3 @string{DAbramavicius = "Abramavicius, Darius"}
4 @string{SRKAinavarapu = "Ainavarapu, Sri Rama Koti"}
5 @string{MDAllen = "Allen, Mark D."}
6 @string{AJP = "American Journal of Physics"}
7 @string{APS = "American Physical Society"}
8 @string{IAndricioaei = "Andricioaei, Ioan"}
9 @string{DAnselmetti = "Anselmetti, D."}
10 @string{AMC = "Applied Mathematics and Computation"}
11 @string{SArcidiacono = "Arcidiacono, S."}
12 @string{CRArciola = "Arciola, Carla Renata"}
13 @string{WABaase = "Baase, Walter A."}
14 @string{CLBadilla = "Badilla, Carmen L."}
15 @string{MMBalamurali = "Balamurali, M. M."}
16 @string{MBalsera = "Balsera, M."}
17 @string{GBaneyx = "Baneyx, Gretchen"}
18 @string{RBar-Ziv = "Bar-Ziv, Roy"}
19 @string{DBarrick = "Barrick, Doug"}
20 @string{FWBartels = "Bartels, F. W."}
21 @string{BBarz = "Barz, Bogdan"}
22 @string{TBasche = "Basche, Th."}
23 @string{LBaugh = "Baugh, Loren"}
24 @string{JBechhoefer = "Bechhoefer, John"}
25 @string{GSBeddard = "Beddard, Godfrey S."}
26 @string{GIBell = "Bell, G. I."}
27 @string{VBenes = "Benes, Vladimir"}
28 @string{FBerkemeier = "Berkemeier, Felix"}
29 @string{BJBerne = "Berne, Bruce J."}
30 @string{MBertz = "Bertz, Morten"}
31 @string{RBBest = "Best, Robert B."}
32 @string{NBhasin = "Bhasin, Nishant"}
33 @string{KSBillings = "Billings, Kate S."}
34 @string{Biochemistry = "Biochemistry"}
35 @string{BiophysJ = "Biophys J"}
36 @string{BPS:P = "Biophysical Society Annual Meeting (Poster)"}
37 @string{JABirchler = "Birchler, James A."}
38 @string{AWBlake = "Blake, Anthony W."}
39 @string{MBooth = "Booth, Michael"}
40 @string{MBorkovec = "Borkovec, Michal"}
41 @string{EBraverman = "Braverman, Elena"}
42 @string{WABreyer = "Breyer, Wendy A."}
43 @string{pub-NETWORK-THEORY:adr = "Bristol, UK"}
44 @string{DJBrockwell = "Brockwell, David J."}
45 @string{SEBroedel = "Broedel, Sheldon E."}
46 @string{BDBrower-Toland = "Brower-Toland, Brent D."}
47 @string{VBrumfeld = "Brumfeld, Vlad"}
48 @string{JDBryngelson = "Bryngelson, J. D."}
49 @string{BBullard = "Bullard, Belinda"}
50 @string{CBustamante = "Bustamante, Carlos"}
51 @string{YBustanji = "Bustanji, Yasser"}
52 @string{CUP = "Cambridge University Press"}
53 @string{IDCampbell = "Campbell, Iain D."}
54 @string{YCao = "Cao, Yi"}
55 @string{PCarl = "Carl, Philippe"}
56 @string{BACarnes = "Carnes, B. A."}
57 @string{MCarrion-Vazquez = "Carrion-Vazquez, Mariano"}
58 @string{CCecconi = "Cecconi, Ciro"}
59 @string{ERChapman = "Chapman, Edwin R."}
60 @string{Chemphyschem = "Chemphyschem"}
61 @string{JChoy = "Choy, Jason"}
62 @string{JClarke = "Clarke, Jane"}
63 @string{JClarkson = "Clarkson, John"}
64 @string{MConti = "Conti, Matteo"}
65 @string{GCowan = "Cowan, Glen"}
66 @string{DCraig = "Craig, David"}
67 @string{FWDahlquist = "Dahlquist, Frederick W."}
68 @string{JDavies = "Davies, Jim"}
69 @string{WFDeGrado = "DeGrado, William F."}
70 @string{Demography = "Demography"}
71 @string{HDietz = "Dietz, Hendrik"}
72 @string{RIDima = "Dima, Ruxandra I."}
73 @string{DEDischer = "Discher, Dennis E."}
74 @string{LDougan = "Dougan, Lorna"}
75 @string{OKDudko = "Dudko, Olga K."}
76 @string{EMBORep = "EMBO Rep"}
77 @string{REckel = "Eckel, R."}
78 @string{MElbaum = "Elbaum, Michael"}
79 @string{E:NHPL = "Elsevier, North-Holland Personal Library"}
80 @string{TEndo = "Endo, Toshiya"}
81 @string{HPErickson = "Erickson, Harold P."}
82 @string{MEsaki = "Esaki, Masatoshi"}
83 @string{EEvans = "Evans, E."}
84 @string{MEvstigneev = "Evstigneev, M."}
85 @string{JMFernandez = "Fernandez, Julio M."}
86 @string{AEFilippov = "Filippov, A. E."}
87 @string{BFlannery = "Flannery, B."}
88 @string{FoldDes = "Fold Des"}
89 @string{SAFossey = "Fossey, S. A."}
90 @string{SBFowler = "Fowler, Susan B."}
91 @string{HFujita = "Fujita, Hideaki"}
92 @string{TFunck = "Funck, Theodor"}
93 @string{MGalassi = "Galassi, Mark"}
94 @string{MGao = "Gao, Mu"}
95 @string{TGarcia = "Garcia, Tzintzuni"}
96 @string{HEGaub = "Gaub, Hermann E."}
97 @string{MGautel = "Gautel, Mathias"}
98 @string{LAGavrilov = "Gavrilov, L. A."}
99 @string{NSGavrilova = "Gavrilova, N. S."}
100 @string{CGergely = "Gergely, C."}
101 @string{JGlaser = "Glaser, Jens"}
102 @string{BGompertz = "Gompertz, Benjamin"}
103 @string{BGough = "Gough, Brian"}
104 @string{HGranzier = "Granzier, Henk"}
105 @string{FGrater = "Grater, Frauke"}
106 @string{CGrossman = "Grossman, C."}
107 @string{HGrubmuller = {Grubm{\"u}ller, Helmut}}
108 @string{HJGuntherodt = "Guntherodt, Hans-Joachim"}
109 @string{PHanggi = {H\"anggi, Peter}}
110 @string{JAHaack = "Haack, Julie A."}
111 @string{RJHajjar = "Hajjar, Roger J."}
112 @string{FHan = "Han, Fangpu"}
113 @string{HGHansma = "Hansma, H. G."}
114 @string{PKHansma = "Hansma, Paul K."}
115 @string{JWHatfield = "Hatfield, John William"}
116 @string{JHemmerle = "Hemmerle, J."}
117 @string{BHeymann = "Heymann, B."}
118 @string{HHinssen = "Hinssen, Horst"}
119 @string{PHinterdorfer = "Hinterdorfer, Peter"}
120 @string{RMHochstrasser = "Hochstrasser, Robin M."}
121 @string{WDHoff = "Hoff, Wouter D."}
122 @string{JKHHorber = "Horber, J. K. H."}
123 @string{CKHu = "Hu, Chin-Kun"}
124 @string{HHHuang = "Huang, Hector H."}
125 @string{FHugosson = "Hugosson, Fredrik"}
126 @string{GHummer = "Hummer, Gerhard"}
127 @string{WLHung = "Hung, Wen-Liang"}
128 @string{JLHutter = "Hutter, Jeffrey L."}
129 @string{CHyeon = "Hyeon, Changbong"}
130 @string{AIrback = "Irback, Anders"}
131 @string{SIzrailev = "Izrailev, S."}
132 @string{JBiotechnol = "J Biotechnol"}
133 @string{JMathBiol = "J Math Biol"}
134 @string{JTheorBiol = "J Theor Biol"}
135 @string{JChemPhys = "J. Chem. Phys."}
136 @string{LJanosi = "Janosi, Lorant"}
137 @string{JJAP = "Japanese Journal of Applied Physics"}
138 @string{YJia = "Jia, Yiwei"}
139 @string{SJiang = "Jiang, Shaoyi"}
140 @string{CPJohnson = "Johnson, Colin P."}
141 @string{EJones = "Jones, Eric"}
142 @string{DAJuckett = "Juckett, D. A."}
143 @string{GJungman = "Jungman, Gerard"}
144 @string{DKaftan = "Kaftan, David"}
145 @string{RKapon = "Kapon, Ruti"}
146 @string{AKardinal = "Kardinal, Angelika"}
147 @string{MKarplus = "Karplus, Martin"}
148 @string{FKienberger = "Kienberger, Ferry"}
149 @string{WTKing = "King, W. Trevor"}
150 @string{JKlafter = "Klafter, J."}
151 @string{AKleiner = "Kleiner, Ariel"}
152 @string{DKKlimov = "Klimov, Dmitri K."}
153 @string{IKosztin = "Kosztin, Ioan"}
154 @string{HAKramers = "Kramers, H.A."}
155 @string{AKrammer = "Krammer, Andre"}
156 @string{KKroy = "Kroy, Klaus"}
157 @string{MKulke = "Kulke, Michael"}
158 @string{CHKwok = "Kwok, Carol H."}
159 @string{DLabeit = "Labeit, Dietmar"}
160 @string{SLabeit = "Labeit, Siegfried"}
161 @string{SLahmers = "Lahmers, Sunshine"}
162 @string{CLam = "Lam, Canaan"}
163 @string{JCLamb = "Lamb, Jonathan C."}
164 @string{LANG = "Langmuir"}
165 @string{WLLau = "Lau, Wai Leung"}
166 @string{MCLeake = "Leake, Mark C."}
167 @string{HLee = "Lee, Haeshin"}
168 @string{SLee = "Lee, Sunyoung"}
169 @string{RLemmen = "Lemmen, Robert"}
170 @string{OLequin = "Lequin, Olivier"}
171 @string{HLi = "Li, Hongbin"}
172 @string{MSLi = "Li, Mai Suan"}
173 @string{FCLin = "Lin, Fan-Chi"}
174 @string{WALinke = "Linke, Wolfgang A."}
175 @string{JTLis = "Lis, John T."}
176 @string{WLiu = "Liu, W."}
177 @string{HLu = "Lu, Hui"}
178 @string{ZLuthey-Schulten = "Luthey-Schulten, Z."}
179 @string{MMaaloum = "Maaloum, M."}
180 @string{Macromolecules = "Macromolecules"}
181 @string{SMajid = "Majid, Sophia"}
182 @string{DEMakarov = "Makarov, Dmitrii E."}
183 @string{AMalec = "Malec, Arien"}
184 @string{RMamdani = "Mamdani, Reneeta"}
185 @string{EMandello = "Mandello, Enrico"}
186 @string{GManderson = "Manderson, Gavin"}
187 @string{JFMarko = "Marko, John F."}
188 @string{PEMarszalek = "Marszalek, Piotr E."}
189 @string{JMathe = "Math{\'e}, J{\'e}r{\^o}me"}
190 @string{AMatouschek = "Matouschek, Andreas"}
191 @string{BWMatthews = "Matthews, Brian W."}
192 @string{McGraw-Hill = "McGraw-Hill"}
193 @string{MechAgeingDev = "Mech Ageing Dev"}
194 @string{AMeller = "Meller, Amit"}
195 @string{CCMello = "Mello, Cecilia C."}
196 @string{RMerkel = "Merkel, R."}
197 @string{HMetiu = "Metiu, Horia"}
198 @string{MMickler = "Mickler, Moritz"}
199 @string{SMitternacht = "Mitternacht, Simon"}
200 @string{SMohanty = "Mohanty, Sandipan"}
201 @string{UMohideen = "Mohideen, U."}
202 @string{VMontana = "Montana, Vedrana"}
203 @string{LMontanaro = "Montanaro, Lucio"}
204 @string{SMukamel = "Mukamel, Shaul"}
205 @string{NSB = "Nat Struct Biol"}
206 @string{NSMB = "Nat Struct Mol Biol"}
207 @string{CNeagoe = "Neagoe, Ciprian"}
208 @string{NetworkTheoryLtd = "Network Theory Ltd."}
209 @string{RNevo = "Nevo, Reinat"}
210 @string{NJP = "New Journal of Physics"}
211 @string{SPNg = "Ng, Sean P."}
212 @string{MNguyen-Duong = "Nguyen-Duong, M."}
213 @string{SNie = "Nie, S."}
214 @string{AANoegel = "Noegel, Angelika A."}
215 @string{RANome = "Nome, Rene A."}
216 @string{JNummela = "Nummela, Jeremiah"}
217 @string{AFOberhauser = "Oberhauser, Andres F."}
218 @string{FOesterhelt = "Oesterhelt, Filipp"}
219 @string{TOhashi = "Ohashi, Tomoo"}
220 @string{TOliphant = "Oliphant, Travis"}
221 @string{PDOlmsted = "Olmsted, Peter D."}
222 @string{SJOlshansky = "Olshansky, S. J."}
223 @string{JNOnuchic = "Onuchic, J. N."}
224 @string{YOono = "Oono, Y."}
225 @string{CAOpitz = "Opitz, Christiane A."}
226 @string{KOroszlan = "Oroszlan, Krisztina"}
227 @string{EOroudjev = "Oroudjev, E."}
228 @string{OUP = "Oxford University Press"}
229 @string{EPaci = "Paci, Emanuele"}
230 @string{VParpura = "Parpura, Vladimir"}
231 @string{QPeng = "Peng, Qing"}
232 @string{OPerisic = "Perisic, Ognjen"}
233 @string{CLPeterson = "Peterson, Craig L."}
234 @string{PPeterson = "Peterson, Pearu"}
235 @string{PTRSL = "Philosophical Transactions of the Royal Society of London"}
236 @string{PRL = "Phys Rev Lett"}
237 @string{PRE = "Phys. Rev. E"}
238 @string{Physica = "Physica"}
239 @string{CPickett = "Pickett, Chris"}
240 @string{WPress = "Press, W."}
241 @string{PNAS = "Proceedings of the National Academy of Sciences U.S.A"}
242 @string{ProtSci = "Protein Sci"}
243 @string{Proteins = "Proteins"}
244 @string{SRQuake = "Quake, Stephen R."}
245 @string{SERadford = "Radford, Sheena E."}
246 @string{MRaible = "Raible, M."}
247 @string{NRamsey = "Ramsey, Norman"}
248 @string{LGRandles = "Randles, Lucy G."}
249 @string{SDRedick = "Redick, Sambra D."}
250 @string{ZReich = "Reich, Ziv"}
251 @string{PReimann = "Reimann, P."}
252 @string{RMP = "Rev. Mod. Phys."}
253 @string{RSI = "Review of Scientific Instruments"}
254 @string{FRief = "Rief, Frederick"}
255 @string{MRief = "Rief, Matthias"}
256 @string{KRitchie = "Ritchie, K."}
257 @string{RBRobertson = "Robertson, Ragan B."}
258 @string{HRoder = "Roder, Heinrich"}
259 @string{RRos = "Ros, R."}
260 @string{BRosenberg = "Rosenberg, B."}
261 @string{FRossi = "Rossi, Fabrice"}
262 @string{BSamori = "Samori, Bruno"}
263 @string{ASarkar = "Sarkar, Atom"}
264 @string{TSato = "Sato, Takehiro"}
265 @string{PSchaaf = "Schaaf, P."}
266 @string{RSchafer = "Schafer, Rolf"}
267 @string{NFScherer = "Scherer, Norbert F."}
268 @string{MSchleicher = "Schleicher, Michael"}
269 @string{MSchlierf = "Schlierf, Michael"}
270 @string{KSchulten = "Schulten, Klaus"}
271 @string{ZSchulten = "Schulten, Zan"}
272 @string{ISchwaiger = "Schwaiger, Ingo"}
273 @string{Science = "Science"}
274 @string{USeifert = "Seifert, Udo"}
275 @string{BSenger = "Senger, B."}
276 @string{EShakhnovich = "Shakhnovich, Eugene"}
277 @string{DSharma = "Sharma, Deepak"}
278 @string{YJSheng = "Sheng, Yu-Jane"}
279 @string{JShillcock = "Shillcock, Julian"}
280 @string{EDSiggia = "Siggia, Eric D."}
281 @string{CLSmith = "Smith, Corey L."}
282 @string{DASmith = "Smith, D. Alastair"}
283 @string{SSmith = "Smith, S."}
284 @string{JSoares = "Soares, J."}
285 @string{NDSocci = "Socci, N. D."}
286 @string{DWSpeicher = "Speicher, David W."}
287 @string{SStepaniants = "Stepaniants, S."}
288 @string{AStout = "Stout, A."}
289 @string{CStroh = "Stroh, Cordula"}
290 @string{TStrunz = "Strunz, Torsten"}
291 @string{ASzabo = "Szabo, Attila"}
292 @string{DSTalaga = "Talaga, David S."}
293 @string{PTalkner = "Talkner, Peter"}
294 @string{JTang = "Tang, Jianyong"}
295 @string{STeukolsky = "Teukolsky, S."}
296 @string{JCP = "The Journal of Chemical Physics"}
297 @string{RS = "The Royal Society"}
298 @string{JTheiler = "Theiler, James"}
299 @string{DThirumalai = "Thirumalai, D."}
300 @string{JBThompson = "Thompson, J. B."}
301 @string{TTlusty = "Tlusty, Tsvi"}
302 @string{JLToca-Herrera = "Toca-Herrera, Jose L."}
303 @string{JTrinick = "Trinick, John"}
304 @string{CHTsai = "Tsai, Chih-Hui"}
305 @string{HKTsao = "Tsao, Heng-Kwong"}
306 @string{MUrbakh = "Urbakh, M."}
307 @string{IRVetter = "Vetter, Ingrid R."}
308 @string{WVetterling = "Vetterling, W."}
309 @string{JCVoegel = "Voegel, J.-C."}
310 @string{VVogel = "Vogel, Viola"}
311 @string{KAWalther = "Walther, Kirstin A."}
312 @string{EBWalton = "Walton, Emily B."}
313 @string{MDWang = "Wang, Michelle D."}
314 @string{KWatanabe = "Watanabe, Kaori"}
315 @string{APWiita = "Wiita, Arun P."}
316 @string{Wikipedia = "Wikipedia"}
317 @string{AJWilcox = "Wilcox, Alexander J."}
318 @string{SWilson = "Wilson, Scott"}
319 @string{CWitt = "Witt, Christian"}
320 @string{PGWolynes = "Wolynes, P. G."}
321 @string{JWWu = "Wu, Jong-Wuu"}
322 @string{YWu = "Wu, Yiming"}
323 @string{GYang = "Yang, Guoliang"}
324 @string{YYang = "Yang, Yao"}
325 @string{RCYeh = "Yeh, Richard C."}
326 @string{WYu = "Yu, Weichang"}
327 @string{JMZhao = "Zhao, Jason Ming"}
328 @string{WZhuang = "Zhuang, Wei"}
329 @string{RCZinober = "Zinober, Rebecca C."}
330 @string{others = "others"}
331 @string{NGvanKampen = "van Kampen, N.G."}
332 @string{GvanRossum = "van Rossum, Guido"}
333 @string{KJvanVliet = "van Vliet, Krystyn J."}
335 @article { balsera97,
336 author = MBalsera #" and "# SStepaniants #" and "# SIzrailev #" and "#
337 YOono #" and "# KSchulten,
338 title = "Reconstructing potential energy functions from simulated force-
339 induced unbinding processes.",
345 pages = "1281--1287",
347 eprint = "http://www.biophysj.org/cgi/reprint/73/3/1281.pdf",
348 url = "http://www.biophysj.org/cgi/content/abstract/73/3/1281",
349 keywords = "Binding Sites; Biopolymers; Kinetics; Ligands; Microscopy,
350 Atomic Force; Models, Chemical; Molecular Conformation; Protein
351 Conformation; Proteins; Reproducibility of Results; Stochastic
352 Processes; Thermodynamics",
353 abstract = "One-dimensional stochastic models demonstrate that molecular
354 dynamics simulations of a few nanoseconds can be used to reconstruct
355 the essential features of the binding potential of macromolecules. This
356 can be accomplished by inducing the unbinding with the help of external
357 forces applied to the molecules, and discounting the irreversible work
358 performed on the system by these forces. The fluctuation-dissipation
359 theorem sets a fundamental limit on the precision with which the
360 binding potential can be reconstructed by this method. The uncertainty
361 in the resulting potential is linearly proportional to the irreversible
362 component of work performed on the system during the simulation. These
363 results provide an a priori estimate of the energy barriers observable
364 in molecular dynamics simulations."
368 author = GBaneyx #" and "# LBaugh #" and "# VVogel,
369 title = "{Supramolecular Chemistry And Self-assembly Special Feature:
370 Fibronectin extension and unfolding within cell matrix fibrils
371 controlled by cytoskeletal tension}",
376 pages = "5139--5143",
377 doi = "10.1073/pnas.072650799",
378 eprint = "http://www.pnas.org/cgi/reprint/99/8/5139.pdf",
379 url = "http://www.pnas.org/cgi/content/abstract/99/8/5139",
380 abstract = "Evidence is emerging that mechanical stretching can alter the
381 functional states of proteins. Fibronectin (Fn) is a large,
382 extracellular matrix protein that is assembled by cells into elastic
383 fibrils and subjected to contractile forces. Assembly into fibrils
384 coincides with expression of biological recognition sites that are
385 buried in Fn's soluble state. To investigate how supramolecular
386 assembly of Fn into fibrillar matrix enables cells to mechanically
387 regulate its structure, we used fluorescence resonance energy transfer
388 (FRET) as an indicator of Fn conformation in the fibrillar matrix of
389 NIH 3T3 fibroblasts. Fn was randomly labeled on amine residues with
390 donor fluorophores and site-specifically labeled on cysteine residues
391 in modules FnIII7 and FnIII15 with acceptor fluorophores.
392 Intramolecular FRET was correlated with known structural changes of Fn
393 in denaturing solution, then applied in cell culture as an indicator of
394 Fn conformation within the matrix fibrils of NIH 3T3 fibroblasts. Based
395 on the level of FRET, Fn in many fibrils was stretched by cells so that
396 its dimer arms were extended and at least one FnIII module unfolded.
397 When cytoskeletal tension was disrupted using cytochalasin D, FRET
398 increased, indicating refolding of Fn within fibrils. These results
399 suggest that cell-generated force is required to maintain Fn in
400 partially unfolded conformations. The results support a model of Fn
401 fibril elasticity based on unraveling and refolding of FnIII modules.
402 We also observed variation of FRET between and along single fibrils,
403 indicating variation in the degree of unfolding of Fn in fibrils.
404 Molecular mechanisms by which mechanical force can alter the structure
405 of Fn, converting tensile forces into biochemical cues, are discussed."
409 author = TBasche #" and "# SNie #" and "# JMFernandez,
410 title = "{Single molecules}",
415 pages = "10527--10528",
416 doi = "10.1073/pnas.191365898",
417 eprint = "http://www.pnas.org/cgi/reprint/98/19/10527.pdf",
418 url = "http://www.pnas.org"
421 @article { bechhoefer02,
422 author = JBechhoefer #" and "# SWilson,
423 title = "Faster, cheaper, safer optical tweezers for the undergraduate
432 doi = "10.1119/1.1445403",
433 url = "http://link.aip.org/link/?AJP/70/393/1",
434 keywords = "student experiments; safety; radiation pressure; laser beam
436 note = "Good discussion of the effect of correlation time on calibration.
437 Excellent detail on power spectrum derivation and thermal noise for
438 extremely overdamped oscillators in Appendix A (references
439 \cite{reif65}). References work on deconvolving thermal noise from
440 other noise\cite{cowan98}",
441 project = "Cantilever Calibration"
446 title = "Models for the specific adhesion of cells to cells.",
455 url = "http://www.jstor.org/stable/1746930",
456 keywords = "Antigen-Antibody Reactions; Cell Adhesion; Cell Membrane;
457 Chemistry, Physical; Electrophysiology; Enzymes; Glycoproteins;
458 Kinetics; Ligands; Membrane Proteins; Models, Biological; Receptors,
460 abstract = "A theoretical framework is proposed for the analysis of
461 adhesion between cells or of cells to surfaces when the adhesion is
462 mediated by reversible bonds between specific molecules such as antigen
463 and antibody, lectin and carbohydrate, or enzyme and substrate. From a
464 knowledge of the reaction rates for reactants in solution and of their
465 diffusion constants both in solution and on membranes, it is possible
466 to estimate reaction rates for membrane-bound reactants. Two models are
467 developed for predicting the rate of bond formation between cells and
468 are compared with experiments. The force required to separate two cells
469 is shown to be greater than the expected electrical forces between
470 cells, and of the same order of magnitude as the forces required to
471 pull gangliosides and perhaps some integral membrane proteins out of
473 note = "The Bell model and a fair bit of cell bonding background.",
474 project = "sawtooth simulation"
478 author = RBBest #" and "# SBFowler #" and "# JLToca-Herrera #" and "#
480 title = "{A simple method for probing the mechanical unfolding pathway of
481 proteins in detail}",
486 pages = "12143--12148",
487 doi = "10.1073/pnas.192351899",
488 eprint = "http://www.pnas.org/cgi/reprint/99/19/12143.pdf",
489 url = "http://www.pnas.org/cgi/content/abstract/99/19/12143",
490 abstract = "Atomic force microscopy is an exciting new single-molecule
491 technique to add to the toolbox of protein (un)folding methods.
492 However, detailed analysis of the unfolding of proteins on application
493 of force has, to date, relied on protein molecular dynamics simulations
494 or a qualitative interpretation of mutant data. Here we describe how
495 protein engineering {Phi} value analysis can be adapted to characterize
496 the transition states for mechanical unfolding of proteins. Single-
497 molecule studies also have an advantage over bulk experiments, in that
498 partial {Phi} values arising from partial structure in the transition
499 state can be clearly distinguished from those averaged over alternate
500 pathways. We show that unfolding rate constants derived in the standard
501 way by using Monte Carlo simulations are not reliable because of the
502 errors involved. However, it is possible to circumvent these problems,
503 providing the unfolding mechanism is not changed by mutation, either by
504 a modification of the Monte Carlo procedure or by comparing mutant and
505 wild-type data directly. The applicability of the method is tested on
506 simulated data sets and experimental data for mutants of titin I27."
509 @article { braverman08,
510 author = EBraverman #" and "# RMamdani,
511 title = "Continuous versus pulse harvesting for population models in
512 constant and variable environment.",
521 doi = "10.1007/s00285-008-0169-z",
523 "http://www.springerlink.com/content/a1m23v50201m2401/fulltext.pdf",
524 url = "http://www.springerlink.com/content/a1m23v50201m2401/",
525 abstract = "We consider both autonomous and nonautonomous population models
526 subject to either impulsive or continuous harvesting. It is
527 demonstrated in the paper that the impulsive strategy can be as good as
528 the continuous one, but cannot outperform it. We introduce a model,
529 where certain harm to the population is incorporated in each harvesting
530 event, and study it for the logistic and the Gompertz laws of growth.
531 In this case, impulsive harvesting is not only the optimal strategy but
532 is the only possible one.",
533 note = "An example of non-exponential Gomperz law."
536 @article { brockwell02,
537 author = DJBrockwell #" and "# GSBeddard #" and "# JClarkson #" and "#
538 RCZinober #" and "# AWBlake #" and "# JTrinick #" and "# PDOlmsted #"
539 and "# DASmith #" and "# SERadford,
540 title = "The effect of core destabilization on the mechanical resistance of
549 eprint = "http://www.biophysj.org/cgi/reprint/83/1/458.pdf",
550 url = "http://www.biophysj.org/cgi/content/abstract/83/1/458",
551 keywords = "Amino Acid Sequence; Dose-Response Relationship, Drug;
552 Kinetics; Magnetic Resonance Spectroscopy; Models, Molecular; Molecular
553 Sequence Data; Monte Carlo Method; Muscle Proteins; Mutation; Peptide
554 Fragments; Protein Denaturation; Protein Folding; Protein Kinases;
555 Protein Structure, Secondary; Protein Structure, Tertiary; Proteins;
557 abstract = "It is still unclear whether mechanical unfolding probes the
558 same pathways as chemical denaturation. To address this point, we have
559 constructed a concatamer of five mutant I27 domains (denoted (I27)(5)*)
560 and used it for mechanical unfolding studies. This protein consists of
561 four copies of the mutant C47S, C63S I27 and a single copy of C63S I27.
562 These mutations severely destabilize I27 (DeltaDeltaG(UN) = 8.7 and
563 17.9 kJ mol(-1) for C63S I27 and C47S, C63S I27, respectively). Both
564 mutations maintain the hydrogen bond network between the A' and G
565 strands postulated to be the major region of mechanical resistance for
566 I27. Measuring the speed dependence of the force required to unfold
567 (I27)(5)* in triplicate using the atomic force microscope allowed a
568 reliable assessment of the intrinsic unfolding rate constant of the
569 protein to be obtained (2.0 x 10(-3) s(-1)). The rate constant of
570 unfolding measured by chemical denaturation is over fivefold faster
571 (1.1 x 10(-2) s(-1)), suggesting that these techniques probe different
572 unfolding pathways. Also, by comparing the parameters obtained from the
573 mechanical unfolding of a wild-type I27 concatamer with that of
574 (I27)(5)*, we show that although the observed forces are considerably
575 lower, core destabilization has little effect on determining the
576 mechanical sensitivity of this domain."
579 @article { brower-toland02,
580 author = BDBrower-Toland #" and "# CLSmith #" and "# RCYeh #" and "# JTLis
581 #" and "# CLPeterson #" and "# MDWang,
582 title = "{From the Cover: Mechanical disruption of individual nucleosomes
583 reveals a reversible multistage release of DNA}",
588 pages = "1960--1965",
589 doi = "10.1073/pnas.022638399",
590 eprint = "http://www.pnas.org/cgi/reprint/99/4/1960.pdf",
591 url = "http://www.pnas.org/cgi/content/abstract/99/4/1960",
592 abstract = "The dynamic structure of individual nucleosomes was examined by
593 stretching nucleosomal arrays with a feedback-enhanced optical trap.
594 Forced disassembly of each nucleosome occurred in three stages.
595 Analysis of the data using a simple worm-like chain model yields 76 bp
596 of DNA released from the histone core at low stretching force.
597 Subsequently, 80 bp are released at higher forces in two stages: full
598 extension of DNA with histones bound, followed by detachment of
599 histones. When arrays were relaxed before the dissociated state was
600 reached, nucleosomes were able to reassemble and to repeat the
601 disassembly process. The kinetic parameters for nucleosome disassembly
602 also have been determined."
605 @article { bryngelson87,
606 author = JDBryngelson #" and "# PGWolynes,
607 title = "Spin glasses and the statistical mechanics of protein folding.",
613 pages = "7524--7528",
615 keywords = "Kinetics; Mathematics; Models, Theoretical; Protein
616 Conformation; Proteins; Stochastic Processes",
617 abstract = "The theory of spin glasses was used to study a simple model of
618 protein folding. The phase diagram of the model was calculated, and the
619 results of dynamics calculations are briefly reported. The relation of
620 these results to folding experiments, the relation of these hypotheses
621 to previous protein folding theories, and the implication of these
622 hypotheses for protein folding prediction schemes are discussed.",
623 note = "Seminal protein folding via energy landscape paper."
626 @article { bryngelson95,
627 author = JDBryngelson #" and "# JNOnuchic #" and "# NDSocci #" and "#
629 title = "Funnels, pathways, and the energy landscape of protein folding: a
638 doi = "10.1002/prot.340210302",
639 keywords = "Amino Acid Sequence; Chemistry, Physical; Computer Simulation;
640 Data Interpretation, Statistical; Kinetics; Models, Chemical; Molecular
641 Sequence Data; Protein Biosynthesis; Protein Conformation; Protein
642 Folding; Proteins; Thermodynamics",
643 abstract = "The understanding, and even the description of protein folding
644 is impeded by the complexity of the process. Much of this complexity
645 can be described and understood by taking a statistical approach to the
646 energetics of protein conformation, that is, to the energy landscape.
647 The statistical energy landscape approach explains when and why unique
648 behaviors, such as specific folding pathways, occur in some proteins
649 and more generally explains the distinction between folding processes
650 common to all sequences and those peculiar to individual sequences.
651 This approach also gives new, quantitative insights into the
652 interpretation of experiments and simulations of protein folding
653 thermodynamics and kinetics. Specifically, the picture provides simple
654 explanations for folding as a two-state first-order phase transition,
655 for the origin of metastable collapsed unfolded states and for the
656 curved Arrhenius plots observed in both laboratory experiments and
657 discrete lattice simulations. The relation of these quantitative ideas
658 to folding pathways, to uniexponential vs. multiexponential behavior in
659 protein folding experiments and to the effect of mutations on folding
660 is also discussed. The success of energy landscape ideas in protein
661 structure prediction is also described. The use of the energy landscape
662 approach for analyzing data is illustrated with a quantitative analysis
663 of some recent simulations, and a qualitative analysis of experiments
664 on the folding of three proteins. The work unifies several previously
665 proposed ideas concerning the mechanism protein folding and delimits
666 the regions of validity of these ideas under different thermodynamic
670 @article { bullard06,
671 author = BBullard #" and "# TGarcia #" and "# VBenes #" and "# MCLeake #"
672 and "# WALinke #" and "# AFOberhauser,
673 title = "{The molecular elasticity of the insect flight muscle proteins
674 projectin and kettin}",
679 pages = "4451--4456",
680 doi = "10.1073/pnas.0509016103",
681 eprint = "http://www.pnas.org/cgi/reprint/103/12/4451.pdf",
682 url = "http://www.pnas.org/cgi/content/abstract/103/12/4451",
683 abstract = "Projectin and kettin are titin-like proteins mainly responsible
684 for the high passive stiffness of insect indirect flight muscles, which
685 is needed to generate oscillatory work during flight. Here we report
686 the mechanical properties of kettin and projectin by single-molecule
687 force spectroscopy. Force-extension and force-clamp curves obtained
688 from Lethocerus projectin and Drosophila recombinant projectin or
689 kettin fragments revealed that fibronectin type III domains in
690 projectin are mechanically weaker (unfolding force, Fu {approx} 50-150
691 pN) than Ig-domains (Fu {approx} 150-250 pN). Among Ig domains in
692 Sls/kettin, the domains near the N terminus are less stable than those
693 near the C terminus. Projectin domains refolded very fast [85% at 15
694 s-1 (25{degrees}C)] and even under high forces (15-30 pN). Temperature
695 affected the unfolding forces with a Q10 of 1.3, whereas the refolding
696 speed had a Q10 of 2-3, probably reflecting the cooperative nature of
697 the folding mechanism. High bending rigidities of projectin and kettin
698 indicated that straightening the proteins requires low forces. Our
699 results suggest that titin-like proteins in indirect flight muscles
700 could function according to a folding-based-spring mechanism."
703 @article { bustamante94,
704 author = CBustamante #" and "# JFMarko #" and "# EDSiggia #" and "#
706 title = "Entropic elasticity of lambda-phage {DNA}.",
713 pages = "1599--1600",
715 keywords = "Bacteriophage lambda; DNA, Viral; Least-Squares Analysis;
717 note = "WLC interpolation formula."
720 @article { bustanji03,
721 author = YBustanji #" and "# CRArciola #" and "# MConti #" and "#
722 EMandello #" and "# LMontanaro #" and "# BSamori,
723 title = "{Dynamics of the interaction between a fibronectin molecule and a
724 living bacterium under mechanical force}",
729 pages = "13292--13297",
730 doi = "10.1073/pnas.1735343100",
731 eprint = "http://www.pnas.org/cgi/reprint/100/23/13292.pdf",
732 url = "http://www.pnas.org/cgi/content/abstract/100/23/13292",
733 abstract = "Fibronectin (Fn) is an important mediator of bacterial
734 invasions and of persistent infections like that of Staphylococcus
735 epidermis. Similar to many other types of cell-protein adhesion, the
736 binding between Fn and S. epidermidis takes place under physiological
737 shear rates. We investigated the dynamics of the interaction between
738 individual living S. epidermidis cells and single Fn molecules under
739 mechanical force by using the scanning force microscope. The mechanical
740 strength of this interaction and the binding site in the Fn molecule
741 were determined. The energy landscape of the binding/unbinding process
742 was mapped, and the force spectrum and the association and dissociation
743 rate constants of the binding pair were measured. The interaction
744 between S. epidermidis cells and Fn molecules is compared with those of
745 two other protein/ligand pairs known to mediate different dynamic
746 states of adhesion of cells under a hydrodynamic flow: the firm
747 adhesion mediated by biotin/avidin interactions, and the rolling
748 adhesion, mediated by L-selectin/P-selectin glycoprotein ligand-1
749 interactions. The inner barrier in the energy landscape of the Fn case
750 characterizes a high-energy binding mode that can sustain larger
751 deformations and for significantly longer times than the correspondent
752 high-strength L-selectin/P-selectin glycoprotein ligand-1 binding mode.
753 The association kinetics of the former interaction is much slower to
754 settle than the latter. On this basis, the observations made at the
755 macroscopic scale by other authors of a strong lability of the
756 bacterial adhesions mediated by Fn under high turbulent flow are
757 rationalized at the molecular level."
761 author = YCao #" and "# MMBalamurali #" and "# DSharma #" and "# HLi,
762 title = "{A functional single-molecule binding assay via force
768 pages = "15677--15681",
769 doi = "10.1073/pnas.0705367104",
770 eprint = "http://www.pnas.org/cgi/reprint/104/40/15677.pdf",
771 url = "http://www.pnas.org/cgi/content/abstract/104/40/15677",
772 abstract = "Proteinligand interactions, including proteinprotein
773 interactions, are ubiquitously essential in biological processes and
774 also have important applications in biotechnology. A wide range of
775 methodologies have been developed for quantitative analysis of
776 proteinligand interactions. However, most of them do not report direct
777 functional/structural consequence of ligand binding. Instead they only
778 detect the change of physical properties, such as fluorescence and
779 refractive index, because of the colocalization of protein and ligand,
780 and are susceptible to false positives. Thus, important information
781 about the functional state of proteinligand complexes cannot be
782 obtained directly. Here we report a functional single-molecule binding
783 assay that uses force spectroscopy to directly probe the functional
784 consequence of ligand binding and report the functional state of
785 proteinligand complexes. As a proof of principle, we used protein G and
786 the Fc fragment of IgG as a model system in this study. Binding of Fc
787 to protein G does not induce major structural changes in protein G but
788 results in significant enhancement of its mechanical stability. Using
789 mechanical stability of protein G as an intrinsic functional reporter,
790 we directly distinguished and quantified Fc-bound and Fc-free forms of
791 protein G on a single-molecule basis and accurately determined their
792 dissociation constant. This single-molecule functional binding assay is
793 label-free, nearly background-free, and can detect functional
794 heterogeneity, if any, among proteinligand interactions. This
795 methodology opens up avenues for studying proteinligand interactions in
796 a functional context, and we anticipate that it will find broad
797 application in diverse proteinligand systems."
801 author = PCarl #" and "# CHKwok #" and "# GManderson #" and "# DWSpeicher
803 title = "{Forced unfolding modulated by disulfide bonds in the Ig domains
804 of a cell adhesion molecule}",
809 pages = "1565--1570",
810 doi = "10.1073/pnas.031409698",
811 eprint = "http://www.pnas.org/cgi/reprint/98/4/1565.pdf",
812 url = "http://www.pnas.org/cgi/content/abstract/98/4/1565",
816 @article { carrion-vazquez99a,
817 author = MCarrion-Vazquez #" and "# AFOberhauser #" and "# SBFowler #" and
818 "# PEMarszalek #" and "# SEBroedel #" and "# JClarke #" and "#
820 title = "Mechanical and chemical unfolding of a single protein: A
828 pages = "3694--3699",
829 doi = "10.1073/pnas.96.7.3694",
830 eprint = "http://www.pnas.org/cgi/reprint/96/7/3694.pdf",
831 url = "http://www.pnas.org/cgi/content/abstract/96/7/3694"
834 @article { carrion-vazquez99b,
835 author = MCarrion-Vazquez #" and "# PEMarszalek #" and "# AFOberhauser #"
837 title = "Atomic force microscopy captures length phenotypes in single
845 pages = "11288--11292",
846 doi = "10.1073/pnas.96.20.11288",
847 eprint = "http://www.pnas.org/cgi/reprint/96/20/11288.pdf",
848 url = "http://www.pnas.org/cgi/content/abstract/96/20/11288",
854 title = "Statistical Data Analysis",
857 address = "New York",
858 note = "Noise deconvolution in Chapter 11",
859 project = "Cantilever Calibration"
863 author = DCraig #" and "# AKrammer #" and "# KSchulten #" and "# VVogel,
864 title = "{Comparison of the early stages of forced unfolding for
865 fibronectin type III modules}",
870 pages = "5590--5595",
871 doi = "10.1073/pnas.101582198",
872 eprint = "http://www.pnas.org/cgi/reprint/98/10/5590.pdf",
873 url = "http://www.pnas.org/cgi/content/abstract/98/10/5590",
878 author = HDietz #" and "# MRief,
879 title = "{Exploring the energy landscape of GFP by single-molecule
880 mechanical experiments}",
885 pages = "16192--16197",
886 doi = "10.1073/pnas.0404549101",
887 eprint = "http://www.pnas.org/cgi/reprint/101/46/16192.pdf",
888 url = "http://www.pnas.org/cgi/content/abstract/101/46/16192",
889 abstract = "We use single-molecule force spectroscopy to drive single GFP
890 molecules from the native state through their complex energy landscape
891 into the completely unfolded state. Unlike many smaller proteins,
892 mechanical GFP unfolding proceeds by means of two subsequent
893 intermediate states. The transition from the native state to the first
894 intermediate state occurs near thermal equilibrium at {approx}35 pN and
895 is characterized by detachment of a seven-residue N-terminal
896 {alpha}-helix from the beta barrel. We measure the equilibrium free
897 energy cost associated with this transition as 22 kBT. Detachment of
898 this small {alpha}-helix completely destabilizes GFP thermodynamically
899 even though the {beta}-barrel is still intact and can bear load.
900 Mechanical stability of the protein on the millisecond timescale,
901 however, is determined by the activation barrier of unfolding the
902 {beta}-barrel out of this thermodynamically unstable intermediate
903 state. High bandwidth, time-resolved measurements of the cantilever
904 relaxation phase upon unfolding of the {beta}-barrel revealed a second
905 metastable mechanical intermediate with one complete {beta}-strand
906 detached from the barrel. Quantitative analysis of force distributions
907 and lifetimes lead to a detailed picture of the complex mechanical
908 unfolding pathway through a rough energy landscape.",
909 note = "Nice energy-landscape-to-one-dimension compression graphic.
910 Unfolding Green Flourescent Protein (GFP) towards using it as an
911 embedded force probe.",
912 project = "Energy landscape roughness"
916 author = HDietz #" and "# FBerkemeier #" and "# MBertz #" and "# MRief,
917 title = "{Anisotropic deformation response of single protein molecules}",
922 pages = "12724--12728",
923 doi = "10.1073/pnas.0602995103",
924 eprint = "http://www.pnas.org/cgi/reprint/103/34/12724.pdf",
925 url = "http://www.pnas.org/cgi/content/abstract/103/34/12724",
926 abstract = "Single-molecule methods have given experimental access to the
927 mechanical properties of single protein molecules. So far, access has
928 been limited to mostly one spatial direction of force application.
929 Here, we report single-molecule experiments that explore the mechanical
930 properties of a folded protein structure in precisely controlled
931 directions by applying force to selected amino acid pairs. We
932 investigated the deformation response of GFP in five selected
933 directions. We found fracture forces widely varying from 100 pN up to
934 600 pN. We show that straining the GFP structure in one of the five
935 directions induces partial fracture of the protein into a half-folded
936 intermediate structure. From potential widths we estimated directional
937 spring constants of the GFP structure and found values ranging from 1
938 N/m up to 17 N/m. Our results show that classical continuum mechanics
939 and simple mechanistic models fail to describe the complex mechanics of
940 the GFP protein structure and offer insights into the mechanical design
941 of protein materials."
945 author = HDietz #" and "# MRief,
946 title = "{Protein structure by mechanical triangulation}",
951 pages = "1244--1247",
952 doi = "10.1073/pnas.0509217103",
953 eprint = "http://www.pnas.org/cgi/reprint/103/5/1244.pdf",
954 url = "http://www.pnas.org/cgi/content/abstract/103/5/1244",
955 abstract = "Knowledge of protein structure is essential to understand
956 protein function. High-resolution protein structure has so far been the
957 domain of ensemble methods. Here, we develop a simple single-molecule
958 technique to measure spatial position of selected residues within a
959 folded and functional protein structure in solution. Construction and
960 mechanical unfolding of cysteine-engineered polyproteins with
961 controlled linkage topology allows measuring intramolecular distance
962 with angstrom precision. We demonstrate the potential of this technique
963 by determining the position of three residues in the structure of green
964 fluorescent protein (GFP). Our results perfectly agree with the GFP
965 crystal structure. Mechanical triangulation can find many applications
966 where current bulk structural methods fail."
970 author = HDietz #" and "# MRief,
971 title = "Detecting Molecular Fingerprints in Single Molecule Force
972 Spectroscopy Using Pattern Recognition",
977 pages = "5540--5542",
979 doi = "10.1143/JJAP.46.5540",
980 url = "http://jjap.ipap.jp/link?JJAP/46/5540/",
981 keywords = "single molecule, protein mechanics, force spectroscopy, AFM,
982 pattern recognition, GFP",
983 abstract = "Single molecule force spectroscopy has given experimental
984 access to the mechanical properties of protein molecules. Typically,
985 less than 1% of the experimental recordings reflect true single
986 molecule events due to abundant surface and multiple-molecule
987 interactions. A key issue in single molecule force spectroscopy is thus
988 to identify the characteristic mechanical `fingerprint' of a specific
989 protein in noisy data sets. Here, we present an objective pattern
990 recognition algorithm that is able to identify fingerprints in such
992 note = "Automatic force curve selection. Seems a bit shoddy. Details
996 @article { discher06,
997 author = DEDischer #" and "# NBhasin #" and "# CPJohnson,
998 title = "{Covalent chemistry on distended proteins}",
1003 pages = "7533--7534",
1004 doi = "10.1073/pnas.0602388103",
1005 eprint = "http://www.pnas.org/cgi/reprint/103/20/7533.pdf",
1006 url = "http://www.pnas.org"
1010 author = OKDudko #" and "# AEFilippov #" and "# JKlafter #" and "#
1012 title = "Beyond the conventional description of dynamic force spectroscopy
1013 of adhesion bonds.",
1020 pages = "11378--11381",
1022 doi = "10.1073/pnas.1534554100",
1023 eprint = "http://www.pnas.org/content/100/20/11378.full.pdf",
1024 url = "http://www.pnas.org/content/100/20/11378.abstract",
1025 keywords = "Spectrum Analysis; Temperature",
1026 abstract = "Dynamic force spectroscopy of single molecules is described by
1027 a model that predicts a distribution of rupture forces, the
1028 corresponding mean rupture force, and variance, which are all amenable
1029 to experimental tests. The distribution has a pronounced asymmetry,
1030 which has recently been observed experimentally. The mean rupture force
1031 follows a (lnV)2/3 dependence on the pulling velocity, V, and differs
1032 from earlier predictions. Interestingly, at low pulling velocities, a
1033 rebinding process is obtained whose signature is an intermittent
1034 behavior of the spring force, which delays the rupture. An extension to
1035 include conformational changes of the adhesion complex is proposed,
1036 which leads to the possibility of bimodal distributions of rupture
1041 author = OKDudko #" and "# GHummer #" and "# ASzabo,
1042 title = "Intrinsic rates and activation free energies from single-molecule
1043 pulling experiments.",
1052 doi = "10.1103/PhysRevLett.96.108101",
1053 keywords = "Biophysics; Computer Simulation; Data Interpretation,
1054 Statistical; Kinetics; Micromanipulation; Models, Chemical; Models,
1055 Molecular; Molecular Conformation; Muscle Proteins; Nucleic Acid
1056 Conformation; Protein Binding; Protein Denaturation; Protein Folding;
1057 Protein Kinases; RNA; Stress, Mechanical; Thermodynamics; Time Factors",
1058 abstract = "We present a unified framework for extracting kinetic
1059 information from single-molecule pulling experiments at constant force
1060 or constant pulling speed. Our procedure provides estimates of not only
1061 (i) the intrinsic rate coefficient and (ii) the location of the
1062 transition state but also (iii) the free energy of activation. By
1063 analyzing simulated data, we show that the resulting rates of force-
1064 induced rupture are significantly more reliable than those obtained by
1065 the widely used approach based on Bell's formula. We consider the
1066 uniqueness of the extracted kinetic information and suggest guidelines
1067 to avoid over-interpretation of experiments."
1071 author = OKDudko #" and "# JMathe #" and "# ASzabo #" and "# AMeller #"
1073 title = "Extracting kinetics from single-molecule force spectroscopy:
1074 nanopore unzipping of {DNA} hairpins.",
1081 pages = "4188--4195",
1083 doi = "10.1529/biophysj.106.102855",
1084 eprint = "http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1877759&blo
1086 keywords = "Computer Simulation; DNA; Elasticity; Mechanics;
1087 Micromanipulation; Microscopy, Atomic Force; Models, Chemical; Models,
1088 Molecular; Nanostructures; Nucleic Acid Conformation; Porosity; Stress,
1090 abstract = "Single-molecule force experiments provide powerful new tools to
1091 explore biomolecular interactions. Here, we describe a systematic
1092 procedure for extracting kinetic information from force-spectroscopy
1093 experiments, and apply it to nanopore unzipping of individual DNA
1094 hairpins. Two types of measurements are considered: unzipping at
1095 constant voltage, and unzipping at constant voltage-ramp speeds. We
1096 perform a global maximum-likelihood analysis of the experimental data
1097 at low-to-intermediate ramp speeds. To validate the theoretical models,
1098 we compare their predictions with two independent sets of data,
1099 collected at high ramp speeds and at constant voltage, by using a
1100 quantitative relation between the two types of measurements.
1101 Microscopic approaches based on Kramers theory of diffusive barrier
1102 crossing allow us to estimate not only intrinsic rates and transition
1103 state locations, as in the widely used phenomenological approach based
1104 on Bell's formula, but also free energies of activation. The problem of
1105 extracting unique and accurate kinetic parameters of a molecular
1106 transition is discussed in light of the apparent success of the
1107 microscopic theories in reproducing the experimental data."
1111 author = EEvans #" and "# KRitchie,
1112 title = "Dynamic strength of molecular adhesion bonds.",
1118 pages = "1541--1555",
1120 eprint = "http://www.biophysj.org/cgi/reprint/72/4/1541.pdf",
1121 url = "http://www.biophysj.org/cgi/content/abstract/72/4/1541",
1122 keywords = "Avidin; Biotin; Chemistry, Physical; Computer Simulation;
1123 Mathematics; Monte Carlo Method; Protein Binding",
1124 abstract = "In biology, molecular linkages at, within, and beneath cell
1125 interfaces arise mainly from weak noncovalent interactions. These bonds
1126 will fail under any level of pulling force if held for sufficient time.
1127 Thus, when tested with ultrasensitive force probes, we expect cohesive
1128 material strength and strength of adhesion at interfaces to be time-
1129 and loading rate-dependent properties. To examine what can be learned
1130 from measurements of bond strength, we have extended Kramers' theory
1131 for reaction kinetics in liquids to bond dissociation under force and
1132 tested the predictions by smart Monte Carlo (Brownian dynamics)
1133 simulations of bond rupture. By definition, bond strength is the force
1134 that produces the most frequent failure in repeated tests of breakage,
1135 i.e., the peak in the distribution of rupture forces. As verified by
1136 the simulations, theory shows that bond strength progresses through
1137 three dynamic regimes of loading rate. First, bond strength emerges at
1138 a critical rate of loading (> or = 0) at which spontaneous dissociation
1139 is just frequent enough to keep the distribution peak at zero force. In
1140 the slow-loading regime immediately above the critical rate, strength
1141 grows as a weak power of loading rate and reflects initial coupling of
1142 force to the bonding potential. At higher rates, there is crossover to
1143 a fast regime in which strength continues to increase as the logarithm
1144 of the loading rate over many decades independent of the type of
1145 attraction. Finally, at ultrafast loading rates approaching the domain
1146 of molecular dynamics simulations, the bonding potential is quickly
1147 overwhelmed by the rapidly increasing force, so that only naked
1148 frictional drag on the structure remains to retard separation. Hence,
1149 to expose the energy landscape that governs bond strength, molecular
1150 adhesion forces must be examined over an enormous span of time scales.
1151 However, a significant gap exists between the time domain of force
1152 measurements in the laboratory and the extremely fast scale of
1153 molecular motions. Using results from a simulation of biotin-avidin
1154 bonds (Izrailev, S., S. Stepaniants, M. Balsera, Y. Oono, and K.
1155 Schulten. 1997. Molecular dynamics study of unbinding of the avidin-
1156 biotin complex. Biophys. J., this issue), we describe how Brownian
1157 dynamics can help bridge the gap between molecular dynamics and probe
1159 project = "sawtooth simulation"
1163 author = EEvans #" and "# KRitchie,
1164 title = "Strength of a weak bond connecting flexible polymer chains.",
1170 pages = "2439--2447",
1172 eprint = "http://www.biophysj.org/cgi/reprint/76/5/2439.pdf",
1173 url = "http://www.biophysj.org/cgi/content/abstract/76/5/2439",
1174 keywords = "Animals; Biophysics; Biopolymers; Microscopy, Atomic Force;
1175 Models, Chemical; Muscle Proteins; Protein Folding; Protein Kinases;
1176 Stochastic Processes; Stress, Mechanical; Thermodynamics",
1177 abstract = "Bond dissociation under steadily rising force occurs most
1178 frequently at a time governed by the rate of loading (Evans and
1179 Ritchie, 1997 Biophys. J. 72:1541-1555). Multiplied by the loading
1180 rate, the breakage time specifies the force for most frequent failure
1181 (called bond strength) that obeys the same dependence on loading rate.
1182 The spectrum of bond strength versus log(loading rate) provides an
1183 image of the energy landscape traversed in the course of unbonding.
1184 However, when a weak bond is connected to very compliant elements like
1185 long polymers, the load applied to the bond does not rise steadily
1186 under constant pulling speed. Because of nonsteady loading, the most
1187 frequent breakage force can differ significantly from that of a bond
1188 loaded at constant rate through stiff linkages. Using generic models
1189 for wormlike and freely jointed chains, we have analyzed the kinetic
1190 process of failure for a bond loaded by pulling the polymer linkages at
1191 constant speed. We find that when linked by either type of polymer
1192 chain, a bond is likely to fail at lower force under steady separation
1193 than through stiff linkages. Quite unexpectedly, a discontinuous jump
1194 can occur in bond strength at slow separation speed in the case of long
1195 polymer linkages. We demonstrate that the predictions of strength
1196 versus log(loading rate) can rationalize conflicting results obtained
1197 recently for unfolding Ig domains along muscle titin with different
1199 note = "Develops Kramers improvement on Bell model for domain unfolding.
1200 Presents unfolding under variable loading rates. Often cited as the
1201 ``Bell-Evans'' model? They derive a unitless treatment, scaling force
1202 by $f_\beta$, TODO; time by $\tau_f$, TODO; elasiticity by compliance
1203 $c(f)$. The appendix has relaxation time formulas for WLC and FJC
1205 project = "sawtooth simulation"
1209 author = MGalassi #" and "# JDavies #" and "# JTheiler #" and "# BGough #"
1210 and "# GJungman #" and "# MBooth #" and "# FRossi,
1211 title = "{GNU} Scientific Library: Reference Manual",
1213 edition = "Second Revised",
1214 pages = "xvi + 601",
1215 xxpages = "xvi + 580",
1216 isbn = "0-9541617-3-4",
1217 isbn-13 = "978-0-9541617-3-6",
1218 lccn = "QA76.73.C15",
1219 publisher = NetworkTheoryLtd,
1220 address = pub-NETWORK-THEORY:adr,
1221 bibdate = "Wed Oct 30 10:44:22 2002",
1222 url = "http://www.network-theory.co.uk/gsl/manual/",
1223 note = "This is the revised and updated second edition of the manual, and
1224 corresponds to version 1.6 of the library."
1228 author = MGao #" and "# DCraig #" and "# OLequin #" and "# IDCampbell #"
1229 and "# VVogel #" and "# KSchulten,
1230 title = "{Structure and functional significance of mechanically unfolded
1231 fibronectin type III1 intermediates}",
1236 pages = "14784--14789",
1237 doi = "10.1073/pnas.2334390100",
1238 eprint = "http://www.pnas.org/cgi/reprint/100/25/14784.pdf",
1239 url = "http://www.pnas.org/cgi/content/abstract/100/25/14784",
1240 abstract = "Fibronectin (FN) forms fibrillar networks coupling cells to the
1241 extracellular matrix. The formation of FN fibrils, fibrillogenesis, is
1242 a tightly regulated process involving the exposure of cryptic binding
1243 sites in individual FN type III (FN-III) repeats presumably exposed by
1244 mechanical tension. The FN-III1 module has been previously proposed to
1245 contain such cryptic sites that promote the assembly of extracellular
1246 matrix FN fibrils. We have combined NMR and steered molecular dynamics
1247 simulations to study the structure and mechanical unfolding pathway of
1248 FN-III1. This study finds that FN-III1 consists of a {beta}-sandwich
1249 structure that unfolds to a mechanically stable intermediate about four
1250 times the length of the native folded state. Considering previous
1251 experimental findings, our studies provide a structural model by which
1252 mechanical stretching of FN-III1 may induce fibrillogenesis through
1253 this partially unfolded intermediate."
1256 @article { gavrilov01,
1257 author = LAGavrilov #" and "# NSGavrilova,
1258 title = "The reliability theory of aging and longevity.",
1262 journal = JTheorBiol,
1267 doi = "10.1006/jtbi.2001.2430",
1268 keywords = "Adult; Aged; Aging; Animals; Humans; Longevity; Middle Aged;
1269 Models, Biological; Survival Rate; Systems Theory",
1270 abstract = "Reliability theory is a general theory about systems failure.
1271 It allows researchers to predict the age-related failure kinetics for a
1272 system of given architecture (reliability structure) and given
1273 reliability of its components. Reliability theory predicts that even
1274 those systems that are entirely composed of non-aging elements (with a
1275 constant failure rate) will nevertheless deteriorate (fail more often)
1276 with age, if these systems are redundant in irreplaceable elements.
1277 Aging, therefore, is a direct consequence of systems redundancy.
1278 Reliability theory also predicts the late-life mortality deceleration
1279 with subsequent leveling-off, as well as the late-life mortality
1280 plateaus, as an inevitable consequence of redundancy exhaustion at
1281 extreme old ages. The theory explains why mortality rates increase
1282 exponentially with age (the Gompertz law) in many species, by taking
1283 into account the initial flaws (defects) in newly formed systems. It
1284 also explains why organisms ``prefer'' to die according to the Gompertz
1285 law, while technical devices usually fail according to the Weibull
1286 (power) law. Theoretical conditions are specified when organisms die
1287 according to the Weibull law: organisms should be relatively free of
1288 initial flaws and defects. The theory makes it possible to find a
1289 general failure law applicable to all adult and extreme old ages, where
1290 the Gompertz and the Weibull laws are just special cases of this more
1291 general failure law. The theory explains why relative differences in
1292 mortality rates of compared populations (within a given species) vanish
1293 with age, and mortality convergence is observed due to the exhaustion
1294 of initial differences in redundancy levels. Overall, reliability
1295 theory has an amazing predictive and explanatory power with a few, very
1296 general and realistic assumptions. Therefore, reliability theory seems
1297 to be a promising approach for developing a comprehensive theory of
1298 aging and longevity integrating mathematical methods with specific
1299 biological knowledge.",
1300 note = "An example of exponential (standard) Gomperz law."
1303 @article { gergely00,
1304 author = CGergely #" and "# JCVoegel #" and "# PSchaaf #" and "# BSenger
1305 #" and "# MMaaloum #" and "# JKHHorber #" and "# JHemmerle,
1306 title = "{Unbinding process of adsorbed proteins under external stress
1307 studied by atomic force microscopy spectroscopy}",
1312 pages = "10802--10807",
1313 doi = "10.1073/pnas.180293097",
1314 eprint = "http://www.pnas.org/cgi/reprint/97/20/10802.pdf",
1315 url = "http://www.pnas.org/cgi/content/abstract/97/20/10802"
1318 @article { gompertz25,
1320 title = "On the Nature of the Function Expressive of the Law of Human
1321 Mortality, and on a New Mode of Determining the Value of Life
1330 copyright = "Copyright \copy\ 1825 The Royal Society",
1331 url = "http://www.jstor.org/stable/107756",
1335 @article { grossman05,
1336 author = CGrossman #" and "# AStout,
1337 title = "Optical Tweezers Advanced Lab",
1341 eprint = "http://chirality.swarthmore.edu/PHYS81/OpticalTweezers.pdf",
1342 note = "Fairly complete overdamped PSD derivation in section 4.3., cites
1343 \cite{tlusty98} and \cite{bechhoefer02} for further details. However,
1344 Tlusty (listed as reference 8) doesn't contain the thermal response
1345 fn.\ derivation it was cited for. Also, the single sided PSD definition
1346 credited to reference 9 (listed as Bechhoefer) looks more like Press
1347 (listed as reference 10). I imagine Grossman and Stout mixed up their
1348 references, and meant to refer to \cite{bechhoefer02} and
1349 \cite{press92} respectively instead.",
1350 project = "Cantilever Calibration"
1353 @article { hanggi90,
1354 author = PHanggi #" and "# PTalkner #" and "# MBorkovec,
1355 title = "Reaction-rate theory: fifty years after Kramers",
1364 doi = "10.1103/RevModPhys.62.251",
1365 eprint = "http://www.physik.uni-augsburg.de/theo1/hanggi/Papers/112.pdf",
1366 url = "http://prola.aps.org/abstract/RMP/v62/i2/p251_1",
1367 note = "\emph{The} Kramers' theory review article. See pages 268--279 for
1368 the Kramers-specific introduction.",
1369 project = "sawtooth simulation"
1372 @article { hatfield99,
1373 author = JWHatfield #" and "# SRQuake,
1374 title = "Dynamic Properties of an Extended Polymer in Solution",
1380 pages = "3548--3551",
1383 doi = "10.1103/PhysRevLett.82.3548",
1384 url = "http://link.aps.org/abstract/PRL/v82/p3548",
1385 note = "Defines WLC and FJC models, citing textbooks.",
1386 project = "sawtooth simulation"
1389 @article { heymann00,
1390 author = BHeymann #" and "# HGrubmuller,
1391 title = "Dynamic force spectroscopy of molecular adhesion bonds.",
1398 pages = "6126--6129",
1400 doi = "10.1103/PhysRevLett.84.6126",
1401 eprint = "http://prola.aps.org/pdf/PRL/v84/i26/p6126_1",
1402 url = "http://prola.aps.org/abstract/PRL/v84/p6126",
1403 abstract = "Recent advances in atomic force microscopy, biomembrane force
1404 probe experiments, and optical tweezers allow one to measure the
1405 response of single molecules to mechanical stress with high precision.
1406 Such experiments, due to limited spatial resolution, typically access
1407 only one single force value in a continuous force profile that
1408 characterizes the molecular response along a reaction coordinate. We
1409 develop a theory that allows one to reconstruct force profiles from
1410 force spectra obtained from measurements at varying loading rates,
1411 without requiring increased resolution. We show that spectra obtained
1412 from measurements with different spring constants contain complementary
1416 @article { hummer01,
1417 author = GHummer #" and "# ASzabo,
1418 title = "{From the Cover: Free energy reconstruction from nonequilibrium
1419 single-molecule pulling experiments}",
1424 pages = "3658--3661",
1425 doi = "10.1073/pnas.071034098",
1426 eprint = "http://www.pnas.org/cgi/reprint/98/7/3658.pdf",
1427 url = "http://www.pnas.org/cgi/content/abstract/98/7/3658"
1430 @article { hummer03,
1431 author = GHummer #" and "# ASzabo,
1432 title = "Kinetics from nonequilibrium single-molecule pulling experiments.",
1440 eprint = "http://www.biophysj.org/cgi/reprint/85/1/5.pdf",
1441 url = "http://www.biophysj.org/cgi/content/abstract/85/1/5",
1442 keywords = "Computer Simulation; Crystallography; Energy Transfer;
1443 Kinetics; Lasers; Micromanipulation; Microscopy, Atomic Force; Models,
1444 Molecular; Molecular Conformation; Motion; Muscle Proteins;
1445 Nanotechnology; Physical Stimulation; Protein Conformation; Protein
1446 Denaturation; Protein Folding; Protein Kinases; Stress, Mechanical",
1447 abstract = "Mechanical forces exerted by laser tweezers or atomic force
1448 microscopes can be used to drive rare transitions in single molecules,
1449 such as unfolding of a protein or dissociation of a ligand. The
1450 phenomenological description of pulling experiments based on Bell's
1451 expression for the force-induced rupture rate is found to be inadequate
1452 when tested against computer simulations of a simple microscopic model
1453 of the dynamics. We introduce a new approach of comparable complexity
1454 to extract more accurate kinetic information about the molecular events
1455 from pulling experiments. Our procedure is based on the analysis of a
1456 simple stochastic model of pulling with a harmonic spring and
1457 encompasses the phenomenological approach, reducing to it in the
1458 appropriate limit. Our approach is tested against computer simulations
1459 of a multimodule titin model with anharmonic linkers and then an
1460 illustrative application is made to the forced unfolding of I27
1461 subunits of the protein titin. Our procedure to extract kinetic
1462 information from pulling experiments is simple to implement and should
1463 prove useful in the analysis of experiments on a variety of systems.",
1465 project = "sawtooth simulation"
1468 @article { hutter93,
1469 author = JLHutter #" and "# JBechhoefer,
1470 title = "Calibration of atomic-force microscope tips",
1476 pages = "1868--1873",
1478 doi = "10.1063/1.1143970",
1479 url = "http://link.aip.org/link/?RSI/64/1868/1",
1480 keywords = "ATOMIC FORCE MICROSCOPY; CALIBRATION; QUALITY FACTOR; PROBES;
1481 RESONANCE; SILICON NITRIDES; MICA; VAN DER WAALS FORCES",
1482 note = "Seminal paper for thermal calibration of AFM cantilevers.",
1483 project = "Cantilever Calibration"
1487 author = CHyeon #" and "# DThirumalai,
1488 title = "Can energy landscape roughness of proteins and {RNA} be measured
1489 by using mechanical unfolding experiments?",
1496 pages = "10249--10253",
1498 doi = "10.1073/pnas.1833310100",
1499 eprint = "http://www.pnas.org/cgi/reprint/100/18/10249.pdf",
1500 url = "http://www.pnas.org/cgi/content/abstract/100/18/10249",
1501 keywords = "Protein Folding; Proteins; RNA; Temperature; Thermodynamics",
1502 abstract = "By considering temperature effects on the mechanical unfolding
1503 rates of proteins and RNA, whose energy landscape is rugged, the
1504 question posed in the title is answered in the affirmative. Adopting a
1505 theory by Zwanzig [Zwanzig, R. (1988) Proc. Natl. Acad. Sci. USA 85,
1506 2029-2030], we show that, because of roughness characterized by an
1507 energy scale epsilon, the unfolding rate at constant force is retarded.
1508 Similarly, in nonequilibrium experiments done at constant loading
1509 rates, the most probable unfolding force increases because of energy
1510 landscape roughness. The effects are dramatic at low temperatures. Our
1511 analysis suggests that, by using temperature as a variable in
1512 mechanical unfolding experiments of proteins and RNA, the ruggedness
1513 energy scale epsilon, can be directly measured.",
1514 note = "Derives the major theory behind my thesis. The Kramers rate
1515 equation is Hanggi Eq. 4.56c (page 275)\cite{hanggi90}.",
1516 project = "Energy Landscape Roughness"
1519 @article { irback05,
1520 author = AIrback #" and "# SMitternacht #" and "# SMohanty,
1521 title = "{Dissecting the mechanical unfolding of ubiquitin}",
1526 pages = "13427--13432",
1527 doi = "10.1073/pnas.0501581102",
1528 eprint = "http://www.pnas.org/cgi/reprint/102/38/13427.pdf",
1529 url = "http://www.pnas.org/cgi/content/abstract/102/38/13427",
1530 abstract = "The unfolding behavior of ubiquitin under the influence of a
1531 stretching force recently was investigated experimentally by single-
1532 molecule constant-force methods. Many observed unfolding traces had a
1533 simple two-state character, whereas others showed clear evidence of
1534 intermediate states. Here, we use Monte Carlo simulations to
1535 investigate the force-induced unfolding of ubiquitin at the atomic
1536 level. In agreement with experimental data, we find that the unfolding
1537 process can occur either in a single step or through intermediate
1538 states. In addition to this randomness, we find that many quantities,
1539 such as the frequency of occurrence of intermediates, show a clear
1540 systematic dependence on the strength of the applied force. Despite
1541 this diversity, one common feature can be identified in the simulated
1542 unfolding events, which is the order in which the secondary-structure
1543 elements break. This order is the same in two- and three-state events
1544 and at the different forces studied. The observed order remains to be
1545 verified experimentally but appears physically reasonable."
1548 @article { izrailev97,
1549 author = SIzrailev #" and "# SStepaniants #" and "# MBalsera #" and "#
1550 YOono #" and "# KSchulten,
1551 title = "Molecular dynamics study of unbinding of the avidin-biotin
1558 pages = "1568--1581",
1560 eprint = "http://www.biophysj.org/cgi/reprint/72/4/1568.pdf",
1561 url = "http://www.biophysj.org/cgi/content/abstract/72/4/1568",
1562 keywords = "Avidin; Binding Sites; Biotin; Computer Simulation; Hydrogen
1563 Bonding; Mathematics; Microscopy, Atomic Force; Microspheres; Models,
1564 Molecular; Molecular Structure; Protein Binding; Protein Conformation;
1565 Protein Folding; Sepharose",
1566 abstract = "We report molecular dynamics simulations that induce, over
1567 periods of 40-500 ps, the unbinding of biotin from avidin by means of
1568 external harmonic forces with force constants close to those of AFM
1569 cantilevers. The applied forces are sufficiently large to reduce the
1570 overall binding energy enough to yield unbinding within the measurement
1571 time. Our study complements earlier work on biotin-streptavidin that
1572 employed a much larger harmonic force constant. The simulations reveal
1573 a variety of unbinding pathways, the role of key residues contributing
1574 to adhesion as well as the spatial range over which avidin binds
1575 biotin. In contrast to the previous studies, the calculated rupture
1576 forces exceed by far those observed. We demonstrate, in the framework
1577 of models expressed in terms of one-dimensional Langevin equations with
1578 a schematic binding potential, the associated Smoluchowski equations,
1579 and the theory of first passage times, that picosecond to nanosecond
1580 simulation of ligand unbinding requires such strong forces that the
1581 resulting protein-ligand motion proceeds far from the thermally
1582 activated regime of millisecond AFM experiments, and that simulated
1583 unbinding cannot be readily extrapolated to the experimentally observed
1587 @article { juckett93,
1588 author = DAJuckett #" and "# BRosenberg,
1589 title = "Comparison of the Gompertz and Weibull functions as descriptors
1590 for human mortality distributions and their intersections.",
1593 journal = MechAgeingDev,
1598 doi = "10.1016/0047-6374(93)90068-3",
1599 keywords = "Adolescent; Adult; Aged; Aged, 80 and over; Aging; Biometry;
1600 Child; Child, Preschool; Data Interpretation, Statistical; Female;
1601 Humans; Infant; Infant, Newborn; Longitudinal Studies; Male; Middle
1602 Aged; Models, Biological; Models, Statistical; Mortality",
1603 abstract = "The Gompertz and Weibull functions are compared with respect to
1604 goodness-of-fit to human mortality distributions; ability to describe
1605 mortality curve intersections; and, parameter interpretation. The
1606 Gompertz function is shown to be a better descriptor for 'all-causes'
1607 of deaths and combined disease categories while the Weibull function is
1608 shown to be a better descriptor of purer, single causes-of-death. A
1609 modified form of the Weibull function maps directly to the inherent
1610 degrees of freedom of human mortality distributions while the Gompertz
1611 function does not. Intersections in the old-age tails of mortality are
1612 explored in the context of both functions and, in particular, the
1613 relationship between distribution intersections, and the Gompertz
1614 ln[R0] versus alpha regression is examined. Evidence is also presented
1615 that mortality intersections are fundamental to the survivorship form
1616 and not the rate (hazard) form. Finally, comparisons are made to the
1617 parameter estimates in recent longitudinal Gompertzian analyses and the
1618 probable errors in those analyses are discussed.",
1619 note = "Nice table of various functions associated with Gompertz and
1624 author = WTKing #" and "# GYang,
1625 title = "Effects of Cantilever Stiffness on Unfolding Force in {AFM}
1633 @article { kleiner07,
1634 author = AKleiner #" and "# EShakhnovich,
1635 title = "The mechanical unfolding of ubiquitin through all-atom Monte Carlo
1636 simulation with a Go-type potential.",
1643 pages = "2054--2061",
1645 doi = "10.1529/biophysj.106.081257",
1646 eprint = "http://www.biophysj.org/cgi/reprint/92/6/2054",
1647 url = "http://www.biophysj.org/cgi/content/full/92/6/2054",
1648 keywords = "Computer Simulation; Models, Chemical; Models, Molecular;
1649 Models, Statistical; Monte Carlo Method; Motion; Protein Conformation;
1650 Protein Denaturation; Protein Folding; Ubiquitin",
1651 abstract = "The mechanical unfolding of proteins under a stretching force
1652 has an important role in living systems and is a logical extension of
1653 the more general protein folding problem. Recent advances in
1654 experimental methodology have allowed the stretching of single
1655 molecules, thus rendering this process ripe for computational study. We
1656 use all-atom Monte Carlo simulation with a G?-type potential to study
1657 the mechanical unfolding pathway of ubiquitin. A detailed, robust,
1658 well-defined pathway is found, confirming existing results in this vein
1659 though using a different model. Additionally, we identify the protein's
1660 fundamental stabilizing secondary structure interactions in the
1661 presence of a stretching force and show that this fundamental
1662 stabilizing role does not persist in the absence of mechanical stress.
1663 The apparent success of simulation methods in studying ubiquitin's
1664 mechanical unfolding pathway indicates their potential usefulness for
1665 future study of the stretching of other proteins and the relationship
1666 between protein structure and the response to mechanical deformation."
1669 @article { klimov00,
1670 author = DKKlimov #" and "# DThirumalai,
1671 title = "{Native topology determines force-induced unfolding pathways in
1672 globular proteins}",
1679 pages = "7254--7259",
1681 doi = "10.1073/pnas.97.13.7254",
1682 eprint = "http://www.pnas.org/cgi/reprint/97/13/7254.pdf",
1683 url = "http://www.pnas.org/cgi/content/abstract/97/13/7254",
1684 keywords = "Animals; Humans; Protein Folding; Proteins; Spectrin",
1685 abstract = "Single-molecule manipulation techniques reveal that stretching
1686 unravels individually folded domains in the muscle protein titin and
1687 the extracellular matrix protein tenascin. These elastic proteins
1688 contain tandem repeats of folded domains with beta-sandwich
1689 architecture. Herein, we propose by stretching two model sequences (S1
1690 and S2) with four-stranded beta-barrel topology that unfolding forces
1691 and pathways in folded domains can be predicted by using only the
1692 structure of the native state. Thermal refolding of S1 and S2 in the
1693 absence of force proceeds in an all-or-none fashion. In contrast, phase
1694 diagrams in the force-temperature (f,T) plane and steered Langevin
1695 dynamics studies of these sequences, which differ in the native
1696 registry of the strands, show that S1 unfolds in an allor-none fashion,
1697 whereas unfolding of S2 occurs via an obligatory intermediate. Force-
1698 induced unfolding is determined by the native topology. After proving
1699 that the simulation results for S1 and S2 can be calculated by using
1700 native topology alone, we predict the order of unfolding events in Ig
1701 domain (Ig27) and two fibronectin III type domains ((9)FnIII and
1702 (10)FnIII). The calculated unfolding pathways for these proteins, the
1703 location of the transition states, and the pulling speed dependence of
1704 the unfolding forces reflect the differences in the way the strands are
1705 arranged in the native states. We also predict the mechanisms of force-
1706 induced unfolding of the coiled-coil spectrin (a three-helix bundle
1707 protein) for all 20 structures deposited in the Protein Data Bank. Our
1708 approach suggests a natural way to measure the phase diagram in the
1709 (f,C) plane, where C is the concentration of denaturants.",
1710 note = "Simulated unfolding timescales for Ig27-like S1 and S2 domains"
1713 @article { kosztin06,
1714 author = IKosztin #" and "# BBarz #" and "# LJanosi,
1715 title = "Calculating potentials of mean force and diffusion coefficients
1716 from nonequilibrium processes without Jarzynski's equality.",
1720 journal = JChemPhys,
1724 doi = "10.1063/1.2166379",
1725 url = "http://link.aip.org/link/?JCPSA6/124/064106/1"
1728 @article { kramers40,
1730 title = "Brownian motion in a field of force and the diffusion model of
1731 chemical reactions.",
1739 doi = "10.1016/S0031-8914(40)90098-2",
1740 url = "http://www.sciencedirect.com/science/article/B6X42-4CB752H-
1741 3G/1/1d9e8dc558b822877c9e1ad55bb08831",
1742 abstract = "A particle which is caught in a potential hole and which,
1743 through the shuttling action of Brownian motion, can escape over a
1744 potential barrier yields a suitable model for elucidating the
1745 applicability of the transition state method for calculating the rate
1746 of chemical reactions.",
1747 note = "Seminal paper on thermally activated barrier crossings."
1751 author = KKroy #" and "# JGlaser,
1752 title = "The glassy wormlike chain",
1758 doi = "10.1088/1367-2630/9/11/416",
1759 eprint = "http://www.iop.org/EJ/article/1367-2630/9/11/416/njp7_11_416.pdf",
1760 url = "http://stacks.iop.org/1367-2630/9/416",
1761 abstract = "We introduce a new model for the dynamics of a wormlike chain
1762 (WLC) in an environment that gives rise to a rough free energy
1763 landscape, which we name the glassy WLC. It is obtained from the common
1764 WLC by an exponential stretching of the relaxation spectrum of its
1765 long-wavelength eigenmodes, controlled by a single parameter
1766 \\boldsymbol{\\cal E} . Predictions for pertinent observables such as
1767 the dynamic structure factor and the microrheological susceptibility
1768 exhibit the characteristics of soft glassy rheology and compare
1769 favourably with experimental data for reconstituted cytoskeletal
1770 networks and live cells. We speculate about the possible microscopic
1771 origin of the stretching, implications for the nonlinear rheology, and
1772 the potential physiological significance of our results.",
1773 note = "Has short section on WLC relaxation time in the weakly bending
1777 @article { labeit03,
1778 author = DLabeit #" and "# KWatanabe #" and "# CWitt #" and "# HFujita #"
1779 and "# YWu #" and "# SLahmers #" and "# TFunck #" and "# SLabeit #" and
1781 title = "Calcium-dependent molecular spring elements in the giant protein
1787 pages = "13716--13721",
1788 doi = "10.1073/pnas.2235652100",
1789 eprint = "http://www.pnas.org/cgi/reprint/100/23/13716.pdf",
1790 url = "http://www.pnas.org/cgi/content/abstract/100/23/13716",
1791 abstract = "Titin (also known as connectin) is a giant protein with a wide
1792 range of cellular functions, including providing muscle cells with
1793 elasticity. Its physiological extension is largely derived from the
1794 PEVK segment, rich in proline (P), glutamate (E), valine (V), and
1795 lysine (K) residues. We studied recombinant PEVK molecules containing
1796 the two conserved elements: {approx}28-residue PEVK repeats and E-rich
1797 motifs. Single molecule experiments revealed that calcium-induced
1798 conformational changes reduce the bending rigidity of the PEVK
1799 fragments, and site-directed mutagenesis identified four glutamate
1800 residues in the E-rich motif that was studied (exon 129), as critical
1801 for this process. Experiments with muscle fibers showed that titin-
1802 based tension is calcium responsive. We propose that the PEVK segment
1803 contains E-rich motifs that render titin a calcium-dependent molecular
1804 spring that adapts to the physiological state of the cell."
1808 author = HLi #" and "# AFOberhauser #" and "# SBFowler #" and "# JClarke
1809 #" and "# JMFernandez,
1810 title = "{Atomic force microscopy reveals the mechanical design of a
1816 pages = "6527--6531",
1817 doi = "10.1073/pnas.120048697",
1818 eprint = "http://www.pnas.org/cgi/reprint/97/12/6527.pdf",
1819 url = "http://www.pnas.org/cgi/content/abstract/97/12/6527",
1824 author = HLi #" and "# AFOberhauser #" and "# SDRedick #" and "#
1825 MCarrion-Vazquez #" and "# HPErickson #" and "# JMFernandez,
1826 title = "{Multiple conformations of PEVK proteins detected by single-
1827 molecule techniques}",
1832 pages = "10682--10686",
1833 doi = "10.1073/pnas.191189098",
1834 eprint = "http://www.pnas.org/cgi/reprint/98/19/10682.pdf",
1835 url = "http://www.pnas.org/cgi/content/abstract/98/19/10682",
1836 abstract = "An important component of muscle elasticity is the PEVK region
1837 of titin, so named because of the preponderance of these amino acids.
1838 However, the PEVK region, similar to other elastomeric proteins, is
1839 thought to form a random coil and therefore its structure cannot be
1840 determined by standard techniques. Here we combine single-molecule
1841 electron microscopy and atomic force microscopy to examine the
1842 conformations of the human cardiac titin PEVK region. In contrast to a
1843 simple random coil, we have found that cardiac PEVK shows a wide range
1844 of elastic conformations with end-to-end distances ranging from 9 to 24
1845 nm and persistence lengths from 0.4 to 2.5 nm. Individual PEVK
1846 molecules retained their distinctive elastic conformations through many
1847 stretch-relaxation cycles, consistent with the view that these PEVK
1848 conformers cannot be interconverted by force. The multiple elastic
1849 conformations of cardiac PEVK may result from varying degrees of
1850 proline isomerization. The single-molecule techniques demonstrated here
1851 may help elucidate the conformation of other proteins that lack a well-
1856 author = MSLi #" and "# CKHu #" and "# DKKlimov #" and "# DThirumalai,
1857 title = "{Multiple stepwise refolding of immunoglobulin domain I27 upon
1858 force quench depends on initial conditions}",
1864 doi = "10.1073/pnas.0503758103",
1865 eprint = "http://www.pnas.org/cgi/reprint/103/1/93.pdf",
1866 url = "http://www.pnas.org/cgi/content/abstract/103/1/93",
1867 abstract = "Mechanical folding trajectories for polyproteins starting from
1868 initially stretched conformations generated by single-molecule atomic
1869 force microscopy experiments [Fernandez, J. M. & Li, H. (2004) Science
1870 303, 1674-1678] show that refolding, monitored by the end-to-end
1871 distance, occurs in distinct multiple stages. To clarify the molecular
1872 nature of folding starting from stretched conformations, we have probed
1873 the folding dynamics, upon force quench, for the single I27 domain from
1874 the muscle protein titin by using a C{alpha}-Go model. Upon temperature
1875 quench, collapse and folding of I27 are synchronous. In contrast,
1876 refolding from stretched initial structures not only increases the
1877 folding and collapse time scales but also decouples the two kinetic
1878 processes. The increase in the folding times is associated primarily
1879 with the stretched state to compact random coil transition.
1880 Surprisingly, force quench does not alter the nature of the refolding
1881 kinetics, but merely increases the height of the free-energy folding
1882 barrier. Force quench refolding times scale as f1.gif, where {Delta}xf
1883 {approx} 0.6 nm is the location of the average transition state along
1884 the reaction coordinate given by end-to-end distance. We predict that
1885 {tau}F and the folding mechanism can be dramatically altered by the
1886 initial and/or final values of force. The implications of our results
1887 for design and analysis of experiments are discussed."
1891 author = WLiu #" and "# VMontana #" and "# ERChapman #" and "# UMohideen
1893 title = "{Botulinum toxin type B micromechanosensor}",
1898 pages = "13621--13625",
1899 doi = "10.1073/pnas.2233819100",
1900 eprint = "http://www.pnas.org/cgi/reprint/100/23/13621.pdf",
1901 url = "http://www.pnas.org/cgi/content/abstract/100/23/13621",
1902 abstract = "Botulinum neurotoxin (BoNT) types A, B, E, and F are toxic to
1903 humans; early and rapid detection is essential for adequate medical
1904 treatment. Presently available tests for detection of BoNTs, although
1905 sensitive, require hours to days. We report a BoNT-B sensor whose
1906 properties allow detection of BoNT-B within minutes. The technique
1907 relies on the detection of an agarose bead detachment from the tip of a
1908 micromachined cantilever resulting from BoNT-B action on its
1909 substratum, the synaptic protein synaptobrevin 2, attached to the
1910 beads. The mechanical resonance frequency of the cantilever is
1911 monitored for the detection. To suspend the bead off the cantilever we
1912 use synaptobrevin's molecular interaction with another synaptic
1913 protein, syntaxin 1A, that was deposited onto the cantilever tip.
1914 Additionally, this bead detachment technique is general and can be used
1915 in any displacement reaction, such as in receptor-ligand pairs, where
1916 the introduction of one chemical leads to the displacement of another.
1917 The technique is of broad interest and will find uses outside
1921 @article { makarov01,
1922 author = DEMakarov #" and "# PKHansma #" and "# HMetiu,
1923 title = "Kinetic Monte Carlo simulation of titin unfolding",
1929 pages = "9663--9673",
1931 doi = "10.1063/1.1369622",
1932 eprint = "http://hansmalab.physics.ucsb.edu/pdf/297%20-%20Makarov,%20D.E._J
1933 .Chem.Phys._2001.pdf",
1934 url = "http://link.aip.org/link/?JCP/114/9663/1",
1935 keywords = "proteins; hydrogen bonds; digital simulation; Monte Carlo
1936 methods; molecular biophysics; intramolecular mechanics;
1937 macromolecules; atomic force microscopy"
1941 author = JFMarko #" and "# EDSiggia,
1942 title = "Stretching {DNA}",
1945 journal = Macromolecules,
1948 pages = "8759--8770",
1950 eprint = "http://pubs.acs.org/cgi-
1951 bin/archive.cgi/mamobx/1995/28/i26/pdf/ma00130a008.pdf",
1953 "http://pubs3.acs.org/acs/journals/doilookup?in_doi=10.1021/ma00130a008
1956 note = "Derivation of the Worm-like Chain interpolation function."
1959 @article { marszalek02,
1960 author = PEMarszalek #" and "# HLi #" and "# AFOberhauser #" and "#
1962 title = "{Chair-boat transitions in single polysaccharide molecules
1963 observed with force-ramp AFM}",
1968 pages = "4278--4283",
1969 doi = "10.1073/pnas.072435699",
1970 eprint = "http://www.pnas.org/cgi/reprint/99/7/4278.pdf",
1971 url = "http://www.pnas.org/cgi/content/abstract/99/7/4278",
1972 abstract = "Under a stretching force, the sugar ring of polysaccharide
1973 molecules switches from the chair to the boat-like or inverted chair
1974 conformation. This conformational change can be observed by stretching
1975 single polysaccharide molecules with an atomic force microscope. In
1976 those early experiments, the molecules were stretched at a constant
1977 rate while the resulting force changed over wide ranges. However,
1978 because the rings undergo force-dependent transitions, an experimental
1979 arrangement where the force is the free variable introduces an
1980 undesirable level of complexity in the results. Here we demonstrate the
1981 use of force-ramp atomic force microscopy to capture the conformational
1982 changes in single polysaccharide molecules. Force-ramp atomic force
1983 microscopy readily captures the ring transitions under conditions where
1984 the entropic elasticity of the molecule is separated from its
1985 conformational transitions, enabling a quantitative analysis of the
1986 data with a simple two-state model. This analysis directly provides the
1987 physico-chemical characteristics of the ring transitions such as the
1988 width of the energy barrier, the relative energy of the conformers, and
1989 their enthalpic elasticity. Our experiments enhance the ability of
1990 single-molecule force spectroscopy to make high-resolution measurements
1991 of the conformations of single polysaccharide molecules under a
1992 stretching force, making an important addition to polysaccharide
1997 author = CCMello #" and "# DBarrick,
1998 title = "An experimentally determined protein folding energy landscape.",
2005 pages = "14102--14107",
2007 doi = "10.1073/pnas.0403386101",
2008 keywords = "Animals; Ankyrin Repeat; Circular Dichroism; Drosophila
2009 Proteins; Drosophila melanogaster; Gene Deletion; Models, Chemical;
2010 Models, Molecular; Protein Denaturation; Protein Folding; Protein
2011 Structure, Tertiary; Spectrometry, Fluorescence; Thermodynamics; Urea",
2012 abstract = "Energy landscapes have been used to conceptually describe and
2013 model protein folding but have been difficult to measure
2014 experimentally, in large part because of the myriad of partly folded
2015 protein conformations that cannot be isolated and thermodynamically
2016 characterized. Here we experimentally determine a detailed energy
2017 landscape for protein folding. We generated a series of overlapping
2018 constructs containing subsets of the seven ankyrin repeats of the
2019 Drosophila Notch receptor, a protein domain whose linear arrangement of
2020 modular structural units can be fragmented without disrupting
2021 structure. To a good approximation, stabilities of each construct can
2022 be described as a sum of energy terms associated with each repeat. The
2023 magnitude of each energy term indicates that each repeat is
2024 intrinsically unstable but is strongly stabilized by interactions with
2025 its nearest neighbors. These linear energy terms define an equilibrium
2026 free energy landscape, which shows an early free energy barrier and
2027 suggests preferred low-energy routes for folding."
2030 @article { mickler07,
2031 author = MMickler #" and "# RIDima #" and "# HDietz #" and "# CHyeon #"
2032 and "# DThirumalai #" and "# MRief,
2033 title = "Revealing the bifurcation in the unfolding pathways of {GFP} by
2034 using single-molecule experiments and simulations",
2039 pages = "20268--20273",
2040 doi = "10.1073/pnas.0705458104",
2041 eprint = "http://www.pnas.org/cgi/reprint/104/51/20268.pdf",
2042 url = "http://www.pnas.org/cgi/content/abstract/104/51/20268",
2043 keywords = "AFM experiments, coarse-grained simulations, cross-link
2044 mutants, pathway bifurcation, plasticity of energy landscape",
2045 abstract = "Nanomanipulation of biomolecules by using single-molecule
2046 methods and computer simulations has made it possible to visualize the
2047 energy landscape of biomolecules and the structures that are sampled
2048 during the folding process. We use simulations and single-molecule
2049 force spectroscopy to map the complex energy landscape of GFP that is
2050 used as a marker in cell biology and biotechnology. By engineering
2051 internal disulfide bonds at selected positions in the GFP structure,
2052 mechanical unfolding routes are precisely controlled, thus allowing us
2053 to infer features of the energy landscape of the wild-type GFP. To
2054 elucidate the structures of the unfolding pathways and reveal the
2055 multiple unfolding routes, the experimental results are complemented
2056 with simulations of a self-organized polymer (SOP) model of GFP. The
2057 SOP representation of proteins, which is a coarse-grained description
2058 of biomolecules, allows us to perform forced-induced simulations at
2059 loading rates and time scales that closely match those used in atomic
2060 force microscopy experiments. By using the combined approach, we show
2061 that forced unfolding of GFP involves a bifurcation in the pathways to
2062 the stretched state. After detachment of an N-terminal {alpha}-helix,
2063 unfolding proceeds along two distinct pathways. In the dominant
2064 pathway, unfolding starts from the detachment of the primary N-terminal
2065 -strand, while in the minor pathway rupture of the last, C-terminal
2066 -strand initiates the unfolding process. The combined approach has
2067 allowed us to map the features of the complex energy landscape of GFP
2068 including a characterization of the structures, albeit at a coarse-
2069 grained level, of the three metastable intermediates.",
2070 note = "Hiccup in unfolding leg corresponds to unfolding intermediate (See
2071 Figure 2). The unfolding timescale in GFP is about 6 ms."
2075 author = RNevo #" and "# CStroh #" and "# FKienberger #" and "# DKaftan #"
2076 and "# VBrumfeld #" and "# MElbaum #" and "# ZReich #" and "#
2078 title = "A molecular switch between alternative conformational states in
2079 the complex of Ran and importin beta1.",
2087 doi = "10.1038/nsb940",
2088 eprint = "http://www.nature.com/nsmb/journal/v10/n7/pdf/nsb940.pdf",
2089 url = "http://www.nature.com/nsmb/journal/v10/n7/abs/nsb940.html",
2090 keywords = "Guanosine Diphosphate; Guanosine Triphosphate; Microscopy,
2091 Atomic Force; Protein Binding; Protein Conformation; beta Karyopherins;
2092 ran GTP-Binding Protein",
2093 abstract = "Several million macromolecules are exchanged each minute
2094 between the nucleus and cytoplasm by receptor-mediated transport. Most
2095 of this traffic is controlled by the small GTPase Ran, which regulates
2096 assembly and disassembly of the receptor-cargo complexes in the
2097 appropriate cellular compartment. Here we applied dynamic force
2098 spectroscopy to study the interaction of Ran with the nuclear import
2099 receptor importin beta1 (impbeta) at the single-molecule level. We
2100 found that the complex alternates between two distinct conformational
2101 states of different adhesion strength. The application of an external
2102 mechanical force shifts equilibrium toward one of these states by
2103 decreasing the height of the interstate activation energy barrier. The
2104 other state can be stabilized by a functional Ran mutant that increases
2105 this barrier. These results support a model whereby functional control
2106 of Ran-impbeta is achieved by a population shift between pre-existing
2107 alternative conformations."
2111 author = RNevo #" and "# VBrumfeld #" and "# MElbaum #" and "#
2112 PHinterdorfer #" and "# ZReich,
2113 title = "Direct discrimination between models of protein activation by
2114 single-molecule force measurements.",
2120 pages = "2630--2634",
2122 doi = "10.1529/biophysj.104.041889",
2123 eprint = "http://www.biophysj.org/cgi/reprint/87/4/2630.pdf",
2124 url = "http://www.biophysj.org/cgi/content/abstract/87/4/2630",
2125 keywords = "Elasticity; Enzyme Activation; Micromanipulation; Microscopy,
2126 Atomic Force; Models, Chemical; Models, Molecular; Multiprotein
2127 Complexes; Nuclear Proteins; Physical Stimulation; Protein Binding;
2128 Stress, Mechanical; Structure-Activity Relationship; beta Karyopherins;
2129 ran GTP-Binding Protein",
2130 abstract = "The limitations imposed on the analyses of complex chemical and
2131 biological systems by ensemble averaging can be overcome by single-
2132 molecule experiments. Here, we used a single-molecule technique to
2133 discriminate between two generally accepted mechanisms of a key
2134 biological process--the activation of proteins by molecular effectors.
2135 The two mechanisms, namely induced-fit and population-shift, are
2136 normally difficult to discriminate by ensemble approaches. As a model,
2137 we focused on the interaction between the nuclear transport effector,
2138 RanBP1, and two related complexes consisting of the nuclear import
2139 receptor, importin beta, and the GDP- or GppNHp-bound forms of the
2140 small GTPase, Ran. We found that recognition by the effector proceeds
2141 through either an induced-fit or a population-shift mechanism,
2142 depending on the substrate, and that the two mechanisms can be
2143 differentiated by the data."
2147 author = RNevo #" and "# VBrumfeld #" and "# RKapon #" and "#
2148 PHinterdorfer #" and "# ZReich,
2149 title = "Direct measurement of protein energy landscape roughness.",
2157 doi = "10.1038/sj.embor.7400403",
2158 eprint = "http://www.nature.com/embor/journal/v6/n5/pdf/7400403.pdf",
2159 url = "http://www.nature.com/embor/journal/v6/n5/abs/7400403.html",
2160 keywords = "Models, Molecular; Protein Binding; Protein Folding; Spectrum
2161 Analysis; Thermodynamics; beta Karyopherins; ran GTP-Binding Protein",
2162 abstract = "The energy landscape of proteins is thought to have an
2163 intricate, corrugated structure. Such roughness should have important
2164 consequences on the folding and binding kinetics of proteins, as well
2165 as on their equilibrium fluctuations. So far, no direct measurement of
2166 protein energy landscape roughness has been made. Here, we combined a
2167 recent theory with single-molecule dynamic force spectroscopy
2168 experiments to extract the overall energy scale of roughness epsilon
2169 for a complex consisting of the small GTPase Ran and the nuclear
2170 transport receptor importin-beta. The results gave epsilon > 5k(B)T,
2171 indicating a bumpy energy surface, which is consistent with the ability
2172 of importin-beta to accommodate multiple conformations and to interact
2173 with different, structurally distinct ligands.",
2174 note = "Applies H&T\cite{hyeon03} to ligand-receptor binding.",
2175 project = "Energy Landscape Roughness"
2179 author = SPNg #" and "# KSBillings #" and "# TOhashi #" and "# MDAllen #"
2180 and "# RBBest #" and "# LGRandles #" and "# HPErickson #" and "#
2182 title = "{Designing an extracellular matrix protein with enhanced
2183 mechanical stability}",
2188 pages = "9633--9637",
2189 doi = "10.1073/pnas.0609901104",
2190 eprint = "http://www.pnas.org/cgi/reprint/104/23/9633.pdf",
2191 url = "http://www.pnas.org/cgi/content/abstract/104/23/9633",
2192 abstract = "The extracellular matrix proteins tenascin and fibronectin
2193 experience significant mechanical forces in vivo. Both contain a number
2194 of tandem repeating homologous fibronectin type III (fnIII) domains,
2195 and atomic force microscopy experiments have demonstrated that the
2196 mechanical strength of these domains can vary significantly. Previous
2197 work has shown that mutations in the core of an fnIII domain from human
2198 tenascin (TNfn3) reduce the unfolding force of that domain
2199 significantly: The composition of the core is apparently crucial to the
2200 mechanical stability of these proteins. Based on these results, we have
2201 used rational redesign to increase the mechanical stability of the 10th
2202 fnIII domain of human fibronectin, FNfn10, which is directly involved
2203 in integrin binding. The hydrophobic core of FNfn10 was replaced with
2204 that of the homologous, mechanically stronger TNfn3 domain. Despite the
2205 extensive substitution, FNoTNc retains both the three-dimensional
2206 structure and the cell adhesion activity of FNfn10. Atomic force
2207 microscopy experiments reveal that the unfolding forces of the
2208 engineered protein FNoTNc increase by {approx}20% to match those of
2209 TNfn3. Thus, we have specifically designed a protein with increased
2210 mechanical stability. Our results demonstrate that core engineering can
2211 be used to change the mechanical strength of proteins while retaining
2212 functional surface interactions."
2216 author = RANome #" and "# JMZhao #" and "# WDHoff #" and "# NFScherer,
2217 title = "Axis-dependent anisotropy in protein unfolding from integrated
2218 nonequilibrium single-molecule experiments, analysis, and simulation",
2225 pages = "20799--20804",
2227 doi = "10.1073/pnas.0701281105",
2228 eprint = "http://www.pnas.org/cgi/reprint/104/52/20799.pdf",
2229 url = "http://www.pnas.org/cgi/content/abstract/104/52/20799",
2230 keywords = "Anisotropy; Bacterial Proteins; Biophysics; Computer
2231 Simulation; Cysteine; Halorhodospira halophila; Hydrogen Bonding;
2232 Kinetics; Luminescent Proteins; Microscopy, Atomic Force; Molecular
2233 Conformation; Protein Binding; Protein Conformation; Protein
2234 Denaturation; Protein Folding; Protein Structure, Secondary",
2235 abstract = "We present a comprehensive study that integrates experimental
2236 and theoretical nonequilibrium techniques to map energy landscapes
2237 along well defined pull-axis specific coordinates to elucidate
2238 mechanisms of protein unfolding. Single-molecule force-extension
2239 experiments along two different axes of photoactive yellow protein
2240 combined with nonequilibrium statistical mechanical analysis and
2241 atomistic simulation reveal energetic and mechanistic anisotropy.
2242 Steered molecular dynamics simulations and free-energy curves
2243 constructed from the experimental results reveal that unfolding along
2244 one axis exhibits a transition-state-like feature where six hydrogen
2245 bonds break simultaneously with weak interactions observed during
2246 further unfolding. The other axis exhibits a constant (unpeaked) force
2247 profile indicative of a noncooperative transition, with enthalpic
2248 (e.g., H-bond) interactions being broken throughout the unfolding
2249 process. Striking qualitative agreement was found between the force-
2250 extension curves derived from steered molecular dynamics calculations
2251 and the equilibrium free-energy curves obtained by JarzynskiHummerSzabo
2252 analysis of the nonequilibrium work data. The anisotropy persists
2253 beyond pulling distances of more than twice the initial dimensions of
2254 the folded protein, indicating a rich energy landscape to the
2255 mechanically fully unfolded state. Our findings challenge the notion
2256 that cooperative unfolding is a universal feature in protein
2260 @article { nummela07,
2261 author = JNummela #" and "# IAndricioaei,
2262 title = "{Exact Low-Force Kinetics from High-Force Single-Molecule
2268 pages = "3373-3381",
2269 doi = "10.1529/biophysj.107.111658",
2270 eprint = "http://www.biophysj.org/cgi/reprint/93/10/3373.pdf",
2271 url = "http://www.biophysj.org/cgi/content/abstract/93/10/3373",
2272 abstract = "Mechanical forces play a key role in crucial cellular processes
2273 involving force-bearing biomolecules, as well as in novel single-
2274 molecule pulling experiments. We present an exact method that enables
2275 one to extrapolate, to low (or zero) forces, entire time-correlation
2276 functions and kinetic rate constants from the conformational dynamics
2277 either simulated numerically or measured experimentally at a single,
2278 relatively higher, external force. The method has twofold relevance:
2279 1), to extrapolate the kinetics at physiological force conditions from
2280 molecular dynamics trajectories generated at higher forces that
2281 accelerate conformational transitions; and 2), to extrapolate unfolding
2282 rates from experimental force-extension single-molecule curves. The
2283 theoretical formalism, based on stochastic path integral weights of
2284 Langevin trajectories, is presented for the constant-force, constant
2285 loading rate, and constant-velocity modes of the pulling experiments.
2286 For the first relevance, applications are described for simulating the
2287 conformational isomerization of alanine dipeptide; and for the second
2288 relevance, the single-molecule pulling of RNA is considered. The
2289 ability to assign a weight to each trace in the single-molecule data
2290 also suggests a means to quantitatively compare unfolding pathways
2291 under different conditions."
2294 @article { oberhauser01,
2295 author = AFOberhauser #" and "# PKHansma #" and "# MCarrion-Vazquez #" and
2297 title = "{Stepwise unfolding of titin under force-clamp atomic force
2304 doi = "10.1073/pnas.021321798",
2305 eprint = "http://www.pnas.org/cgi/reprint/98/2/468.pdf",
2306 url = "http://www.pnas.org/cgi/content/abstract/98/2/468",
2310 @article { olshansky97,
2311 author = SJOlshansky #" and "# BACarnes,
2312 title = "Ever since Gompertz.",
2315 journal = Demography,
2320 url = "http://www.jstor.org/stable/2061656",
2321 keywords = "Aging; Biometry; History, 19th Century; History, 20th Century;
2322 Humans; Life Tables; Mortality; Sexual Maturation",
2323 abstract = "In 1825 British actuary Benjamin Gompertz made a simple but
2324 important observation that a law of geometrical progression pervades
2325 large portions of different tables of mortality for humans. The simple
2326 formula he derived describing the exponential rise in death rates
2327 between sexual maturity and old age is commonly, referred to as the
2328 Gompertz equation-a formula that remains a valuable tool in demography
2329 and in other scientific disciplines. Gompertz's observation of a
2330 mathematical regularity in the life table led him to believe in the
2331 presence of a low of mortality that explained why common age patterns
2332 of death exist. This law of mortality has captured the attention of
2333 scientists for the past 170 years because it was the first among what
2334 are now several reliable empirical tools for describing the dying-out
2335 process of many living organisms during a significant portion of their
2336 life spans. In this paper we review the literature on Gompertz's law of
2337 mortality and discuss the importance of his observations and insights
2338 in light of research on aging that has taken place since then.",
2339 note = "Hardly any actual math, but the references might be interesting.
2340 I'll look into them if I have the time. Available through several
2344 @article { onuchic96,
2345 author = JNOnuchic #" and "# NDSocci #" and "# ZLuthey-Schulten #" and "#
2347 title = "Protein folding funnels: the nature of the transition state
2355 keywords = "Animals; Cytochrome c Group; Humans; Infant; Protein Folding",
2356 abstract = "BACKGROUND: Energy landscape theory predicts that the folding
2357 funnel for a small fast-folding alpha-helical protein will have a
2358 transition state half-way to the native state. Estimates of the
2359 position of the transition state along an appropriate reaction
2360 coordinate can be obtained from linear free energy relationships
2361 observed for folding and unfolding rate constants as a function of
2362 denaturant concentration. The experimental results of Huang and Oas for
2363 lambda repressor, Fersht and collaborators for C12, and Gray and
2364 collaborators for cytochrome c indicate a free energy barrier midway
2365 between the folded and unfolded regions. This barrier arises from an
2366 entropic bottleneck for the folding process. RESULTS: In keeping with
2367 the experimental results, lattice simulations based on the folding
2368 funnel description show that the transition state is not just a single
2369 conformation, but rather an ensemble of a relatively large number of
2370 configurations that can be described by specific values of one or a few
2371 order parameters (e.g. the fraction of native contacts). Analysis of
2372 this transition state or bottleneck region from our lattice simulations
2373 and from atomistic models for small alpha-helical proteins by Boczko
2374 and Brooks indicates a broad distribution for native contact
2375 participation in the transition state ensemble centered around 50\%.
2376 Importantly, however, the lattice-simulated transition state ensemble
2377 does include some particularly hot contacts, as seen in the
2378 experiments, which have been termed by others a folding nucleus.
2379 CONCLUSIONS: Linear free energy relations provide a crude spectroscopy
2380 of the transition state, allowing us to infer the values of a reaction
2381 coordinate based on the fraction of native contacts. This bottleneck
2382 may be thought of as a collection of delocalized nuclei where different
2383 native contacts will have different degrees of participation. The
2384 agreement between the experimental results and the theoretical
2385 predictions provides strong support for the landscape analysis."
2389 author = CAOpitz #" and "# MKulke #" and "# MCLeake #" and "# CNeagoe #"
2390 and "# HHinssen #" and "# RJHajjar #" and "# WALinke,
2391 title = "{Damped elastic recoil of the titin spring in myofibrils of human
2397 pages = "12688--12693",
2398 doi = "10.1073/pnas.2133733100",
2399 eprint = "http://www.pnas.org/cgi/reprint/100/22/12688.pdf",
2400 url = "http://www.pnas.org/cgi/content/abstract/100/22/12688",
2401 abstract = "The giant protein titin functions as a molecular spring in
2402 muscle and is responsible for most of the passive tension of
2403 myocardium. Because the titin spring is extended during diastolic
2404 stretch, it will recoil elastically during systole and potentially may
2405 influence the overall shortening behavior of cardiac muscle. Here,
2406 titin elastic recoil was quantified in single human heart myofibrils by
2407 using a high-speed charge-coupled device-line camera and a
2408 nanonewtonrange force sensor. Application of a slack-test protocol
2409 revealed that the passive shortening velocity (Vp) of nonactivated
2410 cardiomyofibrils depends on: (i) initial sarcomere length, (ii)
2411 release-step amplitude, and (iii) temperature. Selective digestion of
2412 titin, with low doses of trypsin, decelerated myofibrillar passive
2413 recoil and eventually stopped it. Selective extraction of actin
2414 filaments with a Ca2+-independent gelsolin fragment greatly reduced the
2415 dependency of Vp on release-step size and temperature. These results
2416 are explained by the presence of viscous forces opposing myofibrillar
2417 passive recoil that are caused mainly by weak actin-titin interactions.
2418 Thus, Vp is determined by two distinct factors: titin elastic recoil
2419 and internal viscous drag forces. The recoil could be modeled as that
2420 of a damped entropic spring consisting of independent worm-like chains.
2421 The functional importance of myofibrillar elastic recoil was addressed
2422 by comparing instantaneous Vp to unloaded shortening velocity, which
2423 was measured in demembranated, fully Ca2+-activated, human cardiac
2424 fibers. Titin-driven passive recoil was much faster than active
2425 unloaded shortening velocity in early phases of isotonic contraction.
2426 Damped myofibrillar elastic recoil could help accelerate active
2427 contraction speed of human myocardium during early systolic
2431 @article { oroudjev02,
2432 author = EOroudjev #" and "# JSoares #" and "# SArcidiacono #" and "#
2433 JBThompson #" and "# SAFossey #" and "# HGHansma,
2434 title = "{Segmented nanofibers of spider dragline silk: Atomic force
2435 microscopy and single-molecule force spectroscopy}",
2440 pages = "6460--6465",
2441 doi = "10.1073/pnas.082526499",
2442 eprint = "http://www.pnas.org/cgi/reprint/99/suppl_2/6460.pdf",
2443 url = "http://www.pnas.org/cgi/content/abstract/99/suppl_2/6460",
2444 abstract = "Despite its remarkable materials properties, the structure of
2445 spider dragline silk has remained unsolved. Results from two probe
2446 microscopy techniques provide new insights into the structure of spider
2447 dragline silk. A soluble synthetic protein from dragline silk
2448 spontaneously forms nanofibers, as observed by atomic force microscopy.
2449 These nanofibers have a segmented substructure. The segment length and
2450 amino acid sequence are consistent with a slab-like shape for
2451 individual silk protein molecules. The height and width of nanofiber
2452 segments suggest a stacking pattern of slab-like molecules in each
2453 nanofiber segment. This stacking pattern produces nano-crystals in an
2454 amorphous matrix, as observed previously by NMR and x-ray diffraction
2455 of spider dragline silk. The possible importance of nanofiber formation
2456 to native silk production is discussed. Force spectra for single
2457 molecules of the silk protein demonstrate that this protein unfolds
2458 through a number of rupture events, indicating a modular substructure
2459 within single silk protein molecules. A minimal unfolding module size
2460 is estimated to be around 14 nm, which corresponds to the extended
2461 length of a single repeated module, 38 amino acids long. The structure
2462 of this spider silk protein is distinctly different from the structures
2463 of other proteins that have been analyzed by single-molecule force
2464 spectroscopy, and the force spectra show correspondingly novel
2469 author = EPaci #" and "# MKarplus,
2470 title = "{Unfolding proteins by external forces and temperature: The
2471 importance of topology and energetics}",
2476 pages = "6521--6526",
2477 doi = "10.1073/pnas.100124597",
2478 eprint = "http://www.pnas.org/cgi/reprint/97/12/6521.pdf",
2479 url = "http://www.pnas.org/cgi/content/abstract/97/12/6521"
2483 author = QPeng #" and "# HLi,
2484 title = "{Atomic force microscopy reveals parallel mechanical unfolding
2485 pathways of T4 lysozyme: Evidence for a kinetic partitioning
2491 pages = "1885--1890",
2492 doi = "10.1073/pnas.0706775105",
2493 eprint = "http://www.pnas.org/cgi/reprint/105/6/1885.pdf",
2494 url = "http://www.pnas.org/cgi/content/abstract/105/6/1885",
2495 abstract = "Kinetic partitioning is predicted to be a general mechanism for
2496 proteins to fold into their well defined native three-dimensional
2497 structure from unfolded states following multiple folding pathways.
2498 However, experimental evidence supporting this mechanism is still
2499 limited. By using single-molecule atomic force microscopy, here we
2500 report experimental evidence supporting the kinetic partitioning
2501 mechanism for mechanical unfolding of T4 lysozyme, a small protein
2502 composed of two subdomains. We observed that on stretching from its N
2503 and C termini, T4 lysozyme unfolds by multiple distinct unfolding
2504 pathways: the majority of T4 lysozymes unfold in an all-or-none fashion
2505 by overcoming a dominant unfolding kinetic barrier; and a small
2506 fraction of T4 lysozymes unfold in three-state fashion involving
2507 unfolding intermediate states. The three-state unfolding pathways do
2508 not follow well defined routes, instead they display variability and
2509 diversity in individual unfolding pathways. The unfolding intermediate
2510 states are local energy minima along the mechanical unfolding pathways
2511 and are likely to result from the residual structures present in the
2512 two subdomains after crossing the main unfolding barrier. These results
2513 provide direct evidence for the kinetic partitioning of the mechanical
2514 unfolding pathways of T4 lysozyme, and the complex unfolding behaviors
2515 reflect the stochastic nature of kinetic barrier rupture in mechanical
2516 unfolding processes. Our results demonstrate that single-molecule
2517 atomic force microscopy is an ideal tool to investigate the
2518 folding/unfolding dynamics of complex multimodule proteins that are
2519 otherwise difficult to study using traditional methods."
2523 author = WPress #" and "# STeukolsky #" and "# WVetterling #" and "#
2525 title = "Numerical Recipies in {C}: The Art of Scientific Computing",
2529 address = "New York",
2530 eprint = "http://www.nrbook.com/a/bookcpdf.php",
2531 note = "See sections 12.0, 12.1, 12.3, and 13.4 for a good introduction to
2532 Fourier transforms and power spectrum estimation.",
2533 project = "Cantilever Calibration"
2536 @article { raible04,
2537 author = MRaible #" and "# MEvstigneev #" and "# PReimann #" and "#
2538 FWBartels #" and "# RRos,
2539 title = "Theoretical analysis of dynamic force spectroscopy experiments on
2540 ligand-receptor complexes.",
2544 journal = JBiotechnol,
2549 doi = "10.1016/j.jbiotec.2004.04.017",
2550 keywords = "Binding Sites; Computer Simulation; DNA; DNA-Binding Proteins;
2551 Elasticity; Ligands; Macromolecular Substances; Micromanipulation;
2552 Microscopy, Atomic Force; Models, Chemical; Molecular Biology; Nucleic
2553 Acid Conformation; Physical Stimulation; Protein Binding; Protein
2554 Conformation; Stress, Mechanical",
2555 abstract = "The forced rupture of single chemical bonds in biomolecular
2556 compounds (e.g. ligand-receptor systems) as observed in dynamic force
2557 spectroscopy experiments is addressed. Under the assumption that the
2558 probability of bond rupture depends only on the instantaneously acting
2559 force, a data collapse onto a single master curve is predicted. For
2560 rupture data obtained experimentally by dynamic AFM force spectroscopy
2561 of a ligand-receptor bond between a DNA and a regulatory protein we do
2562 not find such a collapse. We conclude that the above mentioned,
2563 generally accepted assumption is not satisfied and we discuss possible
2567 @article { raible06,
2568 author = MRaible #" and "# MEvstigneev #" and "# FWBartels #" and "#
2569 REckel #" and "# MNguyen-Duong #" and "# RMerkel #" and "# RRos #" and
2570 "# DAnselmetti #" and "# PReimann,
2571 title = "Theoretical analysis of single-molecule force spectroscopy
2572 experiments: heterogeneity of chemical bonds.",
2579 pages = "3851--3864",
2581 doi = "10.1529/biophysj.105.077099",
2582 eprint = "http://www.biophysj.org/cgi/reprint/90/11/3851.pdf",
2583 url = "http://www.biophysj.org/cgi/content/abstract/90/11/3851",
2584 keywords = "Biomechanics; Microscopy, Atomic Force; Models, Molecular;
2585 Statistical Distributions; Thermodynamics",
2586 abstract = "We show that the standard theoretical framework in single-
2587 molecule force spectroscopy has to be extended to consistently describe
2588 the experimental findings. The basic amendment is to take into account
2589 heterogeneity of the chemical bonds via random variations of the force-
2590 dependent dissociation rates. This results in a very good agreement
2591 between theory and rupture data from several different experiments."
2595 author = MRief #" and "# HGrubmuller,
2596 title = "Force spectroscopy of single biomolecules.",
2600 journal = Chemphyschem,
2605 doi = "10.1002/1439-7641(20020315)3:3<255::AID-CPHC255>3.0.CO;2-M",
2606 url = "http://www3.interscience.wiley.com/journal/91016383/abstract",
2607 keywords = "Ligands; Microscopy, Atomic Force; Polysaccharides; Protein
2608 Denaturation; Proteins",
2609 abstract = "Many processes in the body are effected and regulated by highly
2610 specialized protein molecules: These molecules certainly deserve the
2611 name ``biochemical nanomachines''. Recent progress in single-molecule
2612 experiments and corresponding simulations with supercomputers enable us
2613 to watch these ``nanomachines'' at work, revealing a host of astounding
2614 mechanisms. Examples are the fine-tuned movements of the binding pocket
2615 of a receptor protein locking into its ligand molecule and the forced
2616 unfolding of titin, which acts as a molecular shock absorber to protect
2617 muscle cells. At present, we are not capable of designing such high
2618 precision machines, but we are beginning to understand their working
2619 principles and to simulate and predict their function.",
2620 note = "Nice, general review of force spectroscopy to 2002, but not much
2626 title = "Fundamentals of Statistical and Thermal Physics",
2628 publisher = McGraw-Hill,
2629 address = "New York",
2630 note = "Thermal noise for SHOs, in Chapter 15, Sections 6 and 10.",
2631 project = "Cantilever Calibration"
2635 author = MRief #" and "# MGautel #" and "# FOesterhelt #" and "#
2636 JMFernandez #" and "# HEGaub,
2637 title = "{Reversible Unfolding of Individual Titin Immunoglobulin Domains
2643 pages = "1109--1112",
2644 doi = "10.1126/science.276.5315.1109",
2645 eprint = "http://www.sciencemag.org/cgi/reprint/276/5315/1109.pdf",
2646 url = "http://www.sciencemag.org/cgi/content/abstract/276/5315/1109",
2647 note = "Seminal paper for force spectroscopy on Titin. Cited by Dietz
2648 '04\cite{dietz04} (ref 9) as an example of how unfolding large proteins
2649 is easily interpreted (vs. confusing unfolding in bulk), but Titin is a
2650 rather simple example of that, because of it's globular-chain
2652 project = "Energy Landscape Roughness"
2656 author = MRief #" and "# JMFernandez #" and "# HEGaub,
2657 title = "Elastically Coupled Two-Level Systems as a Model for Biopolymer
2664 pages = "4764--4767",
2667 doi = "10.1103/PhysRevLett.81.4764",
2668 eprint = "http://prola.aps.org/pdf/PRL/v81/i21/p4764_1"
2671 @article { sarkar04,
2672 author = ASarkar #" and "# RBRobertson #" and "# JMFernandez,
2673 title = "{Simultaneous atomic force microscope and fluorescence
2674 measurements of protein unfolding using a calibrated evanescent wave}",
2679 pages = "12882--12886",
2680 doi = "10.1073/pnas.0403534101",
2681 eprint = "http://www.pnas.org/cgi/reprint/101/35/12882.pdf",
2682 url = "http://www.pnas.org/cgi/content/abstract/101/35/12882",
2683 abstract = "Fluorescence techniques for monitoring single-molecule dynamics
2684 in the vertical dimension currently do not exist. Here we use an atomic
2685 force microscope to calibrate the distance-dependent intensity decay of
2686 an evanescent wave. The measured evanescent wave transfer function was
2687 then used to convert the vertical motions of a fluorescent particle
2688 into displacement (SD = <1 nm). We demonstrate the use of the
2689 calibrated evanescent wave to resolve the 20.1 {+/-} 0.5-nm step
2690 increases in the length of the small protein ubiquitin during forced
2691 unfolding. The experiments that we report here make an important
2692 contribution to fluorescence microscopy by demonstrating the
2693 unambiguous optical tracking of a single molecule with a resolution
2694 comparable to that of an atomic force microscope."
2698 author = TSato #" and "# MEsaki #" and "# JMFernandez #" and "# TEndo,
2699 title = "{Comparison of the protein-unfolding pathways between
2700 mitochondrial protein import and atomic-force microscopy measurements}",
2705 pages = "17999--18004",
2706 doi = "10.1073/pnas.0504495102",
2707 eprint = "http://www.pnas.org/cgi/reprint/102/50/17999.pdf",
2708 url = "http://www.pnas.org/cgi/content/abstract/102/50/17999",
2709 abstract = "Many newly synthesized proteins have to become unfolded during
2710 translocation across biological membranes. We have analyzed the effects
2711 of various stabilization/destabilization mutations in the Ig-like
2712 module of the muscle protein titin upon its import from the N terminus
2713 or C terminus into mitochondria. The effects of mutations on the import
2714 of the titin module from the C terminus correlate well with those on
2715 forced mechanical unfolding in atomic-force microscopy (AFM)
2716 measurements. On the other hand, as long as turnover of the
2717 mitochondrial Hsp70 system is not rate-limiting for the import, import
2718 of the titin module from the N terminus is sensitive to mutations in
2719 the N-terminal region but not the ones in the C-terminal region that
2720 affect resistance to global unfolding in AFM experiments. We propose
2721 that the mitochondrial-import system can catalyze precursor-unfolding
2722 by reducing the stability of unfolding intermediates."
2725 @article { schlierf04,
2726 author = MSchlierf #" and "# HLi #" and "# JMFernandez,
2727 title = "{The unfolding kinetics of ubiquitin captured with single-molecule
2728 force-clamp techniques}",
2733 pages = "7299--7304",
2734 doi = "10.1073/pnas.0400033101",
2735 eprint = "http://www.pnas.org/cgi/reprint/101/19/7299.pdf",
2736 url = "http://www.pnas.org/cgi/content/abstract/101/19/7299",
2737 abstract = "We use single-molecule force spectroscopy to study the kinetics
2738 of unfolding of the small protein ubiquitin. Upon a step increase in
2739 the stretching force, a ubiquitin polyprotein extends in discrete steps
2740 of 20.3 {+/-} 0.9 nm marking each unfolding event. An average of the
2741 time course of these unfolding events was well described by a single
2742 exponential, which is a necessary condition for a memoryless Markovian
2743 process. Similar ensemble averages done at different forces showed that
2744 the unfolding rate was exponentially dependent on the stretching force.
2745 Stretching a ubiquitin polyprotein with a force that increased at a
2746 constant rate (force-ramp) directly measured the distribution of
2747 unfolding forces. This distribution was accurately reproduced by the
2748 simple kinetics of an all-or-none unfolding process. Our force-clamp
2749 experiments directly demonstrate that an ensemble average of ubiquitin
2750 unfolding events is well described by a two-state Markovian process
2751 that obeys the Arrhenius equation. However, at the single-molecule
2752 level, deviant behavior that is not well represented in the ensemble
2753 average is readily observed. Our experiments make an important addition
2754 to protein spectroscopy by demonstrating an unambiguous method of
2755 analysis of the kinetics of protein unfolding by a stretching force."
2758 @article { schlierf06,
2759 author = MSchlierf #" and "# MRief,
2760 title = "Single-molecule unfolding force distributions reveal a funnel-
2761 shaped energy landscape.",
2770 doi = "10.1529/biophysj.105.077982",
2771 url = "http://www.biophysj.org/cgi/content/abstract/90/4/L33",
2772 keywords = "Models, Molecular; Protein Folding; Proteins; Thermodynamics",
2773 abstract = "The protein folding process is described as diffusion on a
2774 high-dimensional energy landscape. Experimental data showing details of
2775 the underlying energy surface are essential to understanding folding.
2776 So far in single-molecule mechanical unfolding experiments a simplified
2777 model assuming a force-independent transition state has been used to
2778 extract such information. Here we show that this so-called Bell model,
2779 although fitting well to force velocity data, fails to reproduce full
2780 unfolding force distributions. We show that by applying Kramers'
2781 diffusion model, we were able to reconstruct a detailed funnel-like
2782 curvature of the underlying energy landscape and establish full
2783 agreement with the data. We demonstrate that obtaining spatially
2784 resolved details of the unfolding energy landscape from mechanical
2785 single-molecule protein unfolding experiments requires models that go
2786 beyond the Bell model.",
2787 note = "The inspiration behind my sawtooth simulation. Bell model fit to
2788 $f_{unfold}(v)$, but Kramers model fit to unfolding distribution for a
2789 given $v$. Eqn.~3 in the supplement is Evans-Ritchie 1999's
2790 Eqn.~2\cite{evans99}, but it is just ``[dying percent] * [surviving
2791 population] = [deaths]'' (TODO, check). $\nu \equiv k$ is the force
2792 /time-dependent off rate... (TODO) The Kramers' rate equation (second
2793 equation in the paper) is Hanggi Eq.~4.56b (page 275)\cite{hanggi90}.
2794 It is important to extract $k_0$ and $\Delta x$ using every available
2798 @article { schwaiger04,
2799 author = ISchwaiger #" and "# AKardinal #" and "# MSchleicher #" and "#
2800 AANoegel #" and "# MRief,
2801 title = "A mechanical unfolding intermediate in an actin-crosslinking
2811 doi = "10.1038/nsmb705",
2812 eprint = "http://www.nature.com/nsmb/journal/v11/n1/pdf/nsmb705.pdf",
2813 url = "http://www.nature.com/nsmb/journal/v11/n1/full/nsmb705.html",
2814 keywords = "Actins; Animals; Contractile Proteins; Cross-Linking Reagents;
2815 Dictyostelium; Dimerization; Microfilament Proteins; Microscopy, Atomic
2816 Force; Mutagenesis, Site-Directed; Protein Denaturation; Protein
2817 Folding; Protein Structure, Tertiary; Protozoan Proteins",
2818 abstract = "Many F-actin crosslinking proteins consist of two actin-binding
2819 domains separated by a rod domain that can vary considerably in length
2820 and structure. In this study, we used single-molecule force
2821 spectroscopy to investigate the mechanics of the immunoglobulin (Ig)
2822 rod domains of filamin from Dictyostelium discoideum (ddFLN). We find
2823 that one of the six Ig domains unfolds at lower forces than do those of
2824 all other domains and exhibits a stable unfolding intermediate on its
2825 mechanical unfolding pathway. Amino acid inserts into various loops of
2826 this domain lead to contour length changes in the single-molecule
2827 unfolding pattern. These changes allowed us to map the stable core of
2828 approximately 60 amino acids that constitutes the unfolding
2829 intermediate. Fast refolding in combination with low unfolding forces
2830 suggest a potential in vivo role for this domain as a mechanically
2831 extensible element within the ddFLN rod.",
2832 note = "ddFLN unfolding with WLC params for sacrificial domains. Gives
2833 persistence length $p = 0.5\mbox{ nm}$ in ``high force regime'', $p =
2834 0.9\mbox{ nm}$ in ``low force regime'', with a transition at $F =
2836 project = "sawtooth simulation"
2839 @article { schwaiger05,
2840 author = ISchwaiger #" and "# MSchleicher #" and "# AANoegel #" and "#
2842 title = "The folding pathway of a fast-folding immunoglobulin domain
2843 revealed by single-molecule mechanical experiments.",
2851 doi = "10.1038/sj.embor.7400317",
2852 eprint = "http://www.nature.com/embor/journal/v6/n1/pdf/7400317.pdf",
2853 url = "http://www.nature.com/embor/journal/v6/n1/index.html",
2854 keywords = "Animals; Contractile Proteins; Dictyostelium; Immunoglobulins;
2855 Kinetics; Microfilament Proteins; Models, Molecular; Protein Folding;
2856 Protein Structure, Tertiary",
2857 abstract = "The F-actin crosslinker filamin from Dictyostelium discoideum
2858 (ddFLN) has a rod domain consisting of six structurally similar
2859 immunoglobulin domains. When subjected to a stretching force, domain 4
2860 unfolds at a lower force than all the other domains in the chain.
2861 Moreover, this domain shows a stable intermediate along its mechanical
2862 unfolding pathway. We have developed a mechanical single-molecule
2863 analogue to a double-jump stopped-flow experiment to investigate the
2864 folding kinetics and pathway of this domain. We show that an obligatory
2865 and productive intermediate also occurs on the folding pathway of the
2866 domain. Identical mechanical properties suggest that the unfolding and
2867 refolding intermediates are closely related. The folding process can be
2868 divided into two consecutive steps: in the first step 60 C-terminal
2869 amino acids form an intermediate at the rate of 55 s(-1); and in the
2870 second step the remaining 40 amino acids are packed on this core at the
2871 rate of 179 s(-1). This division increases the overall folding rate of
2872 this domain by a factor of ten compared with all other homologous
2873 domains of ddFLN that lack the folding intermediate."
2876 @article { sharma07,
2877 author = DSharma #" and "# OPerisic #" and "# QPeng #" and "# YCao #" and
2878 "# CLam #" and "# HLu #" and "# HLi,
2879 title = "{Single-molecule force spectroscopy reveals a mechanically stable
2880 protein fold and the rational tuning of its mechanical stability}",
2885 pages = "9278--9283",
2886 doi = "10.1073/pnas.0700351104",
2887 eprint = "http://www.pnas.org/cgi/reprint/104/22/9278.pdf",
2888 url = "http://www.pnas.org/cgi/content/abstract/104/22/9278",
2889 abstract = "It is recognized that shear topology of two directly connected
2890 force-bearing terminal [beta]-strands is a common feature among the
2891 vast majority of mechanically stable proteins known so far. However,
2892 these proteins belong to only two distinct protein folds, Ig-like
2893 [beta] sandwich fold and [beta]-grasp fold, significantly hindering
2894 delineating molecular determinants of mechanical stability and rational
2895 tuning of mechanical properties. Here we combine single-molecule atomic
2896 force microscopy and steered molecular dynamics simulation to reveal
2897 that the de novo designed Top7 fold [Kuhlman B, Dantas G, Ireton GC,
2898 Varani G, Stoddard BL, Baker D (2003) Science 302:13641368] represents
2899 a mechanically stable protein fold that is distinct from Ig-like [beta]
2900 sandwich and [beta]-grasp folds. Although the two force-bearing [beta]
2901 strands of Top7 are not directly connected, Top7 displays significant
2902 mechanical stability, demonstrating that the direct connectivity of
2903 force-bearing [beta] strands in shear topology is not mandatory for
2904 mechanical stability. This finding broadens our understanding of the
2905 design of mechanically stable proteins and expands the protein fold
2906 space where mechanically stable proteins can be screened. Moreover, our
2907 results revealed a substructure-sliding mechanism for the mechanical
2908 unfolding of Top7 and the existence of two possible unfolding pathways
2909 with different height of energy barrier. Such insights enabled us to
2910 rationally tune the mechanical stability of Top7 by redesigning its
2911 mechanical unfolding pathway. Our study demonstrates that computational
2912 biology methods (including de novo design) offer great potential for
2913 designing proteins of defined topology to achieve significant and
2914 tunable mechanical properties in a rational and systematic fashion."
2918 author = YJSheng #" and "# SJiang #" and "# HKTsao,
2919 title = "Forced Kramers escape in single-molecule pulling experiments",
2929 doi = "10.1063/1.2046632",
2930 url = "http://link.aip.org/link/?JCP/123/091102/1",
2931 keywords = "molecular biophysics; bonds (chemical); proteins",
2932 note = "Gives appropriate Einstein-S... relation for diffusion to damping",
2933 project = "sawtooth simulation"
2936 @article { shillcock98,
2937 author = JShillcock #" and "# USeifert,
2938 title = "Escape from a metastable well under a time-ramped force",
2944 pages = "7301--7304",
2947 doi = "10.1103/PhysRevE.57.7301",
2948 eprint = "http://prola.aps.org/pdf/PRE/v57/i6/p7301_1",
2949 url = "http://link.aps.org/abstract/PRE/v57/p7301",
2950 project = "sawtooth simulation"
2954 author = NDSocci #" and "# JNOnuchic #" and "# PGWolynes,
2955 title = "Diffusive dynamics of the reaction coordinate for protein folding
2962 pages = "5860-5868",
2964 doi = "10.1063/1.471317",
2965 eprint = "http://arxiv.org/pdf/cond-mat/9601091",
2966 url = "http://link.aip.org/link/?JCP/104/5860/1",
2967 keywords = "PROTEINS; FOLDS; DIFFUSION; MONTE CARLO METHOD; SIMULATION;
2969 abstract = "The quantitative description of model protein folding kinetics
2970 using a diffusive collective reaction coordinate is examined. Direct
2971 folding kinetics, diffusional coefficients and free energy profiles are
2972 determined from Monte Carlo simulations of a 27-mer, 3 letter code
2973 lattice model, which corresponds roughly to a small helical protein.
2974 Analytic folding calculations, using simple diffusive rate theory,
2975 agree extremely well with the full simulation results. Folding in this
2976 system is best seen as a diffusive, funnel-like process.",
2977 note = "A nice introduction to some quantitative ramifications of the
2978 funnel energy landscape. There's also a bit of Kramers' theory and
2979 graph theory thrown in for good measure."
2982 @article { strunz99,
2983 author = TStrunz #" and "# KOroszlan #" and "# RSchafer #" and "#
2985 title = "{Dynamic force spectroscopy of single DNA molecules}",
2990 pages = "11277--11282",
2991 doi = "10.1073/pnas.96.20.11277",
2992 eprint = "http://www.pnas.org/cgi/reprint/96/20/11277.pdf",
2993 url = "http://www.pnas.org/cgi/content/abstract/96/20/11277"
2997 author = AMalec #" and "# CPickett #" and "# FHugosson #" and "# RLemmen,
3003 version = "version 0.9.4",
3004 url = "http://check.sourceforge.net",
3005 abstract = "Check is a unit testing framework for C. It features a simple
3006 interface for defining unit tests, putting little in the way of the
3007 developer. Tests are run in a separate address space, so Check can
3008 catch both assertion failures and code errors that cause segmentation
3009 faults or other signals. The output from unit tests can be used within
3010 source code editors and IDEs."
3020 version = "version 2.11b",
3021 url = "http://www.eecs.harvard.edu/nr/noweb/",
3022 abstract = "Noweb is a simple, extensible literate programming tool.",
3023 note = "Debian package by Federico Di Gregorio"
3027 author = GvanRossum #" and "# others,
3033 version = "version 2.5.1",
3034 url = "http://www.python.org/",
3035 abstract = "Python is a dynamic object-oriented programming language."
3039 author = EJones #" and "# TOliphant #" and "# PPeterson #" and "# others,
3041 title = "{SciPy}: Open source scientific tools for {Python}",
3043 url = "http://www.scipy.org/"
3047 author = ASzabo #" and "# KSchulten #" and "# ZSchulten,
3048 title = "First passage time approach to diffusion controlled reactions",
3054 pages = "4350-4357",
3056 doi = "10.1063/1.439715",
3057 url = "http://link.aip.org/link/?JCP/72/4350/1",
3058 keywords = "DIFFUSION; CHEMICAL REACTIONS; CHEMICAL REACTION KINETICS;
3059 PROBABILITY; DIFFERENTIAL EQUATIONS"
3062 @article { talaga00,
3063 author = DSTalaga #" and "# WLLau #" and "# HRoder #" and "# JTang #" and
3064 "# YJia #" and "# WFDeGrado #" and "# RMHochstrasser,
3065 title = "{Dynamics and folding of single two-stranded coiled-coil peptides
3066 studied by fluorescent energy transfer confocal microscopy}",
3071 pages = "13021--13026",
3072 doi = "10.1073/pnas.97.24.13021",
3073 eprint = "http://www.pnas.org/cgi/reprint/97/24/13021.pdf",
3074 url = "http://www.pnas.org/cgi/content/abstract/97/24/13021"
3077 @article { thirumalai05,
3078 author = DThirumalai #" and "# CHyeon,
3079 title = "{RNA} and Protein Folding: Common Themes and Variations",
3080 affiliation = "Biophysics Program, and Department of Chemistry and
3081 Biochemistry, Institute for Physical Science and Technology, University
3082 of Maryland, College Park, Maryland 20742",
3084 journal = Biochemistry,
3087 pages = "4957--4970",
3090 "http://pubs3.acs.org/acs/journals/doilookup?in_doi=10.1021/bi047314+",
3091 abstract = "Visualizing the navigation of an ensemble of unfolded molecules
3092 through the bumpy energy landscape in search of the native state gives
3093 a pictorial view of biomolecular folding. This picture, when combined
3094 with concepts in polymer theory, provides a unified theory of RNA and
3095 protein folding. Just as for proteins, the major folding free energy
3096 barrier for RNA scales sublinearly with the number of nucleotides,
3097 which allows us to extract the elusive prefactor for RNA folding.
3098 Several folding scenarios can be anticipated by considering variations
3099 in the energy landscape that depend on sequence, native topology, and
3100 external conditions. RNA and protein folding mechanism can be described
3101 by the kinetic partitioning mechanism (KPM) according to which a
3102 fraction () of molecules reaches the native state directly, whereas the
3103 remaining fraction gets kinetically trapped in metastable
3104 conformations. For two-state folders 1. Molecular chaperones are
3105 recruited to assist protein folding whenever is small. We show that the
3106 iterative annealing mechanism, introduced to describe chaperonin-
3107 mediated folding, can be generalized to understand protein-assisted RNA
3108 folding. The major differences between the folding of proteins and RNA
3109 arise in the early stages of folding. For RNA, folding can only begin
3110 after the polyelectrolyte problem is solved, whereas protein collapse
3111 requires burial of hydrophobic residues. Cross-fertilization of ideas
3112 between the two fields should lead to an understanding of how RNA and
3113 proteins solve their folding problems.",
3114 note = "unfolding-refolding"
3117 @article { tlusty98,
3118 author = TTlusty #" and "# AMeller #" and "# RBar-Ziv,
3119 title = "Optical Gradient Forces of Strongly Localized Fields",
3125 pages = "1738--1741",
3128 doi = "10.1103/PhysRevLett.81.1738",
3129 eprint = "http://prola.aps.org/pdf/PRL/v81/i8/p1738_1",
3130 note = "also at \url{http://nanoscience.bu.edu/papers/p1738_1_Meller.pdf}.
3131 Cited by \cite{grossman05} for derivation of thermal response fn.
3132 However, I only see a referenced thermal energy when they list the
3133 likelyhood of a small partical (radius < $R_c$) escaping due to thermal
3134 energy, where $R_c$ is roughly $R_c \sim (k_B T / \alpha I_0)^(1/3)$,
3135 $\alpha$ is a dielectric scaling term, and $I_0$ is the maximum beam
3136 energy density. I imagine Grossman and Stout mixed up this reference.",
3137 project = "Cantilever Calibration"
3140 @book { vanKampen07,
3141 author = NGvanKampen,
3142 title = "Stochastic Processes in Physics and Chemistry",
3146 address = "Amsterdam",
3148 project = "sawtooth simulation"
3151 @article { walther07,
3152 author = KAWalther #" and "# FGrater #" and "# LDougan #" and "# CLBadilla
3153 #" and "# BJBerne #" and "# JMFernandez,
3154 title = "{Signatures of hydrophobic collapse in extended proteins captured
3155 with force spectroscopy}",
3160 pages = "7916--7921",
3161 doi = "10.1073/pnas.0702179104",
3162 eprint = "http://www.pnas.org/cgi/reprint/104/19/7916.pdf",
3163 url = "http://www.pnas.org/cgi/content/abstract/104/19/7916",
3164 abstract = "We unfold and extend single proteins at a high force and then
3165 linearly relax the force to probe their collapse mechanisms. We observe
3166 a large variability in the extent of their recoil. Although chain
3167 entropy makes a small contribution, we show that the observed
3168 variability results from hydrophobic interactions with randomly varying
3169 magnitude from protein to protein. This collapse mechanism is common to
3170 highly extended proteins, including nonfolding elastomeric proteins
3171 like PEVK from titin. Our observations explain the puzzling differences
3172 between the folding behavior of highly extended proteins, from those
3173 folding after chemical or thermal denaturation. Probing the collapse of
3174 highly extended proteins with force spectroscopy allows separation of
3175 the different driving forces in protein folding."
3178 @article { walton08,
3179 author = EBWalton #" and "# SLee #" and "# KJvanVliet,
3180 title = "Extending Bell's model: how force transducer stiffness alters
3181 measured unbinding forces and kinetics of molecular complexes.",
3188 pages = "2621--2630",
3190 doi = "10.1529/biophysj.107.114454",
3191 keywords = "Biotin; Computer Simulation; Elasticity; Kinetics;
3192 Mechanotransduction, Cellular; Models, Chemical; Models, Molecular;
3193 Molecular Motor Proteins; Motion; Streptavidin; Stress, Mechanical;
3195 abstract = "Forced unbinding of complementary macromolecules such as
3196 ligand-receptor complexes can reveal energetic and kinetic details
3197 governing physiological processes ranging from cellular adhesion to
3198 drug metabolism. Although molecular-level experiments have enabled
3199 sampling of individual ligand-receptor complex dissociation events,
3200 disparities in measured unbinding force F(R) among these methods lead
3201 to marked variation in inferred binding energetics and kinetics at
3202 equilibrium. These discrepancies are documented for even the ubiquitous
3203 ligand-receptor pair, biotin-streptavidin. We investigated these
3204 disparities and examined atomic-level unbinding trajectories via
3205 steered molecular dynamics simulations, as well as via molecular force
3206 spectroscopy experiments on biotin-streptavidin. In addition to the
3207 well-known loading rate dependence of F(R) predicted by Bell's model,
3208 we find that experimentally accessible parameters such as the effective
3209 stiffness of the force transducer k can significantly perturb the
3210 energy landscape and the apparent unbinding force of the complex for
3211 sufficiently stiff force transducers. Additionally, at least 20\%
3212 variation in unbinding force can be attributed to minute differences in
3213 initial atomic positions among energetically and structurally
3214 comparable complexes. For force transducers typical of molecular force
3215 spectroscopy experiments and atomistic simulations, this energy barrier
3216 perturbation results in extrapolated energetic and kinetic parameters
3217 of the complex that depend strongly on k. We present a model that
3218 explicitly includes the effect of k on apparent unbinding force of the
3219 ligand-receptor complex, and demonstrate that this correction enables
3220 prediction of unbinding distances and dissociation rates that are
3221 decoupled from the stiffness of actual or simulated molecular linkers.",
3222 note = "Some detailed estimates at U(x)."
3226 author = APWiita #" and "# SRKAinavarapu #" and "# HHHuang #" and "#
3228 title = "{From the Cover: Force-dependent chemical kinetics of disulfide
3229 bond reduction observed with single-molecule techniques}",
3234 pages = "7222--7227",
3235 doi = "10.1073/pnas.0511035103",
3236 eprint = "http://www.pnas.org/cgi/reprint/103/19/7222.pdf",
3237 url = "http://www.pnas.org/cgi/content/abstract/103/19/7222",
3238 abstract = "The mechanism by which mechanical force regulates the kinetics
3239 of a chemical reaction is unknown. Here, we use single-molecule force-
3240 clamp spectroscopy and protein engineering to study the effect of force
3241 on the kinetics of thiol/disulfide exchange. Reduction of disulfide
3242 bonds through the thiol/disulfide exchange chemical reaction is crucial
3243 in regulating protein function and is known to occur in mechanically
3244 stressed proteins. We apply a constant stretching force to single
3245 engineered disulfide bonds and measure their rate of reduction by DTT.
3246 Although the reduction rate is linearly dependent on the concentration
3247 of DTT, it is exponentially dependent on the applied force, increasing
3248 10-fold over a 300-pN range. This result predicts that the disulfide
3249 bond lengthens by 0.34 A at the transition state of the thiol/disulfide
3250 exchange reaction. Our work at the single bond level directly
3251 demonstrates that thiol/disulfide exchange in proteins is a force-
3252 dependent chemical reaction. Our findings suggest that mechanical force
3253 plays a role in disulfide reduction in vivo, a property that has never
3254 been explored by traditional biochemistry. Furthermore, our work also
3255 indicates that the kinetics of any chemical reaction that results in
3256 bond lengthening will be force-dependent."
3259 @article { wikipedia_cubic_function,
3261 key = "wikipedia_cubic_function",
3262 title = "Cubic function",
3266 journal = Wikipedia,
3267 url = "http://en.wikipedia.org/wiki/Cubic_equation"
3270 @article { wilcox05,
3271 author = AJWilcox #" and "# JChoy #" and "# CBustamante #" and "#
3273 title = "{Effect of protein structure on mitochondrial import}",
3278 pages = "15435--15440",
3279 doi = "10.1073/pnas.0507324102",
3280 eprint = "http://www.pnas.org/cgi/reprint/102/43/15435.pdf",
3281 url = "http://www.pnas.org/cgi/content/abstract/102/43/15435",
3282 abstract = "Most proteins that are to be imported into the mitochondrial
3283 matrix are synthesized as precursors, each composed of an N-terminal
3284 targeting sequence followed by a mature domain. Precursors are
3285 recognized through their targeting sequences by receptors at the
3286 mitochondrial surface and are then threaded through import channels
3287 into the matrix. Both the targeting sequence and the mature domain
3288 contribute to the efficiency with which proteins are imported into
3289 mitochondria. Precursors must be in an unfolded conformation during
3290 translocation. Mitochondria can unfold some proteins by changing their
3291 unfolding pathways. The effectiveness of this unfolding mechanism
3292 depends on the local structure of the mature domain adjacent to the
3293 targeting sequence. This local structure determines the extent to which
3294 the unfolding pathway can be changed and, therefore, the unfolding rate
3295 increased. Atomic force microscopy studies find that the local
3296 structures of proteins near their N and C termini also influence their
3297 resistance to mechanical unfolding. Thus, protein unfolding during
3298 import resembles mechanical unfolding, and the specificity of import is
3299 determined by the resistance of the mature domain to unfolding as well
3300 as by the properties of the targeting sequence."
3304 author = JWWu #" and "# WLHung #" and "# CHTsai,
3305 title = "Estimation of parameters of the {G}ompertz distribution using the
3306 least squares method.",
3315 doi = "10.1016/j.amc.2003.08.086",
3316 url = "http://www.sciencedirect.com/science/article/B6TY8-4B3NR1W-B/1/bbaa4
3317 7878ada03c6ef8e681d03bb65d3",
3318 keywords = "Gompertz distribution; Least squares estimate; Maximum
3319 likelihood estimate; First failure-censored; Series system",
3320 abstract = "The Gompertz distribution has been used to describe human
3321 mortality and establish actuarial tables. Recently, this distribution
3322 has been again studied by some authors. The maximum likelihood
3323 estimates for the parameters of the Gompertz distribution has been
3324 discussed by Garg et al. [J. R. Statist. Soc. C 19 (1970) 152]. The
3325 purpose of this paper is to propose unweighted and weighted least
3326 squares estimates for parameters of the Gompertz distribution under the
3327 complete data and the first failure-censored data (series systems; see
3328 [J. Statist. Comput. Simulat. 52 (1995) 337]). A simulation study is
3329 carried out to compare the proposed estimators and the maximum
3330 likelihood estimators. Results of the simulation studies show that the
3331 performance of the weighted least squares estimators is acceptable."
3335 author = GYang #" and "# CCecconi #" and "# WABaase #" and "# IRVetter #"
3336 and "# WABreyer #" and "# JAHaack #" and "# BWMatthews #" and "#
3337 FWDahlquist #" and "# CBustamante,
3338 title = "{Solid-state synthesis and mechanical unfolding of polymers of T4
3345 doi = "10.1073/pnas.97.1.139",
3346 eprint = "http://www.pnas.org/cgi/reprint/97/1/139.pdf",
3347 url = "http://www.pnas.org/cgi/content/abstract/97/1/139"
3351 author = YYang #" and "# FCLin #" and "# GYang,
3352 title = "Temperature control device for single molecule measurements using
3353 the atomic force microscope",
3363 doi = "10.1063/1.2204580",
3364 url = "http://link.aip.org/link/?RSI/77/063701/1",
3365 keywords = "temperature control; atomic force microscopy; thermocouples;
3367 note = "Introduces our temperature control system",
3368 project = "Energy Landscape Roughness"
3372 author = WYu #" and "# JCLamb #" and "# FHan #" and "# JABirchler,
3373 title = "{Telomere-mediated chromosomal truncation in maize}",
3378 pages = "17331--17336",
3379 doi = "10.1073/pnas.0605750103",
3380 eprint = "http://www.pnas.org/cgi/reprint/103/46/17331.pdf",
3381 url = "http://www.pnas.org/cgi/content/abstract/103/46/17331",
3382 abstract = "Direct repeats of Arabidopsis telomeric sequence were
3383 constructed to test telomere-mediated chromosomal truncation in maize.
3384 Two constructs with 2.6 kb of telomeric sequence were used to transform
3385 maize immature embryos by Agrobacterium-mediated transformation. One
3386 hundred seventy-six transgenic lines were recovered in which 231
3387 transgene loci were revealed by a FISH analysis. To analyze chromosomal
3388 truncations that result in transgenes located near chromosomal termini,
3389 Southern hybridization analyses were performed. A pattern of smear in
3390 truncated lines was seen as compared with discrete bands for internal
3391 integrations, because telomeres in different cells are elongated
3392 differently by telomerase. When multiple restriction enzymes were used
3393 to map the transgene positions, the size of the smears shifted in
3394 accordance with the locations of restriction sites on the construct.
3395 This result demonstrated that the transgene was present at the end of
3396 the chromosome immediately before the integrated telomere sequence.
3397 Direct evidence for chromosomal truncation came from the results of
3398 FISH karyotyping, which revealed broken chromosomes with transgene
3399 signals at the ends. These results demonstrate that telomere-mediated
3400 chromosomal truncation operates in plant species. This technology will
3401 be useful for chromosomal engineering in maize as well as other plant
3406 author = JMZhao #" and "# HLee #" and "# RANome #" and "# SMajid #" and "#
3407 NFScherer #" and "# WDHoff,
3408 title = "{Single-molecule detection of structural changes during Per-Arnt-
3409 Sim (PAS) domain activation}",
3414 pages = "11561--11566",
3415 doi = "10.1073/pnas.0601567103",
3416 eprint = "http://www.pnas.org/cgi/reprint/103/31/11561.pdf",
3417 url = "http://www.pnas.org/cgi/content/abstract/103/31/11561",
3418 abstract = "The Per-Arnt-Sim (PAS) domain is a ubiquitous protein module
3419 with a common three-dimensional fold involved in a wide range of
3420 regulatory and sensory functions in all domains of life. The activation
3421 of these functions is thought to involve partial unfolding of N- or
3422 C-terminal helices attached to the PAS domain. Here we use atomic force
3423 microscopy to probe receptor activation in single molecules of
3424 photoactive yellow protein (PYP), a prototype of the PAS domain family.
3425 Mechanical unfolding of Cys-linked PYP multimers in the presence and
3426 absence of illumination reveals that, in contrast to previous studies,
3427 the PAS domain itself is extended by {approx}3 nm (at the 10-pN
3428 detection limit of the measurement) and destabilized by {approx}30% in
3429 the light-activated state of PYP. Comparative measurements and steered
3430 molecular dynamics simulations of two double-Cys PYP mutants that probe
3431 different regions of the PAS domain quantify the anisotropy in
3432 stability and changes in local structure, thereby demonstrating the
3433 partial unfolding of their PAS domain upon activation. These results
3434 establish a generally applicable single-molecule approach for mapping
3435 functional conformational changes to selected regions of a protein. In
3436 addition, the results have profound implications for the molecular
3437 mechanism of PAS domain activation and indicate that stimulus-induced
3438 partial protein unfolding can be used as a signaling mechanism."
3441 @article { zhuang06,
3442 author = WZhuang #" and "# DAbramavicius #" and "# SMukamel,
3443 title = "{Two-dimensional vibrational optical probes for peptide fast
3444 folding investigation}",
3449 pages = "18934--18938",
3450 doi = "10.1073/pnas.0606912103",
3451 eprint = "http://www.pnas.org/cgi/reprint/103/50/18934.pdf",
3452 url = "http://www.pnas.org/cgi/content/abstract/103/50/18934",
3453 abstract = "A simulation study shows that early protein folding events may
3454 be investigated by using a recently developed family of nonlinear
3455 infrared techniques that combine the high temporal and spatial
3456 resolution of multidimensional spectroscopy with the chirality-specific
3457 sensitivity of amide vibrations to structure. We demonstrate how the
3458 structural sensitivity of cross-peaks in two-dimensional correlation
3459 plots of chiral signals of an {alpha} helix and a [beta] hairpin may be
3460 used to clearly resolve structural and dynamical details undetectable
3461 by one-dimensional techniques (e.g. circular dichroism) and identify
3462 structures indistinguishable by NMR."
3465 @article { zinober02,
3466 author = RCZinober #" and "# DJBrockwell #" and "# GSBeddard #" and "#
3467 AWBlake #" and "# PDOlmsted #" and "# SERadford #" and "# DASmith,
3468 title = "Mechanically unfolding proteins: the effect of unfolding history
3469 and the supramolecular scaffold.",
3475 pages = "2759--2765",
3477 doi = "10.1110/ps.0224602",
3478 eprint = "http://www.proteinscience.org/cgi/reprint/11/12/2759.pdf",
3479 url = "http://www.proteinscience.org/cgi/content/abstract/11/12/2759",
3480 keywords = "Computer Simulation; Models, Molecular; Monte Carlo Method;
3481 Protein Folding; Protein Structure, Tertiary; Proteins",
3482 abstract = "The mechanical resistance of a folded domain in a polyprotein
3483 of five mutant I27 domains (C47S, C63S I27)(5)is shown to depend on the
3484 unfolding history of the protein. This observation can be understood on
3485 the basis of competition between two effects, that of the changing
3486 number of domains attempting to unfold, and the progressive increase in
3487 the compliance of the polyprotein as domains unfold. We present Monte
3488 Carlo simulations that show the effect and experimental data that
3489 verify these observations. The results are confirmed using an
3490 analytical model based on transition state theory. The model and
3491 simulations also predict that the mechanical resistance of a domain
3492 depends on the stiffness of the surrounding scaffold that holds the
3493 domain in vivo, and on the length of the unfolded domain. Together,
3494 these additional factors that influence the mechanical resistance of
3495 proteins have important consequences for our understanding of natural
3496 proteins that have evolved to withstand force.",
3498 project = "sawtooth simulation"