--- /dev/null
+% Good, very basic tutorial
+% http://cmtw.harvard.edu/Documentation/TeX/Bibtex/Example.html
+% More detail on the whole process
+% http://www.andy-roberts.net/misc/latex/latextutorial3.html
+% Entry types reference
+% http://newton.ex.ac.uk/tex/pack/bibtex/btxdoc/node6.html
+% Fields reference
+% http://newton.ex.ac.uk/tex/pack/bibtex/btxdoc/node7.html
+% Entry and field reference, but with little discussion
+% http://en.wikipedia.org/wiki/BibTeX
+% Examples of assorted styles
+% http://www.cs.stir.ac.uk/~kjt/software/latex/showbst.html
+% Assorted BibTeX tools
+% http://liinwww.ira.uka.de/bibliography/Bib.Format.html
+%
+% at some point in your latex document
+% \bibliographystyle{prsty} % Phys. Rev. style
+% other syles include abbrv, alpha, plain, unsrt
+%
+% and in your latex document where you want the bibliography:
+% \bibliography{wtk} % wtk.bib is the name of the database
+%
+% compile (using latex for example) with
+% $ latex example
+% $ bibtex example
+% $ latex example
+% $ latex example
+%
+% See possibly the Natbib package for other citation styles & link formats
+% Customize bibliography with Makebst (`latex makebst`),
+% makes .bst bib-style format files according to your specifications.
+%
+% My key style is '<lowercase-main-author-last-name><four-digit-year>',
+% which I can kindof achieve with
+% $ bibtool -f '%-1n(author)%2d(year)' wtk.bib -o wtk1.bib
+% Except any paper with more than one author has a '.ea' appended to the name
+% and bibtool removes all comments :(.
+
+% Define some Journal name shortcuts
+% @String{PRL = "Phys. Rev. Lett."}
+
+% @String{RMP = "Rev. Mod. Phys."}
+
+% @String{LANG = "Langmuir"}
+
+% @String(PNAS="Proc. Nat. Acad. Sci.")
+% @String{RSI = "Rev. Sci. Instrum."}
+
+@Article{hyeon03,
+ author = "Changbong Hyeon and D. Thirumalai",
+ title = "Can energy landscape roughness of proteins and {RNA}
+ be measured by using mechanical unfolding
+ experiments?",
+ journal = "Proc Natl Acad Sci U S A",
+ year = "2003",
+ month = sep,
+ day = "02",
+ volume = "100",
+ number = "18",
+ pages = "10249--10253",
+ keywords = "Protein Folding",
+ keywords = "Proteins",
+ keywords = "RNA",
+ keywords = "Temperature",
+ keywords = "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 Hanggi Eq. 4.56c (page 275)\cite{hanggi90}.",
+ project = "Energy Landscape Roughness",
+}
+
+@Article{nevo05,
+ author = "Reinat Nevo and Vlad Brumfeld and Ruti Kapon and Peter
+ Hinterdorfer and Ziv Reich",
+ title = "Direct measurement of protein energy landscape
+ roughness.",
+ journal = "EMBO Rep",
+ year = "2005",
+ month = may,
+ volume = "6",
+ number = "5",
+ pages = "482--486",
+ keywords = "Models, Molecular",
+ keywords = "Protein Binding",
+ keywords = "Protein Folding",
+ keywords = "Spectrum Analysis",
+ keywords = "Thermodynamics",
+ keywords = "beta Karyopherins",
+ keywords = "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 H&T\cite{hyeon03} to ligand-receptor
+ binding.",
+ project = "Energy Landscape Roughness",
+}
+
+% Altered from original 'Download citation' from Rev Sci Instrum website
+@Article{yang06,
+ author = "Yao Yang and Fan-Chi Lin and Guoliang Yang",
+ collaboration = "",
+ title = "Temperature control device for single molecule
+ measurements using the atomic force microscope",
+ publisher = "AIP",
+ year = "2006",
+ journal = "Review of Scientific Instruments",
+ volume = "77",
+ number = "6",
+ eid = "063701",
+ numpages = "5",
+ pages = "063701",
+ keywords = "temperature control; atomic force microscopy;
+ thermocouples; heat sinks",
+ 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",
+}
+
+% Altered from original 'Download to citation manager' from Highwire Press
+@Article{rief97,
+ author = "Matthias Rief and Mathias Gautel and Filipp Oesterhelt
+ and Julio M. Fernandez and Hermann E. Gaub",
+ title = "{Reversible Unfolding of Individual Titin
+ Immunoglobulin Domains by AFM}",
+ journal = "Science",
+ volume = "276",
+ number = "5315",
+ pages = "1109--1112",
+ doi = "10.1126/science.276.5315.1109",
+ year = "1997",
+ 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 Dietz '04\cite{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 it's globular-chain
+ structure.",
+ project = "Energy Landscape Roughness",
+}
+
+% Altered from original 'Download to citation manager' from scitation.aip.org
+@Article{hutter93,
+ author = "Jeffrey L. Hutter and John Bechhoefer",
+ collaboration = "",
+ title = "Calibration of atomic-force microscope tips",
+ publisher = "AIP",
+ year = "1993",
+ journal = "Review of Scientific Instruments",
+ volume = "64",
+ number = "7",
+ pages = "1868--1873",
+ keywords = "ATOMIC FORCE MICROSCOPY; CALIBRATION; QUALITY FACTOR;
+ PROBES; RESONANCE; SILICON NITRIDES; MICA; VAN DER
+ WAALS FORCES",
+ URL = "http://link.aip.org/link/?RSI/64/1868/1",
+ doi = "10.1063/1.1143970",
+ note = "Seminal paper for thermal calibration of AFM
+ cantilevers.",
+ project = "Cantilever Calibration",
+}
+
+% Originals from PNAS 'download to citation manager'
+
+@Article{dietz04,
+ author = "Hendrik Dietz and Matthias Rief",
+ title = "{Exploring the energy landscape of GFP by
+ single-molecule mechanical experiments}",
+ journal = "Proceedings of the National Academy of Sciences",
+ volume = "101",
+ number = "46",
+ pages = "16192--16197",
+ doi = "10.1073/pnas.0404549101",
+ 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.",
+ 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 = "Takehiro Sato and Masatoshi Esaki and Julio M.
+ Fernandez and Toshiya Endo",
+ title = "{Comparison of the protein-unfolding pathways between
+ mitochondrial protein import and atomic-force
+ microscopy measurements}",
+ journal = "Proceedings of the National Academy of Sciences",
+ volume = "102",
+ number = "50",
+ pages = "17999--18004",
+ doi = "10.1073/pnas.0504495102",
+ 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.",
+ 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 = "Qing Peng and Hongbin Li",
+ title = "{Atomic force microscopy reveals parallel mechanical
+ unfolding pathways of T4 lysozyme: Evidence for a
+ kinetic partitioning mechanism}",
+ journal = "Proceedings of the National Academy of Sciences",
+ volume = "105",
+ number = "6",
+ pages = "1885--1890",
+ doi = "10.1073/pnas.0706775105",
+ 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.",
+ 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 = "Deepak Sharma and Ognjen Perisic and Qing Peng and Yi
+ Cao and Canaan Lam and Hui Lu and Hongbin Li",
+ title = "{Single-molecule force spectroscopy reveals a
+ mechanically stable protein fold and the rational
+ tuning of its mechanical stability}",
+ journal = "Proceedings of the National Academy of Sciences",
+ volume = "104",
+ number = "22",
+ pages = "9278--9283",
+ doi = "10.1073/pnas.0700351104",
+ 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.",
+ 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 = "Andres F. Oberhauser and Paul K. Hansma and Mariano
+ Carrion-Vazquez and Julio M. Fernandez",
+ title = "{Stepwise unfolding of titin under force-clamp atomic
+ force microscopy}",
+ journal = "Proceedings of the National Academy of Sciences",
+ volume = "98",
+ number = "2",
+ pages = "468--472",
+ doi = "10.1073/pnas.021321798",
+ year = "2001",
+ abstract = "",
+ 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 = "Kirstin A. Walther and Frauke Grater and Lorna Dougan
+ and Carmen L. Badilla and Bruce J. Berne and Julio M.
+ Fernandez",
+ title = "{Signatures of hydrophobic collapse in extended
+ proteins captured with force spectroscopy}",
+ journal = "Proceedings of the National Academy of Sciences",
+ volume = "104",
+ number = "19",
+ pages = "7916--7921",
+ doi = "10.1073/pnas.0702179104",
+ 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.",
+ 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 = "Hendrik Dietz and Felix Berkemeier and Morten Bertz
+ and Matthias Rief",
+ title = "{Anisotropic deformation response of single protein
+ molecules}",
+ journal = "Proceedings of the National Academy of Sciences",
+ volume = "103",
+ number = "34",
+ pages = "12724--12728",
+ doi = "10.1073/pnas.0602995103",
+ 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.",
+ URL = "http://www.pnas.org/cgi/content/abstract/103/34/12724",
+ eprint = "http://www.pnas.org/cgi/reprint/103/34/12724.pdf",
+}
+
+@Article{schlierf04,
+ author = "Michael Schlierf and Hongbin Li and Julio M.
+ Fernandez",
+ title = "{The unfolding kinetics of ubiquitin captured with
+ single-molecule force-clamp techniques}",
+ journal = "Proceedings of the National Academy of Sciences",
+ volume = "101",
+ number = "19",
+ pages = "7299--7304",
+ doi = "10.1073/pnas.0400033101",
+ year = "2004",
+ 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.",
+ URL = "http://www.pnas.org/cgi/content/abstract/101/19/7299",
+ eprint = "http://www.pnas.org/cgi/reprint/101/19/7299.pdf",
+}
+
+@Article{labeit03,
+ author = "Dietmar Labeit and Kaori Watanabe and Christian Witt
+ and Hideaki Fujita and Yiming Wu and Sunshine Lahmers
+ and Theodor Funck and Siegfried Labeit and Henk
+ Granzier",
+ title = "Calcium-dependent molecular spring elements in the
+ giant protein titin",
+ journal = "Proceedings of the National Academy of Sciences",
+ volume = "100",
+ number = "23",
+ pages = "13716--13721",
+ doi = "10.1073/pnas.2235652100",
+ 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.",
+ 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 = "Moritz Mickler and Ruxandra I. Dima and Hendrik Dietz
+ and Changbong Hyeon and D. Thirumalai and Matthias
+ Rief",
+ title = "Revealing the bifurcation in the unfolding pathways
+ of {GFP} by using single-molecule experiments and
+ simulations",
+ journal = "Proceedings of the National Academy of Sciences",
+ volume = "104",
+ number = "51",
+ pages = "20268--20273",
+ doi = "10.1073/pnas.0705458104",
+ 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.",
+ 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 = "Arun P. Wiita and Sri Rama Koti Ainavarapu and Hector
+ H. Huang and Julio M. Fernandez",
+ title = "{From the Cover: Force-dependent chemical kinetics of
+ disulfide bond reduction observed with single-molecule
+ techniques}",
+ journal = "Proceedings of the National Academy of Sciences",
+ volume = "103",
+ number = "19",
+ pages = "7222--7227",
+ doi = "10.1073/pnas.0511035103",
+ 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.",
+ 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 = "Belinda Bullard and Tzintzuni Garcia and Vladimir
+ Benes and Mark C. Leake and Wolfgang A. Linke and
+ Andres F. Oberhauser",
+ title = "{The molecular elasticity of the insect flight muscle
+ proteins projectin and kettin}",
+ journal = "Proceedings of the National Academy of Sciences",
+ volume = "103",
+ number = "12",
+ pages = "4451--4456",
+ doi = "10.1073/pnas.0509016103",
+ 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.",
+ 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 = "Hendrik Dietz and Matthias Rief",
+ title = "{Protein structure by mechanical triangulation}",
+ journal = "Proceedings of the National Academy of Sciences",
+ volume = "103",
+ number = "5",
+ pages = "1244--1247",
+ doi = "10.1073/pnas.0509217103",
+ 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.",
+ 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 = "Alexander J. Wilcox and Jason Choy and Carlos
+ Bustamante and Andreas Matouschek",
+ title = "{Effect of protein structure on mitochondrial
+ import}",
+ journal = "Proceedings of the National Academy of Sciences",
+ volume = "102",
+ number = "43",
+ pages = "15435--15440",
+ doi = "10.1073/pnas.0507324102",
+ 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.",
+ 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 = "Piotr E. Marszalek and Hongbin Li and Andres F.
+ Oberhauser and Julio M. Fernandez",
+ title = "{Chair-boat transitions in single polysaccharide
+ molecules observed with force-ramp AFM}",
+ journal = "Proceedings of the National Academy of Sciences",
+ volume = "99",
+ number = "7",
+ pages = "4278--4283",
+ doi = "10.1073/pnas.072435699",
+ 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.",
+ 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 = "David Craig and Andre Krammer and Klaus Schulten and
+ Viola Vogel",
+ title = "{Comparison of the early stages of forced unfolding
+ for fibronectin type III modules}",
+ journal = "Proceedings of the National Academy of Sciences",
+ volume = "98",
+ number = "10",
+ pages = "5590--5595",
+ doi = "10.1073/pnas.101582198",
+ year = "2001",
+ abstract = "",
+ 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 = "Mariano Carrion-Vazquez and Piotr E. Marszalek and
+ Andres F. Oberhauser and Julio M. Fernandez",
+ title = "Atomic force microscopy captures length phenotypes in
+ single proteins",
+ journal = "Proceedings of the National Academy of Sciences",
+ volume = "96",
+ number = "20",
+ pages = "11288--11292",
+ doi = "10.1073/pnas.96.20.11288",
+ year = "1999",
+ abstract = "",
+ 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 = "Yi Cao and M. M. Balamurali and Deepak Sharma and
+ Hongbin Li",
+ title = "{A functional single-molecule binding assay via force
+ spectroscopy}",
+ journal = "Proceedings of the National Academy of Sciences",
+ volume = "104",
+ number = "40",
+ pages = "15677--15681",
+ doi = "10.1073/pnas.0705367104",
+ year = "2007",
+ abstract = "Proteinligand interactions, including proteinprotein
+ 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 proteinligand
+ 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 proteinligand 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 proteinligand interactions in a functional
+ context, and we anticipate that it will find broad
+ application in diverse proteinligand systems.",
+ 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 = "Weichang Yu and Jonathan C. Lamb and Fangpu Han and
+ James A. Birchler",
+ title = "{Telomere-mediated chromosomal truncation in maize}",
+ journal = "Proceedings of the National Academy of Sciences",
+ volume = "103",
+ number = "46",
+ pages = "17331--17336",
+ doi = "10.1073/pnas.0605750103",
+ 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.",
+ 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 = "Jason Ming Zhao and Haeshin Lee and Rene A. Nome and
+ Sophia Majid and Norbert F. Scherer and Wouter D.
+ Hoff",
+ title = "{Single-molecule detection of structural changes
+ during Per-Arnt-Sim (PAS) domain activation}",
+ journal = "Proceedings of the National Academy of Sciences",
+ volume = "103",
+ number = "31",
+ pages = "11561--11566",
+ doi = "10.1073/pnas.0601567103",
+ 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.",
+ 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 = "Mu Gao and David Craig and Olivier Lequin and Iain D.
+ Campbell and Viola Vogel and Klaus Schulten",
+ title = "{Structure and functional significance of mechanically
+ unfolded fibronectin type III1 intermediates}",
+ journal = "Proceedings of the National Academy of Sciences",
+ volume = "100",
+ number = "25",
+ pages = "14784--14789",
+ doi = "10.1073/pnas.2334390100",
+ 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.",
+ 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 = "Christiane A. Opitz and Michael Kulke and Mark C.
+ Leake and Ciprian Neagoe and Horst Hinssen and Roger J.
+ Hajjar and Wolfgang A. Linke",
+ title = "{Damped elastic recoil of the titin spring in
+ myofibrils of human myocardium}",
+ journal = "Proceedings of the National Academy of Sciences",
+ volume = "100",
+ number = "22",
+ pages = "12688--12693",
+ doi = "10.1073/pnas.2133733100",
+ 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.",
+ 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 = "Robert B. Best and Susan B. Fowler and Jose L.
+ Toca-Herrera and Jane Clarke",
+ title = "{A simple method for probing the mechanical unfolding
+ pathway of proteins in detail}",
+ journal = "Proceedings of the National Academy of Sciences",
+ volume = "99",
+ number = "19",
+ pages = "12143--12148",
+ doi = "10.1073/pnas.192351899",
+ 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.",
+ URL = "http://www.pnas.org/cgi/content/abstract/99/19/12143",
+ eprint = "http://www.pnas.org/cgi/reprint/99/19/12143.pdf",
+}
+
+@Article{basche01,
+ author = "Th. Basche and S. Nie and J. M. Fernandez",
+ title = "{Single molecules}",
+ journal = "Proceedings of the National Academy of Sciences",
+ volume = "98",
+ number = "19",
+ pages = "10527--10528",
+ doi = "10.1073/pnas.191365898",
+ year = "2001",
+ URL = "http://www.pnas.org",
+ eprint = "http://www.pnas.org/cgi/reprint/98/19/10527.pdf",
+}
+
+@Article{li01,
+ author = "Hongbin Li and Andres F. Oberhauser and Sambra D.
+ Redick and Mariano Carrion-Vazquez and Harold P.
+ Erickson and Julio M. Fernandez",
+ title = "{Multiple conformations of PEVK proteins detected by
+ single-molecule techniques}",
+ journal = "Proceedings of the National Academy of Sciences",
+ volume = "98",
+ number = "19",
+ pages = "10682--10686",
+ doi = "10.1073/pnas.191189098",
+ 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.",
+ 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 = "Philippe Carl and Carol H. Kwok and Gavin Manderson
+ and David W. Speicher and Dennis E. Discher",
+ title = "{Forced unfolding modulated by disulfide bonds in the
+ Ig domains of a cell adhesion molecule}",
+ journal = "Proceedings of the National Academy of Sciences",
+ volume = "98",
+ number = "4",
+ pages = "1565--1570",
+ doi = "10.1073/pnas.031409698",
+ year = "2001",
+ abstract = "",
+ 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 = "D. K. Klimov and D. Thirumalai",
+ title = "{Native topology determines force-induced unfolding
+ pathways in globular proteins}",
+ journal = "Proceedings of the National Academy of Sciences",
+ volume = "97",
+ number = "13",
+ pages = "7254--7259",
+ doi = "10.1073/pnas.97.13.7254",
+ year = "2000",
+ month = jun,
+ day = "20",
+ keywords = "Animals",
+ keywords = "Humans",
+ keywords = "Protein Folding",
+ keywords = "Proteins",
+ keywords = "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",
+ URL = "http://www.pnas.org/cgi/content/abstract/97/13/7254",
+ URLB = "http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=16532",
+ 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 = "Hongbin Li and Andres F. Oberhauser and Susan B.
+ Fowler and Jane Clarke and Julio M. Fernandez",
+ title = "{Atomic force microscopy reveals the mechanical design
+ of a modular protein}",
+ journal = "Proceedings of the National Academy of Sciences",
+ volume = "97",
+ number = "12",
+ pages = "6527--6531",
+ doi = "10.1073/pnas.120048697",
+ year = "2000",
+ abstract = "",
+ URL = "http://www.pnas.org/cgi/content/abstract/97/12/6527",
+ eprint = "http://www.pnas.org/cgi/reprint/97/12/6527.pdf",
+}
+
+@Article{nome07,
+ author = "Rene A. Nome and Jason Ming Zhao and Wouter D. Hoff
+ and Norbert F. Scherer",
+ title = "Axis-dependent anisotropy in protein unfolding from
+ integrated nonequilibrium single-molecule experiments,
+ analysis, and simulation",
+ journal = "Proceedings of the National Academy of Sciences",
+ volume = "104",
+ number = "52",
+ pages = "20799--20804",
+ doi = "10.1073/pnas.0701281105",
+ year = "2007",
+ month = dec,
+ day = "26",
+ keywords = "Anisotropy",
+ keywords = "Bacterial Proteins",
+ keywords = "Biophysics",
+ keywords = "Computer Simulation",
+ keywords = "Cysteine",
+ keywords = "Halorhodospira halophila",
+ keywords = "Hydrogen Bonding",
+ keywords = "Kinetics",
+ keywords = "Luminescent Proteins",
+ keywords = "Microscopy, Atomic Force",
+ keywords = "Molecular Conformation",
+ keywords = "Protein Binding",
+ keywords = "Protein Conformation",
+ keywords = "Protein Denaturation",
+ keywords = "Protein Folding",
+ keywords = "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 = "Sean P. Ng and Kate S. Billings and Tomoo Ohashi and
+ Mark D. Allen and Robert B. Best and Lucy G. Randles
+ and Harold P. Erickson and Jane Clarke",
+ title = "{Designing an extracellular matrix protein with
+ enhanced mechanical stability}",
+ journal = "Proceedings of the National Academy of Sciences",
+ volume = "104",
+ number = "23",
+ pages = "9633--9637",
+ doi = "10.1073/pnas.0609901104",
+ year = "2007",
+ 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 = "Wei Zhuang and Darius Abramavicius and Shaul Mukamel",
+ title = "{Two-dimensional vibrational optical probes for
+ peptide fast folding investigation}",
+ journal = "Proceedings of the National Academy of Sciences",
+ volume = "103",
+ number = "50",
+ pages = "18934--18938",
+ doi = "10.1073/pnas.0606912103",
+ year = "2006",
+ 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 = "Dennis E. Discher and Nishant Bhasin and Colin P.
+ Johnson",
+ title = "{Covalent chemistry on distended proteins}",
+ journal = "Proceedings of the National Academy of Sciences",
+ volume = "103",
+ number = "20",
+ pages = "7533--7534",
+ doi = "10.1073/pnas.0602388103",
+ year = "2006",
+ URL = "http://www.pnas.org",
+ eprint = "http://www.pnas.org/cgi/reprint/103/20/7533.pdf",
+}
+
+@Article{li06,
+ author = "Mai Suan Li and Chin-Kun Hu and Dmitri K. Klimov and
+ D. Thirumalai",
+ title = "{Multiple stepwise refolding of immunoglobulin domain
+ I27 upon force quench depends on initial conditions}",
+ journal = "Proceedings of the National Academy of Sciences",
+ volume = "103",
+ number = "1",
+ pages = "93--98",
+ doi = "10.1073/pnas.0503758103",
+ year = "2006",
+ 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 = "Anders Irback and Simon Mitternacht and Sandipan
+ Mohanty",
+ title = "{Dissecting the mechanical unfolding of ubiquitin}",
+ journal = "Proceedings of the National Academy of Sciences",
+ volume = "102",
+ number = "38",
+ pages = "13427--13432",
+ doi = "10.1073/pnas.0501581102",
+ year = "2005",
+ 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 = "Atom Sarkar and Ragan B. Robertson and Julio M.
+ Fernandez",
+ title = "{Simultaneous atomic force microscope and fluorescence
+ measurements of protein unfolding using a calibrated
+ evanescent wave}",
+ journal = "Proceedings of the National Academy of Sciences",
+ volume = "101",
+ number = "35",
+ pages = "12882--12886",
+ doi = "10.1073/pnas.0403534101",
+ year = "2004",
+ 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 = "Yasser Bustanji and Carla Renata Arciola and Matteo
+ Conti and Enrico Mandello and Lucio Montanaro and Bruno
+ Samori",
+ title = "{Dynamics of the interaction between a fibronectin
+ molecule and a living bacterium under mechanical
+ force}",
+ journal = "Proceedings of the National Academy of Sciences",
+ volume = "100",
+ number = "23",
+ pages = "13292--13297",
+ doi = "10.1073/pnas.1735343100",
+ year = "2003",
+ 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 = "W. Liu and Vedrana Montana and Edwin R. Chapman and U.
+ Mohideen and Vladimir Parpura",
+ title = "{Botulinum toxin type B micromechanosensor}",
+ journal = "Proceedings of the National Academy of Sciences",
+ volume = "100",
+ number = "23",
+ pages = "13621--13625",
+ doi = "10.1073/pnas.2233819100",
+ year = "2003",
+ 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 = "E. Oroudjev and J. Soares and S. Arcidiacono and J. B.
+ Thompson and S. A. Fossey and H. G. Hansma",
+ title = "{Segmented nanofibers of spider dragline silk: Atomic
+ force microscopy and single-molecule force
+ spectroscopy}",
+ journal = "Proceedings of the National Academy of Sciences",
+ volume = "99",
+ number = "90002",
+ pages = "6460--6465",
+ doi = "10.1073/pnas.082526499",
+ year = "2002",
+ 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 = "Gretchen Baneyx and Loren Baugh and Viola Vogel",
+ title = "{Supramolecular Chemistry And Self-assembly Special
+ Feature: Fibronectin extension and unfolding within
+ cell matrix fibrils controlled by cytoskeletal
+ tension}",
+ journal = "Proceedings of the National Academy of Sciences",
+ volume = "99",
+ number = "8",
+ pages = "5139--5143",
+ doi = "10.1073/pnas.072650799",
+ year = "2002",
+ 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 = "Brent D. Brower-Toland and Corey L. Smith and Richard
+ C. Yeh and John T. Lis and Craig L. Peterson and
+ Michelle D. Wang",
+ title = "{From the Cover: Mechanical disruption of individual
+ nucleosomes reveals a reversible multistage release of
+ DNA}",
+ journal = "Proceedings of the National Academy of Sciences",
+ volume = "99",
+ number = "4",
+ pages = "1960--1965",
+ doi = "10.1073/pnas.022638399",
+ year = "2002",
+ 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 = "Gerhard Hummer and Attila Szabo",
+ title = "{From the Cover: Free energy reconstruction from
+ nonequilibrium single-molecule pulling experiments}",
+ journal = "Proceedings of the National Academy of Sciences",
+ volume = "98",
+ number = "7",
+ pages = "3658--3661",
+ doi = "10.1073/pnas.071034098",
+ year = "2001",
+ URL = "http://www.pnas.org/cgi/content/abstract/98/7/3658",
+ eprint = "http://www.pnas.org/cgi/reprint/98/7/3658.pdf",
+}
+
+@Article{talaga00,
+ author = "David S. Talaga and Wai Leung Lau and Heinrich Roder
+ and Jianyong Tang and Yiwei Jia and William F. DeGrado
+ and Robin M. Hochstrasser",
+ title = "{Dynamics and folding of single two-stranded
+ coiled-coil peptides studied by fluorescent energy
+ transfer confocal microscopy}",
+ journal = "Proceedings of the National Academy of Sciences",
+ volume = "97",
+ number = "24",
+ pages = "13021--13026",
+ doi = "10.1073/pnas.97.24.13021",
+ year = "2000",
+ 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 = "C. Gergely and J.-C. Voegel and P. Schaaf and B.
+ Senger and M. Maaloum and J. K. H. Horber and J.
+ Hemmerle",
+ title = "{Unbinding process of adsorbed proteins under external
+ stress studied by atomic force microscopy
+ spectroscopy}",
+ journal = "Proceedings of the National Academy of Sciences",
+ volume = "97",
+ number = "20",
+ pages = "10802--10807",
+ doi = "10.1073/pnas.180293097",
+ year = "2000",
+ 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 = "Emanuele Paci and Martin Karplus",
+ title = "{Unfolding proteins by external forces and
+ temperature: The importance of topology and
+ energetics}",
+ journal = "Proceedings of the National Academy of Sciences",
+ volume = "97",
+ number = "12",
+ pages = "6521--6526",
+ doi = "10.1073/pnas.100124597",
+ year = "2000",
+ 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 = "Guoliang Yang and Ciro Cecconi and Walter A. Baase and
+ Ingrid R. Vetter and Wendy A. Breyer and Julie A. Haack
+ and Brian W. Matthews and Frederick W. Dahlquist and
+ Carlos Bustamante",
+ title = "{Solid-state synthesis and mechanical unfolding of
+ polymers of T4 lysozyme}",
+ journal = "Proceedings of the National Academy of Sciences",
+ volume = "97",
+ number = "1",
+ pages = "139--144",
+ doi = "10.1073/pnas.97.1.139",
+ year = "2000",
+ 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 = "Torsten Strunz and Krisztina Oroszlan and Rolf Schafer
+ and Hans-Joachim Guntherodt",
+ title = "{Dynamic force spectroscopy of single DNA molecules}",
+ journal = "Proceedings of the National Academy of Sciences",
+ volume = "96",
+ number = "20",
+ pages = "11277--11282",
+ doi = "10.1073/pnas.96.20.11277",
+ year = "1999",
+ 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 = "Mariano Carrion-Vazquez and Andres F. Oberhauser and
+ Susan B. Fowler and Piotr E. Marszalek and Sheldon E.
+ Broedel and Jane Clarke and Julio M. Fernandez",
+ title = "Mechanical and chemical unfolding of a single
+ protein: A comparison",
+ journal = "Proceedings of the National Academy of Sciences",
+ volume = "96",
+ number = "7",
+ pages = "3694--3699",
+ doi = "10.1073/pnas.96.7.3694",
+ year = "1999",
+ 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 = "Reinat Nevo and Vlad Brumfeld and Michael Elbaum and
+ Peter Hinterdorfer and Ziv Reich",
+ title = "Direct discrimination between models of protein
+ activation by single-molecule force measurements.",
+ journal = "Biophys J",
+ year = "2004",
+ month = oct,
+ volume = "87",
+ number = "4",
+ pages = "2630--2634",
+ keywords = "Elasticity",
+ keywords = "Enzyme Activation",
+ keywords = "Micromanipulation",
+ keywords = "Microscopy, Atomic Force",
+ keywords = "Models, Chemical",
+ keywords = "Models, Molecular",
+ keywords = "Multiprotein Complexes",
+ keywords = "Nuclear Proteins",
+ keywords = "Physical Stimulation",
+ keywords = "Protein Binding",
+ keywords = "Stress, Mechanical",
+ keywords = "Structure-Activity Relationship",
+ keywords = "beta Karyopherins",
+ keywords = "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 = "Reinat Nevo and Cordula Stroh and Ferry Kienberger and
+ David Kaftan and Vlad Brumfeld and Michael Elbaum and
+ Ziv Reich and Peter Hinterdorfer",
+ title = "A molecular switch between alternative conformational
+ states in the complex of Ran and importin beta1.",
+ journal = "Nat Struct Biol",
+ year = "2003",
+ month = jul,
+ volume = "10",
+ number = "7",
+ pages = "553--557",
+ keywords = "Guanosine Diphosphate",
+ keywords = "Guanosine Triphosphate",
+ keywords = "Microscopy, Atomic Force",
+ keywords = "Protein Binding",
+ keywords = "Protein Conformation",
+ keywords = "beta Karyopherins",
+ keywords = "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 \cite{tlusty98} and \cite{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 \cite{bechhoefer02} and \cite{press92}
+ respectively instead.",
+ project = "Cantilever Calibration",
+}
+
+@Article{tlusty98,
+ title = "Optical Gradient Forces of Strongly Localized Fields",
+ author = "Tsvi Tlusty and Amit Meller and Roy Bar-Ziv",
+ journal = "Phys. Rev. Lett.",
+ volume = "81",
+ number = "8",
+ pages = "1738--1741",
+ numpages = "3",
+ year = "1998",
+ month = aug,
+ doi = "10.1103/PhysRevLett.81.1738",
+ publisher = "American Physical Society",
+ 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 \cite{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 = "John Bechhoefer 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 \cite{reif65}).
+ References work on deconvolving thermal noise from
+ other noise\cite{cowan98}",
+}
+
+@Book{press02,
+ 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",
+}
+
+@Article{schlierf06,
+ author = "Michael Schlierf and Matthias Rief",
+ title = "Single-molecule unfolding force distributions reveal a
+ funnel-shaped energy landscape.",
+ journal = "Biophys J",
+ year = "2006",
+ month = feb,
+ day = "15",
+ volume = "90",
+ number = "4",
+ pages = "L33--L35",
+ keywords = "Models, Molecular",
+ keywords = "Protein Folding",
+ keywords = "Proteins",
+ keywords = "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 Evans-Ritchie 1999's Eqn.~2\cite{evans99}, 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 Hanggi Eq.~4.56b (page 275)\cite{hanggi90}.
+ 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 = "Hendrik Dietz and Matthias Rief",
+ 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 = "Biophys J",
+ year = "2007",
+ month = mar,
+ day = "15",
+ volume = "92",
+ number = "6",
+ pages = "2054--2061",
+ keywords = "Computer Simulation",
+ keywords = "Models, Chemical",
+ keywords = "Models, Molecular",
+ keywords = "Models, Statistical",
+ keywords = "Monte Carlo Method",
+ keywords = "Motion",
+ keywords = "Protein Conformation",
+ keywords = "Protein Denaturation",
+ keywords = "Protein Folding",
+ keywords = "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 Paul K. Hansma 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,
+ title = "Elastically Coupled Two-Level Systems as a Model for
+ Biopolymer Extensibility",
+ author = "Matthias Rief and Julio M. Fernandez and Hermann E.
+ Gaub",
+ journal = "Phys. Rev. Lett.",
+ volume = "81",
+ number = "21",
+ pages = "4764--4767",
+ numpages = "3",
+ year = "1998",
+ month = nov,
+ doi = "10.1103/PhysRevLett.81.4764",
+ eprint = "http://prola.aps.org/pdf/PRL/v81/i21/p4764_1",
+ publisher = "American Physical Society",
+}
+
+@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 = "Protein Sci",
+ year = "2002",
+ month = dec,
+ volume = "11",
+ number = "12",
+ pages = "2759--2765",
+ keywords = "Computer Simulation",
+ keywords = "Models, Molecular",
+ keywords = "Monte Carlo Method",
+ keywords = "Protein Folding",
+ keywords = "Protein Structure, Tertiary",
+ keywords = "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 = "READ",
+ 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 = "Biophys J",
+ year = "2002",
+ month = jul,
+ volume = "83",
+ number = "1",
+ pages = "458--472",
+ keywords = "Amino Acid Sequence",
+ keywords = "Dose-Response Relationship, Drug",
+ keywords = "Kinetics",
+ keywords = "Magnetic Resonance Spectroscopy",
+ keywords = "Models, Molecular",
+ keywords = "Molecular Sequence Data",
+ keywords = "Monte Carlo Method",
+ keywords = "Muscle Proteins",
+ keywords = "Mutation",
+ keywords = "Peptide Fragments",
+ keywords = "Protein Denaturation",
+ keywords = "Protein Folding",
+ keywords = "Protein Kinases",
+ keywords = "Protein Structure, Secondary",
+ keywords = "Protein Structure, Tertiary",
+ keywords = "Proteins",
+ keywords = "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",
+ URL = "http://www.biophysj.org/cgi/content/abstract/83/1/458",
+ eprint = {http://www.biophysj.org/cgi/reprint/83/1/458.pdf},
+}
+
+@Article{Hummer2003,
+ author = "Gerhard Hummer and Attila Szabo",
+ title = "Kinetics from nonequilibrium single-molecule pulling
+ experiments.",
+ journal = "Biophys J",
+ year = "2003",
+ month = jul,
+ volume = "85",
+ number = "1",
+ pages = "5--15",
+ keywords = "Computer Simulation",
+ keywords = "Crystallography",
+ keywords = "Energy Transfer",
+ keywords = "Kinetics",
+ keywords = "Lasers",
+ keywords = "Micromanipulation",
+ keywords = "Microscopy, Atomic Force",
+ keywords = "Models, Molecular",
+ keywords = "Molecular Conformation",
+ keywords = "Motion",
+ keywords = "Muscle Proteins",
+ keywords = "Nanotechnology",
+ keywords = "Physical Stimulation",
+ keywords = "Protein Conformation",
+ keywords = "Protein Denaturation",
+ keywords = "Protein Folding",
+ keywords = "Protein Kinases",
+ keywords = "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 = "D. Thirumalai and C. Hyeon",
+ 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 Matthias Rief",
+ 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",
+ keywords = "Contractile Proteins",
+ keywords = "Dictyostelium",
+ keywords = "Immunoglobulins",
+ keywords = "Kinetics",
+ keywords = "Microfilament Proteins",
+ keywords = "Models, Molecular",
+ keywords = "Protein Folding",
+ keywords = "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 = "Biophys J",
+ year = "1999",
+ month = may,
+ volume = "76",
+ number = "5",
+ pages = "2439--2447",
+ keywords = "Animals",
+ keywords = "Biophysics",
+ keywords = "Biopolymers",
+ keywords = "Microscopy, Atomic Force",
+ keywords = "Models, Chemical",
+ keywords = "Muscle Proteins",
+ keywords = "Protein Folding",
+ keywords = "Protein Kinases",
+ keywords = "Stochastic Processes",
+ keywords = "Stress, Mechanical",
+ keywords = "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 = "Biophys J",
+ year = "1997",
+ month = apr,
+ volume = "72",
+ number = "4",
+ pages = "1541--1555",
+ keywords = "Avidin",
+ keywords = "Biotin",
+ keywords = "Chemistry, Physical",
+ keywords = "Computer Simulation",
+ keywords = "Mathematics",
+ keywords = "Monte Carlo Method",
+ keywords = "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 Kramers},
+ author = {H\"anggi, Peter and Talkner, Peter and Borkovec, Michal },
+ journal = {Rev. Mod. Phys.},
+ 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",
+ keywords = "Cytochrome c Group",
+ keywords = "Humans",
+ keywords = "Infant",
+ keywords = "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 Matthias Rief",
+ title = "A mechanical unfolding intermediate in an
+ actin-crosslinking protein.",
+ journal = "Nat Struct Mol Biol",
+ year = "2004",
+ month = jan,
+ day = "29",
+ volume = "11",
+ number = "1",
+ pages = "81--85",
+ keywords = "Actins",
+ keywords = "Animals",
+ keywords = "Contractile Proteins",
+ keywords = "Cross-Linking Reagents",
+ keywords = "Dictyostelium",
+ keywords = "Dimerization",
+ keywords = "Microfilament Proteins",
+ keywords = "Microscopy, Atomic Force",
+ keywords = "Mutagenesis, Site-Directed",
+ keywords = "Protein Denaturation",
+ keywords = "Protein Folding",
+ keywords = "Protein Structure, Tertiary",
+ keywords = "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 = "Science",
+ year = "1978",
+ month = may,
+ day = "12",
+ volume = "200",
+ number = "4342",
+ pages = "618--627",
+ keywords = "Antigen-Antibody Reactions",
+ keywords = "Cell Adhesion",
+ keywords = "Cell Membrane",
+ keywords = "Chemistry, Physical",
+ keywords = "Electrophysiology",
+ keywords = "Enzymes",
+ keywords = "Glycoproteins",
+ keywords = "Kinetics",
+ keywords = "Ligands",
+ keywords = "Membrane Proteins",
+ keywords = "Models, Biological",
+ keywords = "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 = "Proc Natl Acad Sci U S A",
+ year = "2004",
+ month = sep,
+ day = "28",
+ volume = "101",
+ number = "39",
+ pages = "14102--14107",
+ keywords = "Animals",
+ keywords = "Ankyrin Repeat",
+ keywords = "Circular Dichroism",
+ keywords = "Drosophila Proteins",
+ keywords = "Drosophila melanogaster",
+ keywords = "Gene Deletion",
+ keywords = "Models, Chemical",
+ keywords = "Models, Molecular",
+ keywords = "Protein Denaturation",
+ keywords = "Protein Folding",
+ keywords = "Protein Structure, Tertiary",
+ keywords = "Spectrometry, Fluorescence",
+ keywords = "Thermodynamics",
+ keywords = "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",
+ keywords = "Chemistry, Physical",
+ keywords = "Computer Simulation",
+ keywords = "Data Interpretation, Statistical",
+ keywords = "Kinetics",
+ keywords = "Models, Chemical",
+ keywords = "Molecular Sequence Data",
+ keywords = "Protein Biosynthesis",
+ keywords = "Protein Conformation",
+ keywords = "Protein Folding",
+ keywords = "Proteins",
+ keywords = "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 = "Proc Natl Acad Sci U S A",
+ year = "1987",
+ month = nov,
+ volume = "84",
+ number = "21",
+ pages = "7524--7528",
+ keywords = "Kinetics",
+ keywords = "Mathematics",
+ keywords = "Models, Theoretical",
+ keywords = "Protein Conformation",
+ keywords = "Proteins",
+ keywords = "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 = "C. Bustamante and J. F. Marko and E. D. Siggia and S.
+ Smith",
+ title = "Entropic elasticity of lambda-phage {DNA}.",
+ journal = "Science",
+ year = "1994",
+ month = sep,
+ day = "09",
+ volume = "265",
+ number = "5178",
+ pages = "1599--1600",
+ keywords = "Bacteriophage lambda",
+ keywords = "DNA, Viral",
+ keywords = "Least-Squares Analysis",
+ keywords = "Thermodynamics",
+ ISSN = "0036-8075",
+ note = "WLC interpolation formula.",
+}
+
+% see the list of BibTeX databases Beebe has compiled
+% http://www.math.utah.edu/~beebe/bibliographies.html
+
+% Beebe: http://www.math.utah.edu/pub/tex/bib/gnu.html
+@String{pub-NETWORK-THEORY = "Network Theory Ltd."}
+@String{pub-NETWORK-THEORY:adr = "Bristol, UK"}
+@Book{galassi05,
+ author = "Mark Galassi and Jim Davies and James Theiler and
+ Brian Gough and Gerard Jungman and Michael Booth and
+ Fabrice Rossi",
+ title = "{GNU} Scientific Library: Reference Manual",
+ publisher = pub-NETWORK-THEORY,
+ address = pub-NETWORK-THEORY:adr,
+ edition = "Second Revised",
+ pages = "xvi + 601",
+ year = "2005",
+ ISBN = "0-9541617-3-4",
+ ISBN-13 = "978-0-9541617-3-6",
+ LCCN = "QA76.73.C15",
+ bibdate = "Wed Oct 30 10:44:22 2002",
+ acknowledgement = ack-nhfb,
+ remark = "This is the revised and updated second edition of the
+ manual, and corresponds to version 1.6 of the
+ library.",
+ URL = "http://www.network-theory.co.uk/gsl/manual/",
+ xxpages = "xvi + 580",
+}
+
+@Misc{sw:check,
+ title = {Check},
+ author = {Arien Malec and Chris Pickett and Fredrik Hugosson and Robert Lemmen},
+ version = {version 0.9.4},
+ year = "2006",
+ month = oct,
+ day = "13",
+ abstract = "Check is a unit testing framework for C. It features a simple interface for defining unit tests, putting little in the way of the developer. Tests are run in a separate address space, so Check can catch both assertion failures and code errors that cause segmentation faults or other signals. The output from unit tests can be used within source code editors and IDEs.",
+ url = {http://check.sourceforge.net},
+}
+
+@Misc{sw:noweb,
+ title = {Noweb},
+ author = {Norman Ramsey},
+ version = {version 2.11b},
+ year = "1997",
+ month = nov,
+ day = "18",
+ abstract = "Noweb is a simple, extensible literate programming tool.",
+ url = {http://www.eecs.harvard.edu/nr/noweb/},
+ note = {Debian package by Federico Di Gregorio},
+}
+
+@Misc{sw:python,
+ title = {Python},
+ author = {Guido {van Rossum} and others},
+ version = {version 2.5.1},
+ year = "2007",
+ month = apr,
+ day = "18",
+ abstract = "Python is a dynamic object-oriented programming language.",
+ url = {http://www.python.org/},
+}
+
+@Misc{sw:scipy,
+ author = {Eric Jones and Travis Oliphant and Pearu Peterson and others},
+ title = {{SciPy}: Open source scientific tools for {Python}},
+ year = {2001--},
+ url = "http://www.scipy.org/"
+}
projects / sawsim.git / commitdiff