi = "10.1073/pnas.0501581102",
+ eprint = "http://www.pnas.org/cgi/reprint/102/38/13427.pdf",
+ url = "http://www.pnas.org/cgi/content/abstract/102/38/13427",
+ abstract = "The unfolding behavior of ubiquitin under the influence of a
+ stretching force recently was investigated experimentally by single-
+ molecule constant-force methods. Many observed unfolding traces had a
+ simple two-state character, whereas others showed clear evidence of
+ intermediate states. Here, we use Monte Carlo simulations to
+ investigate the force-induced unfolding of ubiquitin at the atomic
+ level. In agreement with experimental data, we find that the unfolding
+ process can occur either in a single step or through intermediate
+ states. In addition to this randomness, we find that many quantities,
+ such as the frequency of occurrence of intermediates, show a clear
+ systematic dependence on the strength of the applied force. Despite
+ this diversity, one common feature can be identified in the simulated
+ unfolding events, which is the order in which the secondary-structure
+ elements break. This order is the same in two- and three-state events
+ and at the different forces studied. The observed order remains to be
+ verified experimentally but appears physically reasonable."
+}
+
+@article { izrailev97,
+ author = SIzrailev #" and "# SStepaniants #" and "# MBalsera #" and "#
+ YOono #" and "# KSchultenX,
+ title = "Molecular dynamics study of unbinding of the avidin-biotin
+ complex",
+ year = 1997,
+ month = apr,
+ journal = BPJ,
+ volume = 72,
+ number = 4,
+ pages = "1568--1581",
+ issn = "0006-3495",
+ eprint = "http://www.biophysj.org/cgi/reprint/72/4/1568.pdf",
+ url = "http://www.biophysj.org/cgi/content/abstract/72/4/1568",
+ keywords = "Avidin;Binding Sites;Biotin;Computer Simulation;Hydrogen
+ Bonding;Mathematics;Microscopy, Atomic Force;Microspheres;Models,
+ Molecular;Molecular Structure;Protein Binding;Protein
+ Conformation;Protein Folding;Sepharose",
+ abstract = "We report molecular dynamics simulations that induce, over
+ periods of 40-500 ps, the unbinding of biotin from avidin by means of
+ external harmonic forces with force constants close to those of AFM
+ cantilevers. The applied forces are sufficiently large to reduce the
+ overall binding energy enough to yield unbinding within the measurement
+ time. Our study complements earlier work on biotin-streptavidin that
+ employed a much larger harmonic force constant. The simulations reveal
+ a variety of unbinding pathways, the role of key residues contributing
+ to adhesion as well as the spatial range over which avidin binds
+ biotin. In contrast to the previous studies, the calculated rupture
+ forces exceed by far those observed. We demonstrate, in the framework
+ of models expressed in terms of one-dimensional Langevin equations with
+ a schematic binding potential, the associated Smoluchowski equations,
+ and the theory of first passage times, that picosecond to nanosecond
+ simulation of ligand unbinding requires such strong forces that the
+ resulting protein-ligand motion proceeds far from the thermally
+ activated regime of millisecond AFM experiments, and that simulated
+ unbinding cannot be readily extrapolated to the experimentally observed
+ rupture."
+}
+
+@article { janshoff00,
+ author = AJanshoff #" and "# MNeitzert #" and "# YOberdorfer #" and "#
+ HFuchs,
+ title = "Force Spectroscopy of Molecular Systems-Single Molecule
+ Spectroscopy of Polymers and Biomolecules.",
+ year = 2000,
+ month = sep,
+ day = 15,
+ journal = ACIEE,
+ volume = 39,
+ number = 18,
+ pages = "3212--3237",
+ issn = "1521-3773",
+ doi = "10.1002/1521-3773(20000915)39:18<3212::AID-ANIE3212>3.0.CO;2-X",
+ eprint = "",
+ url = "http://dx.doi.org/10.1002/1521-3773(20000915)39:18<3212::AID-
+ ANIE3212>3.0.CO;2-X",
+ abstract = "How do molecules interact with each other? What happens if a
+ neurotransmitter binds to a ligand-operated ion channel? How do
+ antibodies recognize their antigens? Molecular recognition events play
+ a pivotal role in nature: in enzymatic catalysis and during the
+ replication and transcription of the genome; it is also important for
+ the cohesion of cellular structures and in numerous metabolic reactions
+ that molecules interact with each other in a specific manner.
+ Conventional methods such as calorimetry provide very precise values of
+ binding enthalpies; these are, however, average values obtained from a
+ large ensemble of molecules without knowledge of the dynamics of the
+ molecular recognition event. Which forces occur when a single molecular
+ couple meets and forms a bond? Since the development of the scanning
+ force microscope and force spectroscopy a couple of years ago, tools
+ have now become available for measuring the forces between interfaces
+ with high precision-starting from colloidal forces to the interaction
+ of single molecules. The manipulation of individual molecules using
+ force spectroscopy is also possible. In this way, the mechanical
+ properties on a molecular scale are measurable. The study of single
+ molecules is not an exclusive domain of force spectroscopy; it can also
+ be performed with a surface force apparatus, laser tweezers, or the
+ micropipette technique. Regardless of these techniques, force
+ spectroscopy has been proven as an extraordinary versatile tool. The
+ intention of this review article is to present a critical evaluation of
+ the actual development of static force spectroscopy. The article mainly
+ focuses on experiments dealing with inter- and intramolecular forces-
+ starting with ``simple'' electrostatic forces, then ligand-receptor
+ systems, and finally the stretching of individual molecules."
+}
+
+@article { jollymore09,
+ author = AJollymore #" and "# HClaireLethiasandPeng,
+ title = "Nanomechanical properties of tenascin-{X} revealed by single-
+ molecule force spectroscopy",
+ year = 2009,
+ month = jan,
+ day = 30,
+ journal = JMB,
+ volume = 385,
+ number = 4,
+ pages = "1277--1286",
+ issn = "1089-8638",
+ doi = "10.1016/j.jmb.2008.11.038",
+ url = "http://dx.doi.org/10.1016/j.jmb.2008.11.038",
+ keywords = "Animals;Biomechanics;Cattle;Fibronectins;Kinetics;Microscopy,
+ Atomic Force;Protein Folding;Protein Structure, Tertiary;Spectrum
+ Analysis;Tenascin",
+ abstract = "Tenascin-X is an extracellular matrix protein and binds a
+ variety of molecules in extracellular matrix and on cell membrane.
+ Tenascin-X plays important roles in regulating the structure and
+ mechanical properties of connective tissues. Using single-molecule
+ atomic force microscopy, we have investigated the mechanical properties
+ of bovine tenascin-X in detail. Our results indicated that tenascin-X
+ is an elastic protein and the fibronectin type III (FnIII) domains can
+ unfold under a stretching force and refold to regain their mechanical
+ stability upon the removal of the stretching force. All the 30 FnIII
+ domains of tenascin-X show similar mechanical stability, mechanical
+ unfolding kinetics, and contour length increment upon domain unfolding,
+ despite their large sequence diversity. In contrast to the homogeneity
+ in their mechanical unfolding behaviors, FnIII domains fold at
+ different rates. Using the 10th FnIII domain of tenascin-X (TNXfn10) as
+ a model system, we constructed a polyprotein chimera composed of
+ alternating TNXfn10 and GB1 domains and used atomic force microscopy to
+ confirm that the mechanical properties of TNXfn10 are consistent with
+ those of the FnIII domains of tenascin-X. These results lay the
+ foundation to further study the mechanical properties of individual
+ FnIII domains and establish the relationship between point mutations
+ and mechanical phenotypic effect on tenascin-X. Moreover, our results
+ provided the opportunity to compare the mechanical properties and
+ design of different forms of tenascins. The comparison between
+ tenascin-X and tenascin-C revealed interesting common as well as
+ distinguishing features for mechanical unfolding and folding of
+ tenascin-C and tenascin-X and will open up new avenues to investigate
+ the mechanical functions and architectural design of different forms of
+ tenascins."
+}
+
+@article { jones05,
+ author = REJones #" and "# DPHart,
+ title = "Force interactions between substrates and {SPM} cantilevers
+ immersed in fluids",
+ year = 2005,
+ journal = TribologyInternational,
+ volume = 38,
+ number = 3,
+ pages = "355--361",
+ issn = "0301-679X",
+ doi = "DOI: 10.1016/j.triboint.2004.08.016",
+ url = "http://www.sciencedirect.com/science/article/B6V57-4DN9K7J-1/2/fef91
+ ac022594c2c6a701376d83ecd31",
+ keywords = "AFM;Liquid;Hydrodynamic;Lubrication",
+ abstract = "With the availability of equipment used in Scanning Probe
+ Microscopy (SPM), researchers have been able to probe the local fluid-
+ substrate force interactions with resolutions of pN using a variety of
+ SPM cantilevers. When using such methods, it is essential to
+ differentiate between contributions to the net force on the cantilever.
+ Specifically, the interaction between the cantilever, substrate and
+ fluid, quantified while generating force curves, are discussed and
+ compared with theoretical models for squeeze-film effects and drag on
+ the SPM cantilevers. In addition we have demonstrated a simple method
+ for utilizing the system as a micro-viscometer, independently measuring
+ the viscosity of the lubricant for each test."
+}
+
+@article { juckett93,
+ author = DAJuckett #" and "# BRosenberg,
+ title = "Comparison of the {G}ompertz and {W}eibull functions as
+ descriptors for human mortality distributions and their intersections",
+ year = 1993,
+ month = jun,
+ journal = MechAgeingDev,
+ volume = 69,
+ number = "1--2",
+ pages = "1--31",
+ issn = "0047-6374",
+ doi = "10.1016/0047-6374(93)90068-3",
+ keywords = "Adolescent;Adult;Aged;Aged, 80 and
+ over;Aging;Biometry;Child;Child, Preschool;Data Interpretation,
+ Statistical;Female;Humans;Infant;Infant, Newborn;Longitudinal
+ Studies;Male;Middle Aged;Models, Biological;Models,
+ Statistical;Mortality",
+ abstract = "The Gompertz and Weibull functions are compared with respect to
+ goodness-of-fit to human mortality distributions; ability to describe
+ mortality curve intersections; and, parameter interpretation. The
+ Gompertz function is shown to be a better descriptor for 'all-causes'
+ of deaths and combined disease categories while the Weibull function is
+ shown to be a better descriptor of purer, single causes-of-death. A
+ modified form of the Weibull function maps directly to the inherent
+ degrees of freedom of human mortality distributions while the Gompertz
+ function does not. Intersections in the old-age tails of mortality are
+ explored in the context of both functions and, in particular, the
+ relationship between distribution intersections, and the Gompertz
+ ln[R0] versus alpha regression is examined. Evidence is also presented
+ that mortality intersections are fundamental to the survivorship form
+ and not the rate (hazard) form. Finally, comparisons are made to the
+ parameter estimates in recent longitudinal Gompertzian analyses and the
+ probable errors in those analyses are discussed.",
+ note = "Nice table of various functions associated with Gompertz and
+ Weibull models."
+}
+
+@article { kaplan58,
+ author = ELKaplan #" and "# PMeier,
+ title = "Nonparametric Estimation from Incomplete Observations",
+ year = 1958,
+ month = "jun",
+ journal = JournaloftheAmericanStatisticalAssociation,
+ volume = 53,
+ number = 282,
+ pages = "457--481",
+ issn = 01621459,
+ publisher = AmericanStatisticalAssociation,
+ copyright = "Copyright \copy\ 1958 American Statistical Association",
+ url = "http://www.jstor.org/stable/2281868",
+ abstract = ""
+}
+
+@article { kellermayer03,
+ author = MSZKellermayer #" and "# CBustamante #" and "# HLGranzierX,
+ title = "Mechanics and structure of titin oligomers explored with atomic
+ force microscopy",
+ year = 2003,
+ journal = BiochimicaetBiophysicaActaBBA-Bioenergetics,
+ volume = 1604,
+ number = 2,
+ pages = "105--114",
+ issn = "0005-2728",
+ doi = "10.1016/S0005-2728(03)00029-X",
+ url = "http://dx.doi.org/10.1016/S0005-2728(03)00029-X",
+ keywords = "Titin;Wormlike chain;Unfolding;Elasticity;AFM;Molecular force
+ spectroscopy",
+ abstract = "Titin is a giant polypeptide that spans half of the striated
+ muscle sarcomere and generates passive force upon stretch. To explore
+ the elastic response and structure of single molecules and oligomers of
+ titin, we carried out molecular force spectroscopy and atomic force
+ microscopy (AFM) on purified full-length skeletal-muscle titin. From
+ the force data, apparent persistence lengths as long as ~1.5 nm were
+ obtained for the single, unfolded titin molecule. Furthermore, data
+ suggest that titin molecules may globally associate into oligomers
+ which mechanically behave as independent wormlike chains (WLCs).
+ Consistent with this, AFM of surface-adsorbed titin molecules revealed
+ the presence of oligomers. Although oligomers may form globally via
+ head-to-head association of titin, the constituent molecules otherwise
+ appear independent from each other along their contour. Based on the
+ global association but local independence of titin molecules, we
+ discuss a mechanical model of the sarcomere in which titin molecules
+ with different contour lengths, corresponding to different isoforms,
+ are held in a lattice. The net force response of aligned titin
+ molecules is determined by the persistence length of the tandemly
+ arranged, different WLC components of the individual molecules, the
+ ratio of their overall contour lengths, and by domain unfolding events.
+ Biased domain unfolding in mechanically selected constituent molecules
+ may serve as a compensatory mechanism for contour- and persistence-
+ length differences. Variation in the ratio and contour length of the
+ component chains may provide mechanisms for the fine-tuning of the
+ sarcomeric passive force response.",
+ note = ""
+}
+
+@article { kellermayer97,
+ author = MSKellermayer #" and "# SBSmith #" and "# HLGranzier #" and "#
+ CBustamante,
+ title = "Folding-unfolding transitions in single titin molecules
+ characterized with laser tweezers",
+ year = 1997,
+ month = may,
+ day = 16,
+ journal = SCI,
+ volume = 276,
+ number = 5315,
+ pages = "1112--1116",
+ issn = "0036-8075",
+ keywords = "Amino Acid
+ Sequence;Elasticity;Entropy;Immunoglobulins;Lasers;Models,
+ Chemical;Muscle Contraction;Muscle Proteins;Muscle Relaxation;Muscle,
+ Skeletal;Protein Denaturation;Protein Folding;Protein Kinases;Stress,
+ Mechanical",
+ abstract = "Titin, a giant filamentous polypeptide, is believed to play a
+ fundamental role in maintaining sarcomeric structural integrity and
+ developing what is known as passive force in muscle. Measurements of
+ the force required to stretch a single molecule revealed that titin
+ behaves as a highly nonlinear entropic spring. The molecule unfolds in
+ a high-force transition beginning at 20 to 30 piconewtons and refolds
+ in a low-force transition at approximately 2.5 piconewtons. A fraction
+ of the molecule (5 to 40 percent) remains permanently unfolded,
+ behaving as a wormlike chain with a persistence length (a measure of
+ the chain's bending rigidity) of 20 angstroms. Force hysteresis arises
+ from a difference between the unfolding and refolding kinetics of the
+ molecule relative to the stretch and release rates in the experiments,
+ respectively. Scaling the molecular data up to sarcomeric dimensions
+ reproduced many features of the passive force versus extension curve of
+ muscle fibers."
+}
+
+@article { king10,
+ author = WKing #" and "# MSu #" and "# GYang,
+ title = "{M}onte {C}arlo simulation of mechanical unfolding of proteins
+ based on a simple two-state model",
+ year = 2010,
+ journal = IJBMM,
+ volume = 46,
+ number = 2,
+ pages = "159--166",
+ issn = "0141-8130",
+ doi = "10.1016/j.ijbiomac.2009.12.001",
+ url = "http://www.sciencedirect.com/science/article/B6T7J-
+ 4XWMND2-1/2/7ef768562b4157fc201d450553e5de5e",
+ keywords = "Atomic force microscopy;Mechanical unfolding;Monte Carlo
+ simulation;Worm-like chain;Single molecule methods",
+ abstract = "Single molecule methods are becoming routine biophysical
+ techniques for studying biological macromolecules. In mechanical
+ unfolding of proteins, an externally applied force is used to induce
+ the unfolding of individual protein molecules. Such experiments have
+ revealed novel information that has significantly enhanced our
+ understanding of the function and folding mechanisms of several types
+ of proteins. To obtain information on the unfolding kinetics and the
+ free energy landscape of the protein molecule from mechanical unfolding
+ data, a Monte Carlo simulation based on a simple two-state kinetic
+ model is often used. In this paper, we provide a detailed description
+ of the procedure to perform such simulations and discuss the
+ approximations and assumptions involved. We show that the appearance of
+ the force versus extension curves from mechanical unfolding of proteins
+ is affected by a variety of experimental parameters, such as the length
+ of the protein polymer and the force constant of the cantilever. We
+ also analyze the errors associated with different methods of data
+ pooling and present a quantitative measure of how well the simulation
+ results fit experimental data. These findings will be helpful in
+ experimental design, artifact identification, and data analysis for
+ single molecule studies of various proteins using the mechanical
+ unfolding method."
+}
+
+@article { kleiner07,
+ author = AKleiner #" and "# EShakhnovich,
+ title = "The mechanical unfolding of ubiquitin through all-atom Monte Carlo
+ simulation with a Go-type potential",
+ year = 2007,
+ month = mar,
+ day = 15,
+ journal = BPJ,
+ volume = 92,
+ number = 6,
+ pages = "2054--2061",
+ issn = "0006-3495",
+ doi = "10.1529/biophysj.106.081257",
+ eprint = "http://www.biophysj.org/cgi/reprint/92/6/2054",
+ url = "http://www.biophysj.org/cgi/content/full/92/6/2054",
+ keywords = "Computer Simulation; Models, Chemical; Models, Molecular;
+ Models, Statistical; Monte Carlo Method; Motion; Protein Conformation;
+ Protein Denaturation; Protein Folding; Ubiquitin",
+ abstract = "The mechanical unfolding of proteins under a stretching force
+ has an important role in living systems and is a logical extension of
+ the more general protein folding problem. Recent advances in
+ experimental methodology have allowed the stretching of single
+ molecules, thus rendering this process ripe for computational study. We
+ use all-atom Monte Carlo simulation with a G?-type potential to study
+ the mechanical unfolding pathway of ubiquitin. A detailed, robust,
+ well-defined pathway is found, confirming existing results in this vein
+ though using a different model. Additionally, we identify the protein's
+ fundamental stabilizing secondary structure interactions in the
+ presence of a stretching force and show that this fundamental
+ stabilizing role does not persist in the absence of mechanical stress.
+ The apparent success of simulation methods in studying ubiquitin's
+ mechanical unfolding pathway indicates their potential usefulness for
+ future study of the stretching of other proteins and the relationship
+ between protein structure and the response to mechanical deformation."
+}
+
+@article { klimov00,
+ author = DKlimov #" and "# DThirumalai,
+ title = "Native topology determines force-induced unfolding pathways in
+ globular proteins",
+ year = 2000,
+ month = jun,
+ day = 20,
+ journal = PNAS,
+ volume = 97,
+ number = 13,
+ pages = "7254--7259",
+ issn = "0027-8424",
+ doi = "10.1073/pnas.97.13.7254",
+ eprint = "http://www.pnas.org/cgi/reprint/97/13/7254.pdf",
+ url = "http://www.pnas.org/cgi/content/abstract/97/13/7254",
+ keywords = "Animals; Humans; Protein Folding; Proteins; Spectrin",
+ abstract = "Single-molecule manipulation techniques reveal that stretching
+ unravels individually folded domains in the muscle protein titin and
+ the extracellular matrix protein tenascin. These elastic proteins
+ contain tandem repeats of folded domains with beta-sandwich
+ architecture. Herein, we propose by stretching two model sequences (S1
+ and S2) with four-stranded beta-barrel topology that unfolding forces
+ and pathways in folded domains can be predicted by using only the
+ structure of the native state. Thermal refolding of S1 and S2 in the
+ absence of force proceeds in an all-or-none fashion. In contrast, phase
+ diagrams in the force-temperature (f,T) plane and steered Langevin
+ dynamics studies of these sequences, which differ in the native
+ registry of the strands, show that S1 unfolds in an allor-none fashion,
+ whereas unfolding of S2 occurs via an obligatory intermediate. Force-
+ induced unfolding is determined by the native topology. After proving
+ that the simulation results for S1 and S2 can be calculated by using
+ native topology alone, we predict the order of unfolding events in Ig
+ domain (Ig27) and two fibronectin III type domains ((9)FnIII and
+ (10)FnIII). The calculated unfolding pathways for these proteins, the
+ location of the transition states, and the pulling speed dependence of
+ the unfolding forces reflect the differences in the way the strands are
+ arranged in the native states. We also predict the mechanisms of force-
+ induced unfolding of the coiled-coil spectrin (a three-helix bundle
+ protein) for all 20 structures deposited in the Protein Data Bank. Our
+ approach suggests a natural way to measure the phase diagram in the
+ (f,C) plane, where C is the concentration of denaturants.",
+ note = "Simulated unfolding timescales for Ig27-like S1 and S2 domains"
+}
+
+@article { klimov99,
+ author = DKlimov #" and "# DThirumalai,
+ title = "Stretching single-domain proteins: phase diagram and kinetics of
+ force-induced unfolding",
+ year = 1999,
+ month = may,
+ day = 25,
+ journal = PNAS,
+ volume = 96,
+ number = 11,
+ pages = "6166--6170",
+ issn = "0027-8424",
+ keywords = "Amino Acid Sequence;Kinetics;Models, Chemical;Protein
+ Denaturation;Protein Folding;Proteins;Thermodynamics;Time Factors",
+ abstract = "Single-molecule force spectroscopy reveals unfolding of domains
+ in titin on stretching. We provide a theoretical framework for these
+ experiments by computing the phase diagrams for force-induced unfolding
+ of single-domain proteins using lattice models. The results show that
+ two-state folders (at zero force) unravel cooperatively, whereas
+ stretching of non-two-state folders occurs through intermediates. The
+ stretching rates of individual molecules show great variations
+ reflecting the heterogeneity of force-induced unfolding pathways. The
+ approach to the stretched state occurs in a stepwise ``quantized''
+ manner. Unfolding dynamics and forces required to stretch proteins
+ depend sensitively on topology. The unfolding rates increase
+ exponentially with force f till an optimum value, which is determined
+ by the barrier to unfolding when f = 0. A mapping of these results to
+ proteins shows qualitative agreement with force-induced unfolding of
+ Ig-like domains in titin. We show that single-molecule force
+ spectroscopy can be used to map the folding free energy landscape of
+ proteins in the absence of denaturants."
+}
+
+@article { kosztin06,
+ author = IKosztin #" and "# BBarz #" and "# LJanosi,
+ title = "Calculating potentials of mean force and diffusion coefficients
+ from nonequilibrium processes without Jarzynski's equality",
+ year = 2006,
+ month = feb,
+ day = 10,
+ journal = JChemPhys,
+ volume = 124,
+ pages = 064106,
+ issn = "0031-9007",
+ doi = "10.1063/1.2166379",
+ url = "http://link.aip.org/link/?JCPSA6/124/064106/1"
+}
+
+@article { kramers40,
+ author = HAKramers,
+ title = "Brownian motion in a field of force and the diffusion model of
+ chemical reactions",
+ year = 1940,
+ month = apr,
+ journal = Physica,
+ volume = 7,
+ number = 4,
+ pages = "284--304",
+ issn = "0031-8914",
+ doi = "10.1016/S0031-8914(40)90098-2",
+ url = "http://dx.doi.org/10.1016/S0031-8914(40)90098-2",
+ abstract = "A particle which is caught in a potential hole and which,
+ through the shuttling action of Brownian motion, can escape over a
+ potential barrier yields a suitable model for elucidating the
+ applicability of the transition state method for calculating the rate
+ of chemical reactions.",
+ note = "Seminal paper on thermally activated barrier crossings."
+}
+
+@article { krammer99,
+ author = AKrammerX #" and "# HLuX #" and "# BIsralewitz #" and "#
+ KSchultenX #" and "# VVogelX,
+ title = "Forced unfolding of the fibronectin type {III} module reveals a
+ tensile molecular recognition switch",
+ year = 1999,
+ month = feb,
+ day = 16,
+ journal = PNAS,
+ volume = 96,
+ number = 4,
+ pages = "1351--1356",
+ issn = "0027-8424",
+ keywords = "Amino Acid Sequence;Binding Sites;Computer
+ Simulation;Crystallography, X-Ray;Disulfides;Fibronectins;Hydrogen
+ Bonding;Integrins;Models, Molecular;Oligopeptides;Protein
+ Conformation;Protein Denaturation;Protein Folding;Protein Structure,
+ Secondary;Protein Structure, Tertiary;Software;Tensile Strength",
+ abstract = "The 10th type III module of fibronectin possesses a beta-
+ sandwich structure consisting of seven beta-strands (A-G) that are
+ arranged in two antiparallel sheets. It mediates cell adhesion to
+ surfaces via its integrin binding motif, Arg78, Gly79, and Asp80 (RGD),
+ which is placed at the apex of the loop connecting beta-strands F and
+ G. Steered molecular dynamics simulations in which tension is applied
+ to the protein's terminal ends reveal that the beta-strand G is the
+ first to break away from the module on forced unfolding whereas the
+ remaining fold maintains its structural integrity. The separation of
+ strand G from the remaining fold results in a gradual shortening of the
+ distance between the apex of the RGD-containing loop and the module
+ surface, which potentially reduces the loop's accessibility to surface-
+ bound integrins. The shortening is followed by a straightening of the
+ RGD-loop from a tight beta-turn into a linear conformation, which
+ suggests a further decrease of affinity and selectivity to integrins.
+ The RGD-loop therefore is located strategically to undergo strong
+ conformational changes in the early stretching stages of the module and
+ thus constitutes a mechanosensitive control of ligand recognition."
+}
+
+@article { kreuzer01,
+ author = HJKreuzerX #" and "# SHPayneX,
+ title = "Stretching a macromolecule in an atomic force microscope:
+ statistical mechanical analysis",
+ year = 2001,
+ month = feb,
+ day = 23,
+ journal = PhysRevEStatNonlinSoftMatterPhys,
+ volume = 63,
+ number = "2 Pt 1",
+ pages = 021906,
+ issn = "1539-3755",
+ eprint = "http://www.biophysj.org/cgi/reprint/80/6/2505.pdf",
+ url = "http://www.biophysj.org/cgi/content/abstract/80/6/2505",
+ keywords = "Biophysics;Macromolecular Substances;Microscopy, Atomic
+ Force;Models, Statistical;Models, Theoretical;Statistics as Topic",
+ abstract = "We formulate the proper statistical mechanics to describe the
+ stretching of a macromolecule under a force provided by the cantilever
+ of an atomic force microscope. In the limit of a soft cantilever the
+ generalized ensemble of the coupled molecule/cantilever system reduces
+ to the Gibbs ensemble for an isolated molecule subject to a constant
+ force in which the extension is fluctuating. For a stiff cantilever we
+ obtain the Helmholtz ensemble for an isolated molecule held at a fixed
+ extension with the force fluctuating. Numerical examples are given for
+ poly (ethylene glycol) chains."
+}
+
+@article { kroy07,
+ author = KKroy #" and "# JGlaser,
+ title = "The glassy wormlike chain",
+ year = 2007,
+ journal = NewJournalofPhysics,
+ volume = 9,
+ number = 11,
+ pages = 416,
+ doi = "10.1088/1367-2630/9/11/416",
+ eprint = "http://www.iop.org/EJ/article/1367-2630/9/11/416/njp7_11_416.pdf",
+ url = "http://stacks.iop.org/1367-2630/9/416",
+ abstract = "We introduce a new model for the dynamics of a wormlike chain
+ (WLC) in an environment that gives rise to a rough free energy
+ landscape, which we name the glassy WLC. It is obtained from the common
+ WLC by an exponential stretching of the relaxation spectrum of its
+ long-wavelength eigenmodes, controlled by a single parameter
+ \\boldsymbol{\\cal E} . Predictions for pertinent observables such as
+ the dynamic structure factor and the microrheological susceptibility
+ exhibit the characteristics of soft glassy rheology and compare
+ favourably with experimental data for reconstituted cytoskeletal
+ networks and live cells. We speculate about the possible microscopic
+ origin of the stretching, implications for the nonlinear rheology, and
+ the potential physiological significance of our results.",
+ note = "Has short section on WLC relaxation time in the weakly bending
+ limit."
+}
+
+@article { labeit03,
+ author = DLabeit #" and "# KWatanabe #" and "# CWitt #" and "# HFujita #"
+ and "# YWu #" and "# SLahmers #" and "# TFunck #" and "# SLabeit #" and
+ "# HGranzier,
+ title = "Calcium-dependent molecular spring elements in the giant protein
+ titin",
+ year = 2003,
+ journal = PNAS,
+ volume = 100,
+ number = 23,
+ pages = "13716--13721",
+ doi = "10.1073/pnas.2235652100",
+ eprint = "http://www.pnas.org/cgi/reprint/100/23/13716.pdf",
+ url = "http://www.pnas.org/cgi/content/abstract/100/23/13716",
+ abstract = "Titin (also known as connectin) is a giant protein with a wide
+ range of cellular functions, including providing muscle cells with
+ elasticity. Its physiological extension is largely derived from the
+ PEVK segment, rich in proline (P), glutamate (E), valine (V), and
+ lysine (K) residues. We studied recombinant PEVK molecules containing
+ the two conserved elements: {approx}28-residue PEVK repeats and E-rich
+ motifs. Single molecule experiments revealed that calcium-induced
+ conformational changes reduce the bending rigidity of the PEVK
+ fragments, and site-directed mutagenesis identified four glutamate
+ residues in the E-rich motif that was studied (exon 129), as critical
+ for this process. Experiments with muscle fibers showed that titin-
+ based tension is calcium responsive. We propose that the PEVK segment
+ contains E-rich motifs that render titin a calcium-dependent molecular
+ spring that adapts to the physiological state of the cell."
+}
+
+@article { law03,
+ author = RLaw #" and "# GLiao #" and "# SHarper #" and "# GYang #" and "#
+ DSpeicher #" and "# DDischer,
+ title = "Pathway shifts and thermal softening in temperature-coupled forced
+ unfolding of spectrin domains",
+ year = 2003,
+ month = nov,
+ journal = BPJ,
+ volume = 85,
+ number = 5,
+ pages = "3286--3293",
+ issn = "0006-3495",
+ keywords = "Circular Dichroism;Elasticity;Heat;Microscopy, Atomic
+ Force;Physical Stimulation;Protein Conformation;Protein
+ Denaturation;Protein Folding;Protein Structure,
+ Tertiary;Spectrin;Stress, Mechanical;Temperature",
+ abstract = "Pathways of unfolding a protein depend in principle on the
+ perturbation-whether it is temperature, denaturant, or even forced
+ extension. Widely-shared, helical-bundle spectrin repeats are known to
+ melt at temperatures as low as 40-45 degrees C and are also known to
+ unfold via multiple pathways as single molecules in atomic force
+ microscopy. Given the varied roles of spectrin family proteins in cell
+ deformability, we sought to determine the coupled effects of
+ temperature on forced unfolding. Bimodal distributions of unfolding
+ intervals are seen at all temperatures for the four-repeat beta(1-4)
+ spectrin-an alpha-actinin homolog. The major unfolding length
+ corresponds to unfolding of a single repeat, and a minor peak at twice
+ the length corresponds to tandem repeats. Increasing temperature shows
+ fewer tandem events but has no effect on unfolding intervals. As T
+ approaches T(m), however, mean unfolding forces in atomic force
+ microscopy also decrease; and circular dichroism studies demonstrate a
+ nearly proportional decrease of helical content in solution. The
+ results imply a thermal softening of a helical linker between repeats
+ which otherwise propagates a helix-to-coil transition to adjacent
+ repeats. In sum, structural changes with temperature correlate with
+ both single-molecule unfolding forces and shifts in unfolding
+ pathways."
+}
+
+@article { levinthal68,
+ author = CLevinthal,
+ title = "Are there pathways for protein folding?",
+ year = 1968,
+ journal = JCPPCB,
+ volume = 65,
+ number = 1,
+ pages = "44--45",
+ eprint =
+ "http://www.biochem.wisc.edu/courses/biochem704/Reading/Levinthal1968.p
+ df",
+ note = "\emph{Not} Levinthal's paradox."
+}
+
+@inproceedings { levinthal69,
+ editor = PDebrunner #" and "# JCMTsibris #" and "# EMunck,
+ author = CLevinthal,
+ title = "How to Fold Graciously.",
+ booktitle = "Mossbauer Spectroscopy in Biological Systems",
+ year = 1969,
+ pages = "22--24",
+ publisher = UniversityofIllinoisPressUrbana,
+ address = "Allerton House, Monticello, IL",
+ url = "http://www-miller.ch.cam.ac.uk/levinthal/levinthal.html"
+}
+
+@article { levy02,
+ author = RLevy #" and "# MMaaloum,
+ title = "Measuring the spring constant of atomic force microscope
+ cantilevers: thermal fluctuations and other methods",
+ year = 2002,
+ journal = NANOTECH,
+ volume = 13,
+ number = 1,
+ pages = "33--37",
+ doi = "10.1088/0957-4484/13/1/307",
+ url = "http://stacks.iop.org/0957-4484/13/33",
+ abstract = "Knowledge of the interaction forces between surfaces gained
+ using an atomic force microscope (AFM) is crucial in a variety of
+ industrial and scientific applications and necessitates a precise
+ knowledge of the cantilever spring constant. Many methods have been
+ devised to experimentally determine the spring constants of AFM
+ cantilevers. The thermal fluctuation method is elegant but requires a
+ theoretical model of the bending modes. For a rectangular cantilever,
+ this model is available (Butt and Jaschke). Detailed thermal
+ fluctuation measurements of a series of AFM cantilever beams have been
+ performed in order to test the validity and accuracy of the recent
+ theoretical models. The spring constant of rectangular cantilevers can
+ also be determined easily with the method of Sader and White. We found
+ very good agreement between the two methods. In the case of the
+ V-shaped cantilever, we have shown that the thermal fluctuation method
+ is a valid and accurate approach to the evaluation of the spring
+ constant. A comparison between this method and those of Sader-
+ Neumeister and of Ducker has been established. In some cases, we found
+ disagreement between these two methods; the effect of non-conservation
+ of material properties over all cantilevers from a single chip is
+ qualitatively invoked.",
+ note = "Good review of thermal calibration to 2002, but not much on the
+ derviation of the Lorentzian fit.",
+ project = "Cantilever Calibration"
+}
+
+@article { li00,
+ author = HLi #" and "# AOberhauser #" and "# SFowler #" and "# JClarke #"
+ and "# JFernandez,
+ title = "Atomic force microscopy reveals the mechanical design of a modular
+ protein",
+ year = 2000,
+ journal = PNAS,
+ volume = 97,
+ number = 12,
+ pages = "6527--6531",
+ doi = "10.1073/pnas.120048697",
+ eprint = "http://www.pnas.org/cgi/reprint/97/12/6527.pdf",
+ url = "http://www.pnas.org/cgi/content/abstract/97/12/6527",
+ abstract = "",
+ note = "Unfolding order not from protein-surface interactions. Mechanical
+ unfolding of a chain of interleaved domains $ABABAB\ldots$ yielded a
+ run of $A$ unfoldings followed by a run of $B$ unfoldings."
+}
+
+@article { li01,
+ author = HLi #" and "# AOberhauser #" and "# SRedick #" and "#
+ MCarrionVazquez #" and "# HErickson #" and "# JFernandez,
+ title = "Multiple conformations of {PEVK} proteins detected by single-
+ molecule techniques",
+ year = 2001,
+ journal = PNAS,
+ volume = 98,
+ number = 19,
+ pages = "10682--10686",
+ doi = "10.1073/pnas.191189098",
+ eprint = "http://www.pnas.org/cgi/reprint/98/19/10682.pdf",
+ url = "http://www.pnas.org/cgi/content/abstract/98/19/10682",
+ abstract = "An important component of muscle elasticity is the PEVK region
+ of titin, so named because of the preponderance of these amino acids.
+ However, the PEVK region, similar to other elastomeric proteins, is
+ thought to form a random coil and therefore its structure cannot be
+ determined by standard techniques. Here we combine single-molecule
+ electron microscopy and atomic force microscopy to examine the
+ conformations of the human cardiac titin PEVK region. In contrast to a
+ simple random coil, we have found that cardiac PEVK shows a wide range
+ of elastic conformations with end-to-end distances ranging from 9 to 24
+ nm and persistence lengths from 0.4 to 2.5 nm. Individual PEVK
+ molecules retained their distinctive elastic conformations through many
+ stretch-relaxation cycles, consistent with the view that these PEVK
+ conformers cannot be interconverted by force. The multiple elastic
+ conformations of cardiac PEVK may result from varying degrees of
+ proline isomerization. The single-molecule techniques demonstrated here
+ may help elucidate the conformation of other proteins that lack a well-
+ defined structure."
+}
+
+@article { li03,
+ author = HLi #" and "# JFernandez,
+ title = "Mechanical design of the first proximal Ig domain of human cardiac
+ titin revealed by single molecule force spectroscopy",
+ year = 2003,
+ month = nov,
+ day = 14,
+ journal = JMB,
+ volume = 334,
+ number = 1,
+ pages = "75--86",
+ issn = "0022-2836",
+ doi = "10.1016/j.jmb.2003.09.036",
+ keywords = "Amino Acid Sequence;Disulfides;Humans;Immunoglobulins;Models,
+ Molecular;Molecular Sequence Data;Muscle Proteins;Myocardium;Protein
+ Denaturation;Protein Engineering;Protein Kinases;Protein Structure,
+ Tertiary;Spectrum Analysis",
+ abstract = "The elastic I-band part of muscle protein titin contains two
+ tandem immunoglobulin (Ig) domain regions of distinct mechanical
+ properties. Until recently, the only known structure was that of the
+ I27 module of the distal region, whose mechanical properties have been
+ reported in detail. Recently, the structure of the first proximal
+ domain, I1, has been resolved at 2.1A. In addition to the
+ characteristic beta-sandwich structure of all titin Ig domains, the
+ crystal structure of I1 showed an internal disulfide bridge that was
+ proposed to modulate its mechanical extensibility in vivo. Here, we use
+ single molecule force spectroscopy and protein engineering to examine
+ the mechanical architecture of this domain. In contrast to the
+ predictions made from the X-ray crystal structure, we find that the
+ formation of a disulfide bridge in I1 is a relatively rare event in
+ solution, even under oxidative conditions. Furthermore, our studies of
+ the mechanical stability of I1 modules engineered with point mutations
+ reveal significant differences between the mechanical unfolding of the
+ I1 and I27 modules. Our study illustrates the varying mechanical
+ architectures of the titin Ig modules."
+}
+
+@article { li05,
+ author = LLi #" and "# HHuang #" and "# JMBadilla,
+ title = "Mechanical unfolding intermediates observed by single-molecule
+ force spectroscopy in a fibronectin type {III} module",
+ year = 2005,
+ month = jan,
+ day = 28,
+ journal = JMB,
+ volume = 345,
+ number = 4,
+ pages = "817--826",
+ issn = "0022-2836",
+ doi = "10.1016/j.jmb.2004.11.021",
+ keywords = "Fibronectins;Kinetics;Microscopy, Atomic Force;Models,
+ Molecular;Mutagenesis, Site-Directed;Protein Denaturation;Protein
+ Folding;Protein Structure, Tertiary;Recombinant Fusion Proteins",
+ abstract = "Domain 10 of type III fibronectin (10FNIII) is known to play a
+ pivotal role in the mechanical interactions between cell surface
+ integrins and the extracellular matrix. Recent molecular dynamics
+ simulations have predicted that 10FNIII, when exposed to a stretching
+ force, unfolds along two pathways, each with a distinct, mechanically
+ stable intermediate. Here, we use single-molecule force spectroscopy
+ combined with protein engineering to test these predictions by probing
+ the mechanical unfolding pathway of 10FNIII. Stretching single
+ polyproteins containing the 10FNIII module resulted in sawtooth
+ patterns where 10FNIII was seen unfolding in two consecutive steps. The
+ native state unfolded at 100(+/-20) pN, elongating (10)FNIII by
+ 12(+/-2) nm and reaching a clearly marked intermediate that unfolded at
+ 50(+/-20) pN. Unfolding of the intermediate completed the elongation of
+ the molecule by extending another 19(+/-2) nm. Site-directed
+ mutagenesis of residues in the A and B beta-strands (E9P and L19P)
+ resulted in sawtooth patterns with all-or-none unfolding events that
+ elongated the molecule by 19(+/-2) nm. In contrast, mutating residues
+ in the G beta-strand gave results that were dependent on amino acid
+ position. The mutation I88P in the middle of the G beta-strand resulted
+ in native like unfolding sawtooth patterns showing an intact
+ intermediate state. The mutation Y92P, which is near the end of G beta-
+ strand, produced sawtooth patterns with all-or-none unfolding events
+ that lengthened the molecule by 17(+/-2) nm. These results are
+ consistent with the view that 10FNIII can unfold in two different ways.
+ Along one pathway, the detachment of the A and B beta-strands from the
+ body of the folded module constitute the first unfolding event,
+ followed by the unfolding of the remaining beta-sandwich structure.
+ Along the second pathway, the detachment of the G beta-strands is
+ involved in the first unfolding event. These results are in excellent
+ agreement with the sequence of events predicted by molecular dynamics
+ simulations of the 10FNIII module."
+}
+
+@article { li06,
+ author = MSLi #" and "# CKHu #" and "# DKlimov #" and "# DThirumalai,
+ title = "Multiple stepwise refolding of immunoglobulin domain {I27} upon
+ force quench depends on initial conditions",
+ year = 2006,
+ journal = PNAS,
+ volume = 103,
+ number = 1,
+ pages = "93--98",
+ doi = "10.1073/pnas.0503758103",
+ eprint = "http://www.pnas.org/cgi/reprint/103/1/93.pdf",
+ url = "http://www.pnas.org/cgi/content/abstract/103/1/93",
+ abstract = "Mechanical folding trajectories for polyproteins starting from
+ initially stretched conformations generated by single-molecule atomic
+ force microscopy experiments [Fernandez, J. M. & Li, H. (2004) Science
+ 303, 1674-1678] show that refolding, monitored by the end-to-end
+ distance, occurs in distinct multiple stages. To clarify the molecular
+ nature of folding starting from stretched conformations, we have probed
+ the folding dynamics, upon force quench, for the single I27 domain from
+ the muscle protein titin by using a C{alpha}-Go model. Upon temperature
+ quench, collapse and folding of I27 are synchronous. In contrast,
+ refolding from stretched initial structures not only increases the
+ folding and collapse time scales but also decouples the two kinetic
+ processes. The increase in the folding times is associated primarily
+ with the stretched state to compact random coil transition.
+ Surprisingly, force quench does not alter the nature of the refolding
+ kinetics, but merely increases the height of the free-energy folding
+ barrier. Force quench refolding times scale as f1.gif, where {Delta}xf
+ {approx} 0.6 nm is the location of the average transition state along
+ the reaction coordinate given by end-to-end distance. We predict that
+ {tau}F and the folding mechanism can be dramatically altered by the
+ initial and/or final values of force. The implications of our results
+ for design and analysis of experiments are discussed."
+}
+
+@article { lin91,
+ author = JLin,
+ title = "Divergence measures based on the {S}hannon entropy",
+ year = 1991,
+ month = jan,
+ journal = IEEETransactionsonInformationTheory,
+ volume = 37,
+ number = 1,
+ pages = "145--151",
+ issn = "0018-9448",
+ doi = "10.1109/18.61115",
+ url = "http://ieeexplore.ieee.org/xpl/freeabs_all.jsp?isnumber=2227&arnumbe
+ r=61115&count=35&index=9",
+ keywords = "divergence;dissimilarity measure;discrimintation
+ information;entropy;probability of error bounds",
+ abstract = "A novel class of information-theoretic divergence measures
+ based on the Shannon entropy is introduced. Unlike the well-known
+ Kullback divergences, the new measures do not require the condition of
+ absolute continuity to be satisfied by the probability distributions
+ involved. More importantly, their close relationship with the
+ variational distance and the probability of misclassification error are
+ established in terms of bounds. These bounds are crucial in many
+ applications of divergence measures. The measures are also well
+ characterized by the properties of nonnegativity, finiteness,
+ semiboundedness, and boundedness."
+}
+
+@article { linke08,
+ author = WAAGLinke,
+ title = "Pulling single molecules of titin by {AFM}--recent advances and
+ physiological implications",
+ year = 2008,
+ month = apr,
+ day = 06,
+ journal = PflugersArch,
+ volume = 456,
+ number = 1,
+ pages = "101--115",
+ issn = "0031-6768",
+ doi = "10.1007/s00424-007-0389-x",
+ abstract = "Perturbation of a protein away from its native state by
+ mechanical stress is a physiological process immanent to many cells.
+ The mechanical stability and conformational diversity of proteins under
+ force therefore are important parameters in nature. Molecular-level
+ investigations of ``mechanical proteins'' have enjoyed major
+ breakthroughs over the last decade, a development to which atomic force
+ microscopy (AFM) force spectroscopy has been instrumental. The giant
+ muscle protein titin continues to be a paradigm model in this field. In
+ this paper, we review how single-molecule mechanical measurements of
+ titin using AFM have served to elucidate key aspects of protein
+ unfolding-refolding and mechanisms by which biomolecular elasticity is
+ attained. We outline recent work combining protein engineering and AFM
+ force spectroscopy to establish the mechanical behavior of titin
+ domains using molecular ``fingerprinting.'' Furthermore, we summarize
+ AFM force-extension data demonstrating different mechanical stabilities
+ of distinct molecular-spring elements in titin, compare AFM force-
+ extension to novel force-ramp/force-clamp studies, and elaborate on
+ exciting new results showing that AFM force clamp captures the
+ unfolding and refolding trajectory of single mechanical proteins. Along
+ the way, we discuss the physiological implications of the findings, not
+ least with respect to muscle mechanics. These studies help us
+ understand how proteins respond to forces in cells and how
+ mechanosensing and mechanosignaling events may proceed in vivo."
+}
+
+@article { linke98a,
+ author = WAMRSLinke #" and "# MIvemeyer #" and "# HHosser #" and "# PMundel,
+ title = "Characterizing titin's {I}-band {Ig} domain region as an entropic
+ spring",
+ year = 1998,
+ month = jun,
+ journal = JCS,
+ volume = "111 (Pt 11)",
+ pages = "1567--1574",
+ issn = "0021-9533",
+ doi = "",
+ eprint = "http://jcs.biologists.org/cgi/reprint/111/11/1567",
+ url = "http://jcs.biologists.org/cgi/content/abstract/111/11/1567",
+ keywords = "Animals;Elasticity;Immunoglobulins;Male;Muscle Proteins;Muscle,
+ Skeletal;Protein Kinases;Rats;Rats, Wistar;Structure-Activity
+ Relationship",
+ abstract = "The poly-immunoglobulin domain region of titin, located within
+ the elastic section of this giant muscle protein, determines the
+ extensibility of relaxed myofibrils mainly at shorter physiological
+ lengths. To elucidate this region's contribution to titin elasticity,
+ we measured the elastic properties of the N-terminal I-band Ig region
+ by using immunofluorescence/immunoelectron microscopy and myofibril
+ mechanics and tried to simulate the results with a model of entropic
+ polymer elasticity. Rat psoas myofibrils were stained with titin-
+ specific antibodies flanking the Ig region at the N terminus and C
+ terminus, respectively, to record the extension behaviour of that titin
+ segment. The segment's end-to-end length increased mainly at small
+ stretch, reaching approximately 90\% of the native contour length of
+ the Ig region at a sarcomere length of 2.8 microm. At this extension,
+ the average force per single titin molecule, deduced from the steady-
+ state passive length-tension relation of myofibrils, was approximately
+ 5 or 2.5 pN, depending on whether we assumed a number of 3 or 6 titins
+ per half thick filament. When the force-extension curve constructed for
+ the Ig region was simulated by the wormlike chain model, best fits were
+ obtained for a persistence length, a measure of the chain's bending
+ rigidity, of 21 or 42 nm (for 3 or 6 titins/half thick filament), which
+ correctly reproduced the curve for sarcomere lengths up to 3.4 microm.
+ Systematic deviations between data and fits above that length indicated
+ that forces of >30 pN per titin strand may induce unfolding of Ig
+ modules. We conclude that stretches of at least 5-6 Ig domains, perhaps
+ coinciding with known super repeat patterns of these titin modules in
+ the I-band, may represent the unitary lengths of the wormlike chain.
+ The poly-Ig regions might thus act as compliant entropic springs that
+ determine the minute levels of passive tension at low extensions of a
+ muscle fiber."
+}
+
+@article { linke98b,
+ author = WAMILinke #" and "# PMundel #" and "# MRStockmeier #" and "#
+ BKolmerer,
+ title = "Nature of {PEVK}-titin elasticity in skeletal muscle",
+ year = 1998,
+ month = jul,
+ day = 07,
+ journal = PNAS,
+ volume = 95,
+ number = 14,
+ pages = "8052--8057",
+ issn = "0027-8424",
+ keywords = "Animals;Elasticity;Fluorescent Antibody
+ Technique;Male;Microscopy, Immunoelectron;Muscle Proteins;Muscle,
+ Skeletal;Protein Kinases;Rats;Rats, Wistar;Stress, Mechanical",
+ abstract = "A unique sequence within the giant titin molecule, the PEVK
+ domain, has been suggested to greatly contribute to passive force
+ development of relaxed skeletal muscle during stretch. To explore the
+ nature of PEVK elasticity, we used titin-specific antibodies to stain
+ both ends of the PEVK region in rat psoas myofibrils and determined the
+ region's force-extension relation by combining immunofluorescence and
+ immunoelectron microscopy with isolated myofibril mechanics. We then
+ tried to fit the results with recent models of polymer elasticity. The
+ PEVK segment elongated substantially at sarcomere lengths above 2.4
+ micro(m) and reached its estimated contour length at approximately 3.5
+ micro(m). In immunofluorescently labeled sarcomeres stretched and
+ released repeatedly above 3 micro(m), reversible PEVK lengthening could
+ be readily visualized. At extensions near the contour length, the
+ average force per titin molecule was calculated to be approximately 45
+ pN. Attempts to fit the force-extension curve of the PEVK segment with
+ a standard wormlike chain model of entropic elasticity were successful
+ only for low to moderate extensions. In contrast, the experimental data
+ also could be correctly fitted at high extensions with a modified
+ wormlike chain model that incorporates enthalpic elasticity. Enthalpic
+ contributions are likely to arise from electrostatic stiffening, as
+ evidenced by the ionic-strength dependency of titin-based myofibril
+ stiffness; at high stretch, hydrophobic effects also might become
+ relevant. Thus, at physiological muscle lengths, the PEVK region does
+ not function as a pure entropic spring. Rather, PEVK elasticity may
+ have both entropic and enthalpic origins characterizable by a polymer
+ persistence length and a stretch modulus."
+}
+
+@article { liu03,
+ author = WLiu #" and "# VMontana #" and "# EChapman #" and "# UMohideen #"
+ and "# VParpura,
+ title = "Botulinum toxin type {B} micromechanosensor",
+ year = 2003,
+ journal = PNAS,
+ volume = 100,
+ number = 23,
+ pages = "13621--13625",
+ doi = "10.1073/pnas.2233819100",
+ eprint = "http://www.pnas.org/cgi/reprint/100/23/13621.pdf",
+ url = "http://www.pnas.org/cgi/content/abstract/100/23/13621",
+ abstract = "Botulinum neurotoxin (BoNT) types A, B, E, and F are toxic to
+ humans; early and rapid detection is essential for adequate medical
+ treatment. Presently available tests for detection of BoNTs, although
+ sensitive, require hours to days. We report a BoNT-B sensor whose
+ properties allow detection of BoNT-B within minutes. The technique
+ relies on the detection of an agarose bead detachment from the tip of a
+ micromachined cantilever resulting from BoNT-B action on its
+ substratum, the synaptic protein synaptobrevin 2, attached to the
+ beads. The mechanical resonance frequency of the cantilever is
+ monitored for the detection. To suspend the bead off the cantilever we
+ use synaptobrevin's molecular interaction with another synaptic
+ protein, syntaxin 1A, that was deposited onto the cantilever tip.
+ Additionally, this bead detachment technique is general and can be used
+ in any displacement reaction, such as in receptor-ligand pairs, where
+ the introduction of one chemical leads to the displacement of another.
+ The technique is of broad interest and will find uses outside
+ toxicology."
+}
+
+@article { lois08,
+ author = GLois #" and "# JBlawzdziewicz #" and "# CSOHern,
+ title = "Reliable protein folding on complex energy landscapes: the free
+ energy reaction path",
+ year = 2008,
+ month = sep,
+ day = 15,
+ journal = BPJ,
+ volume = 95,
+ number = 6,
+ pages = "2692--2701",
+ issn = "1542-0086",
+ doi = "10.1529/biophysj.108.133132",
+ abstract = "A theoretical framework is developed to study the dynamics of
+ protein folding. The key insight is that the search for the native
+ protein conformation is influenced by the rate r at which external
+ parameters, such as temperature, chemical denaturant, or pH, are
+ adjusted to induce folding. A theory based on this insight predicts
+ that 1), proteins with complex energy landscapes can fold reliably to
+ their native state; 2), reliable folding can occur as an equilibrium or
+ out-of-equilibrium process; and 3), reliable folding only occurs when
+ the rate r is below a limiting value, which can be calculated from
+ measurements of the free energy. We test these predictions against
+ numerical simulations of model proteins with a single energy scale."
+}
+
+@article { lu00a,
+ author = HLuX #" and "# AKrammerX #" and "# BIsralewitz #" and "# VVogelX
+ #" and "# KSchultenX,
+ title = "Computer modeling of force-induced titin domain unfolding",
+ year = 2000,
+ journal = AdvExpMedBiol,
+ volume = 481,
+ pages = "143--60",
+ issn = "0065-2598",
+ keywords = "Amino Acid Sequence;Animals;Computer
+ Simulation;Elasticity;Fibronectins;Humans;Hydrogen
+ Bonding;Immunoglobulins;Models, Molecular;Muscle Proteins;Muscle,
+ Skeletal;Myofibrils;Protein Conformation;Protein Denaturation;Protein
+ Kinases;Software",
+ abstract = "Titin, a 1 micron long protein found in striated muscle
+ myofibrils, possesses unique elastic and extensibility properties, and
+ is largely composed of a PEVK region and beta-sandwich immunoglobulin
+ (Ig) and fibronectin type III (FnIII) domains. The extensibility
+ behavior of titin has been shown in atomic force microscope and optical
+ tweezer experiments to partially depend on the reversible unfolding of
+ individual Ig and FnIII domains. We performed steered molecular
+ dynamics simulations to stretch single titin Ig domains in solution
+ with pulling speeds of 0.1-1.0 A/ps, and FnIII domains with a pulling
+ speed of 0.5 A/ps. Resulting force-extension profiles exhibit a single
+ dominant peak for each domain unfolding, consistent with the
+ experimentally observed sequential, as opposed to concerted, unfolding
+ of Ig and FnIII domains under external stretching forces. The force
+ peaks can be attributed to an initial burst of a set of backbone
+ hydrogen bonds connected to the domains' terminal beta-strands.
+ Constant force stretching simulations, applying 500-1000 pN of force,
+ were performed on Ig domains. The resulting domain extensions are
+ halted at an initial extension of 10 A until the set of all six
+ hydrogen bonds connecting terminal beta-strands break simultaneously.
+ This behavior is accounted for by a barrier separating folded and
+ unfolded states, the shape of which is consistent with AFM and chemical
+ denaturation data.",
+ note = "discussion in journal on pages 161--2"
+}
+
+@article { lu00b,
+ author = HLuX #" and "# KSchultenX,
+ title = "The key event in force-induced unfolding of Titin's immunoglobulin
+ domains",
+ year = 2000,
+ month = jul,
+ journal = BPJ,
+ volume = 79,
+ number = 1,
+ pages = "51--65",
+ issn = "0006-3495",
+ keywords = "Amino Acid Sequence;Computer Simulation;Double Bind
+ Interaction;Hydrogen Bonding;Immunoglobulins;Microscopy, Atomic
+ Force;Models, Chemical;Models, Molecular;Molecular Sequence Data;Muscle
+ Proteins;Protein Folding;Protein Kinases;Protein Structure,
+ Tertiary;Stress, Mechanical;Water",
+ abstract = "Steered molecular dynamics simulation of force-induced titin
+ immunoglobulin domain I27 unfolding led to the discovery of a
+ significant potential energy barrier at an extension of approximately
+ 14 A on the unfolding pathway that protects the domain against
+ stretching. Previous simulations showed that this barrier is due to the
+ concurrent breaking of six interstrand hydrogen bonds (H-bonds) between
+ beta-strands A' and G that is preceded by the breaking of two to three
+ hydrogen bonds between strands A and B, the latter leading to an
+ unfolding intermediate. The simulation results are supported by
+ Angstrom-resolution atomic force microscopy data. Here we perform a
+ structural and energetic analysis of the H-bonds breaking. It is
+ confirmed that H-bonds between strands A and B break rapidly. However,
+ the breaking of the H-bond between strands A' and G needs to be
+ assisted by fluctuations of water molecules. In nanosecond simulations,
+ water molecules are found to repeatedly interact with the protein
+ backbone atoms, weakening individual interstrand H-bonds until all six
+ A'-G H-bonds break simultaneously under the influence of external
+ stretching forces. Only when those bonds are broken can the generic
+ unfolding take place, which involves hydrophobic interactions of the
+ protein core and exerts weaker resistance against stretching than the
+ key event."
+}
+
+@article { lu98,
+ author = HLuX #" and "# BIsralewitz #" and "# AKrammerX #" and "# VVogelX
+ #" and "# KSchultenX,
+ title = "Unfolding of titin immunoglobulin domains by steered molecular
+ dynamics simulation",
+ year = 1998,
+ month = aug,
+ journal = BPJ,
+ volume = 75,
+ number = 2,
+ pages = "662--671",
+ issn = "0006-3495",
+ doi = "10.1016/S0006-3495(98)77556-3",
+ eprint = "http://download.cell.com/biophysj/pdf/PIIS0006349598775563.pdf",
+ url = "http://www.cell.com/biophysj/abstract/S0006-3495(98)77556-3",
+ keywords = "Amino Acid Sequence;Animals;Computer Simulation;Glutamic
+ Acid;Immunoglobulins;Lysine;Macromolecular Substances;Models,
+ Molecular;Molecular Sequence Data;Muscle
+ Proteins;Myocardium;Proline;Protein Denaturation;Protein
+ Folding;Protein Kinases;Protein Structure, Secondary;Sequence
+ Alignment;Sequence Homology, Amino Acid;Valine",
+ abstract = "Titin, a 1-microm-long protein found in striated muscle
+ myofibrils, possesses unique elastic and extensibility properties in
+ its I-band region, which is largely composed of a PEVK region (70\%
+ proline, glutamic acid, valine, and lysine residue) and seven-strand
+ beta-sandwich immunoglobulin-like (Ig) domains. The behavior of titin
+ as a multistage entropic spring has been shown in atomic force
+ microscope and optical tweezer experiments to partially depend on the
+ reversible unfolding of individual Ig domains. We performed steered
+ molecular dynamics simulations to stretch single titin Ig domains in
+ solution with pulling speeds of 0.5 and 1.0 A/ps. Resulting force-
+ extension profiles exhibit a single dominant peak for each Ig domain
+ unfolding, consistent with the experimentally observed sequential, as
+ opposed to concerted, unfolding of Ig domains under external stretching
+ forces. This force peak can be attributed to an initial burst of
+ backbone hydrogen bonds, which takes place between antiparallel beta-
+ strands A and B and between parallel beta-strands A' and G. Additional
+ features of the simulations, including the position of the force peak
+ and relative unfolding resistance of different Ig domains, can be
+ related to experimental observations."
+}
+
+@article { lu99,
+ author = HLuX #" and "# KSchultenX,
+ title = "Steered molecular dynamics simulations of force-induced protein
+ domain unfolding",
+ year = 1999,
+ month = jun,
+ day = 01,
+ journal = PROT,
+ volume = 35,
+ number = 4,
+ pages = "453--463",
+ issn = "0887-3585",
+ doi = "10.1002/(SICI)1097-0134(19990601)35:4<453::AID-PROT9>3.0.CO;2-M",
+ eprint = "http://www3.interscience.wiley.com/cgi-
+ bin/fulltext/65000328/PDFSTART",
+ url = "http://www3.interscience.wiley.com/journal/65000328/abstract",
+ keywords = "Computer Simulation;Fibronectins;Hydrogen Bonding;Microscopy,
+ Atomic Force;Models, Molecular;Protein Denaturation",
+ abstract = "Steered molecular dynamics (SMD), a computer simulation method
+ for studying force-induced reactions in biopolymers, has been applied
+ to investigate the response of protein domains to stretching apart of
+ their terminal ends. The simulations mimic atomic force microscopy and
+ optical tweezer experiments, but proceed on much shorter time scales.
+ The simulations on different domains for 0.6 nanosecond each reveal two
+ types of protein responses: the first type, arising in certain beta-
+ sandwich domains, exhibits nanosecond unfolding only after a force
+ above 1,500 pN is applied; the second type, arising in a wider class of
+ protein domain structures, requires significantly weaker forces for
+ nanosecond unfolding. In the first case, strong forces are needed to
+ concertedly break a set of interstrand hydrogen bonds which protect the
+ domains against unfolding through stretching; in the second case,
+ stretching breaks backbone hydrogen bonds one by one, and does not
+ require strong forces for this purpose. Stretching of beta-sandwich
+ (immunoglobulin) domains has been investigated further revealing a
+ specific relationship between response to mechanical strain and the
+ architecture of beta-sandwich domains."
+}
+
+@article { makarov01,
+ author = DEMakarov #" and "# PHansma #" and "# HMetiu,
+ title = "Kinetic Monte Carlo simulation of titin unfolding",
+ collaboration = "",
+ year = 2001,
+ journal = JCP,
+ volume = 114,
+ number = 21,
+ pages = "9663--9673",
+ publisher = AIP,
+ doi = "10.1063/1.1369622",
+ eprint = "http://hansmalab.physics.ucsb.edu/pdf/297%20-%20Makarov,%20D.E._J
+ .Chem.Phys._2001.pdf",
+ url = "http://link.aip.org/link/?JCP/114/9663/1",
+ keywords = "proteins; hydrogen bonds; digital simulation; Monte Carlo
+ methods; molecular biophysics; intramolecular mechanics;
+ macromolecules; atomic force microscopy"
+}
+
+@article { marko95,
+ author = JFMarko #" and "# EDSiggia,
+ title = "Stretching {DNA}",
+ affiliation = "",
+ year = 1995,
+ journal = Macromolecules,
+ volume = 28,
+ number = 26,
+ pages = "8759--8770",
+ issn = "0024-9297",
+ eprint = "http://pubs.acs.org/cgi-
+ bin/archive.cgi/mamobx/1995/28/i26/pdf/ma00130a008.pdf",
+ url =
+ "http://pubs3.acs.org/acs/journals/doilookup?in_doi=10.1021/ma00130a008
+ ",
+ abstract = "",
+ note = "Derivation of the Worm-like Chain interpolation function."
+}
+
+@article { marszalek02,
+ author = PMarszalek #" and "# HLi #" and "# AOberhauser #" and "#
+ JFernandez,
+ title = "Chair-boat transitions in single polysaccharide molecules observed
+ with force-ramp {AFM}",
+ year = 2002,
+ journal = PNAS,
+ volume = 99,
+ number = 7,
+ pages = "4278--4283",
+ doi = "10.1073/pnas.072435699",
+ eprint = "http://www.pnas.org/cgi/reprint/99/7/4278.pdf",
+ url = "http://www.pnas.org/cgi/content/abstract/99/7/4278",
+ abstract = "Under a stretching force, the sugar ring of polysaccharide
+ molecules switches from the chair to the boat-like or inverted chair
+ conformation. This conformational change can be observed by stretching
+ single polysaccharide molecules with an atomic force microscope. In
+ those early experiments, the molecules were stretched at a constant
+ rate while the resulting force changed over wide ranges. However,
+ because the rings undergo force-dependent transitions, an experimental
+ arrangement where the force is the free variable introduces an
+ undesirable level of complexity in the results. Here we demonstrate the
+ use of force-ramp atomic force microscopy to capture the conformational
+ changes in single polysaccharide molecules. Force-ramp atomic force
+ microscopy readily captures the ring transitions under conditions where
+ the entropic elasticity of the molecule is separated from its
+ conformational transitions, enabling a quantitative analysis of the
+ data with a simple two-state model. This analysis directly provides the
+ physico-chemical characteristics of the ring transitions such as the
+ width of the energy barrier, the relative energy of the conformers, and
+ their enthalpic elasticity. Our experiments enhance the ability of
+ single-molecule force spectroscopy to make high-resolution measurements
+ of the conformations of single polysaccharide molecules under a
+ stretching force, making an important addition to polysaccharide
+ spectroscopy."
+}
+
+@article { marszalek99,
+ author = PMarszalek #" and "# HLu #" and "# HLi #" and "# MCarrionVazquez
+ #" and "# JMOberhauser,
+ title = "Mechanical unfolding intermediates in titin modules",
+ year = 1999,
+ month = nov,
+ day = 04,
+ journal = NAT,
+ volume = 402,
+ number = 6757,
+ pages = "100--103",
+ issn = "0028-0836",
+ doi = "10.1038/47083",
+ eprint = "http://www.nature.com/nature/journal/v402/n6757/pdf/402100a0.pdf",
+ url = "http://www.nature.com/nature/journal/v402/n6757/abs/402100a0.html",
+ keywords = "Biomechanics;Computer Simulation;Humans;Hydrogen
+ Bonding;Microscopy, Atomic Force;Models, Molecular;Muscle
+ Proteins;Myocardium;Protein Folding;Protein Kinases;Recombinant
+ Proteins",
+ abstract = "The modular protein titin, which is responsible for the passive
+ elasticity of muscle, is subjected to stretching forces. Previous work
+ on the experimental elongation of single titin molecules has suggested
+ that force causes consecutive unfolding of each domain in an all-or-
+ none fashion. To avoid problems associated with the heterogeneity of
+ the modular, naturally occurring titin, we engineered single proteins
+ to have multiple copies of single immunoglobulin domains of human
+ cardiac titin. Here we report the elongation of these molecules using
+ the atomic force microscope. We find an abrupt extension of each domain
+ by approximately 7 A before the first unfolding event. This fast
+ initial extension before a full unfolding event produces a reversible
+ 'unfolding intermediate' Steered molecular dynamics simulations show
+ that the rupture of a pair of hydrogen bonds near the amino terminus of
+ the protein domain causes an extension of about 6 A, which is in good
+ agreement with our observations. Disruption of these hydrogen bonds by
+ site-directed mutagenesis eliminates the unfolding intermediate. The
+ unfolding intermediate extends titin domains by approximately 15\% of
+ their slack length, and is therefore likely to be an important
+ previously unrecognized component of titin elasticity."
+}
+
+@article { mcpherson01,
+ author = JDMcPherson #" and "# MMarra #" and "# LHillier #" and "#
+ RHWaterston #" and "# AChinwalla #" and "# JWallis #" and "# MSekhon #"
+ and "# KWylie #" and "# ERMardis #" and "# RKWilson #" and "# RFulton
+ #" and "# TAKucaba #" and "# CWagner-McPherson #" and "# WBBarbazuk #"
+ and "# SGGregory #" and "# SJHumphray #" and "# LFrench #" and "#
+ RSEvans #" and "# GBethel #" and "# AWhittaker #" and "# JLHolden #"
+ and "# OTMcCann #" and "# ADunham #" and "# CSoderlund #" and "#
+ CEScott #" and "# DRBentley #" and "# GSchuler #" and "# HCChen #" and
+ "# WJang #" and "# EDGreen #" and "# JRIdol #" and "# VVMaduro #" and
+ "# KTMontgomery #" and "# ELee #" and "# AMiller #" and "# SEmerling #"
+ and "# Kucherlapati #" and "# RGibbs #" and "# SScherer #" and "#
+ JHGorrell #" and "# ESodergren #" and "# KClerc-Blankenburg #" and "#
+ PTabor #" and "# SNaylor #" and "# DGarcia #" and "# PJdeJong #" and "#
+ JJCatanese #" and "# NNowak #" and "# KOsoegawa #" and "# SQin #" and
+ "# LRowen #" and "# AMadan #" and "# MDors #" and "# LHood #" and "#
+ BTrask #" and "# CFriedman #" and "# HMassa #" and "# VGCheung #" and
+ "# IRKirsch #" and "# TReid #" and "# RYonescu #" and "# JWeissenbach
+ #" and "# TBruls #" and "# RHeilig #" and "# EBranscomb #" and "#
+ AOlsen #" and "# NDoggett #" and "# JFCheng #" and "# THawkins #" and
+ "# RMMyers #" and "# JShang #" and "# LRamirez #" and "# JSchmutz #"
+ and "# OVelasquez #" and "# KDixon #" and "# NEStone #" and "# DRCox #"
+ and "# DHaussler #" and "# WJKent #" and "# TFurey #" and "# SRogic #"
+ and "# SKennedy #" and "# SJones #" and "# ARosenthal #" and "# GWen #"
+ and "# MSchilhabel #" and "# GGloeckner #" and "# GNyakatura #" and "#
+ RSiebert #" and "# BSchlegelberger #" and "# JKorenberg #" and "#
+ XNChen #" and "# AFujiyama #" and "# MHattori #" and "# AToyoda #" and
+ "# TYada #" and "# HSPark #" and "# YSakaki #" and "# NShimizu #" and
+ "# SAsakawa #" and "# KKawasaki #" and "# TSasaki #" and "# AShintani
+ #" and "# AShimizu #" and "# KShibuya #" and "# JKudoh #" and "#
+ SMinoshima #" and "# JRamser #" and "# PSeranski #" and "# CHoff #" and
+ "# APoustka #" and "# RReinhardt #" and "# HLehrach,
+ title = "A physical map of the human genome.",
+ year = 2001,
+ month = feb,
+ day = 15,
+ journal = NAT,
+ volume = 409,
+ number = 6822,
+ pages = "934--941",
+ issn = "0028-0836",
+ doi = "10.1038/35057157",
+ eprint = "http://www.nature.com/nature/journal/v409/n6822/pdf/409934a0.pdf",
+ url = "http://www.nature.com/nature/journal/v409/n6822/full/409934a0.html",
+ keywords = "Chromosomes, Artificial, Bacterial;Cloning, Molecular;Contig
+ Mapping;DNA Fingerprinting;Gene Duplication;Genome, Human;Humans;In
+ Situ Hybridization, Fluorescence;Repetitive Sequences, Nucleic Acid",
+ abstract = "The human genome is by far the largest genome to be sequenced,
+ and its size and complexity present many challenges for sequence
+ assembly. The International Human Genome Sequencing Consortium
+ constructed a map of the whole genome to enable the selection of clones
+ for sequencing and for the accurate assembly of the genome sequence.
+ Here we report the construction of the whole-genome bacterial
+ artificial chromosome (BAC) map and its integration with previous
+ landmark maps and information from mapping efforts focused on specific
+ chromosomal regions. We also describe the integration of sequence data
+ with the map."
+}
+
+@article { mello04,
+ author = CCMello #" and "# DBarrick,
+ title = "An experimentally determined protein folding energy landscape",
+ year = 2004,
+ month = sep,
+ day = 28,
+ journal = PNAS,
+ volume = 101,
+ number = 39,
+ pages = "14102--14107",
+ issn = "0027-8424",
+ doi = "10.1073/pnas.0403386101",
+ keywords = "Animals; Ankyrin Repeat; Circular Dichroism; Drosophila
+ Proteins; Drosophila melanogaster; Gene Deletion; Models, Chemical;
+ Models, Molecular; Protein Denaturation; Protein Folding; Protein
+ Structure, Tertiary; Spectrometry, Fluorescence; Thermodynamics; Urea",
+ abstract = "Energy landscapes have been used to conceptually describe and
+ model protein folding but have been difficult to measure
+ experimentally, in large part because of the myriad of partly folded
+ protein conformations that cannot be isolated and thermodynamically
+ characterized. Here we experimentally determine a detailed energy
+ landscape for protein folding. We generated a series of overlapping
+ constructs containing subsets of the seven ankyrin repeats of the
+ Drosophila Notch receptor, a protein domain whose linear arrangement of
+ modular structural units can be fragmented without disrupting
+ structure. To a good approximation, stabilities of each construct can
+ be described as a sum of energy terms associated with each repeat. The
+ magnitude of each energy term indicates that each repeat is
+ intrinsically unstable but is strongly stabilized by interactions with
+ its nearest neighbors. These linear energy terms define an equilibrium
+ free energy landscape, which shows an early free energy barrier and
+ suggests preferred low-energy routes for folding."
+}
+
+@article { merkel99,
+ author = RMerkel #" and "# PNassoy #" and "# ALeung #" and "# KRitchie #"
+ and "# EEvans,
+ title = "Energy landscapes of receptor-ligand bonds explored with dynamic
+ force spectroscopy",
+ year = 1999,
+ month = jan,
+ day = 07,
+ journal = NAT,
+ volume = 397,
+ number = 6714,
+ pages = "50--53",
+ issn = "0028-0836",
+ doi = "10.1038/16219",
+ url = "http://www.nature.com/nature/journal/v397/n6714/full/397050a0.html",
+ keywords = "Biotin;Microscopy, Atomic Force;Protein Binding;Streptavidin",
+ abstract = "Atomic force microscopy (AFM) has been used to measure the
+ strength of bonds between biological receptor molecules and their
+ ligands. But for weak noncovalent bonds, a dynamic spectrum of bond
+ strengths is predicted as the loading rate is altered, with the
+ measured strength being governed by the prominent barriers traversed in
+ the energy landscape along the force-driven bond-dissociation pathway.
+ In other words, the pioneering early AFM measurements represent only a
+ single point in a continuous spectrum of bond strengths, because theory
+ predicts that these will depend on the rate at which the load is
+ applied. Here we report the strength spectra for the bonds between
+ streptavidin (or avidin) and biotins-the prototype of receptor-ligand
+ interactions used in earlier AFM studies, and which have been modelled
+ by molecular dynamics. We have probed bond formation over six orders of
+ magnitude in loading rate, and find that the bond survival time
+ diminished from about 1 min to 0.001 s with increasing loading rate
+ over this range. The bond strength, meanwhile, increased from about 5
+ pN to 170 pN. Thus, although they are among the strongest noncovalent
+ linkages in biology (affinity of 10(13) to 10(15) M(-1)), these bonds
+ in fact appear strong or weak depending on how fast they are loaded. We
+ are also able to relate the activation barriers derived from our
+ strength spectra to the shape of the energy landscape derived from
+ simulations of the biotin-avidin complex."
+}
+
+@article { metropolis87,
+ author = NMetropolis,
+ title = "The Beginning of the Monte Carlo Method",
+ year = 1987,
+ journal = LosAlamosScience,
+ volume = 15,
+ pages = "125--130",
+ publisher = LosAlamosNationalLaboratory,
+ url = "http://library.lanl.gov/cgi-bin/getfile?15-12.pdf"
+}
+
+@article { mickler07,
+ author = MMickler #" and "# RDima #" and "# CDietz #" and "# DThirumalai #"
+ and "# MRief,
+ title = "Revealing the bifurcation in the unfolding pathways of {GFP} by
+ using single-molecule experiments and simulations",
+ year = 2007,
+ journal = PNAS,
+ volume = 104,
+ number = 51,
+ pages = "20268--20273",
+ doi = "10.1073/pnas.0705458104",
+ eprint = "http://www.pnas.org/cgi/reprint/104/51/20268.pdf",
+ url = "http://www.pnas.org/cgi/content/abstract/104/51/20268",
+ keywords = "AFM experiments, coarse-grained simulations, cross-link
+ mutants, pathway bifurcation, plasticity of energy landscape",
+ abstract = "Nanomanipulation of biomolecules by using single-molecule
+ methods and computer simulations has made it possible to visualize the
+ energy landscape of biomolecules and the structures that are sampled
+ during the folding process. We use simulations and single-molecule
+ force spectroscopy to map the complex energy landscape of GFP that is
+ used as a marker in cell biology and biotechnology. By engineering
+ internal disulfide bonds at selected positions in the GFP structure,
+ mechanical unfolding routes are precisely controlled, thus allowing us
+ to infer features of the energy landscape of the wild-type GFP. To
+ elucidate the structures of the unfolding pathways and reveal the
+ multiple unfolding routes, the experimental results are complemented
+ with simulations of a self-organized polymer (SOP) model of GFP. The
+ SOP representation of proteins, which is a coarse-grained description
+ of biomolecules, allows us to perform forced-induced simulations at
+ loading rates and time scales that closely match those used in atomic
+ force microscopy experiments. By using the combined approach, we show
+ that forced unfolding of GFP involves a bifurcation in the pathways to
+ the stretched state. After detachment of an N-terminal {alpha}-helix,
+ unfolding proceeds along two distinct pathways. In the dominant
+ pathway, unfolding starts from the detachment of the primary N-terminal
+ -strand, while in the minor pathway rupture of the last, C-terminal
+ -strand initiates the unfolding process. The combined approach has
+ allowed us to map the features of the complex energy landscape of GFP
+ including a characterization of the structures, albeit at a coarse-
+ grained level, of the three metastable intermediates.",
+ note = "Hiccup in unfolding leg corresponds to unfolding intermediate (See
+ Figure 2). The unfolding timescale in GFP is about 6 ms."
+}
+
+@article { nevo03,
+ author = RNevo #" and "# CStroh #" and "# FKienberger #" and "# DKaftan #"
+ and "# VBrumfeld #" and "# MElbaum #" and "# ZReich #" and "#
+ PHinterdorfer,
+ title = "A molecular switch between alternative conformational states in
+ the complex of {Ran} and importin beta1",
+ year = 2003,
+ month = jul,
+ journal = NSB,
+ volume = 10,
+ number = 7,
+ pages = "553--557",
+ issn = "1072-8368",
+ doi = "10.1038/nsb940",
+ eprint = "http://www.nature.com/nsmb/journal/v10/n7/pdf/nsb940.pdf",
+ url = "http://www.nature.com/nsmb/journal/v10/n7/abs/nsb940.html",
+ keywords = "Guanosine Diphosphate; Guanosine Triphosphate; Microscopy,
+ Atomic Force; Protein Binding; Protein Conformation; beta Karyopherins;
+ ran GTP-Binding Protein",
+ abstract = "Several million macromolecules are exchanged each minute
+ between the nucleus and cytoplasm by receptor-mediated transport. Most
+ of this traffic is controlled by the small GTPase Ran, which regulates
+ assembly and disassembly of the receptor-cargo complexes in the
+ appropriate cellular compartment. Here we applied dynamic force
+ spectroscopy to study the interaction of Ran with the nuclear import
+ receptor importin beta1 (impbeta) at the single-molecule level. We
+ found that the complex alternates between two distinct conformational
+ states of different adhesion strength. The application of an external
+ mechanical force shifts equilibrium toward one of these states by
+ decreasing the height of the interstate activation energy barrier. The
+ other state can be stabilized by a functional Ran mutant that increases
+ this barrier. These results support a model whereby functional control
+ of Ran-impbeta is achieved by a population shift between pre-existing
+ alternative conformations."
+}
+
+@article { nevo04,
+ author = RNevo #" and "# VBrumfeld #" and "# MElbaum #" and "#
+ PHinterdorfer #" and "# ZReich,
+ title = "Direct discrimination between models of protein activation by
+ single-molecule force measurements",
+ year = 2004,
+ month = oct,
+ journal = BPJ,
+ volume = 87,
+ number = 4,
+ pages = "2630--2634",
+ issn = "0006-3495",
+ doi = "10.1529/biophysj.104.041889",
+ eprint = "http://www.biophysj.org/cgi/reprint/87/4/2630.pdf",
+ url = "http://www.biophysj.org/cgi/content/abstract/87/4/2630",
+ keywords = "Elasticity; Enzyme Activation; Micromanipulation; Microscopy,
+ Atomic Force; Models, Chemical; Models, Molecular; Multiprotein
+ Complexes; Nuclear Proteins; Physical Stimulation; Protein Binding;
+ Stress, Mechanical; Structure-Activity Relationship; beta Karyopherins;
+ ran GTP-Binding Protein",
+ abstract = "The limitations imposed on the analyses of complex chemical and
+ biological systems by ensemble averaging can be overcome by single-
+ molecule experiments. Here, we used a single-molecule technique to
+ discriminate between two generally accepted mechanisms of a key
+ biological process--the activation of proteins by molecular effectors.
+ The two mechanisms, namely induced-fit and population-shift, are
+ normally difficult to discriminate by ensemble approaches. As a model,
+ we focused on the interaction between the nuclear transport effector,
+ RanBP1, and two related complexes consisting of the nuclear import
+ receptor, importin beta, and the GDP- or GppNHp-bound forms of the
+ small GTPase, Ran. We found that recognition by the effector proceeds
+ through either an induced-fit or a population-shift mechanism,
+ depending on the substrate, and that the two mechanisms can be
+ differentiated by the data."
+}
+
+@article { nevo05,
+ author = RNevo #" and "# VBrumfeld #" and "# RKapon #" and "# PHinterdorfer
+ #" and "# ZReich,
+ title = "Direct measurement of protein energy landscape roughness",
+ year = 2005,
+ month = may,
+ journal = EMBO,
+ volume = 6,
+ number = 5,
+ pages = "482--486",
+ issn = "1469-221X",
+ doi = "10.1038/sj.embor.7400403",
+ eprint = "http://www.nature.com/embor/journal/v6/n5/pdf/7400403.pdf",
+ url = "http://www.nature.com/embor/journal/v6/n5/abs/7400403.html",
+ keywords = "Models, Molecular; Protein Binding; Protein Folding; Spectrum
+ Analysis; Thermodynamics; beta Karyopherins; ran GTP-Binding Protein",
+ abstract = "The energy landscape of proteins is thought to have an
+ intricate, corrugated structure. Such roughness should have important
+ consequences on the folding and binding kinetics of proteins, as well
+ as on their equilibrium fluctuations. So far, no direct measurement of
+ protein energy landscape roughness has been made. Here, we combined a
+ recent theory with single-molecule dynamic force spectroscopy
+ experiments to extract the overall energy scale of roughness epsilon
+ for a complex consisting of the small GTPase Ran and the nuclear
+ transport receptor importin-beta. The results gave epsilon > 5k(B)T,
+ indicating a bumpy energy surface, which is consistent with the ability
+ of importin-beta to accommodate multiple conformations and to interact
+ with different, structurally distinct ligands.",
+ note = "Applies \citet{hyeon03} to ligand-receptor binding.",
+ project = "Energy Landscape Roughness"
+}
+
+@article { ng07,
+ author = SNg #" and "# KBillings #" and "# TOhashi #" and "# MAllen #" and
+ "# RBest #" and "# LRandles #" and "# HErickson #" and "# JClarke,
+ title = "Designing an extracellular matrix protein with enhanced mechanical
+ stability",
+ year = 2007,
+ journal = PNAS,
+ volume = 104,
+ number = 23,
+ pages = "9633--9637",
+ doi = "10.1073/pnas.0609901104",
+ eprint = "http://www.pnas.org/cgi/reprint/104/23/9633.pdf",
+ url = "http://www.pnas.org/cgi/content/abstract/104/23/9633",
+ abstract = "The extracellular matrix proteins tenascin and fibronectin
+ experience significant mechanical forces in vivo. Both contain a number
+ of tandem repeating homologous fibronectin type III (fnIII) domains,
+ and atomic force microscopy experiments have demonstrated that the
+ mechanical strength of these domains can vary significantly. Previous
+ work has shown that mutations in the core of an fnIII domain from human
+ tenascin (TNfn3) reduce the unfolding force of that domain
+ significantly: The composition of the core is apparently crucial to the
+ mechanical stability of these proteins. Based on these results, we have
+ used rational redesign to increase the mechanical stability of the 10th
+ fnIII domain of human fibronectin, FNfn10, which is directly involved
+ in integrin binding. The hydrophobic core of FNfn10 was replaced with
+ that of the homologous, mechanically stronger TNfn3 domain. Despite the
+ extensive substitution, FNoTNc retains both the three-dimensional
+ structure and the cell adhesion activity of FNfn10. Atomic force
+ microscopy experiments reveal that the unfolding forces of the
+ engineered protein FNoTNc increase by {approx}20% to match those of
+ TNfn3. Thus, we have specifically designed a protein with increased
+ mechanical stability. Our results demonstrate that core engineering can
+ be used to change the mechanical strength of proteins while retaining
+ functional surface interactions."
+}
+
+@article { nome07,
+ author = RNome #" and "# JZhao #" and "# WHoff #" and "# NScherer,
+ title = "Axis-dependent anisotropy in protein unfolding from integrated
+ nonequilibrium single-molecule experiments, analysis, and simulation",
+ year = 2007,
+ month = dec,
+ day = 26,
+ journal = PNAS,
+ volume = 104,
+ number = 52,
+ pages = "20799--20804",
+ issn = "1091-6490",
+ doi = "10.1073/pnas.0701281105",
+ eprint = "http://www.pnas.org/cgi/reprint/104/52/20799.pdf",
+ url = "http://www.pnas.org/cgi/content/abstract/104/52/20799",
+ keywords = "Anisotropy; Bacterial Proteins; Biophysics; Computer
+ Simulation; Cysteine; Halorhodospira halophila; Hydrogen Bonding;
+ Kinetics; Luminescent Proteins; Microscopy, Atomic Force; Molecular
+ Conformation; Protein Binding; Protein Conformation; Protein
+ Denaturation; Protein Folding; Protein Structure, Secondary",
+ abstract = "We present a comprehensive study that integrates experimental
+ and theoretical nonequilibrium techniques to map energy landscapes
+ along well defined pull-axis specific coordinates to elucidate
+ mechanisms of protein unfolding. Single-molecule force-extension
+ experiments along two different axes of photoactive yellow protein
+ combined with nonequilibrium statistical mechanical analysis and
+ atomistic simulation reveal energetic and mechanistic anisotropy.
+ Steered molecular dynamics simulations and free-energy curves
+ constructed from the experimental results reveal that unfolding along
+ one axis exhibits a transition-state-like feature where six hydrogen
+ bonds break simultaneously with weak interactions observed during
+ further unfolding. The other axis exhibits a constant (unpeaked) force
+ profile indicative of a noncooperative transition, with enthalpic
+ (e.g., H-bond) interactions being broken throughout the unfolding
+ process. Striking qualitative agreement was found between the force-
+ extension curves derived from steered molecular dynamics calculations
+ and the equilibrium free-energy curves obtained by JarzynskiHummerSzabo
+ analysis of the nonequilibrium work data. The anisotropy persists
+ beyond pulling distances of more than twice the initial dimensions of
+ the folded protein, indicating a rich energy landscape to the
+ mechanically fully unfolded state. Our findings challenge the notion
+ that cooperative unfolding is a universal feature in protein
+ stability."
+}
+
+@book { noy08,
+ editor = ANoy,
+ title = "Handbook of Molecular Force Spectroscopy",
+ year = 2008,
+ isbn = "978-0-387-49987-1",
+ publisher = SPRINGER,
+ note = "The first book about force spectroscopy. Discusses the scaffold
+ effect in section 8.4.1."
+}
+
+@article { nummela07,
+ author = JNummela #" and "# IAndricioaei,
+ title = "{Exact Low-Force Kinetics from High-Force Single-Molecule
+ Unfolding Events}",
+ year = 2007,
+ journal = BPJ,
+ volume = 93,
+ number = 10,
+ pages = "3373--3381",
+ doi = "10.1529/biophysj.107.111658",
+ eprint = "http://www.biophysj.org/cgi/reprint/93/10/3373.pdf",
+ url = "http://www.biophysj.org/cgi/content/abstract/93/10/3373",
+ abstract = "Mechanical forces play a key role in crucial cellular processes
+ involving force-bearing biomolecules, as well as in novel single-
+ molecule pulling experiments. We present an exact method that enables
+ one to extrapolate, to low (or zero) forces, entire time-correlation
+ functions and kinetic rate constants from the conformational dynamics
+ either simulated numerically or measured experimentally at a single,
+ relatively higher, external force. The method has twofold relevance:
+ 1), to extrapolate the kinetics at physiological force conditions from
+ molecular dynamics trajectories generated at higher forces that
+ accelerate conformational transitions; and 2), to extrapolate unfolding
+ rates from experimental force-extension single-molecule curves. The
+ theoretical formalism, based on stochastic path integral weights of
+ Langevin trajectories, is presented for the constant-force, constant
+ loading rate, and constant-velocity modes of the pulling experiments.
+ For the first relevance, applications are described for simulating the
+ conformational isomerization of alanine dipeptide; and for the second
+ relevance, the single-molecule pulling of RNA is considered. The
+ ability to assign a weight to each trace in the single-molecule data
+ also suggests a means to quantitatively compare unfolding pathways
+ under different conditions."
+}
+
+@article { oberhauser01,
+ author = AOberhauser #" and "# PHansma #" and "# MCarrionVazquez #" and "#
+ JFernandez,
+ title = "Stepwise unfolding of titin under force-clamp atomic force
+ microscopy",
+ year = 2001,
+ journal = PNAS,
+ volume = 98,
+ number = 2,
+ pages = "468--472",
+ doi = "10.1073/pnas.021321798",
+ eprint = "http://www.pnas.org/cgi/reprint/98/2/468.pdf",
+ url = "http://www.pnas.org/cgi/content/abstract/98/2/468",
+ abstract = ""
+}
+
+@article { ohler07,
+ author = BOhler,
+ title = "Cantilever spring constant calibration using laser Doppler
+ vibrometry",
+ year = 2007,
+ journal = RSI,
+ volume = 78,
+ number = 6,
+ pages = 063701,
+ numpages = 5,
+ publisher = AIP,
+ eid = 063701,
+ doi = "10.1063/1.2743272",
+ url = "http://link.aip.org/link/?RSI/78/063701/1",
+ keywords = "calibration; vibration measurement; measurement by laser beam;
+ Doppler measurement; measurement uncertainty; atomic force microscopy",
+ note = "Excellent review of thermal calibration to 2007, but nothing in the
+ way of derivations. Compares thermal tune and Sader method with laser
+ Doppler vibrometry.",
+ project = "Cantilever Calibration"
+}
+
+@article { olshansky97,
+ author = SJOlshansky #" and "# BACarnes,
+ title = "Ever since {G}ompertz",
+ year = 1997,
+ month = feb,
+ journal = Demography,
+ volume = 34,
+ number = 1,
+ pages = "1--15",
+ issn = "0070-3370",
+ url = "http://www.jstor.org/stable/2061656",
+ keywords = "Aging;Biometry;History, 19th Century;History, 20th
+ Century;Humans;Life Tables;Mortality;Sexual Maturation",
+ abstract = "In 1825 British actuary Benjamin Gompertz made a simple but
+ important observation that a law of geometrical progression pervades
+ large portions of different tables of mortality for humans. The simple
+ formula he derived describing the exponential rise in death rates
+ between sexual maturity and old age is commonly, referred to as the
+ Gompertz equation-a formula that remains a valuable tool in demography
+ and in other scientific disciplines. Gompertz's observation of a
+ mathematical regularity in the life table led him to believe in the
+ presence of a low of mortality that explained why common age patterns
+ of death exist. This law of mortality has captured the attention of
+ scientists for the past 170 years because it was the first among what
+ are now several reliable empirical tools for describing the dying-out
+ process of many living organisms during a significant portion of their
+ life spans. In this paper we review the literature on Gompertz's law of
+ mortality and discuss the importance of his observations and insights
+ in light of research on aging that has taken place since then.",
+ note = "Hardly any actual math, but the references might be interesting.
+ I'll look into them if I have the time. Available through several
+ repositories."
+}
+
+@article { onuchic96,
+ author = JNOnuchic #" and "# NDSocci #" and "# ZLuthey-Schulten #" and "#
+ PGWolynes,
+ title = "Protein folding funnels: the nature of the transition state
+ ensemble",
+ year = 1996,
+ journal = FoldDes,
+ volume = 1,
+ number = 6,
+ pages = "441--450",
+ issn = "1359-0278",
+ keywords = "Animals; Cytochrome c Group; Humans; Infant; Protein Folding",
+ abstract = "BACKGROUND: Energy landscape theory predicts that the folding
+ funnel for a small fast-folding alpha-helical protein will have a
+ transition state half-way to the native state. Estimates of the
+ position of the transition state along an appropriate reaction
+ coordinate can be obtained from linear free energy relationships
+ observed for folding and unfolding rate constants as a function of
+ denaturant concentration. The experimental results of Huang and Oas for
+ lambda repressor, Fersht and collaborators for C12, and Gray and
+ collaborators for cytochrome c indicate a free energy barrier midway
+ between the folded and unfolded regions. This barrier arises from an
+ entropic bottleneck for the folding process. RESULTS: In keeping with
+ the experimental results, lattice simulations based on the folding
+ funnel description show that the transition state is not just a single
+ conformation, but rather an ensemble of a relatively large number of
+ configurations that can be described by specific values of one or a few
+ order parameters (e.g. the fraction of native contacts). Analysis of
+ this transition state or bottleneck region from our lattice simulations
+ and from atomistic models for small alpha-helical proteins by Boczko
+ and Brooks indicates a broad distribution for native contact
+ participation in the transition state ensemble centered around 50\%.
+ Importantly, however, the lattice-simulated transition state ensemble
+ does include some particularly hot contacts, as seen in the
+ experiments, which have been termed by others a folding nucleus.
+ CONCLUSIONS: Linear free energy relations provide a crude spectroscopy
+ of the transition state, allowing us to infer the values of a reaction
+ coordinate based on the fraction of native contacts. This bottleneck
+ may be thought of as a collection of delocalized nuclei where different
+ native contacts will have different degrees of participation. The
+ agreement between the experimental results and the theoretical
+ predictions provides strong support for the landscape analysis."
+}
+
+@article { optiz03,
+ author = COpitz #" and "# MKulke #" and "# MLeake #" and "# CNeagoe #" and
+ "# HHinssen #" and "# RHajjar #" and "# WLinke,
+ title = "Damped elastic recoil of the titin spring in myofibrils of human
+ myocardium",
+ year = 2003,
+ journal = PNAS,
+ volume = 100,
+ number = 22,
+ pages = "12688--12693",
+ doi = "10.1073/pnas.2133733100",
+ eprint = "http://www.pnas.org/cgi/reprint/100/22/12688.pdf",
+ url = "http://www.pnas.org/cgi/content/abstract/100/22/12688",
+ abstract = "The giant protein titin functions as a molecular spring in
+ muscle and is responsible for most of the passive tension of
+ myocardium. Because the titin spring is extended during diastolic
+ stretch, it will recoil elastically during systole and potentially may
+ influence the overall shortening behavior of cardiac muscle. Here,
+ titin elastic recoil was quantified in single human heart myofibrils by
+ using a high-speed charge-coupled device-line camera and a
+ nanonewtonrange force sensor. Application of a slack-test protocol
+ revealed that the passive shortening velocity (Vp) of nonactivated
+ cardiomyofibrils depends on: (i) initial sarcomere length, (ii)
+ release-step amplitude, and (iii) temperature. Selective digestion of
+ titin, with low doses of trypsin, decelerated myofibrillar passive
+ recoil and eventually stopped it. Selective extraction of actin
+ filaments with a Ca2+-independent gelsolin fragment greatly reduced the
+ dependency of Vp on release-step size and temperature. These results
+ are explained by the presence of viscous forces opposing myofibrillar
+ passive recoil that are caused mainly by weak actin-titin interactions.
+ Thus, Vp is determined by two distinct factors: titin elastic recoil
+ and internal viscous drag forces. The recoil could be modeled as that
+ of a damped entropic spring consisting of independent worm-like chains.
+ The functional importance of myofibrillar elastic recoil was addressed
+ by comparing instantaneous Vp to unloaded shortening velocity, which
+ was measured in demembranated, fully Ca2+-activated, human cardiac
+ fibers. Titin-driven passive recoil was much faster than active
+ unloaded shortening velocity in early phases of isotonic contraction.
+ Damped myofibrillar elastic recoil could help accelerate active
+ contraction speed of human myocardium during early systolic
+ shortening."
+}
+
+@article { oroudjev02,
+ author = EOroudjev #" and "# JSoares #" and "# SArcidiacono #" and "#
+ JThompson #" and "# SFossey #" and "# HHansma,
+ title = "Segmented nanofibers of spider dragline silk: Atomic force
+ microscopy and single-molecule force spectroscopy",
+ year = 2002,
+ journal = PNAS,
+ volume = 99,
+ number = 90002,
+ pages = "6460--6465",
+ doi = "10.1073/pnas.082526499",
+ eprint = "http://www.pnas.org/cgi/reprint/99/suppl_2/6460.pdf",
+ url = "http://www.pnas.org/cgi/content/abstract/99/suppl_2/6460",
+ abstract = "Despite its remarkable materials properties, the structure of
+ spider dragline silk has remained unsolved. Results from two probe
+ microscopy techniques provide new insights into the structure of spider
+ dragline silk. A soluble synthetic protein from dragline silk
+ spontaneously forms nanofibers, as observed by atomic force microscopy.
+ These nanofibers have a segmented substructure. The segment length and
+ amino acid sequence are consistent with a slab-like shape for
+ individual silk protein molecules. The height and width of nanofiber
+ segments suggest a stacking pattern of slab-like molecules in each
+ nanofiber segment. This stacking pattern produces nano-crystals in an
+ amorphous matrix, as observed previously by NMR and x-ray diffraction
+ of spider dragline silk. The possible importance of nanofiber formation
+ to native silk production is discussed. Force spectra for single
+ molecules of the silk protein demonstrate that this protein unfolds
+ through a number of rupture events, indicating a modular substructure
+ within single silk protein molecules. A minimal unfolding module size
+ is estimated to be around 14 nm, which corresponds to the extended
+ length of a single repeated module, 38 amino acids long. The structure
+ of this spider silk protein is distinctly different from the structures
+ of other proteins that have been analyzed by single-molecule force
+ spectroscopy, and the force spectra show correspondingly novel
+ features."
+}
+
+@article { paci00,
+ author = EPaci #" and "# MKarplus,
+ title = "Unfolding proteins by external forces and temperature: The
+ importance of topology and energetics",
+ year = 2000,
+ journal = PNAS,
+ volume = 97,
+ number = 12,
+ pages = "6521--6526",
+ doi = "10.1073/pnas.100124597",
+ eprint = "http://www.pnas.org/cgi/reprint/97/12/6521.pdf",
+ url = "http://www.pnas.org/cgi/content/abstract/97/12/6521"
+}
+
+@article { paci99,
+ author = EPaciX #" and "# MKarplusX,
+ title = "Forced unfolding of fibronectin type 3 modules: an analysis by
+ biased molecular dynamics simulations",
+ year = 1999,
+ month = may,
+ day = 07,
+ journal = JMB,
+ volume = 288,
+ number = 3,
+ pages = "441--459",
+ issn = "0022-2836",
+ doi = "10.1006/jmbi.1999.2670",
+ keywords = "Dimerization;Fibronectins;Humans;Hydrogen Bonding;Microscopy,
+ Atomic Force;Protein Denaturation;Protein Folding",
+ abstract = "Titin, an important constituent of vertebrate muscles, is a
+ protein of the order of a micrometer in length in the folded state.
+ Atomic force microscopy and laser tweezer experiments have been used to
+ stretch titin molecules to more than ten times their folded lengths. To
+ explain the observed relation between force and extension, it has been
+ suggested that the immunoglobulin and fibronectin domains unfold one at
+ a time in an all-or-none fashion. We use molecular dynamics simulations
+ to study the forced unfolding of two different fibronectin type 3
+ domains (the ninth, 9Fn3, and the tenth, 10Fn3, from human fibronectin)
+ and of their heterodimer of known structure. An external biasing
+ potential on the N to C distance is employed and the protein is treated
+ in the polar hydrogen representation with an implicit solvation model.
+ The latter provides an adiabatic solvent response, which is important
+ for the nanosecond unfolding simulation method used here. A series of
+ simulations is performed for each system to obtain meaningful results.
+ The two different fibronectin domains are shown to unfold in the same
+ way along two possible pathways. These involve the partial separation
+ of the ``beta-sandwich'', an essential structural element, and the
+ unfolding of the individual sheets in a stepwise fashion. The biasing
+ potential results are confirmed by constant force unfolding
+ simulations. For the two connected domains, there is complete unfolding
+ of one domain (9Fn3) before major unfolding of the second domain
+ (10Fn3). Comparison of different models for the potential energy
+ function demonstrates that the dominant cohesive element in both
+ proteins is due to the attractive van der Waals interactions;
+ electrostatic interactions play a structural role but appear to make
+ only a small contribution to the stabilization of the domains, in
+ agreement with other studies of beta-sheet stability. The unfolding
+ forces found in the simulations are of the order of those observed
+ experimentally, even though the speed of the former is more than six
+ orders of magnitude greater than that used in the latter."
+}
+
+@article { peng08,
+ author = QPeng #" and "# HLi,
+ title = "Atomic force microscopy reveals parallel mechanical unfolding
+ pathways of T4 lysozyme: Evidence for a kinetic partitioning mechanism",
+ year = 2008,
+ journal = PNAS,
+ volume = 105,
+ number = 6,
+ pages = "1885--1890",
+ doi = "10.1073/pnas.0706775105",
+ eprint = "http://www.pnas.org/cgi/reprint/105/6/1885.pdf",
+ url = "http://www.pnas.org/cgi/content/abstract/105/6/1885",
+ abstract = "Kinetic partitioning is predicted to be a general mechanism for
+ proteins to fold into their well defined native three-dimensional
+ structure from unfolded states following multiple folding pathways.
+ However, experimental evidence supporting this mechanism is still
+ limited. By using single-molecule atomic force microscopy, here we
+ report experimental evidence supporting the kinetic partitioning
+ mechanism for mechanical unfolding of T4 lysozyme, a small protein
+ composed of two subdomains. We observed that on stretching from its N
+ and C termini, T4 lysozyme unfolds by multiple distinct unfolding
+ pathways: the majority of T4 lysozymes unfold in an all-or-none fashion
+ by overcoming a dominant unfolding kinetic barrier; and a small
+ fraction of T4 lysozymes unfold in three-state fashion involving
+ unfolding intermediate states. The three-state unfolding pathways do
+ not follow well defined routes, instead they display variability and
+ diversity in individual unfolding pathways. The unfolding intermediate
+ states are local energy minima along the mechanical unfolding pathways
+ and are likely to result from the residual structures present in the
+ two subdomains after crossing the main unfolding barrier. These results
+ provide direct evidence for the kinetic partitioning of the mechanical
+ unfolding pathways of T4 lysozyme, and the complex unfolding behaviors
+ reflect the stochastic nature of kinetic barrier rupture in mechanical
+ unfolding processes. Our results demonstrate that single-molecule
+ atomic force microscopy is an ideal tool to investigate the
+ folding/unfolding dynamics of complex multimodule proteins that are
+ otherwise difficult to study using traditional methods."
+}
+
+@book { press92,
+ author = WPress #" and "# STeukolsky #" and "# WVetterling #" and "#
+ BFlannery,
+ title = "Numerical Recipies in {C}: The Art of Scientific Computing",
+ year = 1992,
+ edition = 2,
+ publisher = CambridgeUniversityPress,
+ address = "New York",
+ eprint = "http://www.nrbook.com/a/bookcpdf.php",
+ note = "See sections 12.0, 12.1, 12.3, and 13.4 for a good introduction to
+ Fourier transforms and power spectrum estimation.",
+ project = "Cantilever Calibration"
+}
+
+@article { puchner08,
+ author = EPuchner #" and "# GFranzen #" and "# MGautel #" and "# HGaub,
+ title = "Comparing proteins by their unfolding pattern.",
+ year = 2008,
+ month = jul,
+ journal = BPJ,
+ volume = 95,
+ number = 1,
+ pages = "426--434",
+ issn = "1542-0086",
+ doi = "10.1529/biophysj.108.129999",
+ eprint = "http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2426622/pdf/426.pdf",
+ url = "http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2426622/",
+ keywords = "Algorithms;Computer Simulation;Microscopy, Atomic Force;Models,
+ Chemical;Models, Molecular;Protein Denaturation;Protein
+ Folding;Proteins",
+ abstract = "Single molecule force spectroscopy has evolved into an
+ important and extremely powerful technique for investigating the
+ folding potentials of biomolecules. Mechanical tension is applied to
+ individual molecules, and the subsequent, often stepwise unfolding is
+ recorded in force extension traces. However, because the energy
+ barriers of the folding potentials are often close to the thermal
+ energy, both the extensions and the forces at which these barriers are
+ overcome are subject to marked fluctuations. Therefore, force extension
+ traces are an inadequate representation despite widespread use
+ particularly when large populations of proteins need to be compared and
+ analyzed. We show in this article that contour length, which is
+ independent of fluctuations and alterable experimental parameters, is a
+ more appropriate variable than extension. By transforming force
+ extension traces into contour length space, histograms are obtained
+ that directly represent the energy barriers. In contrast to force
+ extension traces, such barrier position histograms can be averaged to
+ investigate details of the unfolding potential. The cross-superposition
+ of barrier position histograms allows us to detect and visualize the
+ order of unfolding events. We show with this approach that in contrast
+ to the sequential unfolding of bacteriorhodopsin, two main steps in the
+ unfolding of the enzyme titin kinase are independent of each other. The
+ potential of this new method for accurate and automated analysis of
+ force spectroscopy data and for novel automated screening techniques is
+ shown with bacteriorhodopsin and with protein constructs containing GFP
+ and titin kinase."
+}
+
+@article { raible04,
+ author = MRaible #" and "# MEvstigneev #" and "# PReimann #" and "#
+ FWBartels #" and "# RRos,
+ title = "Theoretical analysis of dynamic force spectroscopy experiments on
+ ligand-receptor complexes",
+ year = 2004,
+ month = aug,
+ day = 26,
+ journal = JBiotechnol,
+ volume = 112,
+ number = "1-2",
+ pages = "13--23",
+ issn = "0168-1656",
+ doi = "10.1016/j.jbiotec.2004.04.017",
+ keywords = "Binding Sites;Computer Simulation;DNA;DNA-Binding
+ Proteins;Elasticity;Ligands;Macromolecular
+ Substances;Micromanipulation;Microscopy, Atomic Force;Models,
+ Chemical;Molecular Biology;Nucleic Acid Conformation;Physical
+ Stimulation;Protein Binding;Protein Conformation;Stress, Mechanical",
+ abstract = "The forced rupture of single chemical bonds in biomolecular
+ compounds (e.g. ligand-receptor systems) as observed in dynamic force
+ spectroscopy experiments is addressed. Under the assumption that the
+ probability of bond rupture depends only on the instantaneously acting
+ force, a data collapse onto a single master curve is predicted. For
+ rupture data obtained experimentally by dynamic AFM force spectroscopy
+ of a ligand-receptor bond between a DNA and a regulatory protein we do
+ not find such a collapse. We conclude that the above mentioned,
+ generally accepted assumption is not satisfied and we discuss possible
+ explanations."
+}
+
+@article { raible06,
+ author = MRaible #" and "# MEvstigneev #" and "# FWBartels #" and "# REckel
+ #" and "# MNguyen-Duong #" and "# RMerkel #" and "# RRos #" and "#
+ DAnselmetti #" and "# PReimann,
+ title = "Theoretical analysis of single-molecule force spectroscopy
+ experiments: heterogeneity of chemical bonds",
+ year = 2006,
+ month = jun,
+ day = 01,
+ journal = BPJ,
+ volume = 90,
+ number = 11,
+ pages = "3851--3864",
+ issn = "0006-3495",
+ doi = "10.1529/biophysj.105.077099",
+ eprint = "http://www.biophysj.org/cgi/reprint/90/11/3851.pdf",
+ url = "http://www.biophysj.org/cgi/content/abstract/90/11/3851",
+ keywords = "Biomechanics;Microscopy, Atomic Force;Models,
+ Molecular;Statistical Distributions;Thermodynamics",
+ abstract = "We show that the standard theoretical framework in single-
+ molecule force spectroscopy has to be extended to consistently describe
+ the experimental findings. The basic amendment is to take into account
+ heterogeneity of the chemical bonds via random variations of the force-
+ dependent dissociation rates. This results in a very good agreement
+ between theory and rupture data from several different experiments."
+}
+
+@article { rief02,
+ author = MHGRief,
+ title = "Force spectroscopy of single biomolecules",
+ year = 2002,
+ month = mar,
+ day = 12,
+ journal = Chemphyschem,
+ volume = 3,
+ number = 3,
+ pages = "255--261",
+ issn = "1439-4235",
+ doi = "10.1002/1439-7641(20020315)3:3<255::AID-CPHC255>3.0.CO;2-M",
+ url = "http://www3.interscience.wiley.com/journal/91016383/abstract",
+ keywords = "Ligands;Microscopy, Atomic Force;Polysaccharides;Protein
+ Denaturation;Proteins",
+ abstract = "Many processes in the body are effected and regulated by highly
+ specialized protein molecules: These molecules certainly deserve the
+ name ``biochemical nanomachines''. Recent progress in single-molecule
+ experiments and corresponding simulations with supercomputers enable us
+ to watch these ``nanomachines'' at work, revealing a host of astounding
+ mechanisms. Examples are the fine-tuned movements of the binding pocket
+ of a receptor protein locking into its ligand molecule and the forced
+ unfolding of titin, which acts as a molecular shock absorber to protect
+ muscle cells. At present, we are not capable of designing such high
+ precision machines, but we are beginning to understand their working
+ principles and to simulate and predict their function.",
+ note = "Nice, general review of force spectroscopy to 2002, but not much
+ detail."
+}
+
+@book { rief65,
+ author = FRief,
+ title = "Fundamentals of Statistical and Thermal Physics",
+ year = 1965,
+ publisher = McGraw-Hill,
+ address = "New York",
+ note = "Thermal noise for SHOs, in Chapter 15, Sections 6 and 10.",
+ project = "Cantilever Calibration"
+}
+
+@article { rief97a,
+ author = MRief #" and "# MGautel #" and "# FOesterhelt #" and "# JFernandez
+ #" and "# HGaub,
+ title = "Reversible Unfolding of Individual Titin Immunoglobulin Domains by
+ {AFM}",
+ year = 1997,
+ journal = SCI,
+ volume = 276,
+ number = 5315,
+ pages = "1109--1112",
+ doi = "10.1126/science.276.5315.1109",
+ eprint = "http://www.sciencemag.org/cgi/reprint/276/5315/1109.pdf",
+ url = "http://www.sciencemag.org/cgi/content/abstract/276/5315/1109",
+ note = "Seminal paper for force spectroscopy on Titin. Cited by
+ \citet{dietz04} (ref 9) as an example of how unfolding large proteins
+ is easily interpreted (vs.\ confusing unfolding in bulk), but Titin is
+ a rather simple example of that, because of its globular-chain
+ structure.",
+ project = "Energy Landscape Roughness"
+}
+
+@article { rief97b,
+ author = MRief #" and "# HEOesterhelt,
+ title = "Single Molecule Force Spectroscopy on Polysaccharides by Atomic
+ Force Microscopy",
+ year = 1997,
+ month = feb,
+ day = 28,
+ journal = SCI,
+ volume = 275,
+ number = 5304,
+ pages = "1295--1297",
+ issn = "1095-9203",
+ doi = "10.1126/science.275.5304.1295",
+ eprint = "http://www.sciencemag.org/cgi/reprint/275/5304/1295.pdf",
+ url = "http://www.sciencemag.org/cgi/content/abstract/275/5304/1295",
+ abstract = "Recent developments in piconewton instrumentation allow the
+ manipulation of single molecules and measurements of intermolecular as
+ well as intramolecular forces. Dextran filaments linked to a gold
+ surface were probed with the atomic force microscope tip by vertical
+ stretching. At low forces the deformation of dextran was found to be
+ dominated by entropic forces and can be described by the Langevin
+ function with a 6 angstrom Kuhn length. At elevated forces the strand
+ elongation was governed by a twist of bond angles. At higher forces the
+ dextran filaments underwent a distinct conformational change. The
+ polymer stiffened and the segment elasticity was dominated by the
+ bending of bond angles. The conformational change was found to be
+ reversible and was corroborated by molecular dynamics calculations."
+}
+
+@article { rief98,
+ author = MRief #" and "# JFernandez #" and "# HGaub,
+ title = "Elastically Coupled Two-Level Systems as a Model for Biopolymer
+ Extensibility",
+ year = 1998,
+ month = nov,
+ journal = PRL,
+ volume = 81,
+ number = 21,
+ pages = "4764--4767",
+ numpages = 3,
+ publisher = APS,
+ doi = "10.1103/PhysRevLett.81.4764",
+ eprint = "http://prola.aps.org/pdf/PRL/v81/i21/p4764_1",
+ url = "http://prola.aps.org/abstract/PRL/v81/i21/p4764_1",
+ note = "Original details on mechanical unfolding analysis via Monte Carlo
+ simulation."
+}
+
+@article { rief99,
+ author = HERief,
+ title = "Sequence-dependent mechanics of single {DNA} molecules",
+ year = 1999,
+ month = apr,
+ journal = NSB,
+ volume = 6,
+ number = 4,
+ pages = "346--349",
+ issn = "1072-8368",
+ doi = "10.1038/7582",
+ eprint = "http://www.nature.com/nsmb/journal/v6/n4/pdf/nsb0499_346.pdf",
+ url = "http://www.nature.com/nsmb/journal/v6/n4/abs/nsb0499_346.html",
+ keywords = "Bacteriophage lambda;Base Pairing;DNA;DNA, Single-Stranded;DNA,
+ Viral;Gold;Mechanics;Microscopy, Atomic Force;Nucleotides;Spectrum
+ Analysis;Thermodynamics",
+ abstract = "Atomic force microscope-based single-molecule force
+ spectroscopy was employed to measure sequence-dependent mechanical
+ properties of DNA by stretching individual DNA double strands attached
+ between a gold surface and an AFM tip. We discovered that in lambda-
+ phage DNA the previously reported B-S transition, where 'S' represents
+ an overstretched conformation, at 65 pN is followed by a nonequilibrium
+ melting transition at 150 pN. During this transition the DNA is split
+ into single strands that fully recombine upon relaxation. The sequence
+ dependence was investigated in comparative studies with poly(dG-dC) and
+ poly(dA-dT) DNA. Both the B-S and the melting transition occur at
+ significantly lower forces in poly(dA-dT) compared to poly(dG-dC). We
+ made use of the melting transition to prepare single poly(dG-dC) and
+ poly(dA-dT) DNA strands that upon relaxation reannealed into hairpins
+ as a result of their self-complementary sequence. The unzipping of
+ these hairpins directly revealed the base pair-unbinding forces for G-C
+ to be 20 +/- 3 pN and for A-T to be 9 +/- 3 pN."
+}
+
+@article { roters96,
+ author = ARoters #" and "# DJohannsmann,
+ title = "Distance-dependent noise measurements in scanning force
+ microscopy",
+ year = 1996,
+ journal = JPCM,
+ volume = 8,
+ number = 41,
+ pages = "7561-7577",
+ doi = "10.1088/0953-8984",
+ eprint = "http://www.iop.org/EJ/article/0953-8984/8/41/006/c64103.pdf",
+ url = "http://stacks.iop.org/0953-8984/8/7561",
+ abstract = "The changes in the thermal noise spectrum of a scanning-force-
+ microscope cantilever upon approach of the tip to the sample were used
+ to investigate the interactions between the cantilever and the sample.
+ The investigation of thermal noise is the natural choice for dynamic
+ measurements with little disturbance of the sample. In particular, the
+ small amplitudes involved ensure linear dynamic response. It is
+ possible to discriminate between viscous coupling, elastic coupling and
+ changes in the effective mass. The technique is versatile in terms of
+ substrates and environments. Hydrodynamic long-range interactions
+ depending on the sample, the geometry and the ambient medium are
+ observed. The dependence of hydrodynamic interaction on various
+ parameters such as the viscosity and the density of the medium is
+ described. For sufficiently soft surfaces, the method is sensitive to
+ viscoelastic properties of the surface. For example, the viscous
+ coupling to the surface is strongly increased when the surface is
+ covered with a swollen `polymer brush'.",
+ note = "They actually write down Lagrangian formula and give a decent
+ derivation of PSD, but don't show or work out the integrals.",
+ project = "Cantilever Calibration"
+}
+
+@article { ryckaert77,
+ author = JPRyckaert #" and "# GCiccotti #" and "# HJCBerendsen,
+ title = "Numerical integration of the cartesian equations of motion of a
+ system with constraints: molecular dynamics of n-alkanes",
+ year = 1977,
+ journal = JournalofComputationalPhysics,
+ volume = 23,
+ number = 3,
+ pages = "327--341",
+ issn = "0021-9991",
+ doi = "10.1016/0021-9991(77)90098-5",
+ url = "http://dx.doi.org/10.1016/0021-9991(77)90098-5",
+ abstract = "A numerical algorithm integrating the 3N Cartesian equations of
+ motion of a system of N points subject to holonomic constraints is
+ formulated. The relations of constraint remain perfectly fulfilled at
+ each step of the trajectory despite the approximate character of
+ numerical integration. The method is applied to a molecular dynamics
+ simulation of a liquid of 64 n-butane molecules and compared to a
+ simulation using generalized coordinates. The method should be useful
+ for molecular dynamics calculations on large molecules with internal
+ degrees of freedom.",
+ note = "Entry-level explaination of MD with rigid constraints. Explicit
+ Verlet integrator example."
+}
+
+@article { sarkar04,
+ author = ASarkar #" and "# RRobertson #" and "# JFernandez,
+ title = "Simultaneous atomic force microscope and fluorescence measurements
+ of protein unfolding using a calibrated evanescent wave",
+ year = 2004,
+ journal = PNAS,
+ volume = 101,
+ number = 35,
+ pages = "12882--12886",
+ doi = "10.1073/pnas.0403534101",
+ eprint = "http://www.pnas.org/cgi/reprint/101/35/12882.pdf",
+ url = "http://www.pnas.org/cgi/content/abstract/101/35/12882",
+ abstract = "Fluorescence techniques for monitoring single-molecule dynamics
+ in the vertical dimension currently do not exist. Here we use an atomic
+ force microscope to calibrate the distance-dependent intensity decay of
+ an evanescent wave. The measured evanescent wave transfer function was
+ then used to convert the vertical motions of a fluorescent particle
+ into displacement ($SD =< 1$ nm). We demonstrate the use of the
+ calibrated evanescent wave to resolve the 20.1 {+/-} 0.5-nm step
+ increases in the length of the small protein ubiquitin during forced
+ unfolding. The experiments that we report here make an important
+ contribution to fluorescence microscopy by demonstrating the
+ unambiguous optical tracking of a single molecule with a resolution
+ comparable to that of an atomic force microscope."
+}
+
+@article { sato05,
+ author = TSato #" and "# MEsaki #" and "# JFernandez #" and "# TEndo,
+ title = "{Comparison of the protein-unfolding pathways between
+ mitochondrial protein import and atomic-force microscopy measurements}",
+ year = 2005,
+ journal = PNAS,
+ volume = 102,
+ number = 50,
+ pages = "17999--18004",
+ doi = "10.1073/pnas.0504495102",
+ eprint = "http://www.pnas.org/cgi/reprint/102/50/17999.pdf",
+ url = "http://www.pnas.org/cgi/content/abstract/102/50/17999",
+ abstract = "Many newly synthesized proteins have to become unfolded during
+ translocation across biological membranes. We have analyzed the effects
+ of various stabilization/destabilization mutations in the Ig-like
+ module of the muscle protein titin upon its import from the N terminus
+ or C terminus into mitochondria. The effects of mutations on the import
+ of the titin module from the C terminus correlate well with those on
+ forced mechanical unfolding in atomic-force microscopy (AFM)
+ measurements. On the other hand, as long as turnover of the
+ mitochondrial Hsp70 system is not rate-limiting for the import, import
+ of the titin module from the N terminus is sensitive to mutations in
+ the N-terminal region but not the ones in the C-terminal region that
+ affect resistance to global unfolding in AFM experiments. We propose
+ that the mitochondrial-import system can catalyze precursor-unfolding
+ by reducing the stability of unfolding intermediates."
+}
+
+@article { schlierf04,
+ author = MSchlierf #" and "# HLi #" and "# JFernandez,
+ title = "The unfolding kinetics of ubiquitin captured with single-molecule
+ force-clamp techniques",
+ year = 2004,
+ month = may,
+ day = 11,
+ journal = PNAS,
+ volume = 101,
+ number = 19,
+ pages = "7299--7304",
+ issn = "0027-8424",
+ doi = "10.1073/pnas.0400033101",
+ eprint = "http://www.pnas.org/cgi/reprint/101/19/7299.pdf",
+ url = "http://www.pnas.org/cgi/content/abstract/101/19/7299",
+ keywords = "Kinetics;Microscopy, Atomic Force;Probability;Ubiquitin",
+ abstract = "We use single-molecule force spectroscopy to study the kinetics
+ of unfolding of the small protein ubiquitin. Upon a step increase in
+ the stretching force, a ubiquitin polyprotein extends in discrete steps
+ of 20.3 +/- 0.9 nm marking each unfolding event. An average of the time
+ course of these unfolding events was well described by a single
+ exponential, which is a necessary condition for a memoryless Markovian
+ process. Similar ensemble averages done at different forces showed that
+ the unfolding rate was exponentially dependent on the stretching force.
+ Stretching a ubiquitin polyprotein with a force that increased at a
+ constant rate (force-ramp) directly measured the distribution of
+ unfolding forces. This distribution was accurately reproduced by the
+ simple kinetics of an all-or-none unfolding process. Our force-clamp
+ experiments directly demonstrate that an ensemble average of ubiquitin
+ unfolding events is well described by a two-state Markovian process
+ that obeys the Arrhenius equation. However, at the single-molecule
+ level, deviant behavior that is not well represented in the ensemble
+ average is readily observed. Our experiments make an important addition
+ to protein spectroscopy by demonstrating an unambiguous method of
+ analysis of the kinetics of protein unfolding by a stretching force."
+}
+
+@article { schlierf06,
+ author = MSchlierf #" and "# MRief,
+ title = "Single-molecule unfolding force distributions reveal a funnel-
+ shaped energy landscape",
+ year = 2006,
+ month = feb,
+ day = 15,
+ journal = BPJ,
+ volume = 90,
+ number = 4,
+ pages = "L33--L35",
+ issn = "0006-3495",
+ doi = "10.1529/biophysj.105.077982",
+ url = "http://www.biophysj.org/cgi/content/abstract/90/4/L33",
+ keywords = "Models, Molecular; Protein Folding; Proteins; Thermodynamics",
+ abstract = "The protein folding process is described as diffusion on a
+ high-dimensional energy landscape. Experimental data showing details of
+ the underlying energy surface are essential to understanding folding.
+ So far in single-molecule mechanical unfolding experiments a simplified
+ model assuming a force-independent transition state has been used to
+ extract such information. Here we show that this so-called Bell model,
+ although fitting well to force velocity data, fails to reproduce full
+ unfolding force distributions. We show that by applying Kramers'
+ diffusion model, we were able to reconstruct a detailed funnel-like
+ curvature of the underlying energy landscape and establish full
+ agreement with the data. We demonstrate that obtaining spatially
+ resolved details of the unfolding energy landscape from mechanical
+ single-molecule protein unfolding experiments requires models that go
+ beyond the Bell model.",
+ note = "The inspiration behind my sawtooth simulation. Bell model fit to
+ $f_{unfold}(v)$, but Kramers model fit to unfolding distribution for a
+ given $v$. Eqn.~3 in the supplement is \citet{evans99} 1999's Eqn.~2,
+ but it is just ``[dying percent] * [surviving population] = [deaths]''
+ (TODO, check). $\nu \equiv k$ is the force/time-dependent off rate...
+ (TODO) The Kramers' rate equation (second equation in the paper) is
+ \citet{hanggi90} Eq.~4.56b (page 275). It is important to extract $k_0$
+ and $\Delta x$ using every available method."
+}
+
+@article { schwaiger04,
+ author = ISchwaiger #" and "# AKardinal #" and "# MSchleicher #" and "#
+ MAngelikaANoegelandRief,
+ title = "A mechanical unfolding intermediate in an actin-crosslinking
+ protein",
+ year = 2004,
+ month = jan,
+ day = 29,
+ journal = NSMB,
+ volume = 11,
+ number = 1,
+ pages = "81--85",
+ issn = "1545-9993",
+ doi = "10.1038/nsmb705",
+ eprint = "http://www.nature.com/nsmb/journal/v11/n1/pdf/nsmb705.pdf",
+ url = "http://www.nature.com/nsmb/journal/v11/n1/full/nsmb705.html",
+ keywords = "Actins; Animals; Contractile Proteins; Cross-Linking Reagents;
+ Dictyostelium; Dimerization; Microfilament Proteins; Microscopy, Atomic
+ Force; Mutagenesis, Site-Directed; Protein Denaturation; Protein
+ Folding; Protein Structure, Tertiary; Protozoan Proteins",
+ abstract = "Many F-actin crosslinking proteins consist of two actin-binding
+ domains separated by a rod domain that can vary considerably in length
+ and structure. In this study, we used single-molecule force
+ spectroscopy to investigate the mechanics of the immunoglobulin (Ig)
+ rod domains of filamin from Dictyostelium discoideum (ddFLN). We find
+ that one of the six Ig domains unfolds at lower forces than do those of
+ all other domains and exhibits a stable unfolding intermediate on its
+ mechanical unfolding pathway. Amino acid inserts into various loops of
+ this domain lead to contour length changes in the single-molecule
+ unfolding pattern. These changes allowed us to map the stable core of
+ approximately 60 amino acids that constitutes the unfolding
+ intermediate. Fast refolding in combination with low unfolding forces
+ suggest a potential in vivo role for this domain as a mechanically
+ extensible element within the ddFLN rod.",
+ note = "ddFLN unfolding with WLC params for sacrificial domains. Gives
+ persistence length $p = 0.5\mbox{ nm}$ in ``high force regime'', $p =
+ 0.9\mbox{ nm}$ in ``low force regime'', with a transition at $F =
+ 30\mbox{ pN}$.",
+ project = "sawtooth simulation"
+}
+
+@article { schwaiger05,
+ author = ISchwaiger #" and "# MSchleicher #" and "# MAngelikaANoegelandRief,
+ title = "The folding pathway of a fast-folding immunoglobulin domain
+ revealed by single-molecule mechanical experiments",
+ year = 2005,
+ month = jan,
+ journal = EMBORep,
+ volume = 6,
+ number = 1,
+ pages = "46--51",
+ issn = "1469-221X",
+ doi = "10.1038/sj.embor.7400317",
+ eprint = "http://www.nature.com/embor/journal/v6/n1/pdf/7400317.pdf",
+ url = "http://www.nature.com/embor/journal/v6/n1/index.html",
+ keywords = "Animals; Contractile Proteins; Dictyostelium; Immunoglobulins;
+ Kinetics; Microfilament Proteins; Models, Molecular; Protein Folding;
+ Protein Structure, Tertiary",
+ abstract = "The F-actin crosslinker filamin from Dictyostelium discoideum
+ (ddFLN) has a rod domain consisting of six structurally similar
+ immunoglobulin domains. When subjected to a stretching force, domain 4
+ unfolds at a lower force than all the other domains in the chain.
+ Moreover, this domain shows a stable intermediate along its mechanical
+ unfolding pathway. We have developed a mechanical single-molecule
+ analogue to a double-jump stopped-flow experiment to investigate the
+ folding kinetics and pathway of this domain. We show that an obligatory
+ and productive intermediate also occurs on the folding pathway of the
+ domain. Identical mechanical properties suggest that the unfolding and
+ refolding intermediates are closely related. The folding process can be
+ divided into two consecutive steps: in the first step 60 C-terminal
+ amino acids form an intermediate at the rate of 55 s(-1); and in the
+ second step the remaining 40 amino acids are packed on this core at the
+ rate of 179 s(-1). This division increases the overall folding rate of
+ this domain by a factor of ten compared with all other homologous
+ domains of ddFLN that lack the folding intermediate."
+}
+
+@article { sharma07,
+ author = DSharma #" and "# OPerisic #" and "# QPeng #" and "# YCao #" and
+ "# CLam #" and "# HLu #" and "# HLi,
+ title = "Single-molecule force spectroscopy reveals a mechanically stable
+ protein fold and the rational tuning of its mechanical stability",
+ year = 2007,
+ journal = PNAS,
+ volume = 104,
+ number = 22,
+ pages = "9278--9283",
+ doi = "10.1073/pnas.0700351104",
+ eprint = "http://www.pnas.org/cgi/reprint/104/22/9278.pdf",
+ url = "http://www.pnas.org/cgi/content/abstract/104/22/9278",
+ abstract = "It is recognized that shear topology of two directly connected
+ force-bearing terminal [beta]-strands is a common feature among the
+ vast majority of mechanically stable proteins known so far. However,
+ these proteins belong to only two distinct protein folds, Ig-like
+ [beta] sandwich fold and [beta]-grasp fold, significantly hindering
+ delineating molecular determinants of mechanical stability and rational
+ tuning of mechanical properties. Here we combine single-molecule atomic
+ force microscopy and steered molecular dynamics simulation to reveal
+ that the de novo designed Top7 fold [Kuhlman B, Dantas G, Ireton GC,
+ Varani G, Stoddard BL, Baker D (2003) Science 302:13641368] represents
+ a mechanically stable protein fold that is distinct from Ig-like [beta]
+ sandwich and [beta]-grasp folds. Although the two force-bearing [beta]
+ strands of Top7 are not directly connected, Top7 displays significant
+ mechanical stability, demonstrating that the direct connectivity of
+ force-bearing [beta] strands in shear topology is not mandatory for
+ mechanical stability. This finding broadens our understanding of the
+ design of mechanically stable proteins and expands the protein fold
+ space where mechanically stable proteins can be screened. Moreover, our
+ results revealed a substructure-sliding mechanism for the mechanical
+ unfolding of Top7 and the existence of two possible unfolding pathways
+ with different height of energy barrier. Such insights enabled us to
+ rationally tune the mechanical stability of Top7 by redesigning its
+ mechanical unfolding pathway. Our study demonstrates that computational
+ biology methods (including de novo design) offer great potential for
+ designing proteins of defined topology to achieve significant and
+ tunable mechanical properties in a rational and systematic fashion."
+}
+
+@article { sheng05,
+ author = YJSheng #" and "# SJiang #" and "# HKTsao,
+ title = "Forced Kramers escape in single-molecule pulling experiments",
+ collaboration = "",
+ year = 2005,
+ journal = JCP,
+ volume = 123,
+ number = 9,
+ pages = 091102,
+ numpages = 4,
+ publisher = AIP,
+ eid = 091102,
+ doi = "10.1063/1.2046632",
+ url = "http://link.aip.org/link/?JCP/123/091102/1",
+ keywords = "molecular biophysics; bonds (chemical); proteins",
+ note = "Gives appropriate Einstein-S... relation for diffusion to damping",
+ project = "sawtooth simulation"
+}
+
+@article { shillcock98,
+ author = JShillcock #" and "# USeifert,
+ title = "Escape from a metastable well under a time-ramped force",
+ year = 1998,
+ month = "Jun",
+ journal = PhysRevE,
+ volume = 57,
+ number = 6,
+ pages = "7301--7304",
+ numpages = 3,
+ publisher = APS,
+ doi = "10.1103/PhysRevE.57.7301",
+ eprint = "http://prola.aps.org/pdf/PRE/v57/i6/p7301_1",
+ url = "http://link.aps.org/abstract/PRE/v57/p7301",
+ project = "sawtooth simulation"
+}
+
+@article { sims09,
+ author = GESims #" and "# SRJun #" and "# GAWu #" and "# SHKim,
+ title = "Alignment-free genome comparison with feature frequency profiles
+ ({FFP}) and optimal resolutions",
+ year = 2009,
+ month = feb,
+ day = 24,
+ journal = PNAS,
+ volume = 106,
+ number = 8,
+ pages = "2677--2682",
+ issn = "1091-6490",
+ doi = "10.1073/pnas.0813249106",
+ eprint = "http://www.pnas.org/cgi/reprint/106/31/12826",
+ url = "http://www.pnas.org/content/106/8/2677",
+ keywords = "Genome;Introns;Phylogeny",
+ abstract = "For comparison of whole-genome (genic + nongenic) sequences,
+ multiple sequence alignment of a few selected genes is not appropriate.
+ One approach is to use an alignment-free method in which feature (or
+ l-mer) frequency profiles (FFP) of whole genomes are used for
+ comparison-a variation of a text or book comparison method, using word
+ frequency profiles. In this approach it is critical to identify the
+ optimal resolution range of l-mers for the given set of genomes
+ compared. The optimum FFP method is applicable for comparing whole
+ genomes or large genomic regions even when there are no common genes
+ with high homology. We outline the method in 3 stages: (i) We first
+ show how the optimal resolution range can be determined with English
+ books which have been transformed into long character strings by
+ removing all punctuation and spaces. (ii) Next, we test the robustness
+ of the optimized FFP method at the nucleotide level, using a mutation
+ model with a wide range of base substitutions and rearrangements. (iii)
+ Finally, to illustrate the utility of the method, phylogenies are
+ reconstructed from concatenated mammalian intronic genomes; the FFP
+ derived intronic genome topologies for each l within the optimal range
+ are all very similar. The topology agrees with the established
+ mammalian phylogeny revealing that intron regions contain a similar
+ level of phylogenic signal as do coding regions."
+}
+
+@article { smith92,
+ author = SBSmith #" and "# CLFinziandBustamante,
+ title = "Direct mechanical measurements of the elasticity of single {DNA}
+ molecules by using magnetic beads",
+ year = 1992,
+ month = nov,
+ day = 13,
+ journal = SCI,
+ volume = 258,
+ number = 5085,
+ pages = "1122--1126",
+ issn = "0036-8075",
+ doi = "10.1126/science.1439819",
+ eprint = "http://www.sciencemag.org/cgi/reprint/258/5085/1122.pdf",
+ url = "http://www.sciencemag.org/cgi/content/abstract/258/5085/1122",
+ keywords = "Chemistry,
+ Physical;Cisplatin;DNA;Elasticity;Ethidium;Glass;Indoles;Intercalating
+ Agents;Magnetics;Mathematics;Microspheres",
+ abstract = "Single DNA molecules were chemically attached by one end to a
+ glass surface and by their other end to a magnetic bead. Equilibrium
+ positions of the beads were observed in an optical microscope while the
+ beads were acted on by known magnetic and hydrodynamic forces.
+ Extension versus force curves were obtained for individual DNA
+ molecules at three different salt concentrations with forces between
+ 10(-14) and 10(-11) newtons. Deviations from the force curves predicted
+ by the freely jointed chain model suggest that DNA has significant
+ local curvature in solution. Ethidium bromide and
+ 4',6-diamidino-2-phenylindole had little effect on the elastic response
+ of the molecules, but their extent of intercalation was directly
+ measured. Conversely, the effect of bend-inducing cis-
+ diamminedichloroplatinum (II) was large and supports the hypothesis of
+ natural curvature in DNA."
+}
+
+@article { smith96,
+ author = SBSmith #" and "# CYCuiandBustamante,
+ title = "Overstretching {B}-{DNA}: the elastic response of individual
+ double-stranded and single-stranded {DNA} molecules",
+ year = 1996,
+ month = feb,
+ day = 09,
+ journal = SCI,
+ volume = 271,
+ number = 5250,
+ pages = "795--799",
+ issn = "0036-8075",
+ keywords = "Base Composition;Chemistry, Physical;DNA;DNA, Single-
+ Stranded;Elasticity;Nucleic Acid Conformation;Osmolar
+ Concentration;Thermodynamics",
+ abstract = "Single molecules of double-stranded DNA (dsDNA) were stretched
+ with force-measuring laser tweezers. Under a longitudinal stress of
+ approximately 65 piconewtons (pN), dsDNA molecules in aqueous buffer
+ undergo a highly cooperative transition into a stable form with 5.8
+ angstroms rise per base pair, that is, 70\% longer than B form dsDNA.
+ When the stress was relaxed below 65 pN, the molecules rapidly and
+ reversibly contracted to their normal contour lengths. This transition
+ was affected by changes in the ionic strength of the medium and the
+ water activity or by cross-linking of the two strands of dsDNA.
+ Individual molecules of single-stranded DNA were also stretched giving
+ a persistence length of 7.5 angstroms and a stretch modulus of 800 pN.
+ The overstretched form may play a significant role in the energetics of
+ DNA recombination."
+}
+
+@article { socci96,
+ author = NDSocci #" and "# JNOnuchic #" and "# PGWolynes,
+ title = "Diffusive dynamics of the reaction coordinate for protein folding
+ funnels",
+ collaboration = "",
+ year = 1996,
+ journal = JCP,
+ volume = 104,
+ number = 15,
+ pages = "5860--5868",
+ publisher = AIP,
+ doi = "10.1063/1.471317",
+ eprint = "http://arxiv.org/pdf/cond-mat/9601091",
+ url = "http://link.aip.org/link/?JCP/104/5860/1",
+ keywords = "PROTEINS; FOLDS; DIFFUSION; MONTE CARLO METHOD; SIMULATION;
+ FREE ENERGY",
+ abstract = "The quantitative description of model protein folding kinetics
+ using a diffusive collective reaction coordinate is examined. Direct
+ folding kinetics, diffusional coefficients and free energy profiles are
+ determined from Monte Carlo simulations of a 27-mer, 3 letter code
+ lattice model, which corresponds roughly to a small helical protein.
+ Analytic folding calculations, using simple diffusive rate theory,
+ agree extremely well with the full simulation results. Folding in this
+ system is best seen as a diffusive, funnel-like process.",
+ note = "A nice introduction to some quantitative ramifications of the
+ funnel energy landscape. There's also a bit of Kramers' theory and
+ graph theory thrown in for good measure."
+}
+
+@article { socci99,
+ author = NDSocci #" and "# JNOnuchic #" and "# PGWolynes,
+ title = "Stretching lattice models of protein folding",
+ year = 1999,
+ month = mar,
+ day = 02,
+ journal = PNAS,
+ volume = 96,
+ number = 5,
+ pages = "2031--2035",
+ issn = "0027-8424",
+ keywords = "Amino Acid Sequence;Drug Stability;Kinetics;Models,
+ Theoretical;Molecular Sequence Data;Peptides;Protein
+ Denaturation;Protein Folding",
+ abstract = "A new class of experiments that probe folding of individual
+ protein domains uses mechanical stretching to cause the transition. We
+ show how stretching forces can be incorporated in lattice models of
+ folding. For fast folding proteins, the analysis suggests a complex
+ relation between the force dependence and the reaction coordinate for
+ folding."
+}
+
+@article { staple08,
+ author = DBStaple #" and "# SHPayne #" and "# ALCReddin #" and "# HJKreuzer,
+ title = "Model for stretching and unfolding the giant multidomain muscle
+ protein using single-molecule force spectroscopy.",
+ year = 2008,
+ month = dec,
+ day = 12,
+ journal = PRL,
+ volume = 101,
+ number = 24,
+ pages = 248301,
+ issn = "0031-9007",
+ doi = "10.1103/PhysRevLett.101.248301",
+ url = "http://dx.doi.org/10.1103/PhysRevLett.101.248301",
+ keywords = "Kinetics;Microscopy, Atomic Force;Models, Chemical;Muscle
+ Proteins;Protein Conformation;Protein Folding;Protein Kinases;Protein
+ Structure, Tertiary;Thermodynamics",
+ abstract = "Single-molecule manipulation has allowed the forced unfolding
+ of multidomain proteins. Here we outline a theory that not only
+ explains these experiments but also points out a number of difficulties
+ in their interpretation and makes suggestions for further experiments.
+ For titin we reproduce force-extension curves, the dependence of break
+ force on pulling speed, and break-force distributions and also validate
+ two common experimental views: Unfolding titin Ig domains can be
+ explained as stepwise increases in contour length, and increasing force
+ peaks in native Ig sequences represent a hierarchy of bond strengths.
+ Our theory is valid for essentially any molecule that can be unfolded
+ in atomic force microscopy; as a further example, we present force-
+ extension curves for the unfolding of RNA hairpins."
+}
+
+@article { stark01,
+ author = RStark #" and "# TDrobek #" and "# WHeckl,
+ title = "Thermomechanical noise of a free v-shaped cantilever for atomic-
+ force microscopy.",
+ year = 2001,
+ month = jan,
+ journal = ULTRAMIC,
+ volume = 86,
+ number = "1--2",
+ pages = "207--215",
+ issn = "0304-3991",
+ doi = "http://dx.doi.org/10.1016/S0304-3991(00)00077-2",
+ abstract = "We have calculated the thermal noise of a v-shaped AFM
+ cantilever (Microlever, Type E, Thermomicroscopes) by means of a finite
+ element analysis. The modal shapes of the first 10 eigenmodes are
+ displayed as well as the numerical constants, which are needed for the
+ calibration using the thermal noise method. In the first eigenmode,
+ values for the thermomechanical noise of the z-displacement at 22
+ degrees C temperature of square root of u2(1) = A/square root of
+ c(cant) and the photodiode signal (normal-force) of S2(1) = A/square
+ root of c(cant) were obtained. The results also indicate a systematic
+ deviation ofthe spectral density of the thermomechanical noise of
+ v-shaped cantilevers as compared to rectangular beam-shaped
+ cantilevers.",
+ note = "Higher mode adjustments for v-shaped cantilevers from simulation.",
+ project = "Cantilever Calibration"
+}
+
+@article { strick96,
+ author = TRStrick #" and "# JFAllemand #" and "# DBensimon #" and "#
+ ABensimon #" and "# VCroquette,
+ title = "The elasticity of a single supercoiled {DNA} molecule",
+ year = 1996,
+ month = mar,
+ day = 29,
+ journal = SCI,
+ volume = 271,
+ number = 5257,
+ pages = "1835--1837",
+ issn = "0036-8075",
+ keywords = "Bacteriophage lambda;DNA, Superhelical;DNA,
+ Viral;Elasticity;Magnetics;Nucleic Acid Conformation;Temperature",
+ abstract = "Single linear DNA molecules were bound at multiple sites at one
+ extremity to a treated glass cover slip and at the other to a magnetic
+ bead. The DNA was therefore torsionally constrained. A magnetic field
+ was used to rotate the beads and thus to coil and pull the DNA. The
+ stretching force was determined by analysis of the Brownian
+ fluctuations of the bead. Here the elastic behavior of individual
+ lambda DNA molecules over- and underwound by up to 500 turns was
+ studied. A sharp transition was discovered from a low to a high
+ extension state at a force of approximately 0.45 piconewtons for
+ underwound molecules and at a force of approximately 3 piconewtons for
+ overwound ones. These transitions, probably reflecting the formation of
+ alternative structures in stretched coiled DNA molecules, might be
+ relevant for DNA transcription and replication."
+}
+
+@article { strunz99,
+ author = TStrunz #" and "# KOroszlan #" and "# RSchafer #" and "#
+ HJGuntherodt,
+ title = "Dynamic force spectroscopy of single {DNA} molecules",
+ year = 1999,
+ journal = PNAS,
+ volume = 96,
+ number = 20,
+ pages = "11277--11282",
+ doi = "10.1073/pnas.96.20.11277",
+ eprint = "http://www.pnas.org/cgi/reprint/96/20/11277.pdf",
+ url = "http://www.pnas.org/cgi/content/abstract/96/20/11277"
+}
+
+@article { szabo80,
+ author = ASzabo #" and "# KSchulten #" and "# ZSchulten,
+ title = "First passage time approach to diffusion controlled reactions",
+ collaboration = "",
+ year = 1980,
+ journal = JCP,
+ volume = 72,
+ number = 8,
+ pages = "4350--4357",
+ publisher = AIP,
+ doi = "10.1063/1.439715",
+ url = "http://link.aip.org/link/?JCP/72/4350/1",
+ keywords = "DIFFUSION; CHEMICAL REACTIONS; CHEMICAL REACTION KINETICS;
+ PROBABILITY; DIFFERENTIAL EQUATIONS"
+}
+
+@article { talaga00,
+ author = DTalaga #" and "# WLau #" and "# HRoder #" and "# JTang #" and "#
+ YJia #" and "# WDeGrado #" and "# RHochstrasser,
+ title = "Dynamics and folding of single two-stranded coiled-coil peptides
+ studied by fluorescent energy transfer confocal microscopy",
+ year = 2000,
+ journal = PNAS,
+ volume = 97,
+ number = 24,
+ pages = "13021--13026",
+ doi = "10.1073/pnas.97.24.13021",
+ eprint = "http://www.pnas.org/cgi/reprint/97/24/13021.pdf",
+ url = "http://www.pnas.org/cgi/content/abstract/97/24/13021"
+}
+
+@article { thirumalai05,
+ author = DThirumalai #" and "# CHyeon,
+ title = "{RNA} and Protein Folding: Common Themes and Variations",
+ affiliation = "Biophysics Program, and Department of Chemistry and
+ Biochemistry, Institute for Physical Science and Technology, University
+ of Maryland, College Park, Maryland 20742",
+ year = 2005,
+ journal = Biochemistry,
+ volume = 44,
+ number = 13,
+ pages = "4957--4970",
+ issn = "0006-2960",
+ url =
+ "http://pubs3.acs.org/acs/journals/doilookup?in_doi=10.1021/bi047314+",
+ abstract = "Visualizing the navigation of an ensemble of unfolded molecules
+ through the bumpy energy landscape in search of the native state gives
+ a pictorial view of biomolecular folding. This picture, when combined
+ with concepts in polymer theory, provides a unified theory of RNA and
+ protein folding. Just as for proteins, the major folding free energy
+ barrier for RNA scales sublinearly with the number of nucleotides,
+ which allows us to extract the elusive prefactor for RNA folding.
+ Several folding scenarios can be anticipated by considering variations
+ in the energy landscape that depend on sequence, native topology, and
+ external conditions. RNA and protein folding mechanism can be described
+ by the kinetic partitioning mechanism (KPM) according to which a
+ fraction () of molecules reaches the native state directly, whereas the
+ remaining fraction gets kinetically trapped in metastable
+ conformations. For two-state folders 1. Molecular chaperones are
+ recruited to assist protein folding whenever is small. We show that the
+ iterative annealing mechanism, introduced to describe chaperonin-
+ mediated folding, can be generalized to understand protein-assisted RNA
+ folding. The major differences between the folding of proteins and RNA
+ arise in the early stages of folding. For RNA, folding can only begin
+ after the polyelectrolyte problem is solved, whereas protein collapse
+ requires burial of hydrophobic residues. Cross-fertilization of ideas
+ between the two fields should lead to an understanding of how RNA and
+ proteins solve their folding problems.",
+ note = "unfolding-refolding"
+}
+
+@book { thornton04,
+ author = SThornton #" and "# JMarion,
+ title = "Classical Dynamics of Particles and Systems",
+ year = 2004,
+ edition = 5,
+ isbn = "0-534-40896-6",
+ publisher = BrooksCole,
+ address = "Belmont, CA"
+}
+
+@article { tlusty98,
+ author = TTlusty #" and "# AMeller #" and "# RBar-Ziv,
+ title = "Optical Gradient Forces of Strongly Localized Fields",
+ year = 1998,
+ month = aug,
+ journal = PRL,
+ volume = 81,
+ number = 8,
+ pages = "1738--1741",
+ numpages = 3,
+ publisher = APS,
+ doi = "10.1103/PhysRevLett.81.1738",
+ eprint = "http://prola.aps.org/pdf/PRL/v81/i8/p1738_1",
+ note = "also at \url{http://nanoscience.bu.edu/papers/p1738_1_Meller.pdf}.
+ Cited by \citet{grossman05} for derivation of thermal response fn.
+ However, I only see a referenced thermal energy when they list the
+ likelyhood of a small partical (radius < $R_c$) escaping due to thermal
+ energy, where $R_c$ is roughly $R_c \sim (k_B T / \alpha I_0)^(1/3)$,
+ $\alpha$ is a dielectric scaling term, and $I_0$ is the maximum beam
+ energy density. I imagine Grossman and Stout mixed up this reference.",
+ project = "Cantilever Calibration"
+}
+
+@article { tshiprut08,
+ author = ZTshiprut #" and "# JKlafter #" and "# MUrbakh,
+ title = "Single-molecule pulling experiments: when the stiffness of the
+ pulling device matters",
+ year = 2008,
+ month = sep,
+ day = 15,
+ journal = BPJ,
+ volume = 95,
+ number = 6,
+ pages = "L42--L44",
+ issn = "1542-0086",
+ doi = "10.1529/biophysj.108.141580",
+ eprint = "http://www.biophysj.org/cgi/reprint/95/6/L42.pdf",
+ abstract = "Using Langevin modeling, we investigate the role of the
+ experimental setup on the unbinding forces measured in single-molecule
+ pulling experiments. We demonstrate that the stiffness of the pulling
+ device, K(eff), may influence the unbinding forces through its effect
+ on the barrier heights for both unbinding and rebinding processes.
+ Under realistic conditions the effect of K(eff) on the rebinding
+ barrier is shown to play the most important role. This results in a
+ significant increase of the mean unbinding force with the stiffness for
+ a given loading rate. Thus, in contrast to the phenomenological Bell
+ model, we find that the loading rate (the multiplicative value K(eff)V,
+ V being the pulling velocity) is not the only control parameter that
+ determines the mean unbinding force. If interested in intrinsic
+ properties of a molecular system, we recommend probing the system in
+ the parameter range corresponding to a weak spring and relatively high
+ loading rates where rebinding is negligible.",
+ note = "Cites \citet{dudko03} for Kramers' description of irreversible
+ rupture, and claims it is required to explain the deviations in
+ $\avg{F}$ at the same loading rate. Proposes Moese equation as an
+ example potential. Cites \citet{walton08} for experimental evidence of
+ $\avg{F}$ increasing with linker stiffness."
+}
+
+@article { uniprot10,
+ author = TUPConsortium,
+ key = "uniprot10",
+ title = "The Universal Protein Resource (UniProt) in 2010.",
+ year = 2010,
+ month = jan,
+ day = 20,
+ journal = NAR,
+ volume = 38,
+ number = "Database issue",
+ pages = "D142--D148",
+ issn = "1362-4962",
+ doi = "10.1093/nar/gkp846",
+ url = "http://nar.oxfordjournals.org/cgi/content/abstract/38/suppl_1/D142",
+ keywords = "Algorithms;Animals;Computational Biology;Databases, Nucleic
+ Acid;Databases, Protein;Europe;Genome, Fungal;Genome,
+ Viral;Humans;Information Storage and Retrieval;Internet;Protein
+ Isoforms;Proteome;Proteomics;Software",
+ abstract = "The primary mission of UniProt is to support biological
+ research by maintaining a stable, comprehensive, fully classified,
+ richly and accurately annotated protein sequence knowledgebase, with
+ extensive cross-references and querying interfaces freely accessible to
+ the scientific community. UniProt is produced by the UniProt Consortium
+ which consists of groups from the European Bioinformatics Institute
+ (EBI), the Swiss Institute of Bioinformatics (SIB) and the Protein
+ Information Resource (PIR). UniProt is comprised of four major
+ components, each optimized for different uses: the UniProt Archive, the
+ UniProt Knowledgebase, the UniProt Reference Clusters and the UniProt
+ Metagenomic and Environmental Sequence Database. UniProt is updated and
+ distributed every 3 weeks and can be accessed online for searches or
+ download at http://www.uniprot.org."
+}
+
+@misc { uniprot:STRAV,
+ key = "uniprot:STRAV",
+ url = "http://www.uniprot.org/uniprot/P22629"
+}
+
+@book { vanKampen07,
+ author = NGvanKampen,
+ title = "Stochastic Processes in Physics and Chemistry",
+ year = 2007,
+ edition = 3,
+ publisher = ElsevierNorth-HollandPersonalLibrary,
+ address = "Amsterdam",
+ note = "",
+ project = "sawtooth simulation"
+}
+
+@article { venter01,
+ author = JCVenter #" and "# MDAdams #" and "# EWMyers #" and "# PWLi #" and
+ "# RJMural #" and "# GGSutton #" and "# HOSmith #" and "# MYandell #"
+ and "# CAEvans #" and "# RAHolt #" and "# JDGocayne #" and "#
+ PAmanatides #" and "# RMBallew #" and "# DHHuson #" and "# JRWortman #"
+ and "# QZhang #" and "# CDKodira #" and "# XHZheng #" and "# LChen #"
+ and "# MSkupski #" and "# GSubramanian #" and "# PDThomas #" and "#
+ JZhang #" and "# GLGaborMiklos #" and "# CNelson #" and "# SBroder #"
+ and "# AGClark #" and "# JNadeau #" and "# VAMcKusick #" and "# NZinder
+ #" and "# AJLevine #" and "# RJRoberts #" and "# MSimon #" and "#
+ CSlayman #" and "# MHunkapiller #" and "# RBolanos #" and "# ADelcher
+ #" and "# IDew #" and "# DFasulo #" and "# MFlanigan #" and "# LFlorea
+ #" and "# AHalpern #" and "# SHannenhalli #" and "# SKravitz #" and "#
+ SLevy #" and "# CMobarry #" and "# KReinert #" and "# KRemington #" and
+ "# JAbu-Threideh #" and "# EBeasley #" and "# KBiddick #" and "#
+ VBonazzi #" and "# RBrandon #" and "# MCargill #" and "#
+ IChandramouliswaran #" and "# RCharlab #" and "# KChaturvedi #" and "#
+ ZDeng #" and "# VDiFrancesco #" and "# PDunn #" and "# KEilbeck #" and
+ "# CEvangelista #" and "# AEGabrielian #" and "# WGan #" and "# WGe #"
+ and "# FGong #" and "# ZGu #" and "# PGuan #" and "# TJHeiman #" and "#
+ MEHiggins #" and "# RRJi #" and "# ZKe #" and "# KAKetchum #" and "#
+ ZLai #" and "# YLei #" and "# ZLi #" and "# JLi #" and "# YLiang #" and
+ "# XLin #" and "# FLu #" and "# GVMerkulov #" and "# NMilshina #" and
+ "# HMMoore #" and "# AKNaik #" and "# VANarayan #" and "# BNeelam #"
+ and "# DNusskern #" and "# DBRusch #" and "# SSalzberg #" and "# WShao
+ #" and "# BShue #" and "# JSun #" and "# ZWang #" and "# AWang #" and
+ "# XWang #" and "# JWang #" and "# MWei #" and "# RWides #" and "#
+ CXiao #" and "# CYan #" and "# AYao #" and "# JYe #" and "# MZhan #"
+ and "# WZhang #" and "# HZhang #" and "# QZhao #" and "# LZheng #" and
+ "# FZhong #" and "# WZhong #" and "# SZhu #" and "# SZhao #" and "#
+ DGilbert #" and "# SBaumhueter #" and "# GSpier #" and "# CCarter #"
+ and "# ACravchik #" and "# TWoodage #" and "# FAli #" and "# HAn #" and
+ "# AAwe #" and "# DBaldwin #" and "# HBaden #" and "# MBarnstead #" and
+ "# IBarrow #" and "# KBeeson #" and "# DBusam #" and "# ACarver #" and
+ "# ACenter #" and "# MLCheng #" and "# LCurry #" and "# SDanaher #" and
+ "# LDavenport #" and "# RDesilets #" and "# SDietz #" and "# KDodson #"
+ and "# LDoup #" and "# SFerriera #" and "# NGarg #" and "# AGluecksmann
+ #" and "# BHart #" and "# JHaynes #" and "# CHaynes #" and "# CHeiner
+ #" and "# SHladun #" and "# DHostin #" and "# JHouck #" and "# THowland
+ #" and "# CIbegwam #" and "# JJohnson #" and "# FKalush #" and "#
+ LKline #" and "# SKoduru #" and "# ALove #" and "# FMann #" and "# DMay
+ #" and "# SMcCawley #" and "# TMcIntosh #" and "# IMcMullen #" and "#
+ MMoy #" and "# LMoy #" and "# BMurphy #" and "# KNelson #" and "#
+ CPfannkoch #" and "# EPratts #" and "# VPuri #" and "# HQureshi #" and
+ "# MReardon #" and "# RRodriguez #" and "# YHRogers #" and "# DRomblad
+ #" and "# BRuhfel #" and "# RScott #" and "# CSitter #" and "#
+ MSmallwood #" and "# EStewart #" and "# RStrong #" and "# ESuh #" and
+ "# RThomas #" and "# NNTint #" and "# STse #" and "# CVech #" and "#
+ GWang #" and "# JWetter #" and "# SWilliams #" and "# MWilliams #" and
+ "# SWindsor #" and "# EWinn-Deen #" and "# KWolfe #" and "# JZaveri #"
+ and "# KZaveri #" and "# JFAbril #" and "# RGuigo #" and "# MJCampbell
+ #" and "# KVSjolander #" and "# BKarlak #" and "# AKejariwal #" and "#
+ HMi #" and "# BLazareva #" and "# THatton #" and "# ANarechania #" and
+ "# KDiemer #" and "# AMuruganujan #" and "# NGuo #" and "# SSato #" and
+ "# VBafna #" and "# SIstrail #" and "# RLippert #" and "# RSchwartz #"
+ and "# BWalenz #" and "# SYooseph #" and "# DAllen #" and "# ABasu #"
+ and "# JBaxendale #" and "# LBlick #" and "# MCaminha #" and "#
+ JCarnes-Stine #" and "# PCaulk #" and "# YHChiang #" and "# MCoyne #"
+ and "# CDahlke #" and "# AMays #" and "# MDombroski #" and "# MDonnelly
+ #" and "# DEly #" and "# SEsparham #" and "# CFosler #" and "# HGire #"
+ and "# SGlanowski #" and "# KGlasser #" and "# AGlodek #" and "#
+ MGorokhov #" and "# KGraham #" and "# BGropman #" and "# MHarris #" and
+ "# JHeil #" and "# SHenderson #" and "# JHoover #" and "# DJennings #"
+ and "# CJordan #" and "# JJordan #" and "# JKasha #" and "# LKagan #"
+ and "# CKraft #" and "# ALevitsky #" and "# MLewis #" and "# XLiu #"
+ and "# JLopez #" and "# DMa #" and "# WMajoros #" and "# JMcDaniel #"
+ and "# SMurphy #" and "# MNewman #" and "# TNguyen #" and "# NNguyen #"
+ and "# MNodell #" and "# SPan #" and "# JPeck #" and "# MPeterson #"
+ and "# WRowe #" and "# RSanders #" and "# JScott #" and "# MSimpson #"
+ and "# TSmith #" and "# ASprague #" and "# TStockwell #" and "# RTurner
+ #" and "# EVenter #" and "# MWangX #" and "# MWen #" and "# DWu #" and
+ "# MWu #" and "# AXia #" and "# AZandieh #" and "# XZhu,
+ title = "The sequence of the human genome.",
+ year = 2001,
+ month = "Feb",
+ day = 16,
+ journal = SCI,
+ volume = 291,
+ number = 5507,
+ pages = "1304--1351",
+ issn = "0036-8075",
+ doi = "10.1126/science.1058040",
+ eprint = "http://www.sciencemag.org/cgi/content/pdf/291/5507/1304",
+ url = "http://www.sciencemag.org/cgi/content/short/291/5507/1304",
+ keywords = "Algorithms;Animals;Chromosome Banding;Chromosome
+ Mapping;Chromosomes, Artificial, Bacterial;Computational
+ Biology;Consensus Sequence;CpG Islands;DNA, Intergenic;Databases,
+ Factual;Evolution, Molecular;Exons;Female;Gene
+ Duplication;Genes;Genetic Variation;Genome, Human;Human Genome
+ Project;Humans;Introns;Male;Phenotype;Physical Chromosome
+ Mapping;Polymorphism, Single Nucleotide;Proteins;Pseudogenes;Repetitive
+ Sequences, Nucleic Acid;Retroelements;Sequence Analysis, DNA;Species
+ Specificity",
+ abstract = "A 2.91-billion base pair (bp) consensus sequence of the
+ euchromatic portion of the human genome was generated by the whole-
+ genome shotgun sequencing method. The 14.8-billion bp DNA sequence was
+ generated over 9 months from 27,271,853 high-quality sequence reads
+ (5.11-fold coverage of the genome) from both ends of plasmid clones
+ made from the DNA of five individuals. Two assembly strategies-a whole-
+ genome assembly and a regional chromosome assembly-were used, each
+ combining sequence data from Celera and the publicly funded genome
+ effort. The public data were shredded into 550-bp segments to create a
+ 2.9-fold coverage of those genome regions that had been sequenced,
+ without including biases inherent in the cloning and assembly procedure
+ used by the publicly funded group. This brought the effective coverage
+ in the assemblies to eightfold, reducing the number and size of gaps in
+ the final assembly over what would be obtained with 5.11-fold coverage.
+ The two assembly strategies yielded very similar results that largely
+ agree with independent mapping data. The assemblies effectively cover
+ the euchromatic regions of the human chromosomes. More than 90\% of the
+ genome is in scaffold assemblies of 100,000 bp or more, and 25\% of the
+ genome is in scaffolds of 10 million bp or larger. Analysis of the
+ genome sequence revealed 26,588 protein-encoding transcripts for which
+ there was strong corroborating evidence and an additional approximately
+ 12,000 computationally derived genes with mouse matches or other weak
+ supporting evidence. Although gene-dense clusters are obvious, almost
+ half the genes are dispersed in low G+C sequence separated by large
+ tracts of apparently noncoding sequence. Only 1.1\% of the genome is
+ spanned by exons, whereas 24\% is in introns, with 75\% of the genome
+ being intergenic DNA. Duplications of segmental blocks, ranging in size
+ up to chromosomal lengths, are abundant throughout the genome and
+ reveal a complex evolutionary history. Comparative genomic analysis
+ indicates vertebrate expansions of genes associated with neuronal
+ function, with tissue-specific developmental regulation, and with the
+ hemostasis and immune systems. DNA sequence comparisons between the
+ consensus sequence and publicly funded genome data provided locations
+ of 2.1 million single-nucleotide polymorphisms (SNPs). A random pair of
+ human haploid genomes differed at a rate of 1 bp per 1250 on average,
+ but there was marked heterogeneity in the level of polymorphism across
+ the genome. Less than 1\% of all SNPs resulted in variation in
+ proteins, but the task of determining which SNPs have functional
+ consequences remains an open challenge."
+}
+
+@article { verdier70,
+ author = PHVerdier,
+ title = "Relaxation Behavior of the Freely Jointed Chain",
+ collaboration = "",
+ year = 1970,
+ journal = JCP,
+ volume = 52,
+ number = 11,
+ pages = "5512--5517",
+ publisher = AIP,
+ doi = "10.1063/1.1672818",
+ url = "http://link.aip.org/link/?JCP/52/5512/1"
+}
+
+@article { walther07,
+ author = KWalther #" and "# FGrater #" and "# LDougan #" and "# CBadilla #"
+ and "# BBerne #" and "# JFernandez,
+ title = "Signatures of hydrophobic collapse in extended proteins captured
+ with force spectroscopy",
+ year = 2007,
+ journal = PNAS,
+ volume = 104,
+ number = 19,
+ pages = "7916--7921",
+ doi = "10.1073/pnas.0702179104",
+ eprint = "http://www.pnas.org/cgi/reprint/104/19/7916.pdf",
+ url = "http://www.pnas.org/cgi/content/abstract/104/19/7916",
+ abstract = "We unfold and extend single proteins at a high force and then
+ linearly relax the force to probe their collapse mechanisms. We observe
+ a large variability in the extent of their recoil. Although chain
+ entropy makes a small contribution, we show that the observed
+ variability results from hydrophobic interactions with randomly varying
+ magnitude from protein to protein. This collapse mechanism is common to
+ highly extended proteins, including nonfolding elastomeric proteins
+ like PEVK from titin. Our observations explain the puzzling differences
+ between the folding behavior of highly extended proteins, from those
+ folding after chemical or thermal denaturation. Probing the collapse of
+ highly extended proteins with force spectroscopy allows separation of
+ the different driving forces in protein folding."
+}
+
+@article { walton08,
+ author = EBWalton #" and "# SLee #" and "# KJVanVliet,
+ title = "Extending {B}ell's model: how force transducer stiffness alters
+ measured unbinding forces and kinetics of molecular complexes",
+ year = 2008,
+ month = apr,
+ day = 01,
+ journal = BPJ,
+ volume = 94,
+ number = 7,
+ pages = "2621--2630",
+ issn = "1542-0086",
+ doi = "10.1529/biophysj.107.114454",
+ keywords = "Biotin;Computer
+ Simulation;Elasticity;Kinetics;Mechanotransduction, Cellular;Models,
+ Chemical;Models, Molecular;Molecular Motor
+ Proteins;Motion;Streptavidin;Stress, Mechanical;Transducers",
+ abstract = "Forced unbinding of complementary macromolecules such as
+ ligand-receptor complexes can reveal energetic and kinetic details
+ governing physiological processes ranging from cellular adhesion to
+ drug metabolism. Although molecular-level experiments have enabled
+ sampling of individual ligand-receptor complex dissociation events,
+ disparities in measured unbinding force F(R) among these methods lead
+ to marked variation in inferred binding energetics and kinetics at
+ equilibrium. These discrepancies are documented for even the ubiquitous
+ ligand-receptor pair, biotin-streptavidin. We investigated these
+ disparities and examined atomic-level unbinding trajectories via
+ steered molecular dynamics simulations, as well as via molecular force
+ spectroscopy experiments on biotin-streptavidin. In addition to the
+ well-known loading rate dependence of F(R) predicted by Bell's model,
+ we find that experimentally accessible parameters such as the effective
+ stiffness of the force transducer k can significantly perturb the
+ energy landscape and the apparent unbinding force of the complex for
+ sufficiently stiff force transducers. Additionally, at least 20\%
+ variation in unbinding force can be attributed to minute differences in
+ initial atomic positions among energetically and structurally
+ comparable complexes. For force transducers typical of molecular force
+ spectroscopy experiments and atomistic simulations, this energy barrier
+ perturbation results in extrapolated energetic and kinetic parameters
+ of the complex that depend strongly on k. We present a model that
+ explicitly includes the effect of k on apparent unbinding force of the
+ ligand-receptor complex, and demonstrate that this correction enables
+ prediction of unbinding distances and dissociation rates that are
+ decoupled from the stiffness of actual or simulated molecular linkers.",
+ note = "Some detailed estimates at U(x)."
+}
+
+@article { walton86,
+ author = AJWalton,
+ title = "The Abbe theory of imaging: an alternative derivation of the
+ resolution limit",
+ year = 1986,
+ journal = EuropeanJournalofPhysics,
+ volume = 7,
+ number = 1,
+ pages = "62--63",
+ url = "http://stacks.iop.org/0143-0807/7/62"
+}
+
+@article { watanabe05,
+ author = HWatanabe #" and "# TInoue,
+ title = "Conformational dynamics of Rouse chains during creep/recovery
+ processes: a review",
+ year = 2005,
+ journal = JPCM,
+ volume = 17,
+ number = 19,
+ pages = "R607--R636",
+ doi = "10.1088/0953-8984/17/19/R01",
+ eprint = "http://www.iop.org/EJ/article/0953-8984/17/19/R01/cm5_19_R01.pdf",
+ url = "http://stacks.iop.org/0953-8984/17/R607",
+ abstract = "The Rouse model is a well-established model for non-entangled
+ polymer chains and also serves as a fundamental model for entangled
+ chains. The dynamic behaviour of this model under strain-controlled
+ conditions has been fully analysed in the literature. However, despite
+ the importance of the Rouse model, no analysis has been made so far of
+ the orientational anisotropy of the Rouse eigenmodes during the stress-
+ controlled, creep and recovery processes. For completeness of the
+ analysis of the model, the Rouse equation of motion is solved to
+ calculate this anisotropy for monodisperse chains and their binary
+ blends during the creep/recovery processes. The calculation is simple
+ and straightforward, but the result is intriguing in the sense that
+ each Rouse eigenmode during these processes has a distribution in the
+ retardation times. This behaviour, reflecting the interplay/correlation
+ among the Rouse eigenmodes of different orders (and for different
+ chains in the blends) under the constant stress condition, is quite
+ different from the behaviour under rate-controlled flow (where each
+ eigenmode exhibits retardation/relaxation associated with a single
+ characteristic time). Furthermore, the calculation indicates that the
+ Rouse chains exhibit affine deformation on sudden imposition/removal of
+ the stress and the magnitude of this deformation is inversely
+ proportional to the number of bond vectors per chain. In relation to
+ these results, a difference between the creep and relaxation properties
+ is also discussed for chains obeying multiple relaxation mechanisms
+ (Rouse and reptation mechanisms).",
+ note = "Middly-detailed Rouse model review."
+}
+
+@article { wiita06,
+ author = AWiita #" and "# SAinavarapu #" and "# HHuang #" and "# JFernandez,
+ title = "From the Cover: Force-dependent chemical kinetics of disulfide
+ bond reduction observed with single-molecule techniques",
+ year = 2006,
+ journal = PNAS,
+ volume = 103,
+ number = 19,
+ pages = "7222--7227",
+ doi = "10.1073/pnas.0511035103",
+ eprint = "http://www.pnas.org/cgi/reprint/103/19/7222.pdf",
+ url = "http://www.pnas.org/cgi/content/abstract/103/19/7222",
+ abstract = "The mechanism by which mechanical force regulates the kinetics
+ of a chemical reaction is unknown. Here, we use single-molecule force-
+ clamp spectroscopy and protein engineering to study the effect of force
+ on the kinetics of thiol/disulfide exchange. Reduction of disulfide
+ bonds through the thiol/disulfide exchange chemical reaction is crucial
+ in regulating protein function and is known to occur in mechanically
+ stressed proteins. We apply a constant stretching force to single
+ engineered disulfide bonds and measure their rate of reduction by DTT.
+ Although the reduction rate is linearly dependent on the concentration
+ of DTT, it is exponentially dependent on the applied force, increasing
+ 10-fold over a 300-pN range. This result predicts that the disulfide
+ bond lengthens by 0.34 A at the transition state of the thiol/disulfide
+ exchange reaction. Our work at the single bond level directly
+ demonstrates that thiol/disulfide exchange in proteins is a force-
+ dependent chemical reaction. Our findings suggest that mechanical force
+ plays a role in disulfide reduction in vivo, a property that has never
+ been explored by traditional biochemistry. Furthermore, our work also
+ indicates that the kinetics of any chemical reaction that results in
+ bond lengthening will be force-dependent."
+}
+
+@article { wilcox05,
+ author = AWilcox #" and "# JChoy #" and "# CBustamante #" and "#
+ AMatouschek,
+ title = "Effect of protein structure on mitochondrial import",
+ year = 2005,
+ journal = PNAS,
+ volume = 102,
+ number = 43,
+ pages = "15435--15440",
+ doi = "10.1073/pnas.0507324102",
+ eprint = "http://www.pnas.org/cgi/reprint/102/43/15435.pdf",
+ url = "http://www.pnas.org/cgi/content/abstract/102/43/15435",
+ abstract = "Most proteins that are to be imported into the mitochondrial
+ matrix are synthesized as precursors, each composed of an N-terminal
+ targeting sequence followed by a mature domain. Precursors are
+ recognized through their targeting sequences by receptors at the
+ mitochondrial surface and are then threaded through import channels
+ into the matrix. Both the targeting sequence and the mature domain
+ contribute to the efficiency with which proteins are imported into
+ mitochondria. Precursors must be in an unfolded conformation during
+ translocation. Mitochondria can unfold some proteins by changing their
+ unfolding pathways. The effectiveness of this unfolding mechanism
+ depends on the local structure of the mature domain adjacent to the
+ targeting sequence. This local structure determines the extent to which
+ the unfolding pathway can be changed and, therefore, the unfolding rate
+ increased. Atomic force microscopy studies find that the local
+ structures of proteins near their N and C termini also influence their
+ resistance to mechanical unfolding. Thus, protein unfolding during
+ import resembles mechanical unfolding, and the specificity of import is
+ determined by the resistance of the mature domain to unfolding as well
+ as by the properties of the targeting sequence."
+}
+
+@article { wolfsberg01,
+ author = TGWolfsberg #" and "# JMcEntyre #" and "# GDSchuler,
+ title = "Guide to the draft human genome.",
+ year = 2001,
+ month = feb,
+ day = 15,
+ journal = NAT,
+ volume = 409,
+ number = 6822,
+ pages = "824--826",
+ issn = "0028-0836",
+ doi = "10.1038/35057000",
+ eprint = "http://www.nature.com/nature/journal/v409/n6822/pdf/409824a0.pdf",
+ url = "http://www.nature.com/nature/journal/v409/n6822/full/409824a0.html",
+ keywords = "Amino Acid Sequence;Chromosome Mapping;Computational
+ Biology;Genes;Genetic Variation;Genome, Human;Human Genome
+ Project;Humans;Internet;Molecular Sequence Data;Sequence Analysis, DNA",
+ abstract = "There are a number of ways to investigate the structure,
+ function and evolution of the human genome. These include examining the
+ morphology of normal and abnormal chromosomes, constructing maps of
+ genomic landmarks, following the genetic transmission of phenotypes and
+ DNA sequence variations, and characterizing thousands of individual
+ genes. To this list we can now add the elucidation of the genomic DNA
+ sequence, albeit at 'working draft' accuracy. The current challenge is
+ to weave together these disparate types of data to produce the
+ information infrastructure needed to support the next generation of
+ biomedical research. Here we provide an overview of the different
+ sources of information about the human genome and how modern
+ information technology, in particular the internet, allows us to link
+ them together."
+}
+
+@article { wu04,
+ author = JWWu #" and "# WLHung #" and "# CHTsai,
+ title = "Estimation of parameters of the {G}ompertz distribution using the
+ least squares method",
+ year = 2004,
+ month = oct,
+ day = 25,
+ journal = AppliedMathematicsandComputation,
+ volume = 158,
+ number = 1,
+ pages = "133--147",
+ issn = "0096-3003",
+ doi = "10.1016/j.amc.2003.08.086",
+ url = "http://dx.doi.org/10.1016/j.amc.2003.08.086",
+ keywords = "Gompertz distribution; Least squares estimate; Maximum
+ likelihood estimate; First failure-censored; Series system",
+ abstract = "The Gompertz distribution has been used to describe human
+ mortality and establish actuarial tables. Recently, this distribution
+ has been again studied by some authors. The maximum likelihood
+ estimates for the parameters of the Gompertz distribution has been
+ discussed by Garg et al. [J. R. Statist. Soc. C 19 (1970) 152]. The
+ purpose of this paper is to propose unweighted and weighted least
+ squares estimates for parameters of the Gompertz distribution under the
+ complete data and the first failure-censored data (series systems; see
+ [J. Statist. Comput. Simulat. 52 (1995) 337]). A simulation study is
+ carried out to compare the proposed estimators and the maximum
+ likelihood estimators. Results of the simulation studies show that the
+ performance of the weighted least squares estimators is acceptable."
+}
+
+@article { yang00,
+ author = GYang #" and "# CCecconi #" and "# WBaase #" and "# IVetter #" and
+ "# WBreyer #" and "# JHaack #" and "# BMatthews #" and "# FDahlquist #"
+ and "# CBustamante,
+ title = "Solid-state synthesis and mechanical unfolding of polymers of {T4}
+ lysozyme",
+ year = 2000,
+ journal = PNAS,
+ volume = 97,
+ number = 1,
+ pages = "139--144",
+ doi = "10.1073/pnas.97.1.139",
+ eprint = "http://www.pnas.org/cgi/reprint/97/1/139.pdf",
+ url = "http://www.pnas.org/cgi/content/abstract/97/1/139"
+}
+
+@article { yang06,
+ author = YYang #" and "# FCLin #" and "# GYang,
+ title = "Temperature control device for single molecule measurements using
+ the atomic force microscope",
+ collaboration = "",
+ year = 2006,
+ journal = RSI,
+ volume = 77,
+ number = 6,
+ pages = 063701,
+ numpages = 5,
+ publisher = AIP,
+ eid = 063701,
+ doi = "10.1063/1.2204580",
+ url = "http://link.aip.org/link/?RSI/77/063701/1",
+ keywords = "temperature control; atomic force microscopy; thermocouples;
+ heat sinks",
+ note = "Introduces our temperature control system",
+ project = "Energy Landscape Roughness"
+}
+
+@article { yu06,
+ author = WYu #" and "# JLamb #" and "# FHan #" and "# JBirchler,
+ title = "Telomere-mediated chromosomal truncation in maize",
+ year = 2006,
+ journal = PNAS,
+ volume = 103,
+ number = 46,
+ pages = "17331--17336",
+ doi = "10.1073/pnas.0605750103",
+ eprint = "http://www.pnas.org/cgi/reprint/103/46/17331.pdf",
+ url = "http://www.pnas.org/cgi/content/abstract/103/46/17331",
+ abstract = "Direct repeats of Arabidopsis telomeric sequence were
+ constructed to test telomere-mediated chromosomal truncation in maize.
+ Two constructs with 2.6 kb of telomeric sequence were used to transform
+ maize immature embryos by Agrobacterium-mediated transformation. One
+ hundred seventy-six transgenic lines were recovered in which 231
+ transgene loci were revealed by a FISH analysis. To analyze chromosomal
+ truncations that result in transgenes located near chromosomal termini,
+ Southern hybridization analyses were performed. A pattern of smear in
+ truncated lines was seen as compared with discrete bands for internal
+ integrations, because telomeres in different cells are elongated
+ differently by telomerase. When multiple restriction enzymes were used
+ to map the transgene positions, the size of the smears shifted in
+ accordance with the locations of restriction sites on the construct.
+ This result demonstrated that the transgene was present at the end of
+ the chromosome immediately before the integrated telomere sequence.
+ Direct evidence for chromosomal truncation came from the results of
+ FISH karyotyping, which revealed broken chromosomes with transgene
+ signals at the ends. These results demonstrate that telomere-mediated
+ chromosomal truncation operates in plant species. This technology will
+ be useful for chromosomal engineering in maize as well as other plant
+ species."
+}
+
+@article { zhao06,
+ author = JZhao #" and "# HLee #" and "# RNome #" and "# SMajid #" and "#
+ NScherer #" and "# WHoff,
+ title = "Single-molecule detection of structural changes during
+ {P}er-{A}rnt-{S}im ({PAS}) domain activation",
+ year = 2006,
+ journal = PNAS,
+ volume = 103,
+ number = 31,
+ pages = "11561--11566",
+ doi = "10.1073/pnas.0601567103",
+ eprint = "http://www.pnas.org/cgi/reprint/103/31/11561.pdf",
+ url = "http://www.pnas.org/cgi/content/abstract/103/31/11561",
+ abstract = "The Per-Arnt-Sim (PAS) domain is a ubiquitous protein module
+ with a common three-dimensional fold involved in a wide range of
+ regulatory and sensory functions in all domains of life. The activation
+ of these functions is thought to involve partial unfolding of N- or
+ C-terminal helices attached to the PAS domain. Here we use atomic force
+ microscopy to probe receptor activation in single molecules of
+ photoactive yellow protein (PYP), a prototype of the PAS domain family.
+ Mechanical unfolding of Cys-linked PYP multimers in the presence and
+ absence of illumination reveals that, in contrast to previous studies,
+ the PAS domain itself is extended by {approx}3 nm (at the 10-pN
+ detection limit of the measurement) and destabilized by {approx}30% in
+ the light-activated state of PYP. Comparative measurements and steered
+ molecular dynamics simulations of two double-Cys PYP mutants that probe
+ different regions of the PAS domain quantify the anisotropy in
+ stability and changes in local structure, thereby demonstrating the
+ partial unfolding of their PAS domain upon activation. These results
+ establish a generally applicable single-molecule approach for mapping
+ functional conformational changes to selected regions of a protein. In
+ addition, the results have profound implications for the molecular
+ mechanism of PAS domain activation and indicate that stimulus-induced
+ partial protein unfolding can be used as a signaling mechanism."
+}
+
+@article { zhuang06,
+ author = WZhuang #" and "# DAbramavicius #" and "# SMukamel,
+ title = "Two-dimensional vibrational optical probes for peptide fast
+ folding investigation",
+ year = 2006,
+ journal = PNAS,
+ volume = 103,
+ number = 50,
+ pages = "18934--18938",
+ doi = "10.1073/pnas.0606912103",
+ eprint = "http://www.pnas.org/cgi/reprint/103/50/18934.pdf",
+ url = "http://www.pnas.org/cgi/content/abstract/103/50/18934",
+ abstract = "A simulation study shows that early protein folding events may
+ be investigated by using a recently developed family of nonlinear
+ infrared techniques that combine the high temporal and spatial
+ resolution of multidimensional spectroscopy with the chirality-specific
+ sensitivity of amide vibrations to structure. We demonstrate how the
+ structural sensitivity of cross-peaks in two-dimensional correlation
+ plots of chiral signals of an {alpha} helix and a [beta] hairpin may be
+ used to clearly resolve structural and dynamical details undetectable
+ by one-dimensional techniques (e.g. circular dichroism) and identify
+ structures indistinguishable by NMR."
+}
+
+@article { zinober02,
+ author = RCZinober #" and "# DJBrockwell #" and "# GSBeddard #" and "#
+ AWBlake #" and "# PDOlmsted #" and "# SERadford #" and "# DASmith,
+ title = "Mechanically unfolding proteins: the effect of unfolding history
+ and the supramolecular scaffold",
+ year = 2002,
+ month = dec,
+ journal = PS,
+ volume = 11,
+ number = 12,
+ pages = "2759--2765",
+ issn = "0961-8368",
+ doi = "10.1110/ps.0224602",
+ eprint = "http://www.proteinscience.org/cgi/reprint/11/12/2759.pdf",
+ url = "http://www.proteinscience.org/cgi/content/abstract/11/12/2759",
+ keywords = "Computer Simulation; Models, Molecular; Monte Carlo Method;
+ Protein Folding; Protein Structure, Tertiary; Proteins",
+ abstract = "The mechanical resistance of a folded domain in a polyprotein
+ of five mutant I27 domains (C47S, C63S I27)(5)is shown to depend on the
+ unfolding history of the protein. This observation can be understood on
+ the basis of competition between two effects, that of the changing
+ number of domains attempting to unfold, and the progressive increase in
+ the compliance of the polyprotein as domains unfold. We present Monte
+ Carlo simulations that show the effect and experimental data that
+ verify these observations. The results are confirmed using an
+ analytical model based on transition state theory. The model and
+ simulations also predict that the mechanical resistance of a domain
+ depends on the stiffness of the surrounding scaffold that holds the
+ domain in vivo, and on the length of the unfolded domain. Together,
+ these additional factors that influence the mechanical resistance of
+ proteins have important consequences for our understanding of natural
+ proteins that have evolved to withstand force.",
+ note = "Introduces unfolding-order \emph{scaffold effect} on average
+ unfolding force.",
+ project = "sawtooth simulation"
+}
+
+@article { zwanzig92,
+ author = RZwanzig #" and "# ASzaboX #" and "# BBagchi,
+ title = "Levinthal's paradox.",
+ year = 1992,
+ month = jan,
+ day = 01,
+ journal = PNAS,
+ volume = 89,
+ number = 1,
+ pages = "20--22",
+ issn = "0027-8424",
+ eprint =
+ "http://www.ncbi.nlm.nih.gov/pmc/articles/PMC48166/pdf/pnas01075-0036.p
+ df",
+ url = "http://www.ncbi.nlm.nih.gov/pmc/articles/PMC48166/",
+ keywords = "Mathematics;Models, Theoretical;Protein Conformation;Proteins",
+ abstract = "Levinthal's paradox is that finding the native folded state of
+ a protein by a random search among all possible configurations can take
+ an enormously long time. Yet proteins can fold in seconds or less.
+ Mathematical analysis of a simple model shows that a small and
+ physically reasonable energy bias against locally unfavorable
+ configurations, of the order of a few kT, can reduce Levinthal's time
+ to a biologically significant size."
}
+
projects / thesis.git / commitdiff