2 @string{AcP = "Academic Press"}
3 @string{CoRR = "arXiv Computing Research Repository"}.
4 @string{ACM = "Association for Computing Machinery"}
5 @string{KAstrom = "{\AA}str{\"o}m, K.~J."}
6 @string{ACM:SIGCSE = "ACM Special Interest Group on Computer Science Education Bulletin"}
7 @string{ACM:CSur = "ACM Computing Surveys"}
8 @string{ACS:ChemBiol = "ACS Chem Biol"}
10 @string{APL = "Applied Physics Letters"}
11 @string{DAbramavicius = "Abramavicius, Darius"}
12 @string{JFAbril = "Abril, J. F."}
13 @string{JAbu-Threideh = "Abu-Threideh, J."}
14 @string{KAdachi = "Adachi, Kengo"}
15 @string{MDAdams = "Adams, M. D."}
16 @string{AW = "Addison-Wesley Longman Publishing Co., Inc."}
17 @string{AdvExpMedBiol = "Advances in Experimental Medicine and Biology"}
18 @string{SAinavarapu = "Ainavarapu, Sri Rama Koti"}
19 @string{DAioanei = "Aioanei, Daniel"}
20 @string{TRAlbrecht = "Albreacht, T.~R."}
21 @string{AMB = "Algorithms for molecular biology: AMB"}
22 @string{FAli = "Ali, F."}
23 @string{JFAllemand = "Allemand, Jean-Fran\c{c}ois"}
24 @string{DAllen = "Allen, D."}
25 @string{MAllen = "Allen, Mark D."}
26 @string{RAlon = "Alon, Ronen"}
27 @string{PAmanatides = "Amanatides, P."}
28 @string{NMAmer = "Amer, Nabil M."}
29 @string{AJP = "American Journal of Physics"}
30 @string{APS = "American Physical Society"}
31 @string{AS = "American Scientist"}
32 @string{ASA = "American Statistical Association"}
33 @string{HAn = "An, H."}
34 @string{KNAn = "An, Kai-Nan"}
35 @string{ABioChem = "Analytical biochemistry"}
36 @string{BAndreopoulos = "Andreopoulos, Bill"}
37 @string{IAndricioaei = "Andricioaei, Ioan"}
38 @string{ACIEE = "Angew. Chem. Int. Ed. Engl."}
39 @string{ARBBS = "Annu Rev Biophys Biomol Struct"}
40 @string{ARBC = "Annual Review of Biochemistry"}
41 @string{DAnselmetti = "Anselmetti, Dario"}
42 @string{AAntoniadis = "Antoniadis, Anestis"}
43 @string{AMC = "Applied Mathematics and Computation"}
44 @string{SArcidiacono = "Arcidiacono, S"}
45 @string{CArciola = "Arciola, Carla Renata"}
46 @string{ABArtyukhin = "Artyukhin, Alexander B."}
47 @string{DAruliah = "Aruliah, Dhavide A."}
48 @string{SAsakawa = "Asakawa, S."}
49 @string{AAwe = "Awe, A."}
50 @string{SBedard = "B\'edard, Sabrina"}
51 @string{WBaase = "Baase, Walter A."}
52 @string{YBaba = "Baba, Y."}
53 @string{HBaden = "Baden, H."}
54 @string{CBadilla = "Badilla, Carmen L."}
55 @string{VBafna = "Bafna, V."}
56 @string{BBagchi = "Bagchi, B."}
57 @string{MBalamurali = "Balamurali, M. M."}
58 @string{DBaldwin = "Baldwin, D."}
59 @string{ABaljon = "Baljon, Arlette R. C."}
60 @string{RBallerini = "Ballerini, R."}
61 @string{RMBallew = "Ballew, R. M."}
62 @string{MBalsera = "Balsera, M."}
63 @string{GBaneyx = "Baneyx, Gretchen"}
64 @string{RBar-Ziv = "Bar-Ziv, Roy"}
65 @string{WBBarbazuk = "Barbazuk, W. B."}
66 @string{MBarnstead = "Barnstead, M."}
67 @string{DBarrick = "Barrick, Doug"}
68 @string{IBarrow = "Barrow, I."}
69 @string{FWBartels = "Bartels, Frank Wilco"}
70 @string{BBarz = "Barz, Bogdan"}
71 @string{TBasche = "Basche, Th."}
72 @string{PBaschieri = "Baschieri, Paolo"}
73 @string{ABasu = "Basu, A."}
74 @string{LBaugh = "Baugh, Loren"}
75 @string{BBaumgarth = "Baumgarth, Birgit"}
76 @string{SBaumhueter = "Baumhueter, S."}
77 @string{JBaxendale = "Baxendale, J."}
78 @string{EABayer = "Bayer, Edward A."}
79 @string{EBeasley = "Beasley, E."}
80 @string{JBechhoefer = "Bechhoefer, John"}
81 @string{BBechinger = "Bechinger, Burkhard"}
82 @string{ABecker = "Becker, Anke"}
83 @string{GSBeddard = "Beddard, Godfrey S."}
84 @string{TBeebe = "Beebe, Thomas P."}
85 @string{KBeeson = "Beeson, K."}
86 @string{GIBell = "Bell, G. I."}
87 @string{FBenedetti = "Benedetti, Fabrizio"}
88 @string{VBenes = "Benes, Vladimir"}
89 @string{ABensimon = "Bensimon, A."}
90 @string{DBensimon = "Bensimon, David"}
91 @string{DRBentley = "Bentley, D. R."}
92 @string{HJCBerendsen = "Berendsen, Herman J. C."}
93 @string{KBergSorensen = "Berg-S\orensen, K"}
94 @string{EBergantino = "Bergantino, Elisabetta"}
95 @string{DBerk = "Berk, D."}
96 @string{FBerkemeier = "Berkemeier, Felix"}
97 @string{BBerne = "Berne, Bruce J."}
98 @string{MBertz = "Bertz, Morten"}
99 @string{RBest = "Best, Robert B."}
100 @string{GBethel = "Bethel, G."}
101 @string{NBhasin = "Bhasin, Nishant"}
102 @string{KBiddick = "Biddick, K."}
103 @string{KBillings = "Billings, Kate S."}
104 @string{GBinnig = "Binnig, Gerd"}
105 @string{BCBPRC = "Biochemical and Biophysical Research Communications"}
106 @string{Biochem = "Biochemistry"}
107 @string{BBABE = "Biochimica et Biophysica Acta (BBA) - Bioenergetics"}
108 @string{BIOINFO = "Bioinformatics (Oxford, England)"}
109 @string{Biomet = "Biometrika"}
110 @string{BPJ = "Biophysical Journal"}
111 %string{BPJ = "Biophys. J."}
112 @string{BIOSENSE = "Biosensors and Bioelectronics"}
113 @string{BIOTECH = "Biotechnology and Bioengineering"}
114 @string{JBirchler = "Birchler, James A."}
115 @string{AWBlake = "Blake, Anthony W."}
116 @string{JBlawzdziewicz = "Blawzdziewicz, Jerzy"}
117 @string{LBlick = "Blick, L."}
118 @string{RBolanos = "Bolanos, R."}
119 @string{VBonazzi = "Bonazzi, V."}
120 @string{Borgia = "Borgia"}
121 @string{MBorkovec = "Borkovec, Michal"}
122 @string{RBrandon = "Brandon, R."}
123 @string{EBranscomb = "Branscomb, E."}
124 @string{EBraverman = "Braverman, Elena"}
125 @string{WBreyer = "Breyer, Wendy A."}
126 @string{FBrochard-Wyart = "Brochard-Wyart, F."}
127 @string{DJBrockwell = "Brockwell, David J."}
128 @string{SBroder = "Broder, S."}
129 @string{SBroedel = "Broedel, Sheldon E."}
130 @string{ABrolo = "Brolo, Alexandre G."}
131 @string{FBrooks = "Brooks, Jr., Frederick P."}
132 @string{BrooksCole = "Brooks/Cole"}
133 @string{BDBrowerToland = "Brower-Toland, Brent D."}
134 @string{CTBrown = "Brown, C. Titus"}
135 @string{MBrucale = "Brucale, Marco"}
136 @string{TBruls = "Bruls, T."}
137 @string{VBrumfeld = "Brumfeld, Vlad"}
138 @string{JDBryngelson = "Bryngelson, J. D."}
139 @string{LBubacco = "Bubacco, Luigi"}
140 @string{JBuckheit = "Buckheit, Jonathan B."}
141 @string{ABuguin = "Buguin, A."}
142 @string{ABulhassan = "Bulhassan, Ahmed"}
143 @string{BBullard = "Bullard, Belinda"}
144 @string{RBunk = "Bunk, Richard"}
145 @string{NABurnham = "Burnham, N.~A."}
146 @string{DBusam = "Busam, D."}
147 @string{GBussi = "Bussi, Giovanni"}
148 @string{CBustamante = "Bustamante, Carlos"}
149 @string{YBustanji = "Bustanji, Yasser"}
150 @string{HJButt = {Butt, Hans-J\"urgen}}
151 @string{CUP = "Cambridge University Press"}
152 @string{MCaminha = "Caminha, M."}
153 @string{ICampbell = "Campbell, Iain D."}
154 @string{MJCampbell = "Campbell, M. J."}
155 @string{DSCannell = "Cannell, D.~S."}
156 @string{YCao = "Cao, Yi"}
157 @string{MCapitanio = "Capitanio, M."}
158 @string{MCargill = "Cargill, M."}
159 @string{PCarl = "Carl, Philippe"}
160 @string{BACarnes = "Carnes, B. A."}
161 @string{JCarnes-Stine = "Carnes-Stine, J."}
162 @string{MCarrionVazquez = "Carrion-Vazquez, Mariano"}
163 @string{CCarter = "Carter, C."}
164 @string{ACarver = "Carver, A."}
165 @string{JJCatanese = "Catanese, J.~J."}
166 @string{PCaulk = "Caulk, P."}
167 @string{CCecconi = "Cecconi, Ciro"}
168 @string{ACenter = "Center, A."}
169 @string{CTChan = "Chan, C.~T."}
170 @string{HSChan = "Chan, H.~S."}
171 @string{AChand = "Chand, Ami"}
172 @string{IChandramouliswaran = "Chandramouliswaran, I."}
173 @string{CHChang = "Chang, Chung-Hung"}
174 @string{EChapman = "Chapman, Edwin R."}
175 @string{RCharlab = "Charlab, R."}
176 @string{KChaturvedi = "Chaturvedi, K."}
177 @string{AChauhan = "Chauhan, A."}
178 @string{VPChauhan = "Chauhan, V.~P."}
179 @string{CChauzy = "Chauzy, C."}
180 @string{SChe = "Che, Shunai"}
181 @string{CEC = "Chemical Engineering Communications"}
182 @string{CHEMREV = "Chemical reviews"}
183 @string{CHEM = "Chemistry (Weinheim an der Bergstrasse, Germany)"}
184 @string{CPC = "Chemphyschem"}
185 @string{HCChen = "Chen, H. C."}
186 @string{LChen = "Chen, L."}
187 @string{XNChen = "Chen, X. N."}
188 @string{XiChen = "Chen, Xinyong"}
189 @string{XuChen = "Chen, Xuming"}
190 @string{JFCheng = "Cheng, J. F."}
191 @string{MLCheng = "Cheng, M. L."}
192 @string{VGCheung = "Cheung, V. G."}
193 @string{YHChiang = "Chiang, Y. H."}
194 @string{AChinwalla = "Chinwalla, A."}
195 @string{FChow = "Chow, Flora"}
196 @string{JChoy = "Choy, Jason"}
197 @string{BChu = "Chu, Benjamin"}
198 @string{XChu = "Chu, Xueying"}
199 @string{TYChung = "Chung, Tse-Yu"}
200 @string{CLChyan = "Chyan, Chia-Lin"}
201 @string{GCiccotti = "Ciccotti, Giovanni"}
202 @string{JClaerbout = "Claerbout, Jon F."}
203 @string{AGClark = "Clark, A. G."}
204 @string{Clarke = "Clarke"}
205 @string{JClarke = "Clarke, Jane"}
206 @string{JClarkson = "Clarkson, John"}
207 @string{HClausen-Schaumann = "Clausen-Schaumann, H."}
208 @string{JMClaverie = "Claverie, J. M."}
209 @string{WWCleland = "Cleland, W.~W."}
210 @string{KClerc-Blankenburg = "Clerc-Blankenburg, K."}
211 @string{NJCobb = "Cobb, Nathan J."}
212 @string{GHCohen = "Cohen, G.~H."}
213 @string{FSCollins = "Collins, Francis S."}
214 @string{CUP = "Columbia University Press"}
215 @string{CPR = "Computer Physics Reports"}
216 @string{CSE = "Computing in Science \& Engineering"}
217 @string{UniProtConsort = "Consortium, The UniProt"}
218 @string{MConti = "Conti, Matteo"}
219 @string{CEP = "Control Engineering Practice"}
220 @string{GACoon = "Coon, G.~A."}
221 @string{PVCornish = "Cornish, Peter V."}
222 @string{MNCourel = "Courel, M. N."}
223 @string{GCowan = "Cowan, Glen"}
224 @string{DRCox = "Cox, D. R."}
225 @string{MCoyne = "Coyne, M."}
226 @string{DCraig = "Craig, David"}
227 @string{ACravchik = "Cravchik, A."}
228 @string{PSCremer = "Cremer, Paul S."}
229 @string{CCroarkin = "Croarkin, Carroll"}
230 @string{VCroquette = "Croquette, Vincent"}
231 @string{YCui = "Cui, Y."}
232 @string{COSB = "Current Opinion in Structural Biology"}
233 @string{COCB = "Current Opinion in Chemical Biology"}
234 @string{LCurry = "Curry, L."}
235 @string{CDahlke = "Dahlke, C."}
236 @string{FDahlquist = "Dahlquist, Frederick W."}
237 @string{PDalhaimer = "Dalhaimer, Paul"}
238 @string{SDanaher = "Danaher, S."}
239 @string{LDavenport = "Davenport, L."}
240 @string{MCDavies = "Davies, M.~C."}
241 @string{MDavis = "Davis, Matt"}
242 @string{SDecatur = "Decatur, Sean M."}
243 @string{WDeGrado = "DeGrado, William F."}
244 @string{PDebrunner = "Debrunner, P."}
245 @string{ADelcher = "Delcher, A."}
246 @string{WDeLorbe = "DeLorbe, William J."}
247 @string{BDelpech = "Delpech, B."}
248 @string{Demography = "Demography"}
249 @string{ZDeng = "Deng, Z."}
250 @string{RDesilets = "Desilets, R."}
251 @string{IDew = "Dew, I."}
252 @string{CDewhurst = "Dewhurst, Charles"}
253 @string{VDiFrancesco = "Di Francesco, V."}
254 @string{KDiemer = "Diemer, K."}
255 @string{GDietler = "Dietler, Giovanni"}
256 @string{HDietz = "Dietz, Hendrik"}
257 @string{SDietz = "Dietz, S."}
258 @string{EDijkstra = "Dijkstra, Edsger Wybe"}
259 @string{KADill = "Dill, K. A."}
260 @string{RDima = "Dima, Ruxandra I."}
261 @string{DDischer = "Discher, Dennis E."}
262 @string{KDixon = "Dixon, K."}
263 @string{KDodson = "Dodson, K."}
264 @string{NDoggett = "Doggett, N."}
265 @string{MDombroski = "Dombroski, M."}
266 @string{MDonnelly = "Donnelly, M."}
267 @string{DDonoho = "Donoho, David L."}
268 @string{CDornmair = "Dornmair, C."}
269 @string{MDors = "Dors, M."}
270 @string{LDougan = "Dougan, Lorna"}
271 @string{LDoup = "Doup, L."}
272 @string{BDrake = "Drake, B."}
273 @string{TDrobek = "Drobek, T."}
274 @string{Drexel = "Drexel University"}
275 @string{OKDudko = "Dudko, Olga K."}
276 @string{YFDufrene = "Dufr{\^e}ne, Yves F."}
277 @string{ADunham = "Dunham, A."}
278 @string{DDunlap = "Dunlap, D."}
279 @string{PDunn = "Dunn, P."}
280 @string{VDupres = "Dupres, Vincent"}
281 @string{HJDyson = "Dyson, H.~Jane"}
282 @string{EMBORep = "EMBO Rep"}
283 @string{EMBO = "EMBO Rep."}
284 @string{REckel = "Eckel, R."}
285 @string{KEilbeck = "Eilbeck, K."}
286 @string{MElbaum = "Elbaum, Michael"}
287 @string{E:NHPL = "Elsevier, North-Holland Personal Library"}
288 @string{DEly = "Ely, D."}
289 @string{SEmerling = "Emerling, S."}
290 @string{TEndo = "Endo, Toshiya"}
291 @string{SWEnglander = "Englander, S. Walter"}
292 @string{HErickson = "Erickson, Harold P."}
293 @string{MEsaki = "Esaki, Masatoshi"}
294 @string{SEsparham = "Esparham, S."}
295 @string{EBJ = "European biophysics journal: EBJ"}
296 @string{EJP = "European Journal of Physics"}
297 @string{EPL = "Europhysics Letters"}
298 @string{CEvangelista = "Evangelista, C."}
299 @string{CAEvans = "Evans, C. A."}
300 @string{EEvans = "Evans, E."}
301 @string{RSEvans = "Evans, R. S."}
302 @string{MEvstigneev = "Evstigneev, M."}
303 @string{DFasulo = "Fasulo, D."}
304 @string{FEBS = "FEBS letters"}
305 @string{XFei = "Fei, Xiaofang"}
306 @string{JFernandez = "Fernandez, Julio M."}
307 @string{SFerriera = "Ferriera, S."}
308 @string{AEFilippov = "Filippov, A. E."}
309 @string{LFinzi = "Finzi, L."}
310 @string{TEFisher = "Fisher, T. E."}
311 @string{MFlanigan = "Flanigan, M."}
312 @string{BFlannery = "Flannery, B."}
313 @string{LFlorea = "Florea, L."}
314 @string{ELFlorin = "Florin, Ernst-Ludwig"}
315 @string{FoldDes = "Fold Des"}
316 @string{NRForde = "Forde, Nancy R."}
317 @string{CFosler = "Fosler, C."}
318 @string{SFossey = "Fossey, S. A."}
319 @string{SFowler = "Fowler, Susan B."}
320 @string{GFranzen = "Franzen, Gereon"}
321 @string{SFreitag = "Freitag, S."}
322 @string{LFrench = "French, L."}
323 @string{RWFriddle = "Friddle, Raymond W."}
324 @string{CFriedman = "Friedman, C."}
325 @string{RFriedman = "Friedman, Ran"}
326 @string{MFritz = "Fritz, M."}
327 @string{HFuchs = "Fuchs, Harald"}
328 @string{TFujii = "Fujii, Tadashi"}
329 @string{HFujita = "Fujita, Hideaki"}
330 @string{AFujiyama = "Fujiyama, A."}
331 @string{RFulton = "Fulton, R."}
332 @string{TFunck = "Funck, Theodor"}
333 @string{TFurey = "Furey, T."}
334 @string{SFuruike = "Furuike, Shou"}
335 @string{GLGaborMiklos = "Gabor Miklos, G. L."}
336 @string{AEGabrielian = "Gabrielian, A. E."}
337 @string{WGan = "Gan, W."}
338 @string{DNGanchev = "Ganchev, Dragomir N."}
339 @string{MGao = "Gao, Mu"}
340 @string{DGarcia = "Garcia, D."}
341 @string{TGarcia = "Garcia, Tzintzuni"}
342 @string{NGarg = "Garg, N."}
343 @string{HEGaub = "Gaub, Hermann E."}
344 @string{MGautel = "Gautel, Mathias"}
345 @string{LAGavrilov = "Gavrilov, L. A."}
346 @string{NSGavrilova = "Gavrilova, N. S."}
347 @string{WGe = "Ge, W."}
348 @string{UGeisler = "Geisler, Ulrich"}
349 @string{GENE = "Gene"}
350 @string{CGerber = "Gerber, Christoph"}
351 @string{CGergely = "Gergely, C."}
352 @string{RGibbs = "Gibbs, R."}
353 @string{DGilbert = "Gilbert, D."}
354 @string{HGire = "Gire, H."}
355 @string{MGiuntini = "Giuntini, M."}
356 @string{SGlanowski = "Glanowski, S."}
357 @string{JGlaser = "Glaser, Jens"}
358 @string{KGlasser = "Glasser, K."}
359 @string{AGlodek = "Glodek, A."}
360 @string{GGloeckner = "Gloeckner, G."}
361 @string{AGluecksmann = "Gluecksmann, A."}
362 @string{JDGocayne = "Gocayne, J. D."}
363 @string{AGomezCasado = "Gomez-Casado, Alberto"}
364 @string{BGompertz = "Gompertz, Benjamin"}
365 @string{FGong = "Gong, F."}
366 @string{GordonBreach = "Gordon Breach Scientific Publishing Ltd."}
367 @string{MGorokhov = "Gorokhov, M."}
368 @string{JHGorrell = "Gorrell, J. H."}
369 @string{SAGould = "Gould, S.~A."}
370 @string{KGraham = "Graham, K."}
371 @string{HLGranzier = "Granzier, Henk L."}
372 @string{FGrater = "Gr{\"a}ter, Frauke"}
373 @string{EDGreen = "Green, E. D."}
374 @string{SGGregory = "Gregory, S. G."}
375 @string{BGropman = "Gropman, B."}
376 @string{CGrossman = "Grossman, C."}
377 @string{HGrubmuller = {Grubm\"uller, Helmut}}
378 @string{AGrutzner = {Gr\"utzner, Anika}}
379 @string{ZGu = "Gu, Z."}
380 @string{PGuan = "Guan, P."}
381 @string{RGuigo = "Guig\'o, R."}
382 @string{EJGumbel = "Gumbel, Emil Julius"}
383 @string{HJGuntherodt = "Guntherodt, Hans-Joachim"}
384 @string{NGuo = "Guo, N."}
385 @string{YGuo = "Guo, Yi"}
386 @string{MGutman = "Gutman, Menachem"}
387 @string{RTGuy = "Guy, Richard T."}
388 @string{PHanggi = {H\"anggi, Peter}}
389 @string{THa = "Ha, Taekjip"}
390 @string{JHaack = "Haack, Julie A."}
391 @string{SHaddock = "Haddock, Steven H.~D."}
392 @string{GHager = "Hager, Gabriele"}
393 @string{THagglund = "H{\"a}gglund, T."}
394 @string{RHajjar = "Hajjar, Roger J."}
395 @string{AHalpern = "Halpern, A."}
396 @string{KHalvorsen = "Halvorsen, Ken"}
397 @string{FHan = "Han, Fangpu"}
398 @string{CCHang = "Hang, C.~C."}
399 @string{SHannenhalli = "Hannenhalli, S."}
400 @string{HHansma = "Hansma, H. G."}
401 @string{PHansma = "Hansma, Paul K."}
402 @string{DHarbrecht = "Harbrecht, Douglas"}
403 @string{SHarper = "Harper, Sandy"}
404 @string{MHarris = "Harris, M."}
405 @string{BHart = "Hart, B."}
406 @string{DPHart = "Hart, D.P."}
407 @string{JWHatfield = "Hatfield, John William"}
408 @string{THatton = "Hatton, T."}
409 @string{MHattori = "Hattori, M."}
410 @string{DHaussler = "Haussler, D."}
411 @string{THawkins = "Hawkins, T."}
412 @string{CHaynes = "Haynes, C."}
413 @string{JHaynes = "Haynes, J."}
414 @string{WHeckl = "Heckl, W. M."}
415 @string{CVHeer = "Heer, C.~V."}
416 @string{JHeil = "Heil, J."}
417 @string{RHeilig = "Heilig, R."}
418 @string{TJHeiman = "Heiman, T. J."}
419 @string{CHeiner = "Heiner, C."}
420 @string{MHelmes = "Helmes, M."}
421 @string{JHemmerle = "Hemmerle, J."}
422 @string{SHenderson = "Henderson, S."}
423 @string{BHeymann = "Heymann, Berthold"}
424 @string{NHiaro = "Hiaro, N."}
425 @string{MEHiggins = "Higgins, M. E."}
426 @string{THilburn = "Hilburn, Thomas B."}
427 @string{LHillier = "Hillier, L."}
428 @string{HHinssen = "Hinssen, Horst"}
429 @string{PHinterdorfer = "Hinterdorfer, Peter"}
430 @string{HistochemJ = "Histochem J"}
431 @string{SHladun = "Hladun, S."}
432 @string{WKHo = "Ho, W.~K."}
433 @string{RHochstrasser = "Hochstrasser, Robin M."}
434 @string{CSHodges = "Hodges, C.~S."}
435 @string{CHoff = "Hoff, C."}
436 @string{WHoff = "Hoff, Wouter D."}
437 @string{JLHolden = "Holden, J. L."}
438 @string{RAHolt = "Holt, R. A."}
439 @string{GHofmann = "Hofmann, Gerd"}
440 @string{MHonda = "Honda, M."}
441 @string{NPCHong = "Hong, Neil P. Chue"}
442 @string{XHong = "Hong, Xia"}
443 @string{LHood = "Hood, L."}
444 @string{JHoover = "Hoover, J."}
445 @string{JHorber = "Horber, J. K. H."}
446 @string{HHosser = "Hosser, H."}
447 @string{DHostin = "Hostin, D."}
448 @string{JHouck = "Houck, J."}
449 @string{AHoumeida = "Houmeida, Ahmed"}
450 @string{JHoward = "Howard, J."}
451 @string{THowland = "Howland, T."}
452 @string{BHsiao = "Hsiao, Benjamin S."}
453 @string{CKHu = "Hu, Chin-Kun"}
454 @string{DLHu = "Hu, David L."}
455 @string{BHuang = "Huang, Baiqu"}
456 @string{HHuang = "Huang, Hector Han-Li"}
457 @string{MHubain = "Hubain, Maurice"}
458 @string{AJHudspeth = "Hudspeth, A.~J."}
459 @string{KHuff = "Huff, Katy"}
460 @string{JHughes = "Hughes, John"}
461 @string{GHummer = "Hummer, Gerhard"}
462 @string{SJHumphray = "Humphray, S. J."}
463 @string{WLHung = "Hung, Wen-Liang"}
464 @string{MHunkapiller = "Hunkapiller, M."}
465 @string{DHHuson = "Huson, D. H."}
466 @string{JHutter = "Hutter, Jeffrey L."}
467 @string{CHyeon = "Hyeon, Changbong"}
468 @string{IEEE:TIT = "IEEE Transactions on Information Theory"}
469 @string{IEEE:SPM = "IEEE Signal Processing Magazine"}
470 @string{CIbegwam = "Ibegwam, C."}
471 @string{JRIdol = "Idol, J. R."}
472 @string{SImprota = "Improta, S."}
473 @string{TInoue = "Inoue, Tadashi"}
474 @string{IJBMM = "International Journal of Biological Macromolecules"}
475 @string{IJCIS = "International Journal of Computer \& Information Sciences"}
476 @string{AItkin = "Itkin, Anna"}
477 @string{HItoh = "Itoh, Hiroyasu"}
478 @string{AIrback = "Irback, Anders"}
479 @string{AMIsaacs = "Isaacs, Adrian M."}
480 @string{BIsralewitz = "Isralewitz, B."}
481 @string{SIstrail = "Istrail, S."}
482 @string{MIvemeyer = "Ivemeyer, M."}
483 @string{DIzhaky = "Izhaky, David"}
484 @string{SIzrailev = "Izrailev, S."}
485 @string{TJahnke = "J{\"a}hnke, Torsten"}
486 @string{WJang = "Jang, W."}
487 @string{HJanovjak = "Janovjak, Harald"}
488 @string{LJanosi = "Janosi, Lorant"}
489 @string{AJanshoff = "Janshoff, Andreas"}
490 @string{JJAP = "Japanese Journal of Applied Physics"}
491 @string{MJaschke = "Jaschke, Manfred"}
492 @string{DJennings = "Jennings, D."}
493 @string{HFJi = "Ji, Hai-Feng"}
494 @string{RRJi = "Ji, R. R."}
495 @string{YJia = "Jia, Yiwei"}
496 @string{SJiang = "Jiang, Shaoyi"}
497 @string{XJiang = "Jiang, Xingqun"}
498 @string{DJohannsmann = "Johannsmann, Diethelm"}
499 @string{CJohnson = "Johnson, Colin P."}
500 @string{JJohnson = "Johnson, J."}
501 @string{AJollymore = "Jollymore, Ashlee"}
502 @string{REJones = "Jones, R.E."}
503 @string{SJones = "Jones, S."}
504 @string{CJordan = "Jordan, C."}
505 @string{JJordan = "Jordan, J."}
506 %string{JACS = "J Am Chem Soc"}
507 @string{JACS = "Journal of the American Chemical Society"}
508 @string{JASA = "Journal of the American Statistical Association"}
509 @string{JAP = "Journal of Applied Physics"}
510 @string{JBM = "J Biomech"}
511 @string{JBT = "J Biotechnol"}
512 @string{JCPPCB = "Journal de Chimie Physique et de Physico-Chimie Biologique"}
513 @string{JCS = "Journal of Cell Science"}
514 @string{JCompP = "Journal of Computational Physics"}
515 @string{JEChem = "Journal of Electroanalytical Chemistry"}
516 @string{JMathBiol = "J Math Biol"}
517 @string{JMicro = "Journal of Microscopy"}
518 @string{JPhysio = "Journal of Physiology"}
519 @string{JStructBiol = "Journal of Structural Biology"}
520 @string{JTB = "J Theor Biol"}
521 @string{JMB = "Journal of Molecular Biology"}
522 @string{JP:CM = "Journal of Physics: Condensed Matter"}
523 @string{JP:CON = "Journal of Physics: Conference Series"}
524 @string{JRNBS:C = "Journal of Research of the National Bureau of Standards. Section C: Engineering and Instrumentation"}
525 @string{WSJuang = "Juang, F.~S."}
526 @string{DAJuckett = "Juckett, D. A."}
527 @string{SRJun = "Jun, Se-Ran"}
528 @string{DKaftan = "Kaftan, David"}
529 @string{LKagan = "Kagan, L."}
530 @string{FKalush = "Kalush, F."}
531 @string{ELKaplan = "Kaplan, E. L."}
532 @string{RKapon = "Kapon, Ruti"}
533 @string{AKardinal = "Kardinal, Angelika"}
534 @string{BKarlak = "Karlak, B."}
535 @string{MKarplus = "Karplus, Martin"}
536 @string{MKarrenbach = "Karrenbach, Martin"}
537 @string{JKasha = "Kasha, J."}
538 @string{KKawasaki = "Kawasaki, K."}
539 @string{ZKe = "Ke, Z."}
540 @string{AKejariwal = "Kejariwal, A."}
541 @string{MSKellermayer = "Kellermayer, Mikl\'os S. Z."}
542 @string{TKempe = "Kempe, Thomas"}
543 @string{SKennedy = "Kennedy, S."}
544 @string{SBHKent = "Kent, Stephen B. H."}
545 @string{WJKent = "Kent, W. J."}
546 @string{KAKetchum = "Ketchum, K. A."}
547 @string{FKienberger = "Kienberger, Ferry"}
548 @string{SHKim = "Kim, Sung-Hou"}
549 @string{WKing = "King, William Trevor"}
550 @string{KKinosita = "{Kinosita Jr.}, Kazuhiko"}
551 @string{IRKirsch = "Kirsch, I. R."}
552 @string{JKlafter = "Klafter, J."}
553 @string{AKleiner = "Kleiner, Ariel"}
554 @string{DKlimov = "Klimov, Dmitri K."}
555 @string{LKline = "Kline, L."}
556 @string{LKlumb = "Klumb, L."}
557 @string{KAPPP = "Kluwer Academic Publishers--Plenum Publishers"}
558 @string{CDKodira = "Kodira, C. D."}
559 @string{SKoduru = "Koduru, S."}
560 @string{PKoehl = "Koehl, Patrice"}
561 @string{BKolmerer = "Kolmerer, B."}
562 @string{JKorenberg = "Korenberg, J."}
563 @string{IKosztin = "Kosztin, Ioan"}
564 @string{JKovacevic = "Kovacevic, Jelena"}
565 @string{CKraft = "Kraft, C."}
566 @string{HAKramers = "Kramers, H. A."}
567 @string{AKrammer = "Krammer, Andre"}
568 @string{SKravitz = "Kravitz, S."}
569 @string{HJKreuzer = {Kreuzer, Hans J\"urgen}}
570 @string{MMGKrishna = "Krishna, Mallela M. G."}
571 @string{KKroy = "Kroy, Klaus"}
572 @string{HHKu = "Ku, H.~H."}
573 @string{TAKucaba = "Kucaba, T. A."}
574 @string{Kucherlapati = "Kucherlapati"}
575 @string{JKudoh = "Kudoh, J."}
576 @string{MKuhn = "Kuhn, Michael"}
577 @string{MKulke = "Kulke, Michael"}
578 @string{CKwok = "Kwok, Carol H."}
579 @string{RLevy = "L\'evy, R"}
580 @string{DLabeit = "Labeit, Dietmar"}
581 @string{SLabeit = "Labeit, Siegfried"}
582 @string{DLabudde = "Labudde, Dirk"}
583 @string{SLahmers = "Lahmers, Sunshine"}
584 @string{ZLai = "Lai, Z."}
585 @string{CLam = "Lam, Canaan"}
586 @string{JLamb = "Lamb, Jonathan C."}
587 @string{LANG = "Langmuir"}
588 % "Langmuir : the ACS journal of surfaces and colloids",
589 @string{WLau = "Lau, Wai Leung"}
590 @string{RLaw = "Law, Richard"}
591 @string{BLazareva = "Lazareva, B."}
592 @string{MLeake = "Leake, Mark C."}
593 @string{ELee = "Lee, E."}
594 @string{HLee = "Lee, Haeshin"}
595 @string{SLee = "Lee, Sunyoung"}
596 @string{HLehmann = "Lehmann, H."}
597 @string{HLehrach = "Lehrach, H."}
598 @string{YLei = "Lei, Y."}
599 @string{PLelkes = "Lelkes, Peter I."}
600 @string{OLequin = "Lequin, Olivier"}
601 @string{CLethias = "Lethias, Claire"}
602 @string{SLeuba = "Leuba, Sanford H."}
603 @string{ALeung = "Leung, A."}
604 @string{MLeuschner = "Leuschner, Mirko"}
605 @string{AJLevine = "Levine, A. J."}
606 @string{CLevinthal = "Levinthal, Cyrus"}
607 @string{ALevitsky = "Levitsky, A."}
608 @string{SLevy = "Levy, S."}
609 @string{MLewis = "Lewis, M."}
610 @string{JLItalien = "L'Italien, James J."}
611 @string{BLi = "Li, Bing"}
612 @string{CYLi = "Li, Christopher Y."}
613 @string{HLi = "Li, Hongbin"}
614 @string{JLi = "Li, J."}
615 @string{LeLi = "Li, Lewyn"}
616 @string{LiLi = "Li, Lingyu"}
617 @string{MSLi = "Li, Mai Suan"}
618 @string{PWLi = "Li, P. W."}
619 @string{YLi = "Li, Yajun"}
620 @string{ZLi = "Li, Z."}
621 @string{YLiang = "Liang, Y."}
622 @string{GLiao = "Liao, George"}
623 @string{FCLin = "Lin, Fan-Chi"}
624 @string{JLin = "Lin, Jianhua"}
625 @string{SHLin = "Lin, Sheng-Hsien"}
626 @string{XLin = "Lin, X."}
627 @string{JLindahl = "Lindahl, Joakim"}
628 @string{SLindsay = "Lindsay, Stuart M."}
629 @string{WALinke = "Linke, Wolfgang A."}
630 @string{RLippert = "Lippert, R."}
631 @string{JLis = "Lis, John T."}
632 @string{RLiu = "Liu, Runcong"}
633 @string{WLiu = "Liu, W."}
634 @string{XLiu = "Liu, X."}
635 @string{YLiu = "Liu, Yichun"}
636 @string{LLivadaru = "Livadaru, L."}
637 @string{YSLo = "Lo, Yu-Shiu"}
638 @string{GLois = "Lois, Gregg"}
639 @string{JLopez = "Lopez, J."}
640 @string{LANL = "Los Alamos National Laboratory"}
641 @string{LAS = "Los Alamos Science"}
642 @string{ALove = "Love, A."}
643 @string{FLu = "Lu, F."}
644 @string{HLu = "Lu, Hui"}
645 @string{QLu = "Lu, Qinghua"}
646 @string{MLudwig = "Ludwig, Markus"}
647 @string{ZPLuo = "Luo, Zong-Ping"}
648 @string{ZLuthey-Schulten = "Luthey-Schulten, Z."}
649 @string{EMunck = {M\"unck, E.}}
650 @string{DMa = "Ma, D."}
651 @string{LMa = "Ma, Liang"}
652 @string{MMaaloum = "Maaloum, Mounir"}
653 @string{Macromol = "Macromolecules"}
654 @string{AMadan = "Madan, A."}
655 @string{VVMaduro = "Maduro, V. V."}
656 @string{CMaingonnat = "Maingonnat, C."}
657 @string{SMajid = "Majid, Sophia"}
658 @string{WMajoros = "Majoros, W."}
659 @string{DEMakarov = "Makarov, Dmitrii E."}
660 @string{RMamdani = "Mamdani, Reneeta"}
661 @string{SMammi = "Mammi, Stefano"}
662 @string{EMandello = "Mandello, Enrico"}
663 @string{GManderson = "Manderson, Gavin"}
664 @string{FMann = "Mann, F."}
665 @string{AMansson = "M{\aa}nsson, Alf"}
666 @string{ERMardis = "Mardis, E. R."}
667 @string{JMarion = "Marion, J."}
668 @string{JFMarko = "Marko, John F."}
669 @string{MMarra = "Marra, M."}
670 @string{PMarszalek = "Marszalek, Piotr E."}
671 @string{MMartin = "Martin, M. J."}
672 @string{YMartin = "Martin, Y."}
673 @string{HMassa = "Massa, H."}
674 @string{GAMatei = "Matei, G.~A."}
675 @string{DMaterassi = "Materassi, Donatello"}
676 @string{JMathe = "Math\'e, J\'er\^ome"}
677 @string{AMatouschek = "Matouschek, Andreas"}
678 @string{BMatthews = "Matthews, Brian W."}
679 @string{DMay = "May, D."}
680 @string{RMayer = "Mayer, Richard"}
681 @string{LMayne = "Mayne, Leland"}
682 @string{AMays = "Mays, A."}
683 @string{OTMcCann = "McCann, O. T."}
684 @string{SMcCawley = "McCawley, S."}
685 @string{JMcDaniel = "McDaniel, J."}
686 @string{JMcEntyre = "McEntyre, J."}
687 @string{McGraw-Hill = "McGraw-Hill"}
688 @string{TMcIntosh = "McIntosh, T."}
689 @string{VAMcKusick = "McKusick, V. A."}
690 @string{IMcMullen = "McMullen, I."}
691 @string{JDMcPherson = "McPherson, J. D."}
692 @string{TMeasey = "Measey, Thomas J."}
693 @string{MAD = "Mech Ageing Dev"}
694 @string{PMeier = "Meier, Paul"}
695 @string{AMeller = "Meller, Amit"}
696 @string{CCMello = "Mello, Cecilia C."}
697 @string{RMerkel = "Merkel, R."}
698 @string{GVMerkulov = "Merkulov, G. V."}
699 @string{FMerzel = "Merzel, Franci"}
700 @string{HMetiu = "Metiu, Horia"}
701 @string{NMetropolis = "Metropolis, Nicholas"}
702 @string{GMeyer = "Meyer, Gerhard"}
703 @string{HMi = "Mi, H."}
704 @string{LMiao = "Miao, Linlin"}
705 @string{CMicheletti = "Micheletti, Cristian"}
706 @string{MMickler = "Mickler, Moritz"}
707 @string{AMiller = "Miller, A."}
708 @string{NMilshina = "Milshina, N."}
709 @string{SMinoshima = "Minoshima, S."}
710 @string{IMitchell = "Mitchell, Ian"}
711 @string{SMitternacht = "Mitternacht, Simon"}
712 @string{NJMlot = "Mlot, Nathan J."}
713 @string{CMobarry = "Mobarry, C."}
714 @string{NMohandas = "Mohandas, N."}
715 @string{SMohanty = "Mohanty, Sandipan"}
716 @string{UMohideen = "Mohideen, U."}
717 @string{PJMohr = "Mohr, Peter J."}
718 @string{VMontana = "Montana, Vedrana"}
719 @string{LMontanaro = "Montanaro, Lucio"}
720 @string{LMontelius = "Montelius, Lars"}
721 @string{CMontemagno = "Montemagno, Carlo D."}
722 @string{KTMontgomery = "Montgomery, K. T."}
723 @string{HMMoore = "Moore, H. M."}
724 @string{MMorgan = "Morgan, Michael"}
725 @string{LMoy = "Moy, L."}
726 @string{MMoy = "Moy, M."}
727 @string{VMoy = "Moy, Vincent T."}
728 @string{SMukamel = "Mukamel, Shaul"}
729 @string{DJMuller = "M{\"u}ller, Daniel J."}
730 @string{PMundel = "Mundeol, P."}
731 @string{EMuneyuki = "Muneyuki, Eiro"}
732 @string{RJMural = "Mural, R. J."}
733 @string{BMurphy = "Murphy, B."}
734 @string{SMurphy = "Murphy, S."}
735 @string{AMuruganujan = "Muruganujan, A."}
736 @string{FMusiani = "Musiani, Francesco"}
737 @string{EWMyers = "Myers, E. W."}
738 @string{RMMyers = "Myers, R. M."}
739 @string{AMylonakis = "Mylonakis, Andreas"}
740 @string{ENachliel = "Nachliel, Esther"}
741 @string{JNadeau = "Nadeau, J."}
742 @string{AKNaik = "Naik, A. K."}
743 @string{NANO = "Nano letters"}
744 @string{NT = "Nanotechnology"}
745 @string{VANarayan = "Narayan, V. A."}
746 @string{ANarechania = "Narechania, A."}
747 @string{PNassoy = "Nassoy, P."}
748 @string{NBS = "National Bureau of Standards"}
749 @string{NAT = "Nature"}
750 @string{NSB = "Nature Structural Biology"}
751 @string{NSMB = "Nature Structural Molecular Biology"}
752 @string{NRMCB = "Nature Reviews Molecular Cell Biology"}
753 @string{SNaylor = "Naylor, S."}
754 @string{CNeagoe = "Neagoe, Ciprian"}
755 @string{BNeelam = "Neelam, B."}
756 @string{MNeitzert = "Neitzert, Marcus"}
757 @string{CNelson = "Nelson, C."}
758 @string{KNelson = "Nelson, K."}
759 @string{RRNetz = "Netz, R.~R."}
760 @string{NR = "Neurochemical research"}
761 @string{NEURON = "Neuron"}
762 @string{RNevo = "Nevo, Reinat"}
763 @string{NJP = "New Journal of Physics"}
764 @string{DBNewell = "Newell, David B."}
765 @string{MNewman = "Newman, M."}
766 @string{INewton = "Newton, Isaac"}
767 @string{SNg = "Ng, Sean P."}
768 @string{NNguyen = "Nguyen, N."}
769 @string{TNguyen = "Nguyen, T."}
770 @string{MNguyen-Duong = "Nguyen-Duong, M."}
771 @string{INicholls = "Nicholls, Ian A."}
772 @string{NNichols = "Nichols, N.~B."}
773 @string{SNie = "Nie, S."}
774 @string{MNodell = "Nodell, M."}
775 @string{AANoegel = "Noegel, Angelika A."}
776 @string{HNoji = "Noji, Hiroyuki"}
777 @string{RNome = "Nome, Rene A."}
778 @string{NNowak = "Nowak, N."}
779 @string{ANoy = "Noy, Aleksandr"}
780 @string{NAR = "Nucleic Acids Research"}
781 @string{JNummela = "Nummela, Jeremiah"}
782 @string{JNunes = "Nunes, Joao"}
783 @string{DNusskern = "Nusskern, D."}
784 @string{GNyakatura = "Nyakatura, G."}
785 @string{CSOHern = "O'Hern, Corey S."}
786 @string{YOberdorfer = {Oberd\"orfer, York}}
787 @string{AOberhauser = "Oberhauser, Andres F."}
788 @string{FOesterhelt = "Oesterhelt, Filipp"}
789 @string{TOhashi = "Ohashi, Tomoo"}
790 @string{BOhler = "Ohler, Benjamin"}
791 @string{PDOlmsted = "Olmsted, Peter D."}
792 @string{AOlsen = "Olsen, A."}
793 @string{SJOlshansky = "Olshansky, S. J."}
794 @string{POmling = {Omlink, P{\"a}r}}
795 @string{JNOnuchic = "Onuchic, J. N."}
796 @string{YOono = "Oono, Y."}
797 @string{GOppenheim = "Oppenheim, Georges"}
798 @string{COpitz = "Optiz, Christiane A."}
799 @string{KOroszlan = "Oroszlan, Krisztina"}
800 @string{EOroudjev = "Oroudjev, E."}
801 @string{KOsoegawa = "Osoegawa, K."}
802 @string{OUP = "Oxford University Press"}
803 @string{EPaci = "Paci, Emanuele"}
804 @string{SPan = "Pan, S."}
805 @string{HSPark = "Park, H. S."}
806 @string{VParpura = "Parpura, Vladimir"}
807 @string{APastore = "Pastore, A."}
808 @string{APatrinos = "Patrinos, Aristides"}
809 @string{FPavone = "Pavone, F. S."}
810 @string{SHPayne = "Payne, Stephen H."}
811 @string{JPeck = "Peck, J."}
812 @string{HPeng = "Peng, Haibo"}
813 @string{QPeng = "Peng, Qing"}
814 @string{RNPerham = "Perham, Richard N."}
815 @string{OPerisic = "Perisic, Ognjen"}
816 @string{CPeterson = "Peterson, Craig L."}
817 @string{MPeterson = "Peterson, M."}
818 @string{SMPeterson = "Peterson, Susan M."}
819 @string{CPfannkoch = "Pfannkoch, C."}
820 @string{PA = "Pfl{\"u}gers Archiv: European journal of physiology"}
821 @string{PTRSL = "Philosophical Transactions of the Royal Society of London"}
822 @string{PR:E = "Phys Rev E Stat Nonlin Soft Matter Phys"}
823 @string{PRL = "Physical Review Letters"}
824 %string{PRL = "Phys Rev Lett"}
825 @string{Physica = "Physica"}
826 @string{GPing = "Ping, Guanghui"}
827 @string{NPinotsis = "Pinotsis, Nikos"}
828 @string{MPlumbley = "Plumbley, Mark"}
829 @string{PLOS:ONE = "PLOS ONE"}
830 %string{PLOS:ONE = "Public Library of Science ONE"}
831 @string{PLOS:BIO = "PLOS Biology"}
832 @string{DPlunkett = "Plunkett, David"}
833 @string{PPodsiadlo = "Podsiadlo, Paul"}
834 @string{ASPolitou = "Politou, A. S."}
835 @string{APoustka = "Poustka, A."}
836 @string{CBPrater = "Prater, C.~B."}
837 @string{GPratesi = "Pratesi, G."}
838 @string{EPratts = "Pratts, E."}
839 @string{WPress = "Press, W."}
840 @string{PNAS = "Proceedings of the National Academy of Sciences of the
841 United States of America"}
842 @string{PBPMB = "Progress in Biophysics and Molecular Biology"}
843 @string{PS = "Protein Science"}
844 @string{PROT = "Proteins"}
845 @string{RSUP = "Published for the Royal Society at the University Press"}
846 @string{EPuchner = "Puchner, Elias M."}
847 @string{VPuri = "Puri, V."}
848 @string{WPyckhout-Hintzen = "Pyckhout-Hintzen, Wim"}
849 @string{HQin = "Qin, Haina"}
850 @string{SQin = "Qin, S."}
851 @string{SRQuake = "Quake, Stephen R."}
852 @string{CQuate = "Quate, Calvin F."}
853 @string{HQureshi = "Qureshi, H."}
854 @string{SERadford = "Radford, Sheena E."}
855 @string{MRadmacher = "Radmacher, M."}
856 @string{MRaible = "Raible, M."}
857 @string{LRamirez = "Ramirez, L."}
858 @string{JRamser = "Ramser, J."}
859 @string{LRandles = "Randles, Lucy G."}
860 @string{VRaussens = "Raussens, Vincent"}
861 @string{IRay = "Ray, I."}
862 @string{MReardon = "Reardon, M."}
863 @string{ALCReddin = "Reddin, Andrew L. C."}
864 @string{SRedick = "Redick, Sambra D."}
865 @string{ZReich = "Reich, Ziv"}
866 @string{TReid = "Reid, T."}
867 @string{PReimann = "Reimann, P."}
868 @string{KReinert = "Reinert, K."}
869 @string{RReinhardt = "Reinhardt, R."}
870 @string{KRemington = "Remington, K."}
871 @string{RMP = "Rev. Mod. Phys."}
872 @string{RSI = "Review of Scientific Instruments"}
873 @string{FRief = "Rief, Frederick"}
874 @string{MRief = "Rief, Matthias"}
875 @string{KRitchie = "Ritchie, K."}
876 @string{MRobbins = "Robbins, Mark O."}
877 @string{CJRoberts = "Roberts, C.~J."}
878 @string{RJRoberts = "Roberts, R. J."}
879 @string{RRobertson = "Robertson, Ragan B."}
880 @string{HRoder = "Roder, Heinrich"}
881 @string{RRodriguez = "Rodriguez, R."}
882 @string{YHRogers = "Rogers, Y. H."}
883 @string{SRogic = "Rogic, S."}
884 @string{MRoman = "Roman, Marisa B."}
885 @string{GRomano = "Romano, G."}
886 @string{DRomblad = "Romblad, D."}
887 @string{RRos = "Ros, Robert"}
888 @string{BRosenberg = "Rosenberg, B."}
889 @string{JRosengren = "Rosengren, Jenny P."}
890 @string{ARosenthal = "Rosenthal, A."}
891 @string{ARoters = "Roters, Andreas"}
892 @string{WRowe = "Rowe, W."}
893 @string{LRowen = "Rowen, L."}
894 @string{BRuhfel = "Ruhfel, B."}
895 @string{DBRusch = "Rusch, D. B."}
896 @string{JMRuysschaert = "Ruysschaert, Jean-Marie"}
897 @string{JPRyckaert = "Ryckaert, Jean-Paul"}
898 @string{NSakaki = "Sakaki, Naoyoshi"}
899 @string{YSakaki = "Sakaki, Y."}
900 @string{SSalzberg = "Salzberg, S."}
901 @string{BSamori = "Samor{\`i}, Bruno"}
902 @string{MSandal = "Sandal, Massimo"}
903 @string{RSanders = "Sanders, R."}
904 @string{ASarkar = "Sarkar, Atom"}
905 @string{TSasaki = "Sasaki, T."}
906 @string{SSato = "Sato, S."}
907 @string{TSato = "Sato, Takehiro"}
908 @string{PSchaaf = "Schaaf, P."}
909 @string{RSchafer = "Schafer, Rolf"}
910 @string{TESchafer = "Sch{\"a}fer, Tilman E."}
911 @string{NScherer = "Scherer, Norbert F."}
912 @string{SScherer = "Scherer, S."}
913 @string{MSchilhabel = "Schilhabel, M."}
914 @string{HSchillers = "Schillers, Hermann"}
915 @string{BSchlegelberger = "Schlegelberger, B."}
916 @string{MSchleicher = "Schleicher, Michael"}
917 @string{MSchlierf = "Schlierf, Michael"}
918 @string{JSchmidt = "Schmidt, Jacob J."}
919 @string{LSchmitt = "Schmitt, Lutz"}
920 @string{JSchmutz = "Schmutz, J."}
921 @string{GSchuler = "Schuler, G."}
922 @string{GDSchuler = "Schuler, G. D."}
923 @string{KSchulten = "Schulten, Klaus"}
924 @string{ZSchulten = "Schulten, Zan"}
925 @string{MSchwab = "Schwab, M."}
926 @string{ISchwaiger = "Schwaiger, Ingo"}
927 @string{RSchwartz = "Schwartz, R."}
928 @string{RSchweitzerStenner = "Scheitzer-Stenner, Reinhard"}
929 @string{SCI = "Science"}
930 @string{CEScott = "Scott, C. E."}
931 @string{JScott = "Scott, J."}
932 @string{RScott = "Scott, R."}
933 @string{USeifert = "Seifert, Udo"}
934 @string{SKSekatskii = "Sekatskii, Sergey K."}
935 @string{MSekhon = "Sekhon, M."}
936 @string{TSekiguchi = "Sekiguchi, T."}
937 @string{BSenger = "Senger, B."}
938 @string{DBSenn = "Senn, David B."}
939 @string{PSeranski = "Seranski, P."}
940 @string{RSesboue = {Sesbo\"u\'e, R.}}
941 @string{EShakhnovich = "Shakhnovich, Eugene"}
942 @string{GShan = "Shan, Guiye"}
943 @string{JShang = "Shang, J."}
944 @string{WShao = "Shao, W."}
945 @string{DSharma = "Sharma, Deepak"}
946 @string{YJSheng = "Sheng, Yu-Jane"}
947 @string{KShibuya = "Shibuya, K."}
948 @string{JShillcock = "Shillcock, Julian"}
949 @string{AShimizu = "Shimizu, A."}
950 @string{NShimizu = "Shimizu, N."}
951 @string{RShimoKon = "Shimo-Kon, Rieko"}
952 @string{JPShine = "Shine, James P."}
953 @string{AShintani = "Shintani, A."}
954 @string{BShneiderman = "Shneiderman, Ben"}
955 @string{BShue = "Shue, B."}
956 @string{RSiebert = "Siebert, R."}
957 @string{EDSiggia = "Siggia, Eric D."}
958 @string{MSimon = "Simon, M."}
959 @string{MSimpson = "Simpson, M."}
960 @string{GESims = "Sims, Gregory E."}
961 @string{CSitter = "Sitter, C."}
962 @string{KVSjolander = "Sjolander, K. V."}
963 @string{MSkupski = "Skupski, M."}
964 @string{CSlayman = "Slayman, C."}
965 @string{MSmallwood = "Smallwood, M."}
966 @string{CSmith = "Smith, Corey L."}
967 @string{DASmith = "Smith, D. Alastair"}
968 @string{HOSmith = "Smith, H. O."}
969 @string{KBSmith = "Smith, Kathryn B."}
970 @string{SSmith = "Smith, S."}
971 @string{SBSmith = "Smith, S. B."}
972 @string{TSmith = "Smith, T."}
973 @string{JSoares = "Soares, J."}
974 @string{NDSocci = "Socci, N. D."}
975 @string{SEG = "Society of Exploration Geophysicists"}
976 @string{ESodergren = "Sodergren, E."}
977 @string{CSoderlund = "Soderlund, C."}
978 @string{JSong = "Song, Jianxing"}
979 @string{JSpanier = "Spanier, Jonathan E."}
980 @string{DSpeicher = "Speicher, David W."}
981 @string{GSpier = "Spier, G."}
982 @string{ASprague = "Sprague, A."}
983 @string{SPRINGER = "Springer Science + Business Media, LLC"}
984 @string{DBStaple = "Staple, Douglas B."}
985 @string{RStark = "Stark, R. W."}
986 @string{PSStayton = "Stayton, P. S."}
987 @string{REStenkamp = "Stenkamp, R. E."}
988 @string{SStepaniants = "Stepaniants, S."}
989 @string{EStewart = "Stewart, E."}
990 @string{MRStockmeier = "Stockmeier, M. R."}
991 @string{TStockwell = "Stockwell, T."}
992 @string{NEStone = "Stone, N. E."}
993 @string{AStout = "Stout, A."}
994 @string{TRStrick = "Strick, T. R."}
995 @string{CStroh = "Stroh, Cordula"}
996 @string{RStrong = "Strong, R."}
997 @string{JStruckmeier = "Struckmeier, Jens"}
998 @string{STR = "Structure"}
999 @string{TStrunz = "Strunz, Torsten"}
1000 @string{MSu = "Su, Meihong"}
1001 @string{GSubramanian = "Subramanian, G."}
1002 @string{ESuh = "Suh, E."}
1003 @string{JSun = "Sun, J."}
1004 @string{YLSun = "Sun, Yu-Long"}
1005 @string{MSundberg = "Sundberg, Mark"}
1006 @string{WSundquist = "Sundquist, Wesley I."}
1007 @string{KSurewicz = "Surewicz, Krystyna"}
1008 @string{WKSurewicz = "Surewicz, Witold K."}
1009 @string{GGSutton = "Sutton, G. G."}
1010 @string{ASzabo = "Szabo, Attila"}
1011 @string{STagerud = "T{\aa}gerud, Sven"}
1012 @string{PTabor = "Tabor, P."}
1013 @string{ATakahashi = "Takahashi, Akiri"}
1014 @string{DTalaga = "Talaga, David S."}
1015 @string{PTalkner = "Talkner, Peter"}
1016 @string{RTampe = "Tamp{\'e}, Robert"}
1017 @string{JTang = "Tang, Jianyong"}
1018 @string{PTavan = "Tavan, P."}
1019 @string{BNTaylor = "Taylor, Barry N."}
1020 @string{THEMath = "Technische Hogeschool Eindhoven, Nederland,
1021 Onderafdeling der Wiskunde"}
1022 @string{SJBTendler = "Tendler, S.~J.~B."}
1023 @string{ITessari = "Tessari, Isabella"}
1024 @string{STeukolsky = "Teukolsky, S."}
1025 @string{CJ = "The Computer Journal"}
1026 @string{JBC = "The Journal of Biological Chemistry"}
1027 @string{JCP = "The Journal of Chemical Physics"}
1028 @string{JPC:B = "The Journal of Physical Chemistry B"}
1029 @string{JPC:C = "The Journal of Physical Chemistry C"}
1030 @string{RS = "The Royal Society"}
1031 @string{DThirumalai = "Thirumalai, Devarajan"}
1032 @string{PDThomas = "Thomas, P. D."}
1033 @string{RThomas = "Thomas, R."}
1034 @string{JThompson = "Thompson, J. B."}
1035 @string{EJThoreson = "Thoreson, E.~J."}
1036 @string{SThornton = "Thornton, S."}
1037 @string{RWTillmann = "Tillmann, R.~W."}
1038 @string{NNTint = "Tint, N. N."}
1039 @string{BTiribilli = "Tiribilli, Bruno"}
1040 @string{TTlusty = "Tlusty, Tsvi"}
1041 @string{PTobias = "Tobias, Paul"}
1042 @string{JTocaHerrera = "Toca-Herrera, Jose L."}
1043 @string{CATovey = "Tovey, Craig A."}
1044 @string{AToyoda = "Toyoda, A."}
1045 @string{TASME = "Transactions of the American Society of Mechanical Engineers"}
1046 @string{BTrask = "Trask, B."}
1047 @string{TBI = "Tribology International"}
1048 @string{JTrinick = "Trinick, John"}
1049 @string{KTrombitas = "Trombit\'as, K."}
1050 @string{ILTrong = "Trong, I. Le"}
1051 @string{CHTsai = "Tsai, Chih-Hui"}
1052 @string{HKTsao = "Tsao, Heng-Kwong"}
1053 @string{STse = "Tse, S."}
1054 @string{ZTshiprut = "Tshiprut, Z."}
1055 @string{JCMTsibris = "Tsibris, J.C.M."}
1056 @string{LTskhovrebova = "Tskhovrebova, Larissa"}
1057 @string{HWTurnbull = "Turnbull, Herbert Westren"}
1058 @string{RTurner = "Turner, R."}
1059 @string{AUlman = "Ulman, Abraham"}
1060 @string{UltraMic = "Ultramicroscopy"}
1061 @string{UIP:Urbana = "University of Illinois Press, Urbana"}
1062 @string{UTMB = "University of Texas Medical Branch"}
1063 @string{MUrbakh = "Urbakh, M."}
1064 @string{FValle = "Valle, Francesco"}
1065 @string{KJVanVliet = "Van Vliet, Krystyn J."}
1066 @string{PVandewalle = "Vandewalle, Patrick"}
1067 @string{CVech = "Vech, C."}
1068 @string{OVelasquez = "Velasquez, O."}
1069 @string{EVenter = "Venter, E."}
1070 @string{JCVenter = "Venter, J. C."}
1071 @string{PHVerdier = "Verdier, Peter H."}
1072 @string{IVetter = "Vetter, Ingrid R."}
1073 @string{MVetterli = "Vetterli, Martin"}
1074 @string{WVetterling = "Vetterling, W."}
1075 @string{MViani = "Viani, Mario B."}
1076 @string{JCVoegel = "Voegel, J.-C."}
1077 @string{VVogel = "Vogel, Viola"}
1078 @string{CWagner-McPherson = "Wagner-McPherson, C."}
1079 @string{RWahl = "Wahl, Reiner"}
1080 @string{TAWaigh = "Waigh, Thomas A."}
1081 @string{BWalenz = "Walenz, B."}
1082 @string{JWallis = "Wallis, J."}
1083 @string{KWalther = "Walther, Kirstin A."}
1084 @string{AJWalton = "Walton, Alan J"}
1085 @string{EBWalton = "Walton, Emily B."}
1086 @string{AWang = "Wang, A."}
1087 @string{FSWang = "Wang, F.~S."}
1088 @string{GWang = "Wang, G."}
1089 @string{JWang = "Wang, J."}
1090 @string{MWang = "Wang, M."}
1091 @string{MDWang = "Wang, Michelle D."}
1092 @string{SWang = "Wang, Shuang"}
1093 @string{XWang = "Wang, X."}
1094 @string{ZWang = "Wang, Z."}
1095 @string{HWatanabe = "Watanabe, Hiroshi"}
1096 @string{KWatanabe = "Watanabe, Kaori"}
1097 @string{RHWaterston = "Waterston, R. H."}
1098 @string{BWaugh = "Waugh, Ben"}
1099 @string{JWegiel = "Wegiel, J."}
1100 @string{MWei = "Wei, M."}
1101 @string{YWei = "Wei, Yen"}
1102 @string{ALWeisenhorn = "Weisenhorn, A.~L."}
1103 @string{JWeissenbach = "Weissenbach, J."}
1104 @string{BLWelch = "Welch, Bernard Lewis"}
1105 @string{GWen = "Wen, G."}
1106 @string{MWen = "Wen, M."}
1107 @string{JWetter = "Wetter, J."}
1108 @string{EPWhite = "White, Ethan P."}
1109 @string{ANWhitehead = "Whitehead, Alfred North"}
1110 @string{AWhittaker = "Whittaker, A."}
1111 @string{HKWickramasinghe = "Wickramasinghe, H. K."}
1112 @string{RWides = "Wides, R."}
1113 @string{AWiita = "Wiita, Arun P."}
1114 @string{MWilchek = "Wilchek, Meir"}
1115 @string{AWilcox = "Wilcox, Alexander J."}
1116 @string{Williams = "Williams"}
1117 @string{CCWilliams = "Williams, C. C."}
1118 @string{MWilliams = "Williams, M."}
1119 @string{SWilliams = "Williams, S."}
1120 @string{WN = "Williams \& Norgate"}
1121 @string{MWilmanns = "Wilmanns, Matthias"}
1122 @string{GWilson = "Wilson, Greg"}
1123 @string{PWilson = "Wilson, Paul"}
1124 @string{RKWilson = "Wilson, R. K."}
1125 @string{SWilson = "Wilson, Scott"}
1126 @string{SWindsor = "Windsor, S."}
1127 @string{EWinn-Deen = "Winn-Deen, E."}
1128 @string{NWirth = "Wirth, Niklaus"}
1129 @string{HMWisniewski = "Wisniewski, H.~M."}
1130 @string{CWitt = "Witt, Christian"}
1131 @string{KWolfe = "Wolfe, K."}
1132 @string{TGWolfsberg = "Wolfsberg, T. G."}
1133 @string{PGWolynes = "Wolynes, P. G."}
1134 @string{WPWong = "Wong, Wesley P."}
1135 @string{TWoodage = "Woodage, T."}
1136 @string{GRWoodcock = "Woodcock, Glenna R."}
1137 @string{JRWortman = "Wortman, J. R."}
1138 @string{PEWright = "Wright, Peter E."}
1139 @string{DWu = "Wu, D."}
1140 @string{GAWu = "Wu, Guohong A."}
1141 @string{JWWu = "Wu, Jong-Wuu"}
1142 @string{MWu = "Wu, M."}
1143 @string{YWu = "Wu, Yiming"}
1144 @string{GJLWuite = "Wuite, Gijs J. L."}
1145 @string{KWylie = "Wylie, K."}
1146 @string{JXi = "Xi, Jun"}
1147 @string{AXia = "Xia, A."}
1148 @string{CXiao = "Xiao, C."}
1149 @string{SXiao = "Xiao, Senbo"}
1150 @string{TYada = "Yada, T."}
1151 @string{CYan = "Yan, C."}
1152 @string{MYandell = "Yandell, M."}
1153 @string{GYang = "Yang, Guoliang"}
1154 @string{YYang = "Yang, Yao"}
1155 @string{BAYankner = "Yankner, Bruce A."}
1156 @string{AYao = "Yao, A."}
1157 @string{RYasuda = "Yaduso, Ryohei"}
1158 @string{JYe = "Ye, J."}
1159 @string{RYeh = "Yeh, Richard C."}
1160 @string{RYonescu = "Yonescu, R."}
1161 @string{SYooseph = "Yooseph, S."}
1162 @string{MYoshida = "Yoshida, Masasuke"}
1163 @string{WYu = "Yu, Weichang"}
1164 @string{JMYuan = "Yuan, Jian-Min"}
1165 @string{MYuan = "Yuan, Menglan"}
1166 @string{AZandieh = "Zandieh, A."}
1167 @string{JZaveri = "Zaveri, J."}
1168 @string{KZaveri = "Zaveri, K."}
1169 @string{MZhan = "Zhan, M."}
1170 @string{HZhang = "Zhang, H."}
1171 @string{JZhang = "Zhang, J."}
1172 @string{QZhang = "Zhang, Q."}
1173 @string{WZhang = "Zhang, W."}
1174 @string{YZhang = "Zhang, Yanjie"}
1175 @string{ZZhang = "Zhang, Zongtao"}
1176 @string{JZhao = "Zhao, Jason Ming"}
1177 @string{LZhao = "Zhao, Liming"}
1178 @string{QZhao = "Zhao, Q."}
1179 @string{SZhao = "Zhao, S."}
1180 @string{LZheng = "Zheng, L."}
1181 @string{XHZheng = "Zheng, X. H."}
1182 @string{FZhong = "Zhong, F."}
1183 @string{MZhong = "Zhong, Mingya"}
1184 @string{WZhong = "Zhong, W."}
1185 @string{HXZhou = "Zhou, Huan-Xiang"}
1186 @string{SZhu = "Zhu, S."}
1187 @string{XZhu = "Zhu, X."}
1188 @string{YJZhu = "Zhu, Ying-Jie"}
1189 @string{WZhuang = "Zhuang, Wei"}
1190 @string{JZidar = "Zidar, Jernej"}
1191 @string{JZiegler = "Ziegler, J.G."}
1192 @string{NZinder = "Zinder, N."}
1193 @string{RCZinober = "Zinober, Rebecca C."}
1194 @string{JZlatanova = "Zlatanova, Jordanka"}
1195 @string{PZou = "Zou, Peng"}
1196 @string{GZuccheri = "Zuccheri, Giampaolo"}
1197 @string{RZwanzig = "Zwanzig, R."}
1198 @string{arXiv = "arXiv"}
1199 @string{PGdeGennes = "de Gennes, P. G."}
1200 @string{PJdeJong = "de Jong, P. J."}
1201 @string{NGvanKampen = "van Kampen, N.G."}
1202 @string{NIST:SEMATECH = "{NIST/SEMATECH}"}
1203 @string{EDCola = "{\uppercase{d}}i Cola, Emanuela"}
1205 @inbook{ NIST:chi-square,
1206 crossref = {NIST:ESH},
1207 chapter = {1.3.5.15: Chi-Square Goodness-of-Fit Test},
1211 url = {http://www.itl.nist.gov/div898/handbook/eda/section3/eda35f.htm},
1214 @inbook{ NIST:gumbel,
1215 crossref = {NIST:ESH},
1216 chapter = {1.3.6.6.16: Extreme Value Type {I} Distribution},
1220 url = {http://www.itl.nist.gov/div898/handbook/eda/section3/eda366g.htm},
1224 editor = CCroarkin #" and "# PTobias,
1225 author = NIST:SEMATECH,
1226 title = {e-{H}andbook of Statistical Methods},
1229 publisher = NIST:SEMATECH,
1230 address = {Boulder, Colorado},
1231 url = {http://www.itl.nist.gov/div898/handbook/},
1232 note = {This manual was developed from seed material produced by
1236 @misc{ wikipedia:gumbel,
1237 author = "Wikipedia",
1238 title = "Gumbel distribution --- {W}ikipedia{,} The Free Encyclopedia",
1240 url = "http://en.wikipedia.org/wiki/Gumbel_distribution",
1245 title = "Statistics of Extremes",
1248 address = "New York",
1249 note = "TODO: read",
1252 @misc{ wikipedia:GEV,
1253 author = "Wikipedia",
1254 title = "Generalized extreme value distribution --- {W}ikipedia{,}
1255 The Free Encyclopedia",
1257 url = "http://en.wikipedia.org/wiki/Generalized_extreme_value_distribution",
1260 @misc{ wikipedia:gompertz,
1261 author = "Wikipedia",
1262 title = "Gompertz distribution --- {W}ikipedia{,} The Free Encyclopedia",
1264 url = "http://en.wikipedia.org/wiki/Gompertz_distribution",
1267 @misc{ wikipedia:gumbel-t1,
1268 author = "Wikipedia",
1269 title = "Type-1 Gumbel distribution --- {W}ikipedia{,} The Free
1272 url = "http://en.wikipedia.org/wiki/Type-1_Gumbel_distribution",
1275 @misc{ wikipedia:gumbel-t2,
1276 author = "Wikipedia",
1277 title = "Type-2 Gumbel distribution --- {W}ikipedia{,} The Free
1280 url = "http://en.wikipedia.org/wiki/Type-2_Gumbel_distribution",
1283 @article { allemand03,
1284 author = JFAllemand #" and "# DBensimon #" and "# VCroquette,
1285 title = "Stretching {DNA} and {RNA} to probe their interactions with
1294 keywords = "DNA;DNA-Binding
1295 Proteins;Isomerases;Micromanipulation;Microscopy, Atomic Force;Nucleic
1296 Acid Conformation;Nucleotidyltransferases",
1297 abstract = "When interacting with a single stretched DNA, many proteins
1298 modify its end-to-end distance. This distance can be monitored in real
1299 time using various micromanipulation techniques that were initially
1300 used to determine the elastic properties of bare nucleic acids and
1301 their mechanically induced structural transitions. These methods are
1302 currently being applied to the study of DNA enzymes such as DNA and RNA
1303 polymerases, topoisomerases and structural proteins such as RecA. They
1304 permit the measurement of the probability distributions of the rate,
1305 processivity, on-time, affinity and efficiency for a large variety of
1306 DNA-based molecular motors."
1310 author = RAlon #" and "# EABayer #" and "# MWilchek,
1311 title = "Streptavidin contains an {RYD} sequence which mimics the {RGD}
1312 receptor domain of fibronectin",
1319 pages = "1236--1241",
1321 doi = "DOI: 10.1016/0006-291X(90)90526-S",
1322 url = "http://www.sciencedirect.com/science/article/B6WBK-
1323 4F5M7K3-3C/2/c94b612e06efc8534ee24bb1da889811",
1324 keywords = "Amino Acid Sequence;Animals;Bacterial Proteins;Binding
1325 Sites;Cell Line;Cell Membrane;Cricetinae;Fibronectins;Molecular
1326 Sequence Data;Streptavidin",
1327 abstract = "Streptavidin binds at low levels and high affinity to cell
1328 surfaces, the cause of which can be traced to the occurrence of a
1329 sequence containing RYD (Arg-Tyr-Asp) in the protein molecule. This
1330 binding is enhanced in the presence of biotin. Cell-bound streptavidin
1331 can be displaced by fibronectin, as well as by RGD- and RYD-containing
1332 peptides. In addition, streptavidin can displace fibronectin from cell
1333 surfaces. The RYD sequence of streptavidin thus mimics RGD (Arg-Gly-
1334 Asp), the universal recognition domain present in fibronectin and other
1335 adhesion-related molecules. The observed adhesion to cells has no
1336 relevance to biotin-binding since the RYD sequence is not part of the
1337 biotin-binding site of streptavidin. Since the use of streptavidin in
1338 avidin-biotin technology is based on its biotin-binding properties,
1339 researchers are hereby warned against its indiscriminate use in
1340 histochemical and cytochemical studies.",
1341 note = "Biological role of streptavidin."
1344 @article { balsera97,
1345 author = MBalsera #" and "# SStepaniants #" and "# SIzrailev #" and "#
1346 YOono #" and "# KSchulten,
1347 title = "Reconstructing potential energy functions from simulated force-
1348 induced unbinding processes",
1354 pages = "1281--1287",
1356 eprint = "http://www.biophysj.org/cgi/reprint/73/3/1281.pdf",
1357 url = "http://www.biophysj.org/cgi/content/abstract/73/3/1281",
1358 keywords = "Binding Sites;Biopolymers;Kinetics;Ligands;Microscopy, Atomic
1359 Force;Models, Chemical;Molecular Conformation;Protein
1360 Conformation;Proteins;Reproducibility of Results;Stochastic
1361 Processes;Thermodynamics",
1362 abstract = "One-dimensional stochastic models demonstrate that molecular
1363 dynamics simulations of a few nanoseconds can be used to reconstruct
1364 the essential features of the binding potential of macromolecules. This
1365 can be accomplished by inducing the unbinding with the help of external
1366 forces applied to the molecules, and discounting the irreversible work
1367 performed on the system by these forces. The fluctuation-dissipation
1368 theorem sets a fundamental limit on the precision with which the
1369 binding potential can be reconstructed by this method. The uncertainty
1370 in the resulting potential is linearly proportional to the irreversible
1371 component of work performed on the system during the simulation. These
1372 results provide an a priori estimate of the energy barriers observable
1373 in molecular dynamics simulations."
1376 @article { baneyx02,
1377 author = GBaneyx #" and "# LBaugh #" and "# VVogel,
1378 title = "Supramolecular Chemistry And Self-assembly Special Feature:
1379 Fibronectin extension and unfolding within cell matrix fibrils
1380 controlled by cytoskeletal tension",
1385 pages = "5139--5143",
1386 doi = "10.1073/pnas.072650799",
1387 eprint = "http://www.pnas.org/cgi/reprint/99/8/5139.pdf",
1388 url = "http://www.pnas.org/cgi/content/abstract/99/8/5139",
1389 abstract = "Evidence is emerging that mechanical stretching can alter the
1390 functional states of proteins. Fibronectin (Fn) is a large,
1391 extracellular matrix protein that is assembled by cells into elastic
1392 fibrils and subjected to contractile forces. Assembly into fibrils
1393 coincides with expression of biological recognition sites that are
1394 buried in Fn's soluble state. To investigate how supramolecular
1395 assembly of Fn into fibrillar matrix enables cells to mechanically
1396 regulate its structure, we used fluorescence resonance energy transfer
1397 (FRET) as an indicator of Fn conformation in the fibrillar matrix of
1398 NIH 3T3 fibroblasts. Fn was randomly labeled on amine residues with
1399 donor fluorophores and site-specifically labeled on cysteine residues
1400 in modules FnIII7 and FnIII15 with acceptor fluorophores.
1401 Intramolecular FRET was correlated with known structural changes of Fn
1402 in denaturing solution, then applied in cell culture as an indicator of
1403 Fn conformation within the matrix fibrils of NIH 3T3 fibroblasts. Based
1404 on the level of FRET, Fn in many fibrils was stretched by cells so that
1405 its dimer arms were extended and at least one FnIII module unfolded.
1406 When cytoskeletal tension was disrupted using cytochalasin D, FRET
1407 increased, indicating refolding of Fn within fibrils. These results
1408 suggest that cell-generated force is required to maintain Fn in
1409 partially unfolded conformations. The results support a model of Fn
1410 fibril elasticity based on unraveling and refolding of FnIII modules.
1411 We also observed variation of FRET between and along single fibrils,
1412 indicating variation in the degree of unfolding of Fn in fibrils.
1413 Molecular mechanisms by which mechanical force can alter the structure
1414 of Fn, converting tensile forces into biochemical cues, are discussed."
1417 @article { basche01,
1418 author = TBasche #" and "# SNie #" and "# JFernandez,
1419 title = "Single molecules",
1424 pages = "10527--10528",
1425 doi = "10.1073/pnas.191365898",
1426 eprint = "http://www.pnas.org/cgi/reprint/98/19/10527.pdf",
1427 url = "http://www.pnas.org/cgi/content/abstract/98/19/10527",
1428 note = "Mini summary of single-molecule techniques and look to future.
1429 Focuses on AFM, but mentions others."
1432 @article { bechhoefer02,
1433 author = JBechhoefer #" and "# SWilson,
1434 title = "Faster, cheaper, safer optical tweezers for the undergraduate
1443 doi = "10.1119/1.1445403",
1444 url = "http://link.aip.org/link/?AJP/70/393/1",
1445 keywords = "student experiments; safety; radiation pressure; laser beam
1447 note = {Good discussion of the effect of correlation time on
1448 calibration. References work on deconvolving thermal noise from
1449 other noise\citep{cowan98}. Excellent detail on power spectrum
1450 derivation and thermal noise for extremely overdamped
1451 oscillators in Appendix A (references \citet{rief65}), except
1452 that their equation A12 is missing a factor of $1/\pi$. I
1453 pointed this out to John Bechhoefer and he confirmed the
1455 project = "Cantilever Calibration"
1458 @article{ berg-sorensen05,
1459 author = KBergSorensen #" and "# HFlyvbjerg,
1460 title = {The colour of thermal noise in classical Brownian motion: a
1461 feasibility study of direct experimental observation},
1469 doi = {10.1088/1367-2630/7/1/038},
1470 url = {http://stacks.iop.org/1367-2630/7/i=1/a=038},
1471 eprint = {http://iopscience.iop.org/1367-2630/7/1/038/pdf/1367-2630_7_1_038.pdf},
1472 abstract = {One hundred years after Einstein modelled Brownian
1473 motion, a central aspect of this motion in incompressible fluids
1474 has not been verified experimentally: the thermal noise that
1475 drives the Brownian particle, is not white, as in Einstein's
1476 simple theory. It is slightly coloured, due to hydrodynamics and
1477 the fluctuation--dissipation theorem. This theoretical result from
1478 the 1970s was prompted by computer simulation results in apparent
1479 violation of Einstein's theory. We discuss how a direct
1480 experimental observation of this colour might be carried out by
1481 using optical tweezers to separate the thermal noise from the
1482 particle's dynamic response to it. Since the thermal noise is
1483 almost white, very good statistics is necessary to resolve its
1484 colour. That requires stable equipment and long recording times,
1485 possibly making this experiment one for the future only. We give
1486 results for experimental requirements and for stochastic errors as
1487 functions of experimental window and measurement time, and discuss
1488 some potential sources of systematic errors.},
1491 @article { bedard08,
1492 author = SBedard #" and "# MMGKrishna #" and "# LMayne #" and "#
1494 title = "Protein folding: Independent unrelated pathways or predetermined
1495 pathway with optional errors.",
1502 pages = "7182--7187",
1504 doi = "10.1073/pnas.0801864105",
1505 eprint = "http://www.pnas.org/content/105/20/7182.full.pdf",
1506 url = "http://www.pnas.org/content/105/20/7182.full",
1507 keywords = "Biochemistry;Guanidine;Kinetics;Micrococcal Nuclease;Models,
1508 Biological;Models, Chemical;Models, Theoretical;Protein
1509 Conformation;Protein Denaturation;Protein Folding;Protein Structure,
1510 Secondary;Proteins;Proteomics;Reproducibility of
1511 Results;Thermodynamics",
1512 abstract = "The observation of heterogeneous protein folding kinetics has
1513 been widely interpreted in terms of multiple independent unrelated
1514 pathways (IUP model), both experimentally and in theoretical
1515 calculations. However, direct structural information on folding
1516 intermediates and their properties now indicates that all of a protein
1517 population folds through essentially the same stepwise pathway,
1518 determined by cooperative native-like foldon units and the way that the
1519 foldons fit together in the native protein. It is essential to decide
1520 between these fundamentally different folding mechanisms. This article
1521 shows, contrary to previous supposition, that the heterogeneous folding
1522 kinetics observed for the staphylococcal nuclease protein (SNase) does
1523 not require alternative parallel pathways. SNase folding kinetics can
1524 be fit equally well by a single predetermined pathway that allows for
1525 optional misfolding errors, which are known to occur ubiquitously in
1526 protein folding. Structural, kinetic, and thermodynamic information for
1527 the folding intermediates and pathways of many proteins is consistent
1528 with the predetermined pathway-optional error (PPOE) model but contrary
1529 to the properties implied in IUP models."
1534 title = "Models for the specific adhesion of cells to cells",
1543 url = "http://www.jstor.org/stable/1746930",
1544 keywords = "Antigen-Antibody Reactions; Cell Adhesion; Cell Membrane;
1545 Chemistry, Physical; Electrophysiology; Enzymes; Glycoproteins;
1546 Kinetics; Ligands; Membrane Proteins; Models, Biological; Receptors,
1548 abstract = "A theoretical framework is proposed for the analysis of
1549 adhesion between cells or of cells to surfaces when the adhesion is
1550 mediated by reversible bonds between specific molecules such as antigen
1551 and antibody, lectin and carbohydrate, or enzyme and substrate. From a
1552 knowledge of the reaction rates for reactants in solution and of their
1553 diffusion constants both in solution and on membranes, it is possible
1554 to estimate reaction rates for membrane-bound reactants. Two models are
1555 developed for predicting the rate of bond formation between cells and
1556 are compared with experiments. The force required to separate two cells
1557 is shown to be greater than the expected electrical forces between
1558 cells, and of the same order of magnitude as the forces required to
1559 pull gangliosides and perhaps some integral membrane proteins out of
1560 the cell membrane.",
1561 note = "The Bell model and a fair bit of cell bonding background.",
1562 project = "sawtooth simulation"
1566 author = DBerk #" and "# EEvans,
1567 title = "Detachment of agglutinin-bonded red blood cells. {III}. Mechanical
1568 analysis for large contact areas",
1576 keywords = "Cell Adhesion;Erythrocyte Membrane;Erythrocytes;Hemagglutinatio
1577 n;Hemagglutinins;Humans;Kinetics;Mathematics;Models,
1578 Biological;Pressure",
1579 abstract = "An experimental method and analysis are introduced which
1580 provide direct quantitation of the strength of adhesive contact for
1581 large agglutinin-bonded regions between macroscopically smooth membrane
1582 capsules (e.g., red blood cells). The approach yields intrinsic
1583 properties for separation of adherent regions independent of mechanical
1584 deformation of the membrane capsules during detachment. Conceptually,
1585 the micromechanical method involves one rigid test-capsule surface (in
1586 the form of a perfect sphere) held fixed by a micropipette and a second
1587 deformable capsule maneuvered with another micropipette to force
1588 contact with the test capsule. Only the test capsule is bound with
1589 agglutinin so that the maximum number of cross-bridges can be formed
1590 without steric interference. Following formation of a large adhesion
1591 region by mechanical impingement, the deformable capsule is detached
1592 from the rigid capsule surface by progressive aspiration into the
1593 micropipette. For the particular case modeled here, the deformable
1594 capsule is assumed to be a red blood cell which is preswollen by slight
1595 osmotic hydration before the test. The caliber of the detachment
1596 pipette is chosen so that the capsule will form a smooth cylindrical
1597 ``piston'' inside the pipette as it is aspirated. Because of the high
1598 flexibility of the membrane, the capsule naturally seals against the
1599 tube wall by pressurization even though it does not adhere to the
1600 glass. This arrangement maintains perfect axial symmetry and prevents
1601 the membrane from folding or buckling. Hence, it is possible to
1602 rigorously analyze the mechanics of deformation of the cell body to
1603 obtain the crucial ``transducer'' relation between pipette suction
1604 force and the membrane tension applied directly at the perimeter of the
1605 adhesive contact. Further, the geometry of the cell throughout the
1606 detachment process is predicted which provides accurate specification
1607 of the contact angle theta c between surfaces at the perimeter of the
1608 contact. A full analysis of red cell capsules during detachment has
1609 been carried out; however, it is shown that the shear rigidity of the
1610 red cell membrane can often be neglected so that the red cell can be
1611 treated as if it were an underfilled lipid bilayer vesicle. From the
1612 analysis, the mechanical leverage factor (1-cos theta c) and the
1613 membrane tension at the contact perimeter are determined to provide a
1614 complete description of the local mechanics of membrane separation as
1615 functions of large-scale experimental variables (e.g., suction force,
1616 contact diameter, overall cell length).(ABSTRACT TRUNCATED AT 400
1621 author = RBest #" and "# SFowler #" and "# JTocaHerrera #" and "# JClarke,
1622 title = "A simple method for probing the mechanical unfolding pathway of
1623 proteins in detail",
1628 pages = "12143--12148",
1629 doi = "10.1073/pnas.192351899",
1630 eprint = "http://www.pnas.org/cgi/reprint/99/19/12143.pdf",
1631 url = "http://www.pnas.org/cgi/content/abstract/99/19/12143",
1632 abstract = "Atomic force microscopy is an exciting new single-molecule
1633 technique to add to the toolbox of protein (un)folding methods.
1634 However, detailed analysis of the unfolding of proteins on application
1635 of force has, to date, relied on protein molecular dynamics simulations
1636 or a qualitative interpretation of mutant data. Here we describe how
1637 protein engineering {Phi} value analysis can be adapted to characterize
1638 the transition states for mechanical unfolding of proteins. Single-
1639 molecule studies also have an advantage over bulk experiments, in that
1640 partial {Phi} values arising from partial structure in the transition
1641 state can be clearly distinguished from those averaged over alternate
1642 pathways. We show that unfolding rate constants derived in the standard
1643 way by using Monte Carlo simulations are not reliable because of the
1644 errors involved. However, it is possible to circumvent these problems,
1645 providing the unfolding mechanism is not changed by mutation, either by
1646 a modification of the Monte Carlo procedure or by comparing mutant and
1647 wild-type data directly. The applicability of the method is tested on
1648 simulated data sets and experimental data for mutants of titin I27.",
1649 note = "Points out order-of-magnitude errors in $k_{u0}$ estimation from
1650 fitting Monte Carlo simulations."
1654 author = RBest #" and "# GHummer,
1655 title = "Protein folding kinetics under force from molecular simulation.",
1662 pages = "3706--3707",
1664 doi = "10.1021/ja0762691",
1665 keywords = "Computer Simulation;Kinetics;Models, Chemical;Protein
1666 Folding;Stress, Mechanical;Ubiquitin",
1667 abstract = "Despite a large number of studies on the mechanical unfolding
1668 of proteins, there are still relatively few successful attempts to
1669 refold proteins in the presence of a stretching force. We explore
1670 refolding kinetics under force using simulations of a coarse-grained
1671 model of ubiquitin. The effects of force on the folding kinetics can be
1672 fitted by a one-dimensional Kramers theory of diffusive barrier
1673 crossing, resulting in physically meaningful parameters for the height
1674 and location of the folding activation barrier. By comparing parameters
1675 obtained from pulling in different directions, we find that the
1676 unfolded state plays a dominant role in the refolding kinetics. Our
1677 findings explain why refolding becomes very slow at even moderate
1678 pulling forces and suggest how it could be practically observed in
1679 experiments at higher forces."
1683 author = RBest #" and "# EPaci #" and "# GHummer #" and "# OKDudko,
1684 title = "Pulling direction as a reaction coordinate for the mechanical
1685 unfolding of single molecules.",
1692 pages = "5968--5976",
1694 doi = "10.1021/jp075955j",
1695 keywords = "Computer Simulation;Kinetics;Models, Molecular;Protein
1696 Folding;Protein Structure, Tertiary;Time Factors;Ubiquitin",
1697 abstract = "The folding and unfolding kinetics of single molecules, such as
1698 proteins or nucleic acids, can be explored by mechanical pulling
1699 experiments. Determining intrinsic kinetic information, at zero
1700 stretching force, usually requires an extrapolation by fitting a
1701 theoretical model. Here, we apply a recent theoretical approach
1702 describing molecular rupture in the presence of force to unfolding
1703 kinetic data obtained from coarse-grained simulations of ubiquitin.
1704 Unfolding rates calculated from simulations over a broad range of
1705 stretching forces, for different pulling directions, reveal a
1706 remarkable ``turnover'' from a force-independent process at low force
1707 to a force-dependent process at high force, akin to the ``roll-over''
1708 in unfolding rates sometimes seen in studies using chemical denaturant.
1709 While such a turnover in rates is unexpected in one dimension, we
1710 demonstrate that it can occur for dynamics in just two dimensions. We
1711 relate the turnover to the quality of the pulling direction as a
1712 reaction coordinate for the intrinsic folding mechanism. A novel
1713 pulling direction, designed to be the most relevant to the intrinsic
1714 folding pathway, results in the smallest turnover. Our results are in
1715 accord with protein engineering experiments and simulations which
1716 indicate that the unfolding mechanism at high force can differ from the
1717 intrinsic mechanism. The apparent similarity between extrapolated and
1718 intrinsic rates in experiments, unexpected for different unfolding
1719 barriers, can be explained if the turnover occurs at low forces."
1722 @article { borgia08,
1723 author = Borgia #" and "# Williams #" and "# Clarke,
1724 title = "Single-Molecule Studies of Protein Folding",
1732 doi = "10.1146/annurev.biochem.77.060706.093102",
1733 eprint = "http://arjournals.annualreviews.org/doi/pdf/10.1146/annurev.bioch
1734 em.77.060706.093102",
1735 url = "http://arjournals.annualreviews.org/doi/abs/10.1146/annurev.biochem.
1737 abstract = "Although protein-folding studies began several decades ago, it
1738 is only recently that the tools to analyze protein folding at the
1739 single-molecule level have been developed. Advances in single-molecule
1740 fluorescence and force spectroscopy techniques allow investigation of
1741 the folding and dynamics of single protein molecules, both at
1742 equilibrium and as they fold and unfold. The experiments are far from
1743 simple, however, both in execution and in interpretation of the
1744 results. In this review, we discuss some of the highlights of the work
1745 so far and concentrate on cases where comparisons with the classical
1746 experiments can be made. We conclude that, although there have been
1747 relatively few startling insights from single-molecule studies, the
1748 rapid progress that has been made suggests that these experiments have
1749 significant potential to advance our understanding of protein folding.
1750 In particular, new techniques offer the possibility to explore regions
1751 of the energy landscape that are inaccessible to classical ensemble
1752 measurements and, perhaps, to observe rare events undetectable by other
1756 @article { braverman08,
1757 author = EBraverman #" and "# RMamdani,
1758 title = "Continuous versus pulse harvesting for population models in
1759 constant and variable environment",
1763 journal = JMathBiol,
1768 doi = "10.1007/s00285-008-0169-z",
1770 "http://www.springerlink.com/content/a1m23v50201m2401/fulltext.pdf",
1771 url = "http://www.springerlink.com/content/a1m23v50201m2401/",
1772 abstract = "We consider both autonomous and nonautonomous population models
1773 subject to either impulsive or continuous harvesting. It is
1774 demonstrated in the paper that the impulsive strategy can be as good as
1775 the continuous one, but cannot outperform it. We introduce a model,
1776 where certain harm to the population is incorporated in each harvesting
1777 event, and study it for the logistic and the Gompertz laws of growth.
1778 In this case, impulsive harvesting is not only the optimal strategy but
1779 is the only possible one.",
1780 note = "An example of non-exponential Gomperz law."
1783 @article { brochard-wyart99,
1784 author = FBrochard-Wyart #" and "# ABuguin #" and "# PGdeGennes,
1785 title = "Dynamics of taut {DNA} chains",
1792 "http://www.iop.org/EJ/article/0295-5075/47/2/171/epl_47_2_171.pdf",
1793 url = "http://stacks.iop.org/0295-5075/47/171",
1794 abstract = {We discuss the dynamics of stretched DNA chains, subjected to a
1795 tension force f, in a "taut" regime where ph = flp0/kBT $>$ 1 (lp0
1796 being the unperturbed persistence length). We deal with two variables:
1797 the local transverse displacements u, and the longitudinal position of
1798 a monomer u[?]. The variables u and u[?] follow two distinct Rouse
1799 equations, with diffusion coefficients D[?] = f/e (where e is the
1800 solvent viscosity) and D[?] = 4ph1/2D[?]. We apply these ideas to a
1801 discussion of various transient regimes.},
1802 note = "Theory for weakly bending relaxation modes in WLCs and FJCs."
1805 @article { brockwell02,
1806 author = DJBrockwell #" and "# GSBeddard #" and "# JClarkson #" and "#
1807 RCZinober #" and "# AWBlake #" and "# JTrinick #" and "# PDOlmsted #"
1808 and "# DASmith #" and "# SERadford,
1809 title = "The effect of core destabilization on the mechanical resistance of
1818 doi = "10.1016/S0006-3495(02)75182-5",
1819 eprint = "http://www.biophysj.org/cgi/reprint/83/1/458.pdf",
1820 url = "http://www.biophysj.org/cgi/content/abstract/83/1/458",
1821 keywords = "Amino Acid Sequence; Dose-Response Relationship, Drug;
1822 Kinetics; Magnetic Resonance Spectroscopy; Models, Molecular; Molecular
1823 Sequence Data; Monte Carlo Method; Muscle Proteins; Mutation; Peptide
1824 Fragments; Protein Denaturation; Protein Folding; Protein Kinases;
1825 Protein Structure, Secondary; Protein Structure, Tertiary; Proteins;
1827 abstract = "It is still unclear whether mechanical unfolding probes the
1828 same pathways as chemical denaturation. To address this point, we have
1829 constructed a concatamer of five mutant I27 domains (denoted (I27)(5)*)
1830 and used it for mechanical unfolding studies. This protein consists of
1831 four copies of the mutant C47S, C63S I27 and a single copy of C63S I27.
1832 These mutations severely destabilize I27 (DeltaDeltaG(UN) = 8.7 and
1833 17.9 kJ mol(-1) for C63S I27 and C47S, C63S I27, respectively). Both
1834 mutations maintain the hydrogen bond network between the A' and G
1835 strands postulated to be the major region of mechanical resistance for
1836 I27. Measuring the speed dependence of the force required to unfold
1837 (I27)(5)* in triplicate using the atomic force microscope allowed a
1838 reliable assessment of the intrinsic unfolding rate constant of the
1839 protein to be obtained (2.0 x 10(-3) s(-1)). The rate constant of
1840 unfolding measured by chemical denaturation is over fivefold faster
1841 (1.1 x 10(-2) s(-1)), suggesting that these techniques probe different
1842 unfolding pathways. Also, by comparing the parameters obtained from the
1843 mechanical unfolding of a wild-type I27 concatamer with that of
1844 (I27)(5)*, we show that although the observed forces are considerably
1845 lower, core destabilization has little effect on determining the
1846 mechanical sensitivity of this domain."
1849 @article { brockwell03,
1850 author = DJBrockwell #" and "# EPaci #" and "# RCZinober #" and "#
1851 GSBeddard #" and "# PDOlmsted #" and "# DASmith #" and "# RNPerham #"
1853 title = "Pulling geometry defines the mechanical resistance of a beta-sheet
1863 doi = "10.1038/nsb968",
1864 eprint = "http://www.nature.com/nsmb/journal/v10/n9/pdf/nsb968.pdf",
1865 url = "http://www.nature.com/nsmb/journal/v10/n9/abs/nsb968.html",
1866 keywords = "Anisotropy;Escherichia coli;Kinetics;Models, Molecular;Monte
1867 Carlo Method;Protein Folding;Protein Structure, Secondary;Protein
1868 Structure, Tertiary;Proteins;Software;Temperature;Thermodynamics",
1869 abstract = "Proteins show diverse responses when placed under mechanical
1870 stress. The molecular origins of their differing mechanical resistance
1871 are still unclear, although the orientation of secondary structural
1872 elements relative to the applied force vector is thought to have an
1873 important function. Here, by using a method of protein immobilization
1874 that allows force to be applied to the same all-beta protein, E2lip3,
1875 in two different directions, we show that the energy landscape for
1876 mechanical unfolding is markedly anisotropic. These results, in
1877 combination with molecular dynamics (MD) simulations, reveal that the
1878 unfolding pathway depends on the pulling geometry and is associated
1879 with unfolding forces that differ by an order of magnitude. Thus, the
1880 mechanical resistance of a protein is not dictated solely by amino acid
1881 sequence, topology or unfolding rate constant, but depends critically
1882 on the direction of the applied extension.",
1883 note = "Another scaffold effect paper. TODO: details"
1886 @article { brower-toland02,
1887 author = BDBrowerToland #" and "# CSmith #" and "# RYeh #" and "# JLis #"
1888 and "# CPeterson #" and "# MDWang,
1889 title = "From the Cover: Mechanical disruption of individual nucleosomes
1890 reveals a reversible multistage release of {DNA}",
1895 pages = "1960--1965",
1896 doi = "10.1073/pnas.022638399",
1897 eprint = "http://www.pnas.org/cgi/reprint/99/4/1960.pdf",
1898 url = "http://www.pnas.org/cgi/content/abstract/99/4/1960",
1899 abstract = "The dynamic structure of individual nucleosomes was examined by
1900 stretching nucleosomal arrays with a feedback-enhanced optical trap.
1901 Forced disassembly of each nucleosome occurred in three stages.
1902 Analysis of the data using a simple worm-like chain model yields 76 bp
1903 of DNA released from the histone core at low stretching force.
1904 Subsequently, 80 bp are released at higher forces in two stages: full
1905 extension of DNA with histones bound, followed by detachment of
1906 histones. When arrays were relaxed before the dissociated state was
1907 reached, nucleosomes were able to reassemble and to repeat the
1908 disassembly process. The kinetic parameters for nucleosome disassembly
1909 also have been determined."
1912 @article { bryngelson87,
1913 author = JDBryngelson #" and "# PGWolynes,
1914 title = "Spin glasses and the statistical mechanics of protein folding",
1920 pages = "7524--7528",
1922 keywords = "Kinetics; Mathematics; Models, Theoretical; Protein
1923 Conformation; Proteins; Stochastic Processes",
1924 abstract = "The theory of spin glasses was used to study a simple model of
1925 protein folding. The phase diagram of the model was calculated, and the
1926 results of dynamics calculations are briefly reported. The relation of
1927 these results to folding experiments, the relation of these hypotheses
1928 to previous protein folding theories, and the implication of these
1929 hypotheses for protein folding prediction schemes are discussed.",
1930 note = "Seminal protein folding via energy landscape paper."
1933 @article { bryngelson95,
1934 author = JDBryngelson #" and "# JNOnuchic #" and "# NDSocci #" and "#
1936 title = "Funnels, pathways, and the energy landscape of protein folding: a
1945 doi = "10.1002/prot.340210302",
1946 keywords = "Amino Acid Sequence; Chemistry, Physical; Computer Simulation;
1947 Data Interpretation, Statistical; Kinetics; Models, Chemical; Molecular
1948 Sequence Data; Protein Biosynthesis; Protein Conformation; Protein
1949 Folding; Proteins; Thermodynamics",
1950 abstract = "The understanding, and even the description of protein folding
1951 is impeded by the complexity of the process. Much of this complexity
1952 can be described and understood by taking a statistical approach to the
1953 energetics of protein conformation, that is, to the energy landscape.
1954 The statistical energy landscape approach explains when and why unique
1955 behaviors, such as specific folding pathways, occur in some proteins
1956 and more generally explains the distinction between folding processes
1957 common to all sequences and those peculiar to individual sequences.
1958 This approach also gives new, quantitative insights into the
1959 interpretation of experiments and simulations of protein folding
1960 thermodynamics and kinetics. Specifically, the picture provides simple
1961 explanations for folding as a two-state first-order phase transition,
1962 for the origin of metastable collapsed unfolded states and for the
1963 curved Arrhenius plots observed in both laboratory experiments and
1964 discrete lattice simulations. The relation of these quantitative ideas
1965 to folding pathways, to uniexponential vs. multiexponential behavior in
1966 protein folding experiments and to the effect of mutations on folding
1967 is also discussed. The success of energy landscape ideas in protein
1968 structure prediction is also described. The use of the energy landscape
1969 approach for analyzing data is illustrated with a quantitative analysis
1970 of some recent simulations, and a qualitative analysis of experiments
1971 on the folding of three proteins. The work unifies several previously
1972 proposed ideas concerning the mechanism protein folding and delimits
1973 the regions of validity of these ideas under different thermodynamic
1977 @article { bullard06,
1978 author = BBullard #" and "# TGarcia #" and "# VBenes #" and "# MLeake #"
1979 and "# WALinke #" and "# AOberhauser,
1980 title = "The molecular elasticity of the insect flight muscle proteins
1981 projectin and kettin",
1986 pages = "4451--4456",
1987 doi = "10.1073/pnas.0509016103",
1988 eprint = "http://www.pnas.org/cgi/reprint/103/12/4451.pdf",
1989 url = "http://www.pnas.org/cgi/content/abstract/103/12/4451",
1990 abstract = "Projectin and kettin are titin-like proteins mainly responsible
1991 for the high passive stiffness of insect indirect flight muscles, which
1992 is needed to generate oscillatory work during flight. Here we report
1993 the mechanical properties of kettin and projectin by single-molecule
1994 force spectroscopy. Force-extension and force-clamp curves obtained
1995 from Lethocerus projectin and Drosophila recombinant projectin or
1996 kettin fragments revealed that fibronectin type III domains in
1997 projectin are mechanically weaker (unfolding force, Fu {approx} 50-150
1998 pN) than Ig-domains (Fu {approx} 150-250 pN). Among Ig domains in
1999 Sls/kettin, the domains near the N terminus are less stable than those
2000 near the C terminus. Projectin domains refolded very fast [85% at 15
2001 s-1 (25{degrees}C)] and even under high forces (15-30 pN). Temperature
2002 affected the unfolding forces with a Q10 of 1.3, whereas the refolding
2003 speed had a Q10 of 2-3, probably reflecting the cooperative nature of
2004 the folding mechanism. High bending rigidities of projectin and kettin
2005 indicated that straightening the proteins requires low forces. Our
2006 results suggest that titin-like proteins in indirect flight muscles
2007 could function according to a folding-based-spring mechanism."
2010 @article { bustamante08,
2011 author = CBustamante,
2012 title = "In singulo Biochemistry: When Less Is More",
2018 doi = "10.1146/annurev.biochem.012108.120952",
2019 eprint = "http://arjournals.annualreviews.org/doi/pdf/10.1146/annurev.bioch
2021 url = "http://arjournals.annualreviews.org/doi/abs/10.1146/annurev.biochem.
2023 abstract = "It has been over one-and-a-half decades since methods of
2024 single-molecule detection and manipulation were first introduced in
2025 biochemical research. Since then, the application of these methods to
2026 an expanding variety of problems has grown at a vertiginous pace. While
2027 initially many of these experiments led more to confirmatory results
2028 than to new discoveries, today single-molecule methods are often the
2029 methods of choice to establish new mechanism-based results in
2030 biochemical research. Throughout this process, improvements in the
2031 sensitivity, versatility, and both spatial and temporal resolution of
2032 these techniques has occurred hand in hand with their applications. We
2033 discuss here some of the advantages of single-molecule methods over
2034 their bulk counterparts and argue that these advantages should help
2035 establish them as essential tools in the technical arsenal of the
2039 @article { bustamante94,
2040 author = CBustamante #" and "# JFMarko #" and "# EDSiggia #" and "# SSmith,
2041 title = "Entropic elasticity of lambda-phage {DNA}",
2048 pages = "1599--1600",
2050 doi = "10.1126/science.8079175",
2051 eprint = "http://www.sciencemag.org/cgi/reprint/265/5178/1599.pdf",
2052 url = "http://www.sciencemag.org/cgi/content/abstract/265/5178/1599",
2053 keywords = "Bacteriophage lambda; DNA, Viral; Least-Squares Analysis;
2055 note = "WLC interpolation formula."
2058 @article { bustanji03,
2059 author = YBustanji #" and "# CArciola #" and "# MConti #" and "# EMandello
2060 #" and "# LMontanaro #" and "# BSamori,
2061 title = "Dynamics of the interaction between a fibronectin molecule and a
2062 living bacterium under mechanical force",
2067 pages = "13292--13297",
2068 doi = "10.1073/pnas.1735343100",
2069 eprint = "http://www.pnas.org/cgi/reprint/100/23/13292.pdf",
2070 url = "http://www.pnas.org/cgi/content/abstract/100/23/13292",
2071 abstract = "Fibronectin (Fn) is an important mediator of bacterial
2072 invasions and of persistent infections like that of Staphylococcus
2073 epidermis. Similar to many other types of cell-protein adhesion, the
2074 binding between Fn and S. epidermidis takes place under physiological
2075 shear rates. We investigated the dynamics of the interaction between
2076 individual living S. epidermidis cells and single Fn molecules under
2077 mechanical force by using the scanning force microscope. The mechanical
2078 strength of this interaction and the binding site in the Fn molecule
2079 were determined. The energy landscape of the binding/unbinding process
2080 was mapped, and the force spectrum and the association and dissociation
2081 rate constants of the binding pair were measured. The interaction
2082 between S. epidermidis cells and Fn molecules is compared with those of
2083 two other protein/ligand pairs known to mediate different dynamic
2084 states of adhesion of cells under a hydrodynamic flow: the firm
2085 adhesion mediated by biotin/avidin interactions, and the rolling
2086 adhesion, mediated by L-selectin/P-selectin glycoprotein ligand-1
2087 interactions. The inner barrier in the energy landscape of the Fn case
2088 characterizes a high-energy binding mode that can sustain larger
2089 deformations and for significantly longer times than the correspondent
2090 high-strength L-selectin/P-selectin glycoprotein ligand-1 binding mode.
2091 The association kinetics of the former interaction is much slower to
2092 settle than the latter. On this basis, the observations made at the
2093 macroscopic scale by other authors of a strong lability of the
2094 bacterial adhesions mediated by Fn under high turbulent flow are
2095 rationalized at the molecular level."
2099 author = YMartin #" and "# CCWilliams #" and "# HKWickramasinghe,
2100 title = {Atomic force microscope---force mapping and profiling on a
2108 pages = {4723--4729},
2110 issn_online = "1089-7550",
2111 doi = {10.1063/1.338807},
2112 url = {http://jap.aip.org/resource/1/japiau/v61/i10/p4723_s1},
2114 abstract = {A modified version of the atomic force microscope is
2115 introduced that enables a precise measurement of the force between
2116 a tip and a sample over a tip-sample distance range of 30--150
2117 \AA. As an application, the force signal is used to maintain the
2118 tip-sample spacing constant, so that profiling can be achieved
2119 with a spatial resolution of 50 \AA. A second scheme allows the
2120 simultaneous measurement of force and surface profile; this scheme
2121 has been used to obtain material-dependent information from
2122 surfaces of electronic materials.},
2126 author = HJButt #" and "# MJaschke,
2127 title = "Calculation of thermal noise in atomic force microscopy",
2133 doi = "10.1088/0957-4484/6/1/001",
2134 url = "http://stacks.iop.org/0957-4484/6/1",
2135 abstract = "Thermal fluctuations of the cantilever are a fundamental source
2136 of noise in atomic force microscopy. We calculated thermal noise using
2137 the equipartition theorem and considering all possible vibration modes
2138 of the cantilever. The measurable amplitude of thermal noise depends on
2139 the temperature, the spring constant K of the cantilever and on the
2140 method by which the cantilever defletion is detected. If the deflection
2141 is measured directly, e.g. with an interferometer or a scanning
2142 tunneling microscope, the thermal noise of a cantilever with a free end
2143 can be calculated from square root kT/K. If the end of the cantilever
2144 is supported by a hard surface no thermal fluctuations of the
2145 deflection are possible. If the optical lever technique is applied to
2146 measure the deflection, the thermal noise of a cantilever with a free
2147 end is square root 4kT/3K. When the cantilever is supported thermal
2148 noise decreases to square root kT/3K, but it does not vanish.",
2149 note = "Corrections to basic $kx^2 = kB T$ due to higher order modes in
2150 rectangular cantilevers.",
2151 project = "Cantilever Calibration"
2154 @article{ jaschke95,
2155 author = MJaschke #" and "# HJButt,
2156 title = {Height calibration of optical lever atomic force
2157 microscopes by simple laser interferometry},
2162 pages = {1258--1259},
2164 url = {http://rsi.aip.org/resource/1/rsinak/v66/i2/p1258_s1},
2165 doi = {10.1063/1.1146018},
2167 keywords = {atomic force microscopy;calibration;interferometry;laser
2168 beam applications;mirrors;spatial resolution},
2169 abstract = {A new and simple interferometric method for height
2170 calibration of AFM piezo scanners is presented. Except for a small
2171 mirror no additional equipment is required since the fixed
2172 wavelength of the laser diode is used as a calibration
2173 standard. The calibration is appliable in the range between
2174 several ten nm and several μm. Besides vertical calibration many
2175 problems of piezo elements like hysteresis, nonlinearity, creep,
2176 derating, etc. and their dependence on scan parameters or
2177 temperature can be investigated.},
2181 author = YCao #" and "# MBalamurali #" and "# DSharma #" and "# HLi,
2182 title = "A functional single-molecule binding assay via force spectroscopy",
2187 pages = "15677--15681",
2188 doi = "10.1073/pnas.0705367104",
2189 eprint = "http://www.pnas.org/cgi/reprint/104/40/15677.pdf",
2190 url = "http://www.pnas.org/cgi/content/abstract/104/40/15677",
2191 abstract = "Protein-ligand interactions, including protein-protein
2192 interactions, are ubiquitously essential in biological processes and
2193 also have important applications in biotechnology. A wide range of
2194 methodologies have been developed for quantitative analysis of protein-
2195 ligand interactions. However, most of them do not report direct
2196 functional/structural consequence of ligand binding. Instead they only
2197 detect the change of physical properties, such as fluorescence and
2198 refractive index, because of the colocalization of protein and ligand,
2199 and are susceptible to false positives. Thus, important information
2200 about the functional state of proteinligand complexes cannot be
2201 obtained directly. Here we report a functional single-molecule binding
2202 assay that uses force spectroscopy to directly probe the functional
2203 consequence of ligand binding and report the functional state of
2204 protein-ligand complexes. As a proof of principle, we used protein G
2205 and the Fc fragment of IgG as a model system in this study. Binding of
2206 Fc to protein G does not induce major structural changes in protein G
2207 but results in significant enhancement of its mechanical stability.
2208 Using mechanical stability of protein G as an intrinsic functional
2209 reporter, we directly distinguished and quantified Fc-bound and Fc-free
2210 forms of protein G on a single-molecule basis and accurately determined
2211 their dissociation constant. This single-molecule functional binding
2212 assay is label-free, nearly background-free, and can detect functional
2213 heterogeneity, if any, among proteinligand interactions. This
2214 methodology opens up avenues for studying protein-ligand interactions
2215 in a functional context, and we anticipate that it will find broad
2216 application in diverse protein-ligand systems."
2220 author = PCarl #" and "# CKwok #" and "# GManderson #" and "# DSpeicher #"
2222 title = "Forced unfolding modulated by disulfide bonds in the Ig domains of
2223 a cell adhesion molecule",
2228 pages = "1565--1570",
2229 doi = "10.1073/pnas.031409698",
2230 eprint = "http://www.pnas.org/cgi/reprint/98/4/1565.pdf",
2231 url = "http://www.pnas.org/cgi/content/abstract/98/4/1565",
2235 @article { carrion-vazquez00,
2236 author = MCarrionVazquez #" and "# AOberhauser #" and "# TEFisher #" and "#
2237 PMarszalek #" and "# HLi #" and "# JFernandez,
2238 title = "Mechanical design of proteins studied by single-molecule force
2239 spectroscopy and protein engineering",
2245 doi = "10.1016/S0079-6107(00)00017-1",
2247 eprint = "http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1302160&blo
2249 url = "http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1302160",
2250 keywords = "Elasticity;Hydrogen Bonding;Microscopy, Atomic Force;Protein
2251 Denaturation;Protein Engineering;Protein Folding;Recombinant
2252 Proteins;Signal Processing, Computer-Assisted",
2253 abstract = "Mechanical unfolding and refolding may regulate the molecular
2254 elasticity of modular proteins with mechanical functions. The
2255 development of the atomic force microscopy (AFM) has recently enabled
2256 the dynamic measurement of these processes at the single-molecule
2257 level. Protein engineering techniques allow the construction of
2258 homomeric polyproteins for the precise analysis of the mechanical
2259 unfolding of single domains. alpha-Helical domains are mechanically
2260 compliant, whereas beta-sandwich domains, particularly those that
2261 resist unfolding with backbone hydrogen bonds between strands
2262 perpendicular to the applied force, are more stable and appear
2263 frequently in proteins subject to mechanical forces. The mechanical
2264 stability of a domain seems to be determined by its hydrogen bonding
2265 pattern and is correlated with its kinetic stability rather than its
2266 thermodynamic stability. Force spectroscopy using AFM promises to
2267 elucidate the dynamic mechanical properties of a wide variety of
2268 proteins at the single molecule level and provide an important
2269 complement to other structural and dynamic techniques (e.g., X-ray
2270 crystallography, NMR spectroscopy, patch-clamp).",
2271 note = {Surface contact \fref{figure}{2} is a modified version of
2272 \xref{baljon96}{figure}{1}. They are both good pictures for
2273 explaining that the tip's radius of curvature ($\sim 20\U{nm}$) is
2274 larger than the I27 domains\citet{improta96} ($\sim 2\U{nm}$).},
2277 @article { carrion-vazquez03,
2278 author = MCarrionVazquez #" and "# HLi #" and "# HLu #" and "# PMarszalek
2279 #" and "# AOberhauser #" and "# JFernandez,
2280 title = "The mechanical stability of ubiquitin is linkage dependent",
2289 doi = "10.1038/nsb965",
2290 eprint = "http://www.nature.com/nsmb/journal/v10/n9/pdf/nsb965.pdf",
2291 url = "http://www.nature.com/nsmb/journal/v10/n9/abs/nsb965.html",
2292 keywords = "Humans;Hydrogen Bonding;Kinetics;Lysine;Microscopy, Atomic
2293 Force;Models, Molecular;Polyubiquitin;Protein Binding;Protein
2294 Folding;Protein Structure, Tertiary;Ubiquitin",
2295 abstract = "Ubiquitin chains are formed through the action of a set of
2296 enzymes that covalently link ubiquitin either through peptide bonds or
2297 through isopeptide bonds between their C terminus and any of four
2298 lysine residues. These naturally occurring polyproteins allow one to
2299 study the mechanical stability of a protein, when force is applied
2300 through different linkages. Here we used single-molecule force
2301 spectroscopy techniques to examine the mechanical stability of
2302 N-C-linked and Lys48-C-linked ubiquitin chains. We combined these
2303 experiments with steered molecular dynamics (SMD) simulations and found
2304 that the mechanical stability and unfolding pathway of ubiquitin
2305 strongly depend on the linkage through which the mechanical force is
2306 applied to the protein. Hence, a protein that is otherwise very stable
2307 may be easily unfolded by a relatively weak mechanical force applied
2308 through the right linkage. This may be a widespread mechanism in
2309 biological systems."
2312 @article { carrion-vazquez99a,
2313 author = MCarrionVazquez #" and "# PMarszalek #" and "# AOberhauser #" and
2315 title = "Atomic force microscopy captures length phenotypes in single
2321 pages = "11288--11292",
2322 doi = "10.1073/pnas.96.20.11288",
2323 eprint = "http://www.pnas.org/cgi/reprint/96/20/11288.pdf",
2324 url = "http://www.pnas.org/cgi/content/abstract/96/20/11288",
2328 @article { carrion-vazquez99b,
2329 author = MCarrionVazquez #" and "# AOberhauser #" and "# SFowler #" and "#
2330 PMarszalek #" and "# SBroedel #" and "# JClarke #" and "# JFernandez,
2331 title = "Mechanical and chemical unfolding of a single protein: A
2337 pages = "3694--3699",
2338 doi = "10.1073/pnas.96.7.3694",
2339 eprint = "http://www.pnas.org/cgi/reprint/96/7/3694.pdf",
2340 url = "http://www.pnas.org/cgi/content/abstract/96/7/3694"
2344 author = CLChyan #" and "# FCLin #" and "# HPeng #" and "# JMYuan #" and "#
2345 CHChang #" and "# SHLin #" and "# GYang,
2346 title = "Reversible mechanical unfolding of single ubiquitin molecules",
2350 address = "Department of Chemistry, National Dong Hwa University,
2355 pages = "3995--4006",
2357 doi = "10.1529/biophysj.104.042754",
2358 eprint = "http://download.cell.com/biophysj/pdf/PIIS0006349504738643.pdf",
2359 url = "http://www.cell.com/biophysj/abstract/S0006-3495(04)73864-3",
2361 keywords = "Computer
2362 Simulation;Elasticity;Mechanics;Micromanipulation;Microscopy, Atomic
2363 Force;Models, Chemical;Models, Molecular;Protein Conformation;Protein
2364 Denaturation;Protein Folding;Stress, Mechanical;Structure-Activity
2365 Relationship;Ubiquitin",
2366 abstract = "Single-molecule manipulation techniques have enabled the
2367 characterization of the unfolding and refolding process of individual
2368 protein molecules, using mechanical forces to initiate the unfolding
2369 transition. Experimental and computational results following this
2370 approach have shed new light on the mechanisms of the mechanical
2371 functions of proteins involved in several cellular processes, as well
2372 as revealed new information on the protein folding/unfolding free-
2373 energy landscapes. To investigate how protein molecules of different
2374 folds respond to a stretching force, and to elucidate the effects of
2375 solution conditions on the mechanical stability of a protein, we
2376 synthesized polymers of the protein ubiquitin and characterized the
2377 force-induced unfolding and refolding of individual ubiquitin molecules
2378 using an atomic-force-microscope-based single-molecule manipulation
2379 technique. The ubiquitin molecule was highly resistant to a stretching
2380 force, and the mechanical unfolding process was reversible. A model
2381 calculation based on the hydrogen-bonding pattern in the native
2382 structure was performed to explain the origin of this high mechanical
2383 stability. Furthermore, pH effects were studied and it was found that
2384 the forces required to unfold the protein remained constant within a pH
2385 range around the neutral value, and forces decreased as the solution pH
2386 was lowered to more acidic values.",
2387 note = "includes pH effects",
2390 @article { ciccotti86,
2391 author = GCiccotti #" and "# JPRyckaert,
2392 title = "Molecular dynamics simulation of rigid molecules",
2399 doi = "10.1016/0167-7977(86)90022-5",
2400 url = "http://dx.doi.org/10.1016/0167-7977(86)90022-5",
2401 note = "I haven't read this, but it looks like a nice review of MD with
2405 @article { claverie01,
2406 author = JMClaverie,
2407 title = "Gene number. What if there are only 30,000 human genes?",
2414 pages = "1255--1257",
2416 url = "http://www.sciencemag.org/cgi/content/full/291/5507/1255",
2417 keywords = "Animals;Computational Biology;Drug Industry;Expressed Sequence
2418 Tags;Gene Expression;Gene Expression Regulation;Genes;Genetic
2419 Techniques;Genome, Human;Genomics;Human Genome Project;Humans;Models,
2420 Genetic;Polymorphism, Single Nucleotide;Proteins;RNA, Messenger"
2423 @misc { codata-boltzmann,
2424 key = "codata-boltzmann",
2425 crossref = "codata06",
2426 url = "http://physics.nist.gov/cgi-bin/cuu/Value?k"
2429 @article { codata06,
2430 author = PJMohr #" and "# BNTaylor #" and "# DBNewell,
2432 title = "{CODATA} recommended values of the fundamental physical constants:
2442 doi = "10.1103/RevModPhys.80.633"
2445 @article { collins03,
2446 author = FSCollins #" and "# MMorgan #" and "# APatrinos,
2447 title = "The Human Genome Project: Lessons from large-scale biology.",
2456 doi = "10.1126/science.1084564",
2457 eprint = "http://www.sciencemag.org/cgi/reprint/300/5617/286.pdf",
2458 url = "http://www.sciencemag.org/cgi/content/summary/300/5617/277",
2459 keywords = "Access to Information;Computational Biology;Databases, Nucleic
2460 Acid;Genome, Human;Genomics;Government Agencies;History, 20th
2461 Century;Human Genome Project;Humans;International Cooperation;National
2462 Institutes of Health (U.S.);Private Sector;Public Policy;Public
2463 Sector;Publishing;Quality Control;Sequence Analysis, DNA;United States",
2464 note = "See also: \href{http://www.ornl.gov/sci/techresources/Human_Genome/
2465 project/journals/journals.shtml}{Landmark HPG Papers}"
2468 @article { cornish07,
2469 author = PVCornish #" and "# THa,
2470 title = "A survey of single-molecule techniques in chemical biology",
2474 journal = ACS:ChemBiol,
2479 doi = "10.1021/cb600342a",
2480 keywords = "Animals;Data Collection;Humans;Microscopy, Atomic
2481 Force;Microscopy, Fluorescence;Molecular Biology",
2482 abstract = "Single-molecule methods have revolutionized scientific research
2483 by rendering the investigation of once-inaccessible biological
2484 processes amenable to scientific inquiry. Several of the more
2485 established techniques will be emphasized in this Review, including
2486 single-molecule fluorescence microscopy, optical tweezers, and atomic
2487 force microscopy, which have been applied to many diverse biological
2488 processes. Serving as a taste of all the exciting research currently
2489 underway, recent examples will be discussed of translocation of RNA
2490 polymerase, myosin VI walking, protein folding, and enzyme activity. We
2491 will end by providing an assessment of what the future holds, including
2492 techniques that are currently in development."
2497 title = "Statistical Data Analysis",
2500 address = "New York",
2501 note = "Noise deconvolution in Chapter 11",
2502 project = "Cantilever Calibration"
2506 author = DCraig #" and "# AKrammer #" and "# KSchulten #" and "# VVogel,
2507 title = "Comparison of the early stages of forced unfolding for fibronectin
2508 type {III} modules",
2513 pages = "5590--5595",
2514 doi = "10.1073/pnas.101582198",
2515 eprint = "http://www.pnas.org/cgi/reprint/98/10/5590.pdf",
2516 url = "http://www.pnas.org/cgi/content/abstract/98/10/5590",
2520 @article { delpech01,
2521 author = BDelpech #" and "# MNCourel #" and "# CMaingonnat #" and "#
2522 CChauzy #" and "# RSesboue #" and "# GPratesi,
2523 title = "Hyaluronan digestion and synthesis in an experimental model of
2526 month = "September/October",
2527 journal = HistochemJ,
2532 keywords = "Animals;Culture Media;Humans;Hyaluronic
2533 Acid;Hyaluronoglucosaminidase;Mice;Mice, Nude;Neoplasm
2534 Metastasis;Neoplasm Transplantation;Neoplasms, Experimental;Tumor
2536 abstract = "To approach the question of hyaluronan catabolism in tumours,
2537 we have selected the cancer cell line H460M, a highly metastatic cell
2538 line in the nude mouse. H460M cells release hyaluronidase in culture
2539 media at a high rate of 57 pU/cell/h, without producing hyaluronan.
2540 Hyaluronidase was measured in the H460M cell culture medium at the
2541 optimum pH 3.8, and was not found above pH 4.5, with the enzyme-linked
2542 sorbent assay technique and zymography. Tritiated hyaluronan was
2543 digested at pH 3.8 by cells or cell membranes as shown by gel
2544 permeation chromatography, but no activity was recorded at pH 7 with
2545 this technique. Hyaluronan was digested in culture medium by tumour
2546 slices, prepared from tumours developed in nude mice grafted with H460M
2547 cells, showing that hyaluronan could be digested in complex tissue at
2548 physiological pH. Culture of tumour slices with tritiated acetate
2549 resulted in the accumulation within 2 days of radioactive
2550 macromolecules in the culture medium. The radioactive macromolecular
2551 material was mostly digested by Streptomyces hyaluronidase, showing
2552 that hyaluronan was its main component and that hyaluronan synthesis
2553 occurred together with its digestion. These results demonstrate that
2554 the membrane-associated hyaluronidase of H460M cells can act in vivo,
2555 and that hyaluronan, which is synthesised by the tumour stroma, can be
2556 made soluble and reduced to a smaller size by tumour cells before being
2557 internalised and further digested."
2560 @article { diCola05,
2561 author = EDCola #" and "# TAWaigh #" and "# JTrinick #" and "#
2562 LTskhovrebova #" and "# AHoumeida #" and "# WPyckhout-Hintzen #" and "#
2565 title = "Persistence length of titin from rabbit skeletal muscles measured
2566 with scattering and microrheology techniques",
2573 pages = "4095--4106",
2575 doi = "10.1529/biophysj.104.054908",
2576 eprint = "http://download.cell.com/biophysj/pdf/PIIS0006349505734603.pdf",
2577 url = "http://www.cell.com/biophysj/retrieve/pii/S0006349505734603",
2578 keywords = "Animals;Biophysics;Elasticity;Light;Muscle Proteins;Muscle,
2579 Skeletal;Neutrons;Protein Conformation;Protein
2580 Kinases;Rabbits;Rheology;Scattering, Radiation;Temperature",
2581 abstract = "The persistence length of titin from rabbit skeletal muscles
2582 was measured using a combination of static and dynamic light
2583 scattering, and neutron small angle scattering. Values of persistence
2584 length in the range 9-16 nm were found for titin-II, which corresponds
2585 to mainly physiologically inelastic A-band part of the protein, and for
2586 a proteolytic fragment with 100-nm contour length from the
2587 physiologically elastic I-band part. The ratio of the hydrodynamic
2588 radius to the static radius of gyration indicates that the proteins
2589 obey Gaussian statistics typical of a flexible polymer in a -solvent.
2590 Furthermore, measurements of the flexibility as a function of
2591 temperature demonstrate that titin-II and the I-band titin fragment
2592 experience a similar denaturation process; unfolding begins at 318 K
2593 and proceeds in two stages: an initial gradual 50\% change in
2594 persistence length is followed by a sharp unwinding transition at 338
2595 K. Complementary microrheology (video particle tracking) measurements
2596 indicate that the viscoelasticity in dilute solution behaves according
2597 to the Flory/Fox model, providing a value of the radius of gyration for
2598 titin-II (63 +/- 1 nm) in agreement with static light scattering and
2599 small angle neutron scattering results."
2603 author = HDietz #" and "# MRief,
2604 title = "Exploring the energy landscape of {GFP} by single-molecule
2605 mechanical experiments",
2610 pages = "16192--16197",
2611 doi = "10.1073/pnas.0404549101",
2612 eprint = "http://www.pnas.org/cgi/reprint/101/46/16192.pdf",
2613 url = "http://www.pnas.org/cgi/content/abstract/101/46/16192",
2614 abstract = "We use single-molecule force spectroscopy to drive
2615 single GFP molecules from the native state through their
2616 complex energy landscape into the completely unfolded
2617 state. Unlike many smaller proteins, mechanical GFP unfolding
2618 proceeds by means of two subsequent intermediate states. The
2619 transition from the native state to the first intermediate
2620 state occurs near thermal equilibrium at $\approx35\U{pN}$ and
2621 is characterized by detachment of a seven-residue N-terminal
2622 $\alpha$-helix from the beta barrel. We measure the
2623 equilibrium free energy cost associated with this transition
2624 as 22 kBT. Detachment of this small $\alpha$-helix completely
2625 destabilizes GFP thermodynamically even though the
2626 $\beta$-barrel is still intact and can bear load. Mechanical
2627 stability of the protein on the millisecond timescale,
2628 however, is determined by the activation barrier of unfolding
2629 the $\beta$-barrel out of this thermodynamically unstable
2630 intermediate state. High bandwidth, time-resolved measurements
2631 of the cantilever relaxation phase upon unfolding of the
2632 $\beta$-barrel revealed a second metastable mechanical
2633 intermediate with one complete $\beta$-strand detached from
2634 the barrel. Quantitative analysis of force distributions and
2635 lifetimes lead to a detailed picture of the complex mechanical
2636 unfolding pathway through a rough energy landscape.",
2637 note = "Towards use of Green Flourescent Protein (GFP) as an
2638 embedded force probe. Nice energy-landscape-to-one-dimension
2639 compression graphic.",
2640 project = "Energy landscape roughness"
2643 @article { dietz06a,
2644 author = HDietz #" and "# MRief,
2645 title = "Protein structure by mechanical triangulation",
2652 pages = "1244--1247",
2653 doi = "10.1073/pnas.0509217103",
2654 eprint = "http://www.pnas.org/cgi/reprint/103/5/1244.pdf",
2655 url = "http://www.pnas.org/cgi/content/abstract/103/5/1244",
2656 abstract = "Knowledge of protein structure is essential to understand
2657 protein function. High-resolution protein structure has so far been the
2658 domain of ensemble methods. Here, we develop a simple single-molecule
2659 technique to measure spatial position of selected residues within a
2660 folded and functional protein structure in solution. Construction and
2661 mechanical unfolding of cysteine-engineered polyproteins with
2662 controlled linkage topology allows measuring intramolecular distance
2663 with angstrom precision. We demonstrate the potential of this technique
2664 by determining the position of three residues in the structure of green
2665 fluorescent protein (GFP). Our results perfectly agree with the GFP
2666 crystal structure. Mechanical triangulation can find many applications
2667 where current bulk structural methods fail."
2670 @article { dietz06b,
2671 author = HDietz #" and "# FBerkemeier #" and "# MBertz #" and "# MRief,
2672 title = "Anisotropic deformation response of single protein molecules",
2679 pages = "12724--12728",
2680 doi = "10.1073/pnas.0602995103",
2681 eprint = "http://www.pnas.org/cgi/reprint/103/34/12724.pdf",
2682 url = "http://www.pnas.org/cgi/content/abstract/103/34/12724",
2683 abstract = "Single-molecule methods have given experimental access to the
2684 mechanical properties of single protein molecules. So far, access has
2685 been limited to mostly one spatial direction of force application.
2686 Here, we report single-molecule experiments that explore the mechanical
2687 properties of a folded protein structure in precisely controlled
2688 directions by applying force to selected amino acid pairs. We
2689 investigated the deformation response of GFP in five selected
2690 directions. We found fracture forces widely varying from 100 pN up to
2691 600 pN. We show that straining the GFP structure in one of the five
2692 directions induces partial fracture of the protein into a half-folded
2693 intermediate structure. From potential widths we estimated directional
2694 spring constants of the GFP structure and found values ranging from 1
2695 N/m up to 17 N/m. Our results show that classical continuum mechanics
2696 and simple mechanistic models fail to describe the complex mechanics of
2697 the GFP protein structure and offer insights into the mechanical design
2698 of protein materials."
2702 author = HDietz #" and "# MRief,
2703 title = "Detecting Molecular Fingerprints in Single Molecule Force
2704 Spectroscopy Using Pattern Recognition",
2709 pages = "5540--5542",
2711 doi = "10.1143/JJAP.46.5540",
2712 url = "http://jjap.ipap.jp/link?JJAP/46/5540/",
2713 keywords = "single molecule, protein mechanics, force spectroscopy, AFM,
2714 pattern recognition, GFP",
2715 abstract = "Single molecule force spectroscopy has given experimental
2716 access to the mechanical properties of protein molecules. Typically,
2717 less than 1% of the experimental recordings reflect true single
2718 molecule events due to abundant surface and multiple-molecule
2719 interactions. A key issue in single molecule force spectroscopy is thus
2720 to identify the characteristic mechanical `fingerprint' of a specific
2721 protein in noisy data sets. Here, we present an objective pattern
2722 recognition algorithm that is able to identify fingerprints in such
2724 note = "Automatic force curve selection. Seems a bit shoddy. Details
2728 @article{ berkemeier11,
2729 author = FBerkemeier #" and "# MBertz #" and "# SXiao #" and "#
2730 NPinotsis #" and "# MWilmanns #" and "# FGrater #" and "# MRief,
2731 title = "Fast-folding $\alpha$-helices as reversible strain absorbers
2732 in the muscle protein myomesin.",
2737 address = "Physik Department E22, Technische Universit{\"a}t
2738 M{\"u}nchen, James-Franck-Stra{\ss}e, 85748 Garching, Germany.",
2741 pages = "14139--14144",
2742 keywords = "Biomechanics",
2743 keywords = "Kinetics",
2744 keywords = "Microscopy, Atomic Force",
2745 keywords = "Molecular Dynamics Simulation",
2746 keywords = "Muscle Proteins",
2747 keywords = "Protein Folding",
2748 keywords = "Protein Multimerization",
2749 keywords = "Protein Stability",
2750 keywords = "Protein Structure, Secondary",
2751 keywords = "Protein Structure, Tertiary",
2752 keywords = "Protein Unfolding",
2753 abstract = "The highly oriented filamentous protein network of
2754 muscle constantly experiences significant mechanical load during
2755 muscle operation. The dimeric protein myomesin has been identified
2756 as an important M-band component supporting the mechanical
2757 integrity of the entire sarcomere. Recent structural studies have
2758 revealed a long $\alpha$-helical linker between the C-terminal
2759 immunoglobulin (Ig) domains My12 and My13 of myomesin. In this
2760 paper, we have used single-molecule force spectroscopy in
2761 combination with molecular dynamics simulations to characterize
2762 the mechanics of the myomesin dimer comprising immunoglobulin
2763 domains My12-My13. We find that at forces of approximately 30?pN
2764 the $\alpha$-helical linker reversibly elongates allowing the
2765 molecule to extend by more than the folded extension of a full
2766 domain. High-resolution measurements directly reveal the
2767 equilibrium folding/unfolding kinetics of the individual helix. We
2768 show that $\alpha$-helix unfolding mechanically protects the
2769 molecule homodimerization from dissociation at physiologically
2770 relevant forces. As fast and reversible molecular springs the
2771 myomesin $\alpha$-helical linkers are an essential component for
2772 the structural integrity of the M band.",
2774 doi = "10.1073/pnas.1105734108",
2775 URL = "http://www.ncbi.nlm.nih.gov/pubmed/21825161",
2780 author = KADill #" and "# HSChan,
2781 title = "From Levinthal to pathways to funnels.",
2789 doi = "10.1038/nsb0197-10",
2790 eprint = "http://www.nature.com/nsmb/journal/v4/n1/pdf/nsb0197-10.pdf",
2791 url = "http://www.nature.com/nsmb/journal/v4/n1/abs/nsb0197-10.html",
2792 keywords = "Kinetics;Models, Chemical;Protein Folding",
2793 abstract = "While the classical view of protein folding kinetics relies on
2794 phenomenological models, and regards folding intermediates in a
2795 structural way, the new view emphasizes the ensemble nature of protein
2796 conformations. Although folding has sometimes been regarded as a linear
2797 sequence of events, the new view sees folding as parallel microscopic
2798 multi-pathway diffusion-like processes. While the classical view
2799 invoked pathways to solve the problem of searching for the needle in
2800 the haystack, the pathway idea was then seen as conflicting with
2801 Anfinsen's experiments showing that folding is pathway-independent
2802 (Levinthal's paradox). In contrast, the new view sees no inherent
2803 paradox because it eliminates the pathway idea: folding can funnel to a
2804 single stable state by multiple routes in conformational space. The
2805 general energy landscape picture provides a conceptual framework for
2806 understanding both two-state and multi-state folding kinetics. Better
2807 tests of these ideas will come when new experiments become available
2808 for measuring not just averages of structural observables, but also
2809 correlations among their fluctuations. At that point we hope to learn
2810 much more about the real shapes of protein folding landscapes.",
2811 note = "Pretty folding funnel figures."
2814 @article { discher06,
2815 author = DDischer #" and "# NBhasin #" and "# CJohnson,
2816 title = "Covalent chemistry on distended proteins",
2821 pages = "7533--7534",
2822 doi = "10.1073/pnas.0602388103",
2823 eprint = "http://www.pnas.org/cgi/reprint/103/20/7533.pdf",
2824 url = "http://www.pnas.org/cgi/content/abstract/103/20/7533.pdf"
2828 author = OKDudko #" and "# AEFilippov #" and "# JKlafter #" and "# MUrbakh,
2829 title = "Beyond the conventional description of dynamic force spectroscopy
2837 pages = "11378--11381",
2839 doi = "10.1073/pnas.1534554100",
2840 eprint = "http://www.pnas.org/content/100/20/11378.full.pdf",
2841 url = "http://www.pnas.org/content/100/20/11378.abstract",
2842 keywords = "Spectrum Analysis;Temperature",
2843 abstract = "Dynamic force spectroscopy of single molecules is described by
2844 a model that predicts a distribution of rupture forces, the
2845 corresponding mean rupture force, and variance, which are all amenable
2846 to experimental tests. The distribution has a pronounced asymmetry,
2847 which has recently been observed experimentally. The mean rupture force
2848 follows a (lnV)2/3 dependence on the pulling velocity, V, and differs
2849 from earlier predictions. Interestingly, at low pulling velocities, a
2850 rebinding process is obtained whose signature is an intermittent
2851 behavior of the spring force, which delays the rupture. An extension to
2852 include conformational changes of the adhesion complex is proposed,
2853 which leads to the possibility of bimodal distributions of rupture
2858 author = OKDudko #" and "# GHummer #" and "# ASzabo,
2859 title = "Intrinsic rates and activation free energies from single-molecule
2860 pulling experiments",
2869 doi = "10.1103/PhysRevLett.96.108101",
2870 keywords = "Biophysics;Computer Simulation;Data Interpretation,
2871 Statistical;Kinetics;Micromanipulation;Models, Chemical;Models,
2872 Molecular;Molecular Conformation;Muscle Proteins;Nucleic Acid
2873 Conformation;Protein Binding;Protein Denaturation;Protein
2874 Folding;Protein Kinases;RNA;Stress, Mechanical;Thermodynamics;Time
2876 abstract = "We present a unified framework for extracting kinetic
2877 information from single-molecule pulling experiments at constant force
2878 or constant pulling speed. Our procedure provides estimates of not only
2879 (i) the intrinsic rate coefficient and (ii) the location of the
2880 transition state but also (iii) the free energy of activation. By
2881 analyzing simulated data, we show that the resulting rates of force-
2882 induced rupture are significantly more reliable than those obtained by
2883 the widely used approach based on Bell's formula. We consider the
2884 uniqueness of the extracted kinetic information and suggest guidelines
2885 to avoid over-interpretation of experiments."
2889 author = OKDudko #" and "# JMathe #" and "# ASzabo #" and "# AMeller #" and
2891 title = "Extracting kinetics from single-molecule force spectroscopy:
2892 Nanopore unzipping of {DNA} hairpins",
2899 pages = "4188--4195",
2901 doi = "10.1529/biophysj.106.102855",
2902 eprint = "http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1877759&blo
2904 keywords = "Computer
2905 Simulation;DNA;Elasticity;Mechanics;Micromanipulation;Microscopy,
2906 Atomic Force;Models, Chemical;Models, Molecular;Nanostructures;Nucleic
2907 Acid Conformation;Porosity;Stress, Mechanical",
2908 abstract = "Single-molecule force experiments provide powerful new tools to
2909 explore biomolecular interactions. Here, we describe a systematic
2910 procedure for extracting kinetic information from force-spectroscopy
2911 experiments, and apply it to nanopore unzipping of individual DNA
2912 hairpins. Two types of measurements are considered: unzipping at
2913 constant voltage, and unzipping at constant voltage-ramp speeds. We
2914 perform a global maximum-likelihood analysis of the experimental data
2915 at low-to-intermediate ramp speeds. To validate the theoretical models,
2916 we compare their predictions with two independent sets of data,
2917 collected at high ramp speeds and at constant voltage, by using a
2918 quantitative relation between the two types of measurements.
2919 Microscopic approaches based on Kramers theory of diffusive barrier
2920 crossing allow us to estimate not only intrinsic rates and transition
2921 state locations, as in the widely used phenomenological approach based
2922 on Bell's formula, but also free energies of activation. The problem of
2923 extracting unique and accurate kinetic parameters of a molecular
2924 transition is discussed in light of the apparent success of the
2925 microscopic theories in reproducing the experimental data."
2929 author = OKDudko #" and "# GHummer #" and "# ASzabo,
2930 title = "Theory, analysis, and interpretation of single-molecule
2931 force spectroscopy experiments.",
2936 address = "Department of Physics and Center for Theoretical
2937 Biological Physics, University of California at San Diego, La
2938 Jolla, CA 92093, USA.
2939 dudko@physics.ucsd.edu",
2942 pages = "15755--15760",
2944 keywords = "Half-Life",
2945 keywords = "Kinetics",
2946 keywords = "Microscopy, Atomic Force",
2947 keywords = "Motion",
2948 keywords = "Nucleic Acid Conformation",
2949 keywords = "Nucleic Acid Denaturation",
2950 keywords = "Protein Folding",
2951 keywords = "Thermodynamics",
2952 abstract = "Dynamic force spectroscopy probes the kinetic and
2953 thermodynamic properties of single molecules and molecular
2954 assemblies. Here, we propose a simple procedure to extract kinetic
2955 information from such experiments. The cornerstone of our method
2956 is a transformation of the rupture-force histograms obtained at
2957 different force-loading rates into the force-dependent lifetimes
2958 measurable in constant-force experiments. To interpret the
2959 force-dependent lifetimes, we derive a generalization of Bell's
2960 formula that is formally exact within the framework of Kramers
2961 theory. This result complements the analytical expression for the
2962 lifetime that we derived previously for a class of model
2963 potentials. We illustrate our procedure by analyzing the nanopore
2964 unzipping of DNA hairpins and the unfolding of a protein attached
2965 by flexible linkers to an atomic force microscope. Our procedure
2966 to transform rupture-force histograms into the force-dependent
2967 lifetimes remains valid even when the molecular extension is a
2968 poor reaction coordinate and higher-dimensional free-energy
2969 surfaces must be considered. In this case the microscopic
2970 interpretation of the lifetimes becomes more challenging because
2971 the lifetimes can reveal richer, and even nonmonotonic, dependence
2974 doi = "10.1073/pnas.0806085105",
2975 URL = "http://www.ncbi.nlm.nih.gov/pubmed/18852468",
2981 title = "Probing the relation between force--lifetime--and chemistry in
2982 single molecular bonds",
2988 doi = "10.1146/annurev.biophys.30.1.105",
2989 url = "http://arjournals.annualreviews.org/doi/abs/10.1146%2Fannurev.biophys.30.1.105",
2990 keywords = "Biophysics;Kinetics;Microscopy, Atomic Force;Models,
2991 Chemical;Protein Binding;Spectrum Analysis;Time Factors",
2992 abstract = "On laboratory time scales, the energy landscape of a weak bond
2993 along a dissociation pathway is fully explored through Brownian-thermal
2994 excitations, and energy barriers become encoded in a dissociation time
2995 that varies with applied force. Probed with ramps of force over an
2996 enormous range of rates (force/time), this kinetic profile is
2997 transformed into a dynamic spectrum of bond rupture force as a function
2998 of loading rate. On a logarithmic scale in loading rate, the force
2999 spectrum provides an easy-to-read map of the prominent energy barriers
3000 traversed along the force-driven pathway and exposes the differences in
3001 energy between barriers. In this way, the method of dynamic force
3002 spectroscopy (DFS) is being used to probe the complex relation between
3003 force-lifetime-and chemistry in single molecular bonds. Most important,
3004 DFS probes the inner world of molecular interactions to reveal barriers
3005 that are difficult or impossible to detect in assays of near
3006 equilibrium dissociation but that determine bond lifetime and strength
3007 under rapid detachment. To use an ultrasensitive force probe as a
3008 spectroscopic tool, we need to understand the physics of bond
3009 dissociation under force, the impact of experimental technique on the
3010 measurement of detachment force (bond strength), the consequences of
3011 complex interactions in macromolecular bonds, and effects of multiply-
3012 bonded attachments."
3015 @article { evans91a,
3016 author = EEvans #" and "# DBerk #" and "# ALeung,
3017 title = "Detachment of agglutinin-bonded red blood cells. {I}. Forces to
3018 rupture molecular-point attachments",
3026 keywords = "ABO Blood-Group System;Animals;Antibodies,
3027 Monoclonal;Erythrocyte Deformability;Erythrocyte
3028 Membrane;Erythrocytes;Glycophorin;Helix
3029 (Snails);Hemagglutinins;Humans;Immune Sera;Lectins;Mathematics;Models,
3031 abstract = "A simple micromechanical method has been developed to measure
3032 the rupture strength of a molecular-point attachment (focal bond)
3033 between two macroscopically smooth membrane capsules. In the procedure,
3034 one capsule is prepared with a low density coverage of adhesion
3035 molecules, formed as a stiff sphere, and held at fixed position by a
3036 micropipette. The second capsule without adhesion molecules is
3037 pressurized into a spherical shape with low suction by another pipette.
3038 This capsule is maneuvered to initiate point contact at the pole
3039 opposite the stiff capsule which leads to formation of a few (or even
3040 one) molecular attachments. Then, the deformable capsule is slowly
3041 withdrawn by displacement of the pipette. Analysis shows that the end-
3042 to-end extension of the capsule provides a direct measure of the force
3043 at the point contact and, therefore, the rupture strength when
3044 detachment occurs. The range for point forces accessible to this
3045 technique depends on the elastic moduli of the membrane, membrane
3046 tension, and the size of the capsule. For biological and synthetic
3047 vesicle membranes, the range of force lies between 10(-7)-10(-5) dyn
3048 (10(-12)-10(-10) N) which is 100-fold less than presently measurable by
3049 Atomic Force Microscopy! Here, the approach was used to study the
3050 forces required to rupture microscopic attachments between red blood
3051 cells formed by a monoclonal antibody to red cell membrane glycophorin,
3052 anti-A serum, and a lectin from the snail-helix pomatia. Failure of the
3053 attachments appeared to be a stochastic function of the magnitude and
3054 duration of the detachment force. We have correlated the statistical
3055 behavior observed for rupture with a random process model for failure
3056 of small numbers of molecular attachments. The surprising outcome of
3057 the measurements and analysis was that the forces deduced for short-
3058 time failure of 1-2 molecular attachments were nearly the same for all
3059 of the agglutinin, i.e., 1-2 x 10(-6) dyn. Hence, microfluorometric
3060 tests were carried out to determine if labeled agglutinins and/or
3061 labeled surface molecules were transferred between surfaces after
3062 separation of large areas of adhesive contact. The results showed that
3063 the attachments failed because receptors were extracted from the
3067 @article { evans91b,
3068 author = EEvans #" and "# DBerk #" and "# ALeung #" and "# NMohandas,
3069 title = "Detachment of agglutinin-bonded red blood cells. {II}. Mechanical
3070 energies to separate large contact areas",
3078 keywords = "Animals;Antibodies, Monoclonal;Cell Adhesion;Erythrocyte
3079 Membrane;Erythrocytes;Helix
3080 (Snails);Hemagglutination;Hemagglutinins;Humans;Immune
3081 Sera;Kinetics;Lectins;Mathematics",
3082 abstract = "As detailed in a companion paper (Berk, D., and E. Evans. 1991.
3083 Biophys. J. 59:861-872), a method was developed to quantitate the
3084 strength of adhesion between agglutinin-bonded membranes without
3085 ambiguity due to mechanical compliance of the cell body. The
3086 experimental method and analysis were formulated around controlled
3087 assembly and detachment of a pair of macroscopically smooth red blood
3088 cell surfaces. The approach provides precise measurement of the
3089 membrane tension applied at the perimeter of an adhesive contact and
3090 the contact angle theta c between membrane surfaces which defines the
3091 mechanical leverage factor (1-cos theta c) important in the definition
3092 of the work to separate a unit area of contact. Here, the method was
3093 applied to adhesion and detachment of red cells bound together by
3094 different monoclonal antibodies to red cell membrane glycophorin and
3095 the snail-helix pomatia-lectin. For these tests, one of the two red
3096 cells was chemically prefixed in the form of a smooth sphere then
3097 equilibrated with the agglutinin before the adhesion-detachment
3098 procedure. The other cell was not exposed to the agglutinin until it
3099 was forced into contact with the rigid cell surface by mechanical
3100 impingement. Large regions of agglutinin bonding were produced by
3101 impingement but no spontaneous spreading was observed beyond the forced
3102 contact. Measurements of suction force to detach the deformable cell
3103 yielded consistent behavior for all of the agglutinins: i.e., the
3104 strength of adhesion increased progressively with reduction in contact
3105 diameter throughout detachment. This tension-contact diameter behavior
3106 was not altered over a ten-fold range of separation rates. In special
3107 cases, contacts separated smoothly after critical tensions were
3108 reached; these were the highest values attained for tension. Based on
3109 measurements reported in another paper (Evans et al. 1991. Biophys. J.
3110 59:838-848) of the forces required to rupture molecular-point
3111 attachments, the density of cross-bridges was estimated with the
3112 assumption that the tension was proportional to the discrete rupture
3113 force x the number of attachments per unit length. These estimates
3114 showed that only a small fraction of agglutinin formed cross-bridges at
3115 initial assembly and increased progressively with separation. When
3116 critical tension levels were reached, it appeared that nearly all local
3117 agglutinin was involved as cross-bridges. Because one cell surface was
3118 chemically fixed, receptor accumulation was unlikely; thus, microscopic
3119 ``roughness'' and steric repulsion probably modulated formation of
3120 cross-bridges on initial contact.(ABSTRACT TRUNCATED AT 400 WORDS)"
3124 author = EEvans #" and "# KRitchie,
3125 title = "Dynamic strength of molecular adhesion bonds",
3131 pages = "1541--1555",
3133 eprint = "http://www.biophysj.org/cgi/reprint/72/4/1541.pdf",
3134 url = "http://www.biophysj.org/cgi/content/abstract/72/4/1541",
3135 keywords = "Avidin; Biotin; Chemistry, Physical; Computer Simulation;
3136 Mathematics; Monte Carlo Method; Protein Binding",
3137 abstract = "In biology, molecular linkages at, within, and beneath cell
3138 interfaces arise mainly from weak noncovalent interactions. These bonds
3139 will fail under any level of pulling force if held for sufficient time.
3140 Thus, when tested with ultrasensitive force probes, we expect cohesive
3141 material strength and strength of adhesion at interfaces to be time-
3142 and loading rate-dependent properties. To examine what can be learned
3143 from measurements of bond strength, we have extended Kramers' theory
3144 for reaction kinetics in liquids to bond dissociation under force and
3145 tested the predictions by smart Monte Carlo (Brownian dynamics)
3146 simulations of bond rupture. By definition, bond strength is the force
3147 that produces the most frequent failure in repeated tests of breakage,
3148 i.e., the peak in the distribution of rupture forces. As verified by
3149 the simulations, theory shows that bond strength progresses through
3150 three dynamic regimes of loading rate. First, bond strength emerges at
3151 a critical rate of loading (> or = 0) at which spontaneous dissociation
3152 is just frequent enough to keep the distribution peak at zero force. In
3153 the slow-loading regime immediately above the critical rate, strength
3154 grows as a weak power of loading rate and reflects initial coupling of
3155 force to the bonding potential. At higher rates, there is crossover to
3156 a fast regime in which strength continues to increase as the logarithm
3157 of the loading rate over many decades independent of the type of
3158 attraction. Finally, at ultrafast loading rates approaching the domain
3159 of molecular dynamics simulations, the bonding potential is quickly
3160 overwhelmed by the rapidly increasing force, so that only naked
3161 frictional drag on the structure remains to retard separation. Hence,
3162 to expose the energy landscape that governs bond strength, molecular
3163 adhesion forces must be examined over an enormous span of time scales.
3164 However, a significant gap exists between the time domain of force
3165 measurements in the laboratory and the extremely fast scale of
3166 molecular motions. Using results from a simulation of biotin-avidin
3167 bonds (Izrailev, S., S. Stepaniants, M. Balsera, Y. Oono, and K.
3168 Schulten. 1997. Molecular dynamics study of unbinding of the avidin-
3169 biotin complex. Biophys. J., this issue), we describe how Brownian
3170 dynamics can help bridge the gap between molecular dynamics and probe
3172 project = "sawtooth simulation"
3176 author = EEvans #" and "# KRitchie,
3177 title = "Strength of a weak bond connecting flexible polymer chains",
3183 pages = "2439--2447",
3185 eprint = "http://www.biophysj.org/cgi/reprint/76/5/2439.pdf",
3186 url = "http://www.biophysj.org/cgi/content/abstract/76/5/2439",
3187 keywords = "Animals; Biophysics; Biopolymers; Microscopy, Atomic Force;
3188 Models, Chemical; Muscle Proteins; Protein Folding; Protein Kinases;
3189 Stochastic Processes; Stress, Mechanical; Thermodynamics",
3190 abstract = "Bond dissociation under steadily rising force occurs most
3191 frequently at a time governed by the rate of loading (Evans and
3192 Ritchie, 1997 Biophys. J. 72:1541-1555). Multiplied by the loading
3193 rate, the breakage time specifies the force for most frequent failure
3194 (called bond strength) that obeys the same dependence on loading rate.
3195 The spectrum of bond strength versus log(loading rate) provides an
3196 image of the energy landscape traversed in the course of unbonding.
3197 However, when a weak bond is connected to very compliant elements like
3198 long polymers, the load applied to the bond does not rise steadily
3199 under constant pulling speed. Because of nonsteady loading, the most
3200 frequent breakage force can differ significantly from that of a bond
3201 loaded at constant rate through stiff linkages. Using generic models
3202 for wormlike and freely jointed chains, we have analyzed the kinetic
3203 process of failure for a bond loaded by pulling the polymer linkages at
3204 constant speed. We find that when linked by either type of polymer
3205 chain, a bond is likely to fail at lower force under steady separation
3206 than through stiff linkages. Quite unexpectedly, a discontinuous jump
3207 can occur in bond strength at slow separation speed in the case of long
3208 polymer linkages. We demonstrate that the predictions of strength
3209 versus log(loading rate) can rationalize conflicting results obtained
3210 recently for unfolding Ig domains along muscle titin with different
3212 note = "Develops Kramers improvement on Bell model for domain unfolding.
3213 Presents unfolding under variable loading rates. Often cited as the
3214 ``Bell--Evans'' model. They derive a unitless treatment, scaling force
3215 by $f_\beta$, TODO; time by $\tau_f$, TODO; elasiticity by compliance
3216 $c(f)$. The appendix has relaxation time formulas for WLC and FJC
3218 project = "sawtooth simulation"
3221 @article { fernandez04,
3222 author = JFernandez #" and "# HLi,
3223 title = "Force-clamp spectroscopy monitors the folding trajectory of a
3231 pages = "1674--1678",
3233 doi = "10.1126/science.1092497",
3234 eprint = "http://www.sciencemag.org/cgi/reprint/303/5664/1674.pdf",
3235 url = "http://www.sciencemag.org/cgi/content/abstract/303/5664/1674",
3236 keywords = "Chemistry, Physical;Microscopy, Atomic Force;Physicochemical
3237 Phenomena;Polyubiquitin;Protein Conformation;Protein
3238 Denaturation;Protein Folding;Protein Structure, Secondary;Time
3240 abstract = "We used force-clamp atomic force microscopy to measure the end-
3241 to-end length of the small protein ubiquitin during its folding
3242 reaction at the single-molecule level. Ubiquitin was first unfolded and
3243 extended at a high force, then the stretching force was quenched and
3244 protein folding was observed. The folding trajectories were continuous
3245 and marked by several distinct stages. The time taken to fold was
3246 dependent on the contour length of the unfolded protein and the
3247 stretching force applied during folding. The folding collapse was
3248 marked by large fluctuations in the end-to-end length of the protein,
3249 but these fluctuations vanished upon the final folding contraction.
3250 These direct observations of the complete folding trajectory of a
3251 protein provide a benchmark to determine the physical basis of the
3256 author = JHoward #" and "# AJHudspeth,
3257 title = {Mechanical relaxation of the hair bundle mediates
3258 adaptation in mechanoelectrical transduction by the
3259 bullfrog's saccular hair cell.},
3265 pages = {3064--3068},
3267 url = {http://www.ncbi.nlm.nih.gov/pubmed/3495007},
3268 keywords = {Acclimatization},
3269 keywords = {Animals},
3270 keywords = {Electric Conductivity},
3271 keywords = {Electric Stimulation},
3272 keywords = {Hair Cells, Auditory},
3273 keywords = {Membrane Potentials},
3274 keywords = {Microelectrodes},
3275 keywords = {Physical Stimulation},
3276 keywords = {Rana catesbeiana},
3277 keywords = {Saccule and Utricle},
3278 abstract = {Mechanoelectrical transduction by hair cells of the
3279 frog's internal ear displays adaptation: the electrical response
3280 to a maintained deflection of the hair bundle declines over a
3281 period of tens of milliseconds. We investigated the role of
3282 mechanics in adaptation by measuring changes in hair-bundle
3283 stiffness following the application of force stimuli. Following
3284 step stimulation with a glass fiber, the hair bundle of a saccular
3285 hair cell initially had a stiffness of approximately equal to
3286 $1\U{mN/m}$. The stiffness then declined to a steady-state level
3287 near $0.6\U{mN/m}$ with a time course comparable to that of
3288 adaptation in the receptor current. The hair bundle may be modeled
3289 as the parallel combination of a spring, which represents the
3290 rotational stiffness of the stereocilia, and a series spring and
3291 dashpot, which respectively, represent the elastic element
3292 responsible for channel gating and the apparatus for adaptation.},
3297 author = JHoward #" and "# AJHudspeth,
3298 title = {Compliance of the Hair Bundle Associated with Gating of
3299 Mechanoelectrical Transduction Channels in the Bullfrog's Saccular
3306 doi = {10.1016/0896-6273(88)90139-0},
3307 url = {http://www.cell.com/neuron/retrieve/pii/0896627388901390},
3308 eprint = {http://download.cell.com/neuron/pdf/PII0896627388901390.pdf},
3309 note = {Initial thermal calibration paper as cited by
3310 \citet{florin95}. This is not an AFM paper, but it uses the
3311 equipartition theorem to calculate the spring constant of hair
3312 fibers by measuring their tip displacement variance. The
3313 discussion occurs in the \emph{Manufacture and Calibration of
3314 Fibers} section on pages 197--198. Actual details are scarce, but
3315 I believe this is the original source of the ``Lorentzian'' and
3316 ``10\% accuracy'' ideas that have haunted themal calibration ever
3321 author = ELFlorin #" and "# VMoy #" and "# HEGaub,
3322 title = {Adhesion forces between individual ligand-receptor pairs},
3330 doi = {10.1126/science.8153628},
3331 url = {http://www.sciencemag.org/content/264/5157/415.abstract},
3332 eprint = {http://www.sciencemag.org/content/264/5157/415.full.pdf},
3333 abstract ={The adhesion force between the tip of an atomic force
3334 microscope cantilever derivatized with avidin and agarose beads
3335 functionalized with biotin, desthiobiotin, or iminobiotin was
3336 measured. Under conditions that allowed only a limited number of
3337 molecular pairs to interact, the force required to separate tip
3338 and bead was found to be quantized in integer multiples of
3339 $160\pm20$ piconewtons for biotin and $85\pm15$ piconewtons for
3340 iminobiotin. The measured force quanta are interpreted as the
3341 unbinding forces of individual molecular pairs.},
3344 @article { florin95,
3345 author = ELFlorin #" and "# MRief #" and "# HLehmann #" and "# MLudwig #"
3346 and "# CDornmair #" and "# VMoy #" and "# HEGaub,
3347 title = "Sensing specific molecular interactions with the atomic force
3355 doi = "10.1016/0956-5663(95)99227-C",
3356 url = "http://www.sciencedirect.com/science/article/B6TFC-
3357 3XY2HK9-G/2/6f4e9f67e9a1e14c8bbcc478e5360682",
3358 abstract = "One of the unique features of the atomic force microscope (AFM)
3359 is its capacity to measure interactions between tip and sample with
3360 high sensitivity and unparal leled spatial resolution. Since the
3361 development of methods for the functionaliza tion of the tips, the
3362 versatility of the AFM has been expanded to experiments wh ere specific
3363 molecular interactions are measured. For illustration, we present m
3364 easurements of the interaction between complementary strands of DNA. A
3365 necessary prerequisite for the quantitative analysis of the interaction
3366 force is knowledg e of the spring constant of the cantilevers. Here, we
3367 compare different techniqu es that allow for the in situ measurement of
3368 the absolute value of the spring co nstant of cantilevers.",
3369 note = {Good review of calibration to 1995, with experimental
3370 comparison between resonance-shift, reference-spring, and
3371 thermal methods. They incorrectly cite \citet{hutter93} as
3372 being published in 1994.},
3373 project = "Cantilever Calibration"
3376 @article{ burnham03,
3377 author = NABurnham #" and "# XiChen #" and "# CSHodges #" and "#
3378 GAMatei #" and "# EJThoreson #" and "# CJRoberts #" and "#
3379 MCDavies #" and "# SJBTendler,
3380 title = {Comparison of calibration methods for atomic-force
3381 microscopy cantilevers},
3388 url = {http://stacks.iop.org/0957-4484/14/i=1/a=301},
3389 abstract = {The scientific community needs a rapid and reliable way
3390 of accurately determining the stiffness of atomic-force microscopy
3391 cantilevers. We have compared the experimentally determined values
3392 of stiffness for ten cantilever probes using four different
3393 methods. For rectangular silicon cantilever beams of well defined
3394 geometry, the approaches all yield values within 17\% of the
3395 manufacturer's nominal stiffness. One of the methods is new, based
3396 on the acquisition and analysis of thermal distribution functions
3397 of the oscillator's amplitude fluctuations. We evaluate this
3398 method in comparison to the three others and recommend it for its
3399 ease of use and broad applicability.},
3400 note = {Contains both the overdamped (\fref{equation}{6}) and
3401 general (\fref{equation}{8}) power spectral densities used in
3402 thermal cantilever calibration, but punts to textbooks for the
3407 author = NRForde #" and "# DIzhaky #" and "# GRWoodcock #" and "# GJLWuite
3408 #" and "# CBustamante,
3409 title = "Using mechanical force to probe the mechanism of pausing and
3410 arrest during continuous elongation by Escherichia coli {RNA}
3418 pages = "11682--11687",
3420 doi = "10.1073/pnas.142417799",
3421 eprint = "http://www.pnas.org/cgi/reprint/99/18/11682.pdf",
3422 url = "http://www.pnas.org/content/99/18/11682",
3423 keywords = "DNA-Directed RNA Polymerases;Escherichia
3424 coli;Kinetics;Transcription, Genetic",
3425 abstract = "Escherichia coli RNA polymerase translocates along the DNA
3426 discontinuously during the elongation phase of transcription, spending
3427 proportionally more time at some template positions, known as pause and
3428 arrest sites, than at others. Current models of elongation suggest that
3429 the enzyme backtracks at these locations, but the dynamics are
3430 unresolved. Here, we study the role of lateral displacement in pausing
3431 and arrest by applying force to individually transcribing molecules. We
3432 find that an assisting mechanical force does not alter the
3433 translocation rate of the enzyme, but does reduce the efficiency of
3434 both pausing and arrest. Moreover, arrested molecules cannot be rescued
3435 by force, suggesting that arrest occurs by a bipartite mechanism: the
3436 enzyme backtracks along the DNA followed by a conformational change of
3437 the ternary complex (RNA polymerase, DNA and transcript), which cannot
3438 be reversed mechanically."
3441 @article { freitag97,
3442 author = SFreitag #" and "# ILTrong #" and "# LKlumb #" and "# PSStayton #"
3444 title = "Structural studies of the streptavidin binding loop.",
3450 pages = "1157--1166",
3452 doi = "10.1002/pro.5560060604",
3453 keywords = "Allosteric Regulation;Bacterial Proteins;Binding
3454 Sites;Biotin;Crystallography, X-Ray;Hydrogen Bonding;Ligands;Models,
3455 Molecular;Molecular Conformation;Streptavidin;Tryptophan",
3456 abstract = "The streptavidin-biotin complex provides the basis for many
3457 important biotechnological applications and is an interesting model
3458 system for studying high-affinity protein-ligand interactions. We
3459 report here crystallographic studies elucidating the conformation of
3460 the flexible binding loop of streptavidin (residues 45 to 52) in the
3461 unbound and bound forms. The crystal structures of unbound streptavidin
3462 have been determined in two monoclinic crystal forms. The binding loop
3463 generally adopts an open conformation in the unbound species. In one
3464 subunit of one crystal form, the flexible loop adopts the closed
3465 conformation and an analysis of packing interactions suggests that
3466 protein-protein contacts stabilize the closed loop conformation. In the
3467 other crystal form all loops adopt an open conformation. Co-
3468 crystallization of streptavidin and biotin resulted in two additional,
3469 different crystal forms, with ligand bound in all four binding sites of
3470 the first crystal form and biotin bound in only two subunits in a
3471 second. The major change associated with binding of biotin is the
3472 closure of the surface loop incorporating residues 45 to 52. Residues
3473 49 to 52 display a 3(10) helical conformation in unbound subunits of
3474 our structures as opposed to the disordered loops observed in other
3475 structure determinations of streptavidin. In addition, the open
3476 conformation is stabilized by a beta-sheet hydrogen bond between
3477 residues 45 and 52, which cannot occur in the closed conformation. The
3478 3(10) helix is observed in nearly all unbound subunits of both the co-
3479 crystallized and ligand-free structures. An analysis of the temperature
3480 factors of the binding loop regions suggests that the mobility of the
3481 closed loops in the complexed structures is lower than in the open
3482 loops of the ligand-free structures. The two biotin bound subunits in
3483 the tetramer found in the MONO-b1 crystal form are those that
3484 contribute Trp 120 across their respective binding pockets, suggesting
3485 a structural link between these binding sites in the tetramer. However,
3486 there are no obvious signatures of binding site communication observed
3487 upon ligand binding, such as quaternary structure changes or shifts in
3488 the region of Trp 120. These studies demonstrate that while
3489 crystallographic packing interactions can stabilize both the open and
3490 closed forms of the flexible loop, in their absence the loop is open in
3491 the unbound state and closed in the presence of biotin. If present in
3492 solution, the helical structure in the open loop conformation could
3493 moderate the entropic penalty associated with biotin binding by
3494 contributing an order-to-disorder component to the loop closure.",
3495 note = "\href{http://www.rcsb.org/pdb/explore.do?structureId=1SWE}{PDB ID:
3497 \href{http://dx.doi.org/10.2210/pdb1swe/pdb}{10.2210/pdb1swe/pdb}."
3500 @article { friddle08,
3501 author = RWFriddle #" and "# PPodsiadlo #" and "# ABArtyukhin #" and "#
3503 title = "Near-Equilibrium Chemical Force Microscopy",
3508 pages = "4986--4990",
3509 doi = "10.1021/jp7095967",
3510 eprint = "http://pubs.acs.org/doi/pdf/10.1021/jp7095967",
3511 url = "http://pubs.acs.org/doi/abs/10.1021/jp7095967"
3515 author = TFujii #" and "# YLSun #" and "# KNAn #" and "# ZPLuo,
3516 title = "Mechanical properties of single hyaluronan molecules",
3524 keywords = "Biomechanics;Cross-Linking Reagents;Elasticity;Extracellular
3525 Matrix;Humans;Hyaluronic Acid;Lasers;Microspheres;Nanotechnology",
3526 abstract = "Hyaluronan (HA) is a major component of the extracellular
3527 matrix. It plays an important role in the mechanical functions of the
3528 extracellular matrix and stabilization of cells. Currently, its
3529 mechanical properties have been investigated only at the gross level.
3530 In this study, the mechanical properties of single HA molecules were
3531 directly measured with an optical tweezer technique, yielding a
3532 persistence length of 4.5 +/- 1.2 nm. This information may help us to
3533 understand the mechanical roles in the extracellular matrix
3534 infrastructure, cell attachment, and to design tissue engineering and
3535 drug delivery systems where the mechanical functions of HA are
3539 @article { ganchev08,
3540 author = DNGanchev #" and "# NJCobb #" and "# KSurewicz #" and "#
3542 title = "Nanomechanical properties of human prion protein amyloid as probed
3543 by force spectroscopy",
3550 pages = "2909--2915",
3552 doi = "10.1529/biophysj.108.133108",
3553 abstract = "Amyloids are associated with a number of protein misfolding
3554 disorders, including prion diseases. In this study, we used single-
3555 molecule force spectroscopy to characterize the nanomechanical
3556 properties and molecular structure of amyloid fibrils formed by human
3557 prion protein PrP90-231. Force-extension curves obtained by specific
3558 attachment of a gold-covered atomic force microscope tip to engineered
3559 Cys residues could be described by the worm-like chain model for
3560 entropic elasticity of a polymer chain, with the size of the N-terminal
3561 segment that could be stretched entropically depending on the tip
3562 attachment site. The data presented here provide direct information
3563 about the forces required to extract an individual monomer from the
3564 core of the PrP90-231 amyloid, and indicate that the beta-sheet core of
3565 this amyloid starts at residue approximately 164-169. The latter
3566 finding has important implications for the ongoing debate regarding the
3567 structure of PrP amyloid."
3571 author = MGao #" and "# DCraig #" and "# OLequin #" and "# ICampbell #" and
3572 "# VVogel #" and "# KSchulten,
3573 title = "Structure and functional significance of mechanically unfolded
3574 fibronectin type {III1} intermediates",
3579 pages = "14784--14789",
3580 doi = "10.1073/pnas.2334390100",
3581 eprint = "http://www.pnas.org/cgi/reprint/100/25/14784.pdf",
3582 url = "http://www.pnas.org/cgi/content/abstract/100/25/14784",
3583 abstract = "Fibronectin (FN) forms fibrillar networks coupling cells to the
3584 extracellular matrix. The formation of FN fibrils, fibrillogenesis, is
3585 a tightly regulated process involving the exposure of cryptic binding
3586 sites in individual FN type III (FN-III) repeats presumably exposed by
3587 mechanical tension. The FN-III1 module has been previously proposed to
3588 contain such cryptic sites that promote the assembly of extracellular
3589 matrix FN fibrils. We have combined NMR and steered molecular dynamics
3590 simulations to study the structure and mechanical unfolding pathway of
3591 FN-III1. This study finds that FN-III1 consists of a {beta}-sandwich
3592 structure that unfolds to a mechanically stable intermediate about four
3593 times the length of the native folded state. Considering previous
3594 experimental findings, our studies provide a structural model by which
3595 mechanical stretching of FN-III1 may induce fibrillogenesis through
3596 this partially unfolded intermediate."
3599 @article { gavrilov01,
3600 author = LAGavrilov #" and "# NSGavrilova,
3601 title = "The reliability theory of aging and longevity",
3610 doi = "10.1006/jtbi.2001.2430",
3611 keywords = "Adult;Aged;Aging;Animals;Humans;Longevity;Middle Aged;Models,
3612 Biological;Survival Rate;Systems Theory",
3613 abstract = "Reliability theory is a general theory about systems failure.
3614 It allows researchers to predict the age-related failure kinetics for a
3615 system of given architecture (reliability structure) and given
3616 reliability of its components. Reliability theory predicts that even
3617 those systems that are entirely composed of non-aging elements (with a
3618 constant failure rate) will nevertheless deteriorate (fail more often)
3619 with age, if these systems are redundant in irreplaceable elements.
3620 Aging, therefore, is a direct consequence of systems redundancy.
3621 Reliability theory also predicts the late-life mortality deceleration
3622 with subsequent leveling-off, as well as the late-life mortality
3623 plateaus, as an inevitable consequence of redundancy exhaustion at
3624 extreme old ages. The theory explains why mortality rates increase
3625 exponentially with age (the Gompertz law) in many species, by taking
3626 into account the initial flaws (defects) in newly formed systems. It
3627 also explains why organisms ``prefer'' to die according to the Gompertz
3628 law, while technical devices usually fail according to the Weibull
3629 (power) law. Theoretical conditions are specified when organisms die
3630 according to the Weibull law: organisms should be relatively free of
3631 initial flaws and defects. The theory makes it possible to find a
3632 general failure law applicable to all adult and extreme old ages, where
3633 the Gompertz and the Weibull laws are just special cases of this more
3634 general failure law. The theory explains why relative differences in
3635 mortality rates of compared populations (within a given species) vanish
3636 with age, and mortality convergence is observed due to the exhaustion
3637 of initial differences in redundancy levels. Overall, reliability
3638 theory has an amazing predictive and explanatory power with a few, very
3639 general and realistic assumptions. Therefore, reliability theory seems
3640 to be a promising approach for developing a comprehensive theory of
3641 aging and longevity integrating mathematical methods with specific
3642 biological knowledge.",
3643 note = "An example of exponential (standard) Gomperz law."
3646 @article { gergely00,
3647 author = CGergely #" and "# JCVoegel #" and "# PSchaaf #" and "# BSenger #"
3648 and "# MMaaloum #" and "# JHorber #" and "# JHemmerle,
3649 title = "Unbinding process of adsorbed proteins under external stress
3650 studied by atomic force microscopy spectroscopy",
3655 pages = "10802--10807",
3656 doi = "10.1073/pnas.180293097",
3657 eprint = "http://www.pnas.org/cgi/reprint/97/20/10802.pdf",
3658 url = "http://www.pnas.org/cgi/content/abstract/97/20/10802"
3661 @article { gompertz25,
3663 title = "On the Nature of the Function Expressive of the Law of Human
3664 Mortality, and on a New Mode of Determining the Value of Life
3673 copyright = "Copyright \copy\ 1825 The Royal Society",
3674 url = "http://www.jstor.org/stable/107756",
3676 jstor_articletype = "primary_article",
3677 jstor_formatteddate = 1825,
3678 jstor_issuetitle = ""
3683 title = {The significance of the difference between two means when
3684 the population variances are unequal},
3691 keywords = "Population",
3693 url = "http://www.jstor.org/stable/2332010",
3699 title = {The generalization of {Student's} problems when several
3700 different population variances are involved},
3707 keywords = "Population",
3709 url = "http://www.ncbi.nlm.nih.gov/pubmed/20287819",
3710 jstor_url = "http://www.jstor.org/stable/2332510",
3714 @article { granzier97,
3715 author = HLGranzier #" and "# MSKellermayer #" and "# MHelmes #" and "#
3717 title = "Titin elasticity and mechanism of passive force development in rat
3718 cardiac myocytes probed by thin-filament extraction",
3724 pages = "2043--2053",
3726 doi = "10.1016/S0006-3495(97)78234-1",
3727 url = "http://www.cell.com/biophysj/retrieve/pii/S0006349597782341",
3728 keywords = "Amino Acid Sequence;Animals;Biomechanics;Biophysical
3729 Phenomena;Biophysics;Cell Fractionation;Elasticity;Gelsolin;Microscopy,
3730 Immunoelectron;Models, Cardiovascular;Molecular Structure;Muscle
3731 Proteins;Myocardial Contraction;Myocardium;Protein
3732 Kinases;Rats;Sarcomeres",
3733 abstract = "Titin (also known as connectin) is a giant filamentous protein
3734 whose elastic properties greatly contribute to the passive force in
3735 muscle. In the sarcomere, the elastic I-band segment of titin may
3736 interact with the thin filaments, possibly affecting the molecule's
3737 elastic behavior. Indeed, several studies have indicated that
3738 interactions between titin and actin occur in vitro and may occur in
3739 the sarcomere as well. To explore the properties of titin alone, one
3740 must first eliminate the modulating effect of the thin filaments by
3741 selectively removing them. In the present work, thin filaments were
3742 selectively removed from the cardiac myocyte by using a gelsolin
3743 fragment. Partial extraction left behind approximately 100-nm-long thin
3744 filaments protruding from the Z-line, whereas the rest of the I-band
3745 became devoid of thin filaments, exposing titin. By applying a much
3746 more extensive gelsolin treatment, we also removed the remaining short
3747 thin filaments near the Z-line. After extraction, the extensibility of
3748 titin was studied by using immunoelectron microscopy, and the passive
3749 force-sarcomere length relation was determined by using mechanical
3750 techniques. Titin's regional extensibility was not detectably affected
3751 by partial thin-filament extraction. Passive force, on the other hand,
3752 was reduced at sarcomere lengths longer than approximately 2.1 microm,
3753 with a 33 +/- 9\% reduction at 2.6 microm. After a complete extraction,
3754 the slack sarcomere length was reduced to approximately 1.7 microm. The
3755 segment of titin near the Z-line, which is otherwise inextensible,
3756 collapsed toward the Z-line in sarcomeres shorter than approximately
3757 2.0 microm, but it was extended in sarcomeres longer than approximately
3758 2.3 microm. Passive force became elevated at sarcomere lengths between
3759 approximately 1.7 and approximately 2.1 microm, but was reduced at
3760 sarcomere lengths of >2.3 microm. These changes can be accounted for by
3761 modeling titin as two wormlike chains in series, one of which increases
3762 its contour length by recruitment of the titin segment near the Z-line
3763 into the elastic pool."
3766 @article { grossman05,
3767 author = CGrossman #" and "# AStout,
3768 title = "Optical Tweezers Advanced Lab",
3772 eprint = "http://chirality.swarthmore.edu/PHYS81/OpticalTweezers.pdf",
3773 note = {Fairly complete overdamped PSD derivation in
3774 \fref{section}{4.3}. Cites \citet{tlusty98} and
3775 \citet{bechhoefer02} for further details. However, Tlusty
3776 (listed as reference 8) doesn't contain the thermal response
3777 fn.\ derivation it was cited for. Also, the single sided PSD
3778 definition credited to reference 9 (listed as Bechhoefer)
3779 looks more like Press (listed as reference 10). I imagine
3780 Grossman and Stout mixed up their references, and meant to
3781 refer to \citet{bechhoefer02} and \citet{press92} respectively
3783 project = "Cantilever Calibration"
3786 @article { halvorsen09,
3787 author = KHalvorsen #" and "# WPWong,
3788 title = "Massively parallel single-molecule manipulation using centrifugal
3792 url = "http://arxiv.org/abs/0912.5370",
3793 abstract = {Precise manipulation of single molecules has already led to
3794 remarkable insights in physics, chemistry, biology and medicine.
3795 However, widespread adoption of single-molecule techniques has been
3796 impeded by equipment cost and the laborious nature of making
3797 measurements one molecule at a time. We have solved these issues with a
3798 new approach: massively parallel single-molecule force measurements
3799 using centrifugal force. This approach is realized in a novel
3800 instrument that we call the Centrifuge Force Microscope (CFM), in which
3801 objects in an orbiting sample are subjected to a calibration-free,
3802 macroscopically uniform force-field while their micro-to-nanoscopic
3803 motions are observed. We demonstrate high-throughput single-molecule
3804 force spectroscopy with this technique by performing thousands of
3805 rupture experiments in parallel, characterizing force-dependent
3806 unbinding kinetics of an antibody-antigen pair in minutes rather than
3807 days. Additionally, we verify the force accuracy of the instrument by
3808 measuring the well-established DNA overstretching transition at 66
3809 $\pm$ 3 pN. With significant benefits in efficiency, cost, simplicity,
3810 and versatility, "single-molecule centrifugation" has the potential to
3811 revolutionize single-molecule experimentation, and open access to a
3812 wider range of researchers and experimental systems.}
3815 @article { hanggi90,
3816 author = PHanggi #" and "# PTalkner #" and "# MBorkovec,
3817 title = "Reaction-rate theory: Fifty years after {K}ramers",
3826 doi = "10.1103/RevModPhys.62.251",
3827 eprint = "http://www.physik.uni-augsburg.de/theo1/hanggi/Papers/112.pdf",
3828 url = "http://prola.aps.org/abstract/RMP/v62/i2/p251_1",
3829 note = "\emph{The} Kramers' theory review article. See pages 268--279 for
3830 the Kramers-specific introduction.",
3831 project = "sawtooth simulation"
3834 @article { hatfield99,
3835 author = JWHatfield #" and "# SRQuake,
3836 title = "Dynamic Properties of an Extended Polymer in Solution",
3842 pages = "3548--3551",
3845 doi = "10.1103/PhysRevLett.82.3548",
3846 url = "http://link.aps.org/abstract/PRL/v82/p3548",
3847 note = "Defines WLC and FJC models, citing textbooks.",
3848 project = "sawtooth simulation"
3851 @article { heymann00,
3852 author = BHeymann #" and "# HGrubmuller,
3853 title = "Dynamic force spectroscopy of molecular adhesion bonds",
3860 pages = "6126--6129",
3862 doi = "10.1103/PhysRevLett.84.6126",
3863 eprint = "http://prola.aps.org/pdf/PRL/v84/i26/p6126_1",
3864 url = "http://prola.aps.org/abstract/PRL/v84/p6126",
3865 abstract = "Recent advances in atomic force microscopy, biomembrane force
3866 probe experiments, and optical tweezers allow one to measure the
3867 response of single molecules to mechanical stress with high precision.
3868 Such experiments, due to limited spatial resolution, typically access
3869 only one single force value in a continuous force profile that
3870 characterizes the molecular response along a reaction coordinate. We
3871 develop a theory that allows one to reconstruct force profiles from
3872 force spectra obtained from measurements at varying loading rates,
3873 without requiring increased resolution. We show that spectra obtained
3874 from measurements with different spring constants contain complementary
3878 @article { hummer01,
3879 author = GHummer #" and "# ASzabo,
3880 title = "From the Cover: Free energy reconstruction from nonequilibrium
3881 single-molecule pulling experiments",
3886 pages = "3658--3661",
3887 doi = "10.1073/pnas.071034098",
3888 eprint = "http://www.pnas.org/cgi/reprint/98/7/3658.pdf",
3889 url = "http://www.pnas.org/cgi/content/abstract/98/7/3658",
3893 @article { hummer03,
3894 author = GHummer #" and "# ASzabo,
3895 title = "Kinetics from nonequilibrium single-molecule pulling experiments",
3903 eprint = "http://www.biophysj.org/cgi/reprint/85/1/5.pdf",
3904 url = "http://www.biophysj.org/cgi/content/abstract/85/1/5",
3905 keywords = "Computer Simulation; Crystallography; Energy Transfer;
3906 Kinetics; Lasers; Micromanipulation; Microscopy, Atomic Force; Models,
3907 Molecular; Molecular Conformation; Motion; Muscle Proteins;
3908 Nanotechnology; Physical Stimulation; Protein Conformation; Protein
3909 Denaturation; Protein Folding; Protein Kinases; Stress, Mechanical",
3910 abstract = "Mechanical forces exerted by laser tweezers or atomic force
3911 microscopes can be used to drive rare transitions in single molecules,
3912 such as unfolding of a protein or dissociation of a ligand. The
3913 phenomenological description of pulling experiments based on Bell's
3914 expression for the force-induced rupture rate is found to be inadequate
3915 when tested against computer simulations of a simple microscopic model
3916 of the dynamics. We introduce a new approach of comparable complexity
3917 to extract more accurate kinetic information about the molecular events
3918 from pulling experiments. Our procedure is based on the analysis of a
3919 simple stochastic model of pulling with a harmonic spring and
3920 encompasses the phenomenological approach, reducing to it in the
3921 appropriate limit. Our approach is tested against computer simulations
3922 of a multimodule titin model with anharmonic linkers and then an
3923 illustrative application is made to the forced unfolding of I27
3924 subunits of the protein titin. Our procedure to extract kinetic
3925 information from pulling experiments is simple to implement and should
3926 prove useful in the analysis of experiments on a variety of systems.",
3928 project = "sawtooth simulation"
3931 @article { hutter05,
3933 title = "Comment on tilt of atomic force microscope cantilevers: Effect on
3934 spring constant and adhesion measurements.",
3941 pages = "2630--2632",
3943 doi = "10.1021/la047670t",
3944 note = "Tilted cantilever corrections (not needed? see Ohler/VEECO note)",
3945 project = "Cantilever Calibration"
3948 @article { hutter93,
3949 author = JHutter #" and "# JBechhoefer,
3950 title = "Calibration of atomic-force microscope tips",
3955 pages = "1868--1873",
3957 doi = "10.1063/1.1143970",
3958 url = "http://link.aip.org/link/?RSI/64/1868/1",
3959 keywords = {atomic force microscopy; calibration; quality factor; probes;
3960 resonance; silicon nitrides; mica; van der waals forces},
3961 note = {Original equipartition-based calibration method (thermal
3962 calibration), after the brief mention in \citet{howard88}.
3963 This is the first paper I've found that works out the theory
3964 in detail, although they punt to page 431 of \citet{heer72}
3965 instead of listing a formula for their ``Lorentzian''. The
3966 experimental data uses high-$Q$ cantilevers in air, and their
3967 figure 2 shows clear water-layer snap-off. There is a
3968 published erratum\citep{hutter93-erratum}.},
3969 project = "Cantilever Calibration"
3972 @article{ hutter93-erratum,
3973 author = JHutter #" and "# JBechhoefer,
3974 title = "Erratum: Calibration of atomic-force microscope tips",
3982 doi = "10.1063/1.1144449",
3983 url = "http://rsi.aip.org/resource/1/rsinak/v64/i11/p3342_s1",
3984 note = {V.~Croquette pointed out that they should calibrate the
3985 response of their optical-detection electronics.},
3986 project = "Cantilever Calibration",
3991 title = {Statistical mechanics, kinetic theory, and stochastic processes},
3994 address = {New York},
3996 isbn = {0-123-36550-3},
3997 language = {English},
3998 keywords = {Statistical mechanics.; Kinetic theory of gases.; Stochastic processes.},
4002 author = CHyeon #" and "# DThirumalai,
4003 title = "Can energy landscape roughness of proteins and {RNA} be measured
4004 by using mechanical unfolding experiments?",
4011 pages = "10249--10253",
4013 doi = "10.1073/pnas.1833310100",
4014 eprint = "http://www.pnas.org/cgi/reprint/100/18/10249.pdf",
4015 url = "http://www.pnas.org/cgi/content/abstract/100/18/10249",
4016 keywords = "Protein Folding; Proteins; RNA; Temperature; Thermodynamics",
4017 abstract = "By considering temperature effects on the mechanical unfolding
4018 rates of proteins and RNA, whose energy landscape is rugged, the
4019 question posed in the title is answered in the affirmative. Adopting a
4020 theory by Zwanzig [Zwanzig, R. (1988) Proc. Natl. Acad. Sci. USA 85,
4021 2029-2030], we show that, because of roughness characterized by an
4022 energy scale epsilon, the unfolding rate at constant force is retarded.
4023 Similarly, in nonequilibrium experiments done at constant loading
4024 rates, the most probable unfolding force increases because of energy
4025 landscape roughness. The effects are dramatic at low temperatures. Our
4026 analysis suggests that, by using temperature as a variable in
4027 mechanical unfolding experiments of proteins and RNA, the ruggedness
4028 energy scale epsilon, can be directly measured.",
4029 note = "Derives the major theory behind my thesis. The Kramers rate
4030 equation is \xref{hanggi90}{equation}{4.56c} (page 275).",
4031 project = "Energy Landscape Roughness"
4034 @article { improta96,
4035 author = SImprota #" and "# ASPolitou #" and "# APastore,
4036 title = "Immunoglobulin-like modules from titin {I}-band: Extensible
4037 components of muscle elasticity.",
4046 doi = "10.1016/S0969-2126(96)00036-6",
4047 keywords = "Amino Acid Sequence;Immunoglobulins;Magnetic Resonance
4048 Spectroscopy;Models, Molecular;Molecular Sequence Data;Molecular
4049 Structure;Muscle Proteins;Protein Kinases;Protein Structure,
4050 Secondary;Protein Structure, Tertiary;Sequence Alignment",
4051 abstract = "BACKGROUND. The giant muscle protein titin forms a filament
4052 which spans half of the sarcomere and performs, along its length, quite
4053 diverse functions. The region of titin located in the sarcomere I-band
4054 is believed to play a major role in extensibility and passive
4055 elasticity of muscle. In the I-band, the titin sequence consists mostly
4056 of repetitive motifs of tandem immunoglobulin-like (Ig) modules
4057 intercalated by a potentially non-globular region. The highly
4058 repetitive titin architecture suggests that the molecular basis of its
4059 mechanical properties be approached through the characterization of the
4060 isolated components of the I-band and their interfaces. In the present
4061 paper, we report on the structure determination in solution of a
4062 representative Ig module from the I-band (I27) as solved by NMR
4063 techniques. RESULTS. The structure of I27 consists of a beta sandwich
4064 formed by two four-stranded sheets (named ABED and A'GFC). This fold
4065 belongs to the intermediate frame (I frame) of the immunoglobulin
4066 superfamily. Comparison of I27 with another titin module from the
4067 region located in the M-line (M5) shows that two loops (between the B
4068 and C and the F and G strands) are shorter in I27, conferring a less
4069 elongated appearance to this structure. Such a feature is specific to
4070 the Ig domains in the I-band and might therefore be related to the
4071 functions of the protein in this region. The structure of tandem Ig
4072 domains as modeled from I27 suggests the presence of hinge regions
4073 connecting contiguous modules. CONCLUSIONS. We suggest that titin Ig
4074 domains in the I-band function as extensible components of muscle
4075 elasticity by stretching the hinge regions.",
4076 note = "\href{http://www.rcsb.org/pdb/explore.do?structureId=1TIT}{PDB ID:
4078 \href{http://dx.doi.org/10.2210/pdb1tit/pdb}{10.2210/pdb1tit/pdb}."
4081 @article { irback05,
4082 author = AIrback #" and "# SMitternacht #" and "# SMohanty,
4083 title = "Dissecting the mechanical unfolding of ubiquitin",
4088 pages = "13427--13432",
4089 doi = "10.1073/pnas.0501581102",
4090 eprint = "http://www.pnas.org/cgi/reprint/102/38/13427.pdf",
4091 url = "http://www.pnas.org/cgi/content/abstract/102/38/13427",
4092 abstract = "The unfolding behavior of ubiquitin under the influence of a
4093 stretching force recently was investigated experimentally by single-
4094 molecule constant-force methods. Many observed unfolding traces had a
4095 simple two-state character, whereas others showed clear evidence of
4096 intermediate states. Here, we use Monte Carlo simulations to
4097 investigate the force-induced unfolding of ubiquitin at the atomic
4098 level. In agreement with experimental data, we find that the unfolding
4099 process can occur either in a single step or through intermediate
4100 states. In addition to this randomness, we find that many quantities,
4101 such as the frequency of occurrence of intermediates, show a clear
4102 systematic dependence on the strength of the applied force. Despite
4103 this diversity, one common feature can be identified in the simulated
4104 unfolding events, which is the order in which the secondary-structure
4105 elements break. This order is the same in two- and three-state events
4106 and at the different forces studied. The observed order remains to be
4107 verified experimentally but appears physically reasonable."
4110 @article{ grubmuller96,
4111 author = HGrubmuller #" and "# BHeymann #" and "# PTavan,
4112 title = {Ligand binding: molecular mechanics calculation of the
4113 streptavidin-biotin rupture force.},
4117 address = {Theoretische Biophysik, Institut f{\"u}r Medizinische
4118 Optik, Ludwig- Maximilians-Universit{\"a}t M{\"u}nchen,
4119 Germany. Helmut.Grubmueller@ Physik.uni-muenchen.de},
4125 url = {http://www.ncbi.nlm.nih.gov/pubmed/8584939},
4126 eprint = {http://pubman.mpdl.mpg.de/pubman/item/escidoc:1690312:2/component/escidoc:1690313/1690312.pdf},
4128 keywords = {Bacterial Proteins},
4129 keywords = {Biotin},
4130 keywords = {Chemistry, Physical},
4131 keywords = {Computer Simulation},
4132 keywords = {Hydrogen Bonding},
4133 keywords = {Ligands},
4134 keywords = {Microscopy, Atomic Force},
4135 keywords = {Models, Chemical},
4136 keywords = {Molecular Conformation},
4137 keywords = {Physicochemical Phenomena},
4138 keywords = {Protein Conformation},
4139 keywords = {Streptavidin},
4140 keywords = {Thermodynamics},
4141 abstract = {The force required to rupture the streptavidin-biotin
4142 complex was calculated here by computer simulations.
4143 The computed force agrees well with that obtained by
4144 recent single molecule atomic force microscope
4145 experiments. These simulations suggest a detailed
4146 multiple-pathway rupture mechanism involving five major
4147 unbinding steps. Binding forces and specificity are
4148 attributed to a hydrogen bond network between the
4149 biotin ligand and residues within the binding pocket of
4150 streptavidin. During rupture, additional water bridges
4151 substantially enhance the stability of the complex and
4152 even dominate the binding interactions. In contrast,
4153 steric restraints do not appear to contribute to the
4154 binding forces, although conformational motions were
4159 @article { izrailev97,
4160 author = SIzrailev #" and "# SStepaniants #" and "# MBalsera #" and "#
4161 YOono #" and "# KSchulten,
4162 title = "Molecular dynamics study of unbinding of the avidin-biotin
4169 pages = "1568--1581",
4171 eprint = "http://www.biophysj.org/cgi/reprint/72/4/1568.pdf",
4172 url = "http://www.biophysj.org/cgi/content/abstract/72/4/1568",
4173 keywords = "Avidin;Binding Sites;Biotin;Computer Simulation;Hydrogen
4174 Bonding;Mathematics;Microscopy, Atomic Force;Microspheres;Models,
4175 Molecular;Molecular Structure;Protein Binding;Protein
4176 Conformation;Protein Folding;Sepharose",
4177 abstract = "We report molecular dynamics simulations that induce, over
4178 periods of 40-500 ps, the unbinding of biotin from avidin by means of
4179 external harmonic forces with force constants close to those of AFM
4180 cantilevers. The applied forces are sufficiently large to reduce the
4181 overall binding energy enough to yield unbinding within the measurement
4182 time. Our study complements earlier work on biotin-streptavidin that
4183 employed a much larger harmonic force constant. The simulations reveal
4184 a variety of unbinding pathways, the role of key residues contributing
4185 to adhesion as well as the spatial range over which avidin binds
4186 biotin. In contrast to the previous studies, the calculated rupture
4187 forces exceed by far those observed. We demonstrate, in the framework
4188 of models expressed in terms of one-dimensional Langevin equations with
4189 a schematic binding potential, the associated Smoluchowski equations,
4190 and the theory of first passage times, that picosecond to nanosecond
4191 simulation of ligand unbinding requires such strong forces that the
4192 resulting protein-ligand motion proceeds far from the thermally
4193 activated regime of millisecond AFM experiments, and that simulated
4194 unbinding cannot be readily extrapolated to the experimentally observed
4198 @article { janshoff00,
4199 author = AJanshoff #" and "# MNeitzert #" and "# YOberdorfer #" and "#
4201 title = "Force Spectroscopy of Molecular Systems-Single Molecule
4202 Spectroscopy of Polymers and Biomolecules.",
4209 pages = "3212--3237",
4211 doi = "10.1002/1521-3773(20000915)39:18<3212::AID-ANIE3212>3.0.CO;2-X",
4213 url = "http://dx.doi.org/10.1002/1521-3773(20000915)39:18<3212::AID-ANIE3212>3.0.CO;2-X",
4214 abstract = "How do molecules interact with each other? What happens if a
4215 neurotransmitter binds to a ligand-operated ion channel? How do
4216 antibodies recognize their antigens? Molecular recognition events play
4217 a pivotal role in nature: in enzymatic catalysis and during the
4218 replication and transcription of the genome; it is also important for
4219 the cohesion of cellular structures and in numerous metabolic reactions
4220 that molecules interact with each other in a specific manner.
4221 Conventional methods such as calorimetry provide very precise values of
4222 binding enthalpies; these are, however, average values obtained from a
4223 large ensemble of molecules without knowledge of the dynamics of the
4224 molecular recognition event. Which forces occur when a single molecular
4225 couple meets and forms a bond? Since the development of the scanning
4226 force microscope and force spectroscopy a couple of years ago, tools
4227 have now become available for measuring the forces between interfaces
4228 with high precision-starting from colloidal forces to the interaction
4229 of single molecules. The manipulation of individual molecules using
4230 force spectroscopy is also possible. In this way, the mechanical
4231 properties on a molecular scale are measurable. The study of single
4232 molecules is not an exclusive domain of force spectroscopy; it can also
4233 be performed with a surface force apparatus, laser tweezers, or the
4234 micropipette technique. Regardless of these techniques, force
4235 spectroscopy has been proven as an extraordinary versatile tool. The
4236 intention of this review article is to present a critical evaluation of
4237 the actual development of static force spectroscopy. The article mainly
4238 focuses on experiments dealing with inter- and intramolecular forces-
4239 starting with ``simple'' electrostatic forces, then ligand-receptor
4240 systems, and finally the stretching of individual molecules."
4243 @article { jollymore09,
4244 author = AJollymore #" and "# CLethias #" and "# QPeng #" and "# YCao #"
4246 title = "Nanomechanical properties of tenascin-{X} revealed by single-
4247 molecule force spectroscopy",
4254 pages = "1277--1286",
4256 doi = "10.1016/j.jmb.2008.11.038",
4257 url = "http://dx.doi.org/10.1016/j.jmb.2008.11.038",
4258 keywords = "Animals;Biomechanics;Cattle;Fibronectins;Kinetics;Microscopy,
4259 Atomic Force;Protein Folding;Protein Structure, Tertiary;Spectrum
4261 abstract = "Tenascin-X is an extracellular matrix protein and binds a
4262 variety of molecules in extracellular matrix and on cell membrane.
4263 Tenascin-X plays important roles in regulating the structure and
4264 mechanical properties of connective tissues. Using single-molecule
4265 atomic force microscopy, we have investigated the mechanical properties
4266 of bovine tenascin-X in detail. Our results indicated that tenascin-X
4267 is an elastic protein and the fibronectin type III (FnIII) domains can
4268 unfold under a stretching force and refold to regain their mechanical
4269 stability upon the removal of the stretching force. All the 30 FnIII
4270 domains of tenascin-X show similar mechanical stability, mechanical
4271 unfolding kinetics, and contour length increment upon domain unfolding,
4272 despite their large sequence diversity. In contrast to the homogeneity
4273 in their mechanical unfolding behaviors, FnIII domains fold at
4274 different rates. Using the 10th FnIII domain of tenascin-X (TNXfn10) as
4275 a model system, we constructed a polyprotein chimera composed of
4276 alternating TNXfn10 and GB1 domains and used atomic force microscopy to
4277 confirm that the mechanical properties of TNXfn10 are consistent with
4278 those of the FnIII domains of tenascin-X. These results lay the
4279 foundation to further study the mechanical properties of individual
4280 FnIII domains and establish the relationship between point mutations
4281 and mechanical phenotypic effect on tenascin-X. Moreover, our results
4282 provided the opportunity to compare the mechanical properties and
4283 design of different forms of tenascins. The comparison between
4284 tenascin-X and tenascin-C revealed interesting common as well as
4285 distinguishing features for mechanical unfolding and folding of
4286 tenascin-C and tenascin-X and will open up new avenues to investigate
4287 the mechanical functions and architectural design of different forms of
4292 author = REJones #" and "# DPHart,
4293 title = "Force interactions between substrates and {SPM} cantilevers
4294 immersed in fluids",
4301 doi = "DOI: 10.1016/j.triboint.2004.08.016",
4302 url = "http://www.sciencedirect.com/science/article/B6V57-4DN9K7J-1/2/fef91
4303 ac022594c2c6a701376d83ecd31",
4304 keywords = "AFM;Liquid;Hydrodynamic;Lubrication",
4305 abstract = "With the availability of equipment used in Scanning Probe
4306 Microscopy (SPM), researchers have been able to probe the local fluid-
4307 substrate force interactions with resolutions of pN using a variety of
4308 SPM cantilevers. When using such methods, it is essential to
4309 differentiate between contributions to the net force on the cantilever.
4310 Specifically, the interaction between the cantilever, substrate and
4311 fluid, quantified while generating force curves, are discussed and
4312 compared with theoretical models for squeeze-film effects and drag on
4313 the SPM cantilevers. In addition we have demonstrated a simple method
4314 for utilizing the system as a micro-viscometer, independently measuring
4315 the viscosity of the lubricant for each test."
4318 @article { juckett93,
4319 author = DAJuckett #" and "# BRosenberg,
4320 title = "Comparison of the {G}ompertz and {W}eibull functions as
4321 descriptors for human mortality distributions and their intersections",
4329 doi = "10.1016/0047-6374(93)90068-3",
4330 keywords = "Adolescent;Adult;Aged;Aged, 80 and
4331 over;Aging;Biometry;Child;Child, Preschool;Data Interpretation,
4332 Statistical;Female;Humans;Infant;Infant, Newborn;Longitudinal
4333 Studies;Male;Middle Aged;Models, Biological;Models,
4334 Statistical;Mortality",
4335 abstract = "The Gompertz and Weibull functions are compared with respect to
4336 goodness-of-fit to human mortality distributions; ability to describe
4337 mortality curve intersections; and, parameter interpretation. The
4338 Gompertz function is shown to be a better descriptor for 'all-causes'
4339 of deaths and combined disease categories while the Weibull function is
4340 shown to be a better descriptor of purer, single causes-of-death. A
4341 modified form of the Weibull function maps directly to the inherent
4342 degrees of freedom of human mortality distributions while the Gompertz
4343 function does not. Intersections in the old-age tails of mortality are
4344 explored in the context of both functions and, in particular, the
4345 relationship between distribution intersections, and the Gompertz
4346 ln[R0] versus alpha regression is examined. Evidence is also presented
4347 that mortality intersections are fundamental to the survivorship form
4348 and not the rate (hazard) form. Finally, comparisons are made to the
4349 parameter estimates in recent longitudinal Gompertzian analyses and the
4350 probable errors in those analyses are discussed.",
4351 note = "Nice table of various functions associated with Gompertz and
4355 @article { kaplan58,
4356 author = ELKaplan #" and "# PMeier,
4357 title = "Nonparametric Estimation from Incomplete Observations",
4366 copyright = "Copyright \copy\ 1958 American Statistical Association",
4367 url = "http://www.jstor.org/stable/2281868",
4371 @article { kellermayer03,
4372 author = MSKellermayer #" and "# CBustamante #" and "# HLGranzier,
4373 title = "Mechanics and structure of titin oligomers explored with atomic
4381 doi = "10.1016/S0005-2728(03)00029-X",
4382 url = "http://dx.doi.org/10.1016/S0005-2728(03)00029-X",
4383 keywords = "Titin;Wormlike chain;Unfolding;Elasticity;AFM;Molecular force
4385 abstract = "Titin is a giant polypeptide that spans half of the striated
4386 muscle sarcomere and generates passive force upon stretch. To explore
4387 the elastic response and structure of single molecules and oligomers of
4388 titin, we carried out molecular force spectroscopy and atomic force
4389 microscopy (AFM) on purified full-length skeletal-muscle titin. From
4390 the force data, apparent persistence lengths as long as ~1.5 nm were
4391 obtained for the single, unfolded titin molecule. Furthermore, data
4392 suggest that titin molecules may globally associate into oligomers
4393 which mechanically behave as independent wormlike chains (WLCs).
4394 Consistent with this, AFM of surface-adsorbed titin molecules revealed
4395 the presence of oligomers. Although oligomers may form globally via
4396 head-to-head association of titin, the constituent molecules otherwise
4397 appear independent from each other along their contour. Based on the
4398 global association but local independence of titin molecules, we
4399 discuss a mechanical model of the sarcomere in which titin molecules
4400 with different contour lengths, corresponding to different isoforms,
4401 are held in a lattice. The net force response of aligned titin
4402 molecules is determined by the persistence length of the tandemly
4403 arranged, different WLC components of the individual molecules, the
4404 ratio of their overall contour lengths, and by domain unfolding events.
4405 Biased domain unfolding in mechanically selected constituent molecules
4406 may serve as a compensatory mechanism for contour- and persistence-
4407 length differences. Variation in the ratio and contour length of the
4408 component chains may provide mechanisms for the fine-tuning of the
4409 sarcomeric passive force response.",
4413 @article { kellermayer97,
4414 author = MSKellermayer #" and "# SBSmith #" and "# HLGranzier #" and "#
4416 title = "Folding-unfolding transitions in single titin molecules
4417 characterized with laser tweezers",
4424 pages = "1112--1116",
4426 keywords = "Amino Acid
4427 Sequence;Elasticity;Entropy;Immunoglobulins;Lasers;Models,
4428 Chemical;Muscle Contraction;Muscle Proteins;Muscle Relaxation;Muscle,
4429 Skeletal;Protein Denaturation;Protein Folding;Protein Kinases;Stress,
4431 abstract = "Titin, a giant filamentous polypeptide, is believed to play a
4432 fundamental role in maintaining sarcomeric structural integrity and
4433 developing what is known as passive force in muscle. Measurements of
4434 the force required to stretch a single molecule revealed that titin
4435 behaves as a highly nonlinear entropic spring. The molecule unfolds in
4436 a high-force transition beginning at 20 to 30 piconewtons and refolds
4437 in a low-force transition at approximately 2.5 piconewtons. A fraction
4438 of the molecule (5 to 40 percent) remains permanently unfolded,
4439 behaving as a wormlike chain with a persistence length (a measure of
4440 the chain's bending rigidity) of 20 angstroms. Force hysteresis arises
4441 from a difference between the unfolding and refolding kinetics of the
4442 molecule relative to the stretch and release rates in the experiments,
4443 respectively. Scaling the molecular data up to sarcomeric dimensions
4444 reproduced many features of the passive force versus extension curve of
4449 author = WKing #" and "# MSu #" and "# GYang,
4450 title = "{M}onte {C}arlo simulation of mechanical unfolding of proteins
4451 based on a simple two-state model",
4455 address = "Department of Physics, Drexel University, 3141
4456 Chestnut Street, Philadelphia, PA 19104, USA.",
4462 alternative_issn = "1879-0003",
4463 doi = "10.1016/j.ijbiomac.2009.12.001",
4464 url = "http://www.sciencedirect.com/science/article/B6T7J-
4465 4XWMND2-1/2/7ef768562b4157fc201d450553e5de5e",
4467 keywords = "Atomic force microscopy;Mechanical unfolding;Monte Carlo
4468 simulation;Worm-like chain;Single molecule methods",
4469 abstract = "Single molecule methods are becoming routine biophysical
4470 techniques for studying biological macromolecules. In mechanical
4471 unfolding of proteins, an externally applied force is used to induce
4472 the unfolding of individual protein molecules. Such experiments have
4473 revealed novel information that has significantly enhanced our
4474 understanding of the function and folding mechanisms of several types
4475 of proteins. To obtain information on the unfolding kinetics and the
4476 free energy landscape of the protein molecule from mechanical unfolding
4477 data, a Monte Carlo simulation based on a simple two-state kinetic
4478 model is often used. In this paper, we provide a detailed description
4479 of the procedure to perform such simulations and discuss the
4480 approximations and assumptions involved. We show that the appearance of
4481 the force versus extension curves from mechanical unfolding of proteins
4482 is affected by a variety of experimental parameters, such as the length
4483 of the protein polymer and the force constant of the cantilever. We
4484 also analyze the errors associated with different methods of data
4485 pooling and present a quantitative measure of how well the simulation
4486 results fit experimental data. These findings will be helpful in
4487 experimental design, artifact identification, and data analysis for
4488 single molecule studies of various proteins using the mechanical
4492 @article { kleiner07,
4493 author = AKleiner #" and "# EShakhnovich,
4494 title = "The mechanical unfolding of ubiquitin through all-atom Monte Carlo
4495 simulation with a Go-type potential",
4502 pages = "2054--2061",
4504 doi = "10.1529/biophysj.106.081257",
4505 eprint = "http://www.biophysj.org/cgi/reprint/92/6/2054",
4506 url = "http://www.biophysj.org/cgi/content/full/92/6/2054",
4507 keywords = "Computer Simulation; Models, Chemical; Models, Molecular;
4508 Models, Statistical; Monte Carlo Method; Motion; Protein Conformation;
4509 Protein Denaturation; Protein Folding; Ubiquitin",
4510 abstract = "The mechanical unfolding of proteins under a stretching force
4511 has an important role in living systems and is a logical extension of
4512 the more general protein folding problem. Recent advances in
4513 experimental methodology have allowed the stretching of single
4514 molecules, thus rendering this process ripe for computational study. We
4515 use all-atom Monte Carlo simulation with a G?-type potential to study
4516 the mechanical unfolding pathway of ubiquitin. A detailed, robust,
4517 well-defined pathway is found, confirming existing results in this vein
4518 though using a different model. Additionally, we identify the protein's
4519 fundamental stabilizing secondary structure interactions in the
4520 presence of a stretching force and show that this fundamental
4521 stabilizing role does not persist in the absence of mechanical stress.
4522 The apparent success of simulation methods in studying ubiquitin's
4523 mechanical unfolding pathway indicates their potential usefulness for
4524 future study of the stretching of other proteins and the relationship
4525 between protein structure and the response to mechanical deformation."
4528 @article { klimov00,
4529 author = DKlimov #" and "# DThirumalai,
4530 title = "Native topology determines force-induced unfolding pathways in
4538 pages = "7254--7259",
4540 doi = "10.1073/pnas.97.13.7254",
4541 eprint = "http://www.pnas.org/cgi/reprint/97/13/7254.pdf",
4542 url = "http://www.pnas.org/cgi/content/abstract/97/13/7254",
4543 keywords = "Animals; Humans; Protein Folding; Proteins; Spectrin",
4544 abstract = "Single-molecule manipulation techniques reveal that stretching
4545 unravels individually folded domains in the muscle protein titin and
4546 the extracellular matrix protein tenascin. These elastic proteins
4547 contain tandem repeats of folded domains with beta-sandwich
4548 architecture. Herein, we propose by stretching two model sequences (S1
4549 and S2) with four-stranded beta-barrel topology that unfolding forces
4550 and pathways in folded domains can be predicted by using only the
4551 structure of the native state. Thermal refolding of S1 and S2 in the
4552 absence of force proceeds in an all-or-none fashion. In contrast, phase
4553 diagrams in the force-temperature (f,T) plane and steered Langevin
4554 dynamics studies of these sequences, which differ in the native
4555 registry of the strands, show that S1 unfolds in an allor-none fashion,
4556 whereas unfolding of S2 occurs via an obligatory intermediate. Force-
4557 induced unfolding is determined by the native topology. After proving
4558 that the simulation results for S1 and S2 can be calculated by using
4559 native topology alone, we predict the order of unfolding events in Ig
4560 domain (Ig27) and two fibronectin III type domains ((9)FnIII and
4561 (10)FnIII). The calculated unfolding pathways for these proteins, the
4562 location of the transition states, and the pulling speed dependence of
4563 the unfolding forces reflect the differences in the way the strands are
4564 arranged in the native states. We also predict the mechanisms of force-
4565 induced unfolding of the coiled-coil spectrin (a three-helix bundle
4566 protein) for all 20 structures deposited in the Protein Data Bank. Our
4567 approach suggests a natural way to measure the phase diagram in the
4568 (f,C) plane, where C is the concentration of denaturants.",
4569 note = {Simulated unfolding time scales for Ig27-like S1 and S2 domains.},
4572 @article { klimov99,
4573 author = DKlimov #" and "# DThirumalai,
4574 title = "Stretching single-domain proteins: Phase diagram and kinetics of
4575 force-induced unfolding",
4582 pages = "6166--6170",
4584 keywords = "Amino Acid Sequence;Kinetics;Models, Chemical;Protein
4585 Denaturation;Protein Folding;Proteins;Thermodynamics;Time Factors",
4586 abstract = "Single-molecule force spectroscopy reveals unfolding of domains
4587 in titin on stretching. We provide a theoretical framework for these
4588 experiments by computing the phase diagrams for force-induced unfolding
4589 of single-domain proteins using lattice models. The results show that
4590 two-state folders (at zero force) unravel cooperatively, whereas
4591 stretching of non-two-state folders occurs through intermediates. The
4592 stretching rates of individual molecules show great variations
4593 reflecting the heterogeneity of force-induced unfolding pathways. The
4594 approach to the stretched state occurs in a stepwise ``quantized''
4595 manner. Unfolding dynamics and forces required to stretch proteins
4596 depend sensitively on topology. The unfolding rates increase
4597 exponentially with force f till an optimum value, which is determined
4598 by the barrier to unfolding when f = 0. A mapping of these results to
4599 proteins shows qualitative agreement with force-induced unfolding of
4600 Ig-like domains in titin. We show that single-molecule force
4601 spectroscopy can be used to map the folding free energy landscape of
4602 proteins in the absence of denaturants."
4605 @article { kosztin06,
4606 author = IKosztin #" and "# BBarz #" and "# LJanosi,
4607 title = "Calculating potentials of mean force and diffusion coefficients
4608 from nonequilibrium processes without Jarzynski's equality",
4616 doi = "10.1063/1.2166379",
4617 url = "http://link.aip.org/link/?JCPSA6/124/064106/1"
4620 @article { kramers40,
4622 title = "Brownian motion in a field of force and the diffusion model of
4623 chemical reactions",
4631 doi = "10.1016/S0031-8914(40)90098-2",
4632 url = "http://dx.doi.org/10.1016/S0031-8914(40)90098-2",
4633 abstract = "A particle which is caught in a potential hole and which,
4634 through the shuttling action of Brownian motion, can escape over a
4635 potential barrier yields a suitable model for elucidating the
4636 applicability of the transition state method for calculating the rate
4637 of chemical reactions.",
4638 note = "Seminal paper on thermally activated barrier crossings."
4641 @article { krammer99,
4642 author = AKrammer #" and "# HLu #" and "# BIsralewitz #" and "# KSchulten
4644 title = "Forced unfolding of the fibronectin type {III} module reveals a
4645 tensile molecular recognition switch",
4652 pages = "1351--1356",
4654 keywords = "Amino Acid Sequence;Binding Sites;Computer
4655 Simulation;Crystallography, X-Ray;Disulfides;Fibronectins;Hydrogen
4656 Bonding;Integrins;Models, Molecular;Oligopeptides;Protein
4657 Conformation;Protein Denaturation;Protein Folding;Protein Structure,
4658 Secondary;Protein Structure, Tertiary;Software;Tensile Strength",
4659 abstract = "The 10th type III module of fibronectin possesses a beta-
4660 sandwich structure consisting of seven beta-strands (A-G) that are
4661 arranged in two antiparallel sheets. It mediates cell adhesion to
4662 surfaces via its integrin binding motif, Arg78, Gly79, and Asp80 (RGD),
4663 which is placed at the apex of the loop connecting beta-strands F and
4664 G. Steered molecular dynamics simulations in which tension is applied
4665 to the protein's terminal ends reveal that the beta-strand G is the
4666 first to break away from the module on forced unfolding whereas the
4667 remaining fold maintains its structural integrity. The separation of
4668 strand G from the remaining fold results in a gradual shortening of the
4669 distance between the apex of the RGD-containing loop and the module
4670 surface, which potentially reduces the loop's accessibility to surface-
4671 bound integrins. The shortening is followed by a straightening of the
4672 RGD-loop from a tight beta-turn into a linear conformation, which
4673 suggests a further decrease of affinity and selectivity to integrins.
4674 The RGD-loop therefore is located strategically to undergo strong
4675 conformational changes in the early stretching stages of the module and
4676 thus constitutes a mechanosensitive control of ligand recognition."
4679 @article { kreuzer01,
4680 author = HJKreuzer #" and "# SHPayne,
4681 title = "Stretching a macromolecule in an atomic force microscope:
4682 statistical mechanical analysis",
4691 eprint = "http://www.biophysj.org/cgi/reprint/80/6/2505.pdf",
4692 url = "http://www.biophysj.org/cgi/content/abstract/80/6/2505",
4693 keywords = "Biophysics;Macromolecular Substances;Microscopy, Atomic
4694 Force;Models, Statistical;Models, Theoretical;Statistics as Topic",
4695 abstract = "We formulate the proper statistical mechanics to describe the
4696 stretching of a macromolecule under a force provided by the cantilever
4697 of an atomic force microscope. In the limit of a soft cantilever the
4698 generalized ensemble of the coupled molecule/cantilever system reduces
4699 to the Gibbs ensemble for an isolated molecule subject to a constant
4700 force in which the extension is fluctuating. For a stiff cantilever we
4701 obtain the Helmholtz ensemble for an isolated molecule held at a fixed
4702 extension with the force fluctuating. Numerical examples are given for
4703 poly (ethylene glycol) chains."
4707 author = KKroy #" and "# JGlaser,
4708 title = "The glassy wormlike chain",
4714 doi = "10.1088/1367-2630/9/11/416",
4715 eprint = "http://www.iop.org/EJ/article/1367-2630/9/11/416/njp7_11_416.pdf",
4716 url = "http://stacks.iop.org/1367-2630/9/416",
4717 abstract = "We introduce a new model for the dynamics of a wormlike chain
4718 (WLC) in an environment that gives rise to a rough free energy
4719 landscape, which we name the glassy WLC. It is obtained from the common
4720 WLC by an exponential stretching of the relaxation spectrum of its
4721 long-wavelength eigenmodes, controlled by a single parameter
4722 \\boldsymbol{\\cal E} . Predictions for pertinent observables such as
4723 the dynamic structure factor and the microrheological susceptibility
4724 exhibit the characteristics of soft glassy rheology and compare
4725 favourably with experimental data for reconstituted cytoskeletal
4726 networks and live cells. We speculate about the possible microscopic
4727 origin of the stretching, implications for the nonlinear rheology, and
4728 the potential physiological significance of our results.",
4729 note = "Has short section on WLC relaxation time in the weakly bending
4733 @article { labeit03,
4734 author = DLabeit #" and "# KWatanabe #" and "# CWitt #" and "# HFujita #"
4735 and "# YWu #" and "# SLahmers #" and "# TFunck #" and "# SLabeit #" and
4737 title = "Calcium-dependent molecular spring elements in the giant protein
4743 pages = "13716--13721",
4744 doi = "10.1073/pnas.2235652100",
4745 eprint = "http://www.pnas.org/cgi/reprint/100/23/13716.pdf",
4746 url = "http://www.pnas.org/cgi/content/abstract/100/23/13716",
4747 abstract = "Titin (also known as connectin) is a giant protein with a wide
4748 range of cellular functions, including providing muscle cells with
4749 elasticity. Its physiological extension is largely derived from the
4750 PEVK segment, rich in proline (P), glutamate (E), valine (V), and
4751 lysine (K) residues. We studied recombinant PEVK molecules containing
4752 the two conserved elements: {approx}28-residue PEVK repeats and E-rich
4753 motifs. Single molecule experiments revealed that calcium-induced
4754 conformational changes reduce the bending rigidity of the PEVK
4755 fragments, and site-directed mutagenesis identified four glutamate
4756 residues in the E-rich motif that was studied (exon 129), as critical
4757 for this process. Experiments with muscle fibers showed that titin-
4758 based tension is calcium responsive. We propose that the PEVK segment
4759 contains E-rich motifs that render titin a calcium-dependent molecular
4760 spring that adapts to the physiological state of the cell."
4764 author = SLabeit #" and "# BKolmerer,
4765 title = "Titins: Giant proteins in charge of muscle ultrastructure
4771 address = "European Molecular Biology Laboratory, Heidelberg, Germany.",
4775 keywords = "Actin Cytoskeleton",
4776 keywords = "Amino Acid Sequence",
4777 keywords = "Animals",
4778 keywords = "DNA, Complementary",
4779 keywords = "Elasticity",
4780 keywords = "Fibronectins",
4781 keywords = "Humans",
4782 keywords = "Immunoglobulins",
4783 keywords = "Molecular Sequence Data",
4784 keywords = "Muscle Contraction",
4785 keywords = "Muscle Proteins",
4786 keywords = "Muscle, Skeletal",
4787 keywords = "Myocardium",
4788 keywords = "Protein Kinases",
4789 keywords = "Rabbits",
4790 keywords = "Repetitive Sequences, Nucleic Acid",
4791 keywords = "Sarcomeres",
4792 abstract = "In addition to thick and thin filaments, vertebrate
4793 striated muscle contains a third filament system formed by the
4794 giant protein titin. Single titin molecules extend from Z discs to
4795 M lines and are longer than 1 micrometer. The titin filament
4796 contributes to muscle assembly and resting tension, but more
4797 details are not known because of the large size of the
4798 protein. The complete complementary DNA sequence of human cardiac
4799 titin was determined. The 82-kilobase complementary DNA predicts a
4800 3-megadalton protein composed of 244 copies of immunoglobulin and
4801 fibronectin type III (FN3) domains. The architecture of sequences
4802 in the A band region of titin suggests why thick filament
4803 structure is conserved among vertebrates. In the I band region,
4804 comparison of titin sequences from muscles of different passive
4805 tension identifies two elements that correlate with tissue
4806 stiffness. This suggests that titin may act as two springs in
4807 series. The differential expression of the springs provides a
4808 molecular explanation for the diversity of sarcomere length and
4809 resting tension in vertebrate striated muscles.",
4811 URL = "http://www.ncbi.nlm.nih.gov/pubmed/7569978",
4816 author = RLaw #" and "# GLiao #" and "# SHarper #" and "# GYang #" and "#
4817 DSpeicher #" and "# DDischer,
4818 title = "Pathway shifts and thermal softening in temperature-coupled forced
4819 unfolding of spectrin domains",
4820 address = "Biophysical Engineering Lab, Institute for Medicine and
4821 Engineering, and School of Engineering and Applied Science,
4822 University of Pennsylvania, Philadelphia, Pennsylvania
4829 pages = "3286--3293",
4831 keywords = "Circular Dichroism;Elasticity;Heat;Microscopy, Atomic
4832 Force;Physical Stimulation;Protein Conformation;Protein
4833 Denaturation;Protein Folding;Protein Structure,
4834 Tertiary;Spectrin;Stress, Mechanical;Temperature",
4835 abstract = "Pathways of unfolding a protein depend in principle on the
4836 perturbation-whether it is temperature, denaturant, or even forced
4837 extension. Widely-shared, helical-bundle spectrin repeats are known to
4838 melt at temperatures as low as 40-45 degrees C and are also known to
4839 unfold via multiple pathways as single molecules in atomic force
4840 microscopy. Given the varied roles of spectrin family proteins in cell
4841 deformability, we sought to determine the coupled effects of
4842 temperature on forced unfolding. Bimodal distributions of unfolding
4843 intervals are seen at all temperatures for the four-repeat beta(1-4)
4844 spectrin-an alpha-actinin homolog. The major unfolding length
4845 corresponds to unfolding of a single repeat, and a minor peak at twice
4846 the length corresponds to tandem repeats. Increasing temperature shows
4847 fewer tandem events but has no effect on unfolding intervals. As T
4848 approaches T(m), however, mean unfolding forces in atomic force
4849 microscopy also decrease; and circular dichroism studies demonstrate a
4850 nearly proportional decrease of helical content in solution. The
4851 results imply a thermal softening of a helical linker between repeats
4852 which otherwise propagates a helix-to-coil transition to adjacent
4853 repeats. In sum, structural changes with temperature correlate with
4854 both single-molecule unfolding forces and shifts in unfolding
4856 doi = "10.1016/S0006-3495(03)74747-X",
4857 URL = "http://www.ncbi.nlm.nih.gov/pubmed/14581229",
4861 @article { levinthal68,
4862 author = CLevinthal,
4863 title = "Are there pathways for protein folding?",
4870 "http://www.biochem.wisc.edu/courses/biochem704/Reading/Levinthal1968.p
4872 note = "\emph{Not} Levinthal's paradox."
4875 @inproceedings { levinthal69,
4876 editor = PDebrunner #" and "# JCMTsibris #" and "# EMunck,
4877 author = CLevinthal,
4878 title = "How to Fold Graciously.",
4879 booktitle = "Mossbauer Spectroscopy in Biological Systems",
4882 publisher = UIP:Urbana,
4883 address = "Allerton House, Monticello, IL",
4884 url = "http://www-miller.ch.cam.ac.uk/levinthal/levinthal.html"
4888 author = RLevy #" and "# MMaaloum,
4889 title = "Measuring the spring constant of atomic force microscope
4890 cantilevers: Thermal fluctuations and other methods",
4896 doi = "10.1088/0957-4484/13/1/307",
4897 url = "http://stacks.iop.org/0957-4484/13/33",
4898 abstract = "Knowledge of the interaction forces between surfaces gained
4899 using an atomic force microscope (AFM) is crucial in a variety of
4900 industrial and scientific applications and necessitates a precise
4901 knowledge of the cantilever spring constant. Many methods have been
4902 devised to experimentally determine the spring constants of AFM
4903 cantilevers. The thermal fluctuation method is elegant but requires a
4904 theoretical model of the bending modes. For a rectangular cantilever,
4905 this model is available (Butt and Jaschke). Detailed thermal
4906 fluctuation measurements of a series of AFM cantilever beams have been
4907 performed in order to test the validity and accuracy of the recent
4908 theoretical models. The spring constant of rectangular cantilevers can
4909 also be determined easily with the method of Sader and White. We found
4910 very good agreement between the two methods. In the case of the
4911 V-shaped cantilever, we have shown that the thermal fluctuation method
4912 is a valid and accurate approach to the evaluation of the spring
4913 constant. A comparison between this method and those of Sader-
4914 Neumeister and of Ducker has been established. In some cases, we found
4915 disagreement between these two methods; the effect of non-conservation
4916 of material properties over all cantilevers from a single chip is
4917 qualitatively invoked.",
4918 note = "Good review of thermal calibration to 2002, but not much on the
4919 derviation of the Lorentzian fit.",
4920 project = "Cantilever Calibration"
4924 author = HLi #" and "# AOberhauser #" and "# SFowler #" and "# JClarke #"
4926 title = "Atomic force microscopy reveals the mechanical design of a modular
4932 pages = "6527--6531",
4933 doi = "10.1073/pnas.120048697",
4934 eprint = "http://www.pnas.org/cgi/reprint/97/12/6527.pdf",
4935 url = "http://www.pnas.org/cgi/content/abstract/97/12/6527",
4937 note = "Unfolding order not from protein-surface interactions. Mechanical
4938 unfolding of a chain of interleaved domains $ABABAB\ldots$ yielded a
4939 run of $A$ unfoldings followed by a run of $B$ unfoldings."
4943 author = HLi #" and "# AOberhauser #" and "# SRedick #" and "#
4944 MCarrionVazquez #" and "# HErickson #" and "# JFernandez,
4945 title = "Multiple conformations of {PEVK} proteins detected by single-
4946 molecule techniques",
4951 pages = "10682--10686",
4952 doi = "10.1073/pnas.191189098",
4953 eprint = "http://www.pnas.org/cgi/reprint/98/19/10682.pdf",
4954 url = "http://www.pnas.org/cgi/content/abstract/98/19/10682",
4955 abstract = "An important component of muscle elasticity is the PEVK region
4956 of titin, so named because of the preponderance of these amino acids.
4957 However, the PEVK region, similar to other elastomeric proteins, is
4958 thought to form a random coil and therefore its structure cannot be
4959 determined by standard techniques. Here we combine single-molecule
4960 electron microscopy and atomic force microscopy to examine the
4961 conformations of the human cardiac titin PEVK region. In contrast to a
4962 simple random coil, we have found that cardiac PEVK shows a wide range
4963 of elastic conformations with end-to-end distances ranging from 9 to 24
4964 nm and persistence lengths from 0.4 to 2.5 nm. Individual PEVK
4965 molecules retained their distinctive elastic conformations through many
4966 stretch-relaxation cycles, consistent with the view that these PEVK
4967 conformers cannot be interconverted by force. The multiple elastic
4968 conformations of cardiac PEVK may result from varying degrees of
4969 proline isomerization. The single-molecule techniques demonstrated here
4970 may help elucidate the conformation of other proteins that lack a well-
4975 author = HLi #" and "# JFernandez,
4976 title = "Mechanical design of the first proximal Ig domain of human cardiac
4977 titin revealed by single molecule force spectroscopy",
4986 doi = "10.1016/j.jmb.2003.09.036",
4987 keywords = "Amino Acid Sequence;Disulfides;Humans;Immunoglobulins;Models,
4988 Molecular;Molecular Sequence Data;Muscle Proteins;Myocardium;Protein
4989 Denaturation;Protein Engineering;Protein Kinases;Protein Structure,
4990 Tertiary;Spectrum Analysis",
4991 abstract = "The elastic I-band part of muscle protein titin contains two
4992 tandem immunoglobulin (Ig) domain regions of distinct mechanical
4993 properties. Until recently, the only known structure was that of the
4994 I27 module of the distal region, whose mechanical properties have been
4995 reported in detail. Recently, the structure of the first proximal
4996 domain, I1, has been resolved at 2.1A. In addition to the
4997 characteristic beta-sandwich structure of all titin Ig domains, the
4998 crystal structure of I1 showed an internal disulfide bridge that was
4999 proposed to modulate its mechanical extensibility in vivo. Here, we use
5000 single molecule force spectroscopy and protein engineering to examine
5001 the mechanical architecture of this domain. In contrast to the
5002 predictions made from the X-ray crystal structure, we find that the
5003 formation of a disulfide bridge in I1 is a relatively rare event in
5004 solution, even under oxidative conditions. Furthermore, our studies of
5005 the mechanical stability of I1 modules engineered with point mutations
5006 reveal significant differences between the mechanical unfolding of the
5007 I1 and I27 modules. Our study illustrates the varying mechanical
5008 architectures of the titin Ig modules."
5012 author = LeLi #" and "# HHuang #" and "# CBadilla #" and "# JFernandez,
5013 title = "Mechanical unfolding intermediates observed by single-molecule
5014 force spectroscopy in a fibronectin type {III} module",
5023 doi = "10.1016/j.jmb.2004.11.021",
5024 keywords = "Fibronectins;Kinetics;Microscopy, Atomic Force;Models,
5025 Molecular;Mutagenesis, Site-Directed;Protein Denaturation;Protein
5026 Folding;Protein Structure, Tertiary;Recombinant Fusion Proteins",
5027 abstract = "Domain 10 of type III fibronectin (10FNIII) is known to play a
5028 pivotal role in the mechanical interactions between cell surface
5029 integrins and the extracellular matrix. Recent molecular dynamics
5030 simulations have predicted that 10FNIII, when exposed to a stretching
5031 force, unfolds along two pathways, each with a distinct, mechanically
5032 stable intermediate. Here, we use single-molecule force spectroscopy
5033 combined with protein engineering to test these predictions by probing
5034 the mechanical unfolding pathway of 10FNIII. Stretching single
5035 polyproteins containing the 10FNIII module resulted in sawtooth
5036 patterns where 10FNIII was seen unfolding in two consecutive steps. The
5037 native state unfolded at 100(+/-20) pN, elongating (10)FNIII by
5038 12(+/-2) nm and reaching a clearly marked intermediate that unfolded at
5039 50(+/-20) pN. Unfolding of the intermediate completed the elongation of
5040 the molecule by extending another 19(+/-2) nm. Site-directed
5041 mutagenesis of residues in the A and B beta-strands (E9P and L19P)
5042 resulted in sawtooth patterns with all-or-none unfolding events that
5043 elongated the molecule by 19(+/-2) nm. In contrast, mutating residues
5044 in the G beta-strand gave results that were dependent on amino acid
5045 position. The mutation I88P in the middle of the G beta-strand resulted
5046 in native like unfolding sawtooth patterns showing an intact
5047 intermediate state. The mutation Y92P, which is near the end of G beta-
5048 strand, produced sawtooth patterns with all-or-none unfolding events
5049 that lengthened the molecule by 17(+/-2) nm. These results are
5050 consistent with the view that 10FNIII can unfold in two different ways.
5051 Along one pathway, the detachment of the A and B beta-strands from the
5052 body of the folded module constitute the first unfolding event,
5053 followed by the unfolding of the remaining beta-sandwich structure.
5054 Along the second pathway, the detachment of the G beta-strands is
5055 involved in the first unfolding event. These results are in excellent
5056 agreement with the sequence of events predicted by molecular dynamics
5057 simulations of the 10FNIII module."
5061 author = MSLi #" and "# CKHu #" and "# DKlimov #" and "# DThirumalai,
5062 title = "Multiple stepwise refolding of immunoglobulin domain {I27} upon
5063 force quench depends on initial conditions",
5069 doi = "10.1073/pnas.0503758103",
5070 eprint = "http://www.pnas.org/cgi/reprint/103/1/93.pdf",
5071 url = "http://www.pnas.org/cgi/content/abstract/103/1/93",
5072 abstract = "Mechanical folding trajectories for polyproteins starting from
5073 initially stretched conformations generated by single-molecule atomic
5074 force microscopy experiments [Fernandez, J. M. & Li, H. (2004) Science
5075 303, 1674-1678] show that refolding, monitored by the end-to-end
5076 distance, occurs in distinct multiple stages. To clarify the molecular
5077 nature of folding starting from stretched conformations, we have probed
5078 the folding dynamics, upon force quench, for the single I27 domain from
5079 the muscle protein titin by using a C{alpha}-Go model. Upon temperature
5080 quench, collapse and folding of I27 are synchronous. In contrast,
5081 refolding from stretched initial structures not only increases the
5082 folding and collapse time scales but also decouples the two kinetic
5083 processes. The increase in the folding times is associated primarily
5084 with the stretched state to compact random coil transition.
5085 Surprisingly, force quench does not alter the nature of the refolding
5086 kinetics, but merely increases the height of the free-energy folding
5087 barrier. Force quench refolding times scale as f1.gif, where {Delta}xf
5088 {approx} 0.6 nm is the location of the average transition state along
5089 the reaction coordinate given by end-to-end distance. We predict that
5090 {tau}F and the folding mechanism can be dramatically altered by the
5091 initial and/or final values of force. The implications of our results
5092 for design and analysis of experiments are discussed."
5097 title = "Divergence measures based on the {S}hannon entropy",
5105 doi = "10.1109/18.61115",
5106 url = "http://ieeexplore.ieee.org/xpl/freeabs_all.jsp?isnumber=2227&arnumbe
5107 r=61115&count=35&index=9",
5108 keywords = "divergence;dissimilarity measure;discrimintation
5109 information;entropy;probability of error bounds",
5110 abstract = "A novel class of information-theoretic divergence measures
5111 based on the Shannon entropy is introduced. Unlike the well-known
5112 Kullback divergences, the new measures do not require the condition of
5113 absolute continuity to be satisfied by the probability distributions
5114 involved. More importantly, their close relationship with the
5115 variational distance and the probability of misclassification error are
5116 established in terms of bounds. These bounds are crucial in many
5117 applications of divergence measures. The measures are also well
5118 characterized by the properties of nonnegativity, finiteness,
5119 semiboundedness, and boundedness."
5123 author = WALinke #" and "# AGrutzner,
5124 title = "Pulling single molecules of titin by {AFM}--recent advances and
5125 physiological implications",
5134 doi = "10.1007/s00424-007-0389-x",
5135 abstract = "Perturbation of a protein away from its native state by
5136 mechanical stress is a physiological process immanent to many cells.
5137 The mechanical stability and conformational diversity of proteins under
5138 force therefore are important parameters in nature. Molecular-level
5139 investigations of ``mechanical proteins'' have enjoyed major
5140 breakthroughs over the last decade, a development to which atomic force
5141 microscopy (AFM) force spectroscopy has been instrumental. The giant
5142 muscle protein titin continues to be a paradigm model in this field. In
5143 this paper, we review how single-molecule mechanical measurements of
5144 titin using AFM have served to elucidate key aspects of protein
5145 unfolding-refolding and mechanisms by which biomolecular elasticity is
5146 attained. We outline recent work combining protein engineering and AFM
5147 force spectroscopy to establish the mechanical behavior of titin
5148 domains using molecular ``fingerprinting.'' Furthermore, we summarize
5149 AFM force-extension data demonstrating different mechanical stabilities
5150 of distinct molecular-spring elements in titin, compare AFM force-
5151 extension to novel force-ramp/force-clamp studies, and elaborate on
5152 exciting new results showing that AFM force clamp captures the
5153 unfolding and refolding trajectory of single mechanical proteins. Along
5154 the way, we discuss the physiological implications of the findings, not
5155 least with respect to muscle mechanics. These studies help us
5156 understand how proteins respond to forces in cells and how
5157 mechanosensing and mechanosignaling events may proceed in vivo."
5160 @article { linke98a,
5161 author = WALinke #" and "# MRStockmeier #" and "# MIvemeyer #" and "#
5162 HHosser #" and "# PMundel,
5163 title = "Characterizing titin's {I}-band {Ig} domain region as an entropic
5168 volume = "111 (Pt 11)",
5169 pages = "1567--1574",
5172 eprint = "http://jcs.biologists.org/cgi/reprint/111/11/1567",
5173 url = "http://jcs.biologists.org/cgi/content/abstract/111/11/1567",
5174 keywords = "Animals;Elasticity;Immunoglobulins;Male;Muscle Proteins;Muscle,
5175 Skeletal;Protein Kinases;Rats;Rats, Wistar;Structure-Activity
5177 abstract = "The poly-immunoglobulin domain region of titin, located within
5178 the elastic section of this giant muscle protein, determines the
5179 extensibility of relaxed myofibrils mainly at shorter physiological
5180 lengths. To elucidate this region's contribution to titin elasticity,
5181 we measured the elastic properties of the N-terminal I-band Ig region
5182 by using immunofluorescence/immunoelectron microscopy and myofibril
5183 mechanics and tried to simulate the results with a model of entropic
5184 polymer elasticity. Rat psoas myofibrils were stained with titin-
5185 specific antibodies flanking the Ig region at the N terminus and C
5186 terminus, respectively, to record the extension behaviour of that titin
5187 segment. The segment's end-to-end length increased mainly at small
5188 stretch, reaching approximately 90\% of the native contour length of
5189 the Ig region at a sarcomere length of 2.8 microm. At this extension,
5190 the average force per single titin molecule, deduced from the steady-
5191 state passive length-tension relation of myofibrils, was approximately
5192 5 or 2.5 pN, depending on whether we assumed a number of 3 or 6 titins
5193 per half thick filament. When the force-extension curve constructed for
5194 the Ig region was simulated by the wormlike chain model, best fits were
5195 obtained for a persistence length, a measure of the chain's bending
5196 rigidity, of 21 or 42 nm (for 3 or 6 titins/half thick filament), which
5197 correctly reproduced the curve for sarcomere lengths up to 3.4 microm.
5198 Systematic deviations between data and fits above that length indicated
5199 that forces of >30 pN per titin strand may induce unfolding of Ig
5200 modules. We conclude that stretches of at least 5-6 Ig domains, perhaps
5201 coinciding with known super repeat patterns of these titin modules in
5202 the I-band, may represent the unitary lengths of the wormlike chain.
5203 The poly-Ig regions might thus act as compliant entropic springs that
5204 determine the minute levels of passive tension at low extensions of a
5208 @article { linke98b,
5209 author = WALinke #" and "# MIvemeyer #" and "# PMundel #" and "#
5210 MRStockmeier #" and "# BKolmerer,
5211 title = "Nature of {PEVK}-titin elasticity in skeletal muscle",
5218 pages = "8052--8057",
5220 keywords = "Animals;Elasticity;Fluorescent Antibody
5221 Technique;Male;Microscopy, Immunoelectron;Muscle Proteins;Muscle,
5222 Skeletal;Protein Kinases;Rats;Rats, Wistar;Stress, Mechanical",
5223 abstract = "A unique sequence within the giant titin molecule, the PEVK
5224 domain, has been suggested to greatly contribute to passive force
5225 development of relaxed skeletal muscle during stretch. To explore the
5226 nature of PEVK elasticity, we used titin-specific antibodies to stain
5227 both ends of the PEVK region in rat psoas myofibrils and determined the
5228 region's force-extension relation by combining immunofluorescence and
5229 immunoelectron microscopy with isolated myofibril mechanics. We then
5230 tried to fit the results with recent models of polymer elasticity. The
5231 PEVK segment elongated substantially at sarcomere lengths above 2.4
5232 micro(m) and reached its estimated contour length at approximately 3.5
5233 micro(m). In immunofluorescently labeled sarcomeres stretched and
5234 released repeatedly above 3 micro(m), reversible PEVK lengthening could
5235 be readily visualized. At extensions near the contour length, the
5236 average force per titin molecule was calculated to be approximately 45
5237 pN. Attempts to fit the force-extension curve of the PEVK segment with
5238 a standard wormlike chain model of entropic elasticity were successful
5239 only for low to moderate extensions. In contrast, the experimental data
5240 also could be correctly fitted at high extensions with a modified
5241 wormlike chain model that incorporates enthalpic elasticity. Enthalpic
5242 contributions are likely to arise from electrostatic stiffening, as
5243 evidenced by the ionic-strength dependency of titin-based myofibril
5244 stiffness; at high stretch, hydrophobic effects also might become
5245 relevant. Thus, at physiological muscle lengths, the PEVK region does
5246 not function as a pure entropic spring. Rather, PEVK elasticity may
5247 have both entropic and enthalpic origins characterizable by a polymer
5248 persistence length and a stretch modulus."
5252 author = WLiu #" and "# VMontana #" and "# EChapman #" and "# UMohideen #"
5254 title = "Botulinum toxin type {B} micromechanosensor",
5259 pages = "13621--13625",
5260 doi = "10.1073/pnas.2233819100",
5261 eprint = "http://www.pnas.org/cgi/reprint/100/23/13621.pdf",
5262 url = "http://www.pnas.org/cgi/content/abstract/100/23/13621",
5263 abstract = "Botulinum neurotoxin (BoNT) types A, B, E, and F are toxic to
5264 humans; early and rapid detection is essential for adequate medical
5265 treatment. Presently available tests for detection of BoNTs, although
5266 sensitive, require hours to days. We report a BoNT-B sensor whose
5267 properties allow detection of BoNT-B within minutes. The technique
5268 relies on the detection of an agarose bead detachment from the tip of a
5269 micromachined cantilever resulting from BoNT-B action on its
5270 substratum, the synaptic protein synaptobrevin 2, attached to the
5271 beads. The mechanical resonance frequency of the cantilever is
5272 monitored for the detection. To suspend the bead off the cantilever we
5273 use synaptobrevin's molecular interaction with another synaptic
5274 protein, syntaxin 1A, that was deposited onto the cantilever tip.
5275 Additionally, this bead detachment technique is general and can be used
5276 in any displacement reaction, such as in receptor-ligand pairs, where
5277 the introduction of one chemical leads to the displacement of another.
5278 The technique is of broad interest and will find uses outside
5283 author = GLois #" and "# JBlawzdziewicz #" and "# CSOHern,
5284 title = "Reliable protein folding on complex energy landscapes: the free
5285 energy reaction path",
5292 pages = "2692--2701",
5294 doi = "10.1529/biophysj.108.133132",
5295 abstract = "A theoretical framework is developed to study the dynamics of
5296 protein folding. The key insight is that the search for the native
5297 protein conformation is influenced by the rate r at which external
5298 parameters, such as temperature, chemical denaturant, or pH, are
5299 adjusted to induce folding. A theory based on this insight predicts
5300 that 1), proteins with complex energy landscapes can fold reliably to
5301 their native state; 2), reliable folding can occur as an equilibrium or
5302 out-of-equilibrium process; and 3), reliable folding only occurs when
5303 the rate r is below a limiting value, which can be calculated from
5304 measurements of the free energy. We test these predictions against
5305 numerical simulations of model proteins with a single energy scale."
5309 author = HLu #" and "# AKrammer #" and "# BIsralewitz #" and "# VVogel #"
5311 title = "Computer modeling of force-induced titin domain unfolding",
5313 journal = AdvExpMedBiol,
5317 url = {http://www.ncbi.nlm.nih.gov/pubmed/10987071},
5318 keywords = "Amino Acid Sequence;Animals;Computer
5319 Simulation;Elasticity;Fibronectins;Humans;Hydrogen
5320 Bonding;Immunoglobulins;Models, Molecular;Muscle Proteins;Muscle,
5321 Skeletal;Myofibrils;Protein Conformation;Protein Denaturation;Protein
5323 abstract = "Titin, a 1 micron long protein found in striated muscle
5324 myofibrils, possesses unique elastic and extensibility properties, and
5325 is largely composed of a PEVK region and beta-sandwich immunoglobulin
5326 (Ig) and fibronectin type III (FnIII) domains. The extensibility
5327 behavior of titin has been shown in atomic force microscope and optical
5328 tweezer experiments to partially depend on the reversible unfolding of
5329 individual Ig and FnIII domains. We performed steered molecular
5330 dynamics simulations to stretch single titin Ig domains in solution
5331 with pulling speeds of 0.1-1.0 A/ps, and FnIII domains with a pulling
5332 speed of 0.5 A/ps. Resulting force-extension profiles exhibit a single
5333 dominant peak for each domain unfolding, consistent with the
5334 experimentally observed sequential, as opposed to concerted, unfolding
5335 of Ig and FnIII domains under external stretching forces. The force
5336 peaks can be attributed to an initial burst of a set of backbone
5337 hydrogen bonds connected to the domains' terminal beta-strands.
5338 Constant force stretching simulations, applying 500-1000 pN of force,
5339 were performed on Ig domains. The resulting domain extensions are
5340 halted at an initial extension of 10 A until the set of all six
5341 hydrogen bonds connecting terminal beta-strands break simultaneously.
5342 This behavior is accounted for by a barrier separating folded and
5343 unfolded states, the shape of which is consistent with AFM and chemical
5344 denaturation data.",
5345 note = "discussion in journal on pages 161--2"
5349 author = HLu #" and "# KSchulten,
5350 title = "The key event in force-induced unfolding of Titin's immunoglobulin
5359 doi = {10.1016/S0006-3495(00)76273-4},
5360 url = {http://www.cell.com/biophysj/abstract/S0006-3495%2800%2976273-4},
5361 eprint = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1300915/pdf/10866937.pdf},
5362 keywords = "Amino Acid Sequence;Computer Simulation;Double Bind
5363 Interaction;Hydrogen Bonding;Immunoglobulins;Microscopy, Atomic
5364 Force;Models, Chemical;Models, Molecular;Molecular Sequence Data;Muscle
5365 Proteins;Protein Folding;Protein Kinases;Protein Structure,
5366 Tertiary;Stress, Mechanical;Water",
5367 abstract = "Steered molecular dynamics simulation of force-induced titin
5368 immunoglobulin domain I27 unfolding led to the discovery of a
5369 significant potential energy barrier at an extension of approximately
5370 14 A on the unfolding pathway that protects the domain against
5371 stretching. Previous simulations showed that this barrier is due to the
5372 concurrent breaking of six interstrand hydrogen bonds (H-bonds) between
5373 beta-strands A' and G that is preceded by the breaking of two to three
5374 hydrogen bonds between strands A and B, the latter leading to an
5375 unfolding intermediate. The simulation results are supported by
5376 Angstrom-resolution atomic force microscopy data. Here we perform a
5377 structural and energetic analysis of the H-bonds breaking. It is
5378 confirmed that H-bonds between strands A and B break rapidly. However,
5379 the breaking of the H-bond between strands A' and G needs to be
5380 assisted by fluctuations of water molecules. In nanosecond simulations,
5381 water molecules are found to repeatedly interact with the protein
5382 backbone atoms, weakening individual interstrand H-bonds until all six
5383 A'-G H-bonds break simultaneously under the influence of external
5384 stretching forces. Only when those bonds are broken can the generic
5385 unfolding take place, which involves hydrophobic interactions of the
5386 protein core and exerts weaker resistance against stretching than the
5391 author = HLu #" and "# BIsralewitz #" and "# AKrammer #" and "# VVogel #"
5393 title = "Unfolding of titin immunoglobulin domains by steered molecular
5394 dynamics simulation",
5402 doi = "10.1016/S0006-3495(98)77556-3",
5403 eprint = "http://download.cell.com/biophysj/pdf/PIIS0006349598775563.pdf",
5404 url = "http://www.cell.com/biophysj/abstract/S0006-3495(98)77556-3",
5405 keywords = "Amino Acid Sequence;Animals;Computer Simulation;Glutamic
5406 Acid;Immunoglobulins;Lysine;Macromolecular Substances;Models,
5407 Molecular;Molecular Sequence Data;Muscle
5408 Proteins;Myocardium;Proline;Protein Denaturation;Protein
5409 Folding;Protein Kinases;Protein Structure, Secondary;Sequence
5410 Alignment;Sequence Homology, Amino Acid;Valine",
5411 abstract = "Titin, a 1-microm-long protein found in striated muscle
5412 myofibrils, possesses unique elastic and extensibility properties in
5413 its I-band region, which is largely composed of a PEVK region (70\%
5414 proline, glutamic acid, valine, and lysine residue) and seven-strand
5415 beta-sandwich immunoglobulin-like (Ig) domains. The behavior of titin
5416 as a multistage entropic spring has been shown in atomic force
5417 microscope and optical tweezer experiments to partially depend on the
5418 reversible unfolding of individual Ig domains. We performed steered
5419 molecular dynamics simulations to stretch single titin Ig domains in
5420 solution with pulling speeds of 0.5 and 1.0 A/ps. Resulting force-
5421 extension profiles exhibit a single dominant peak for each Ig domain
5422 unfolding, consistent with the experimentally observed sequential, as
5423 opposed to concerted, unfolding of Ig domains under external stretching
5424 forces. This force peak can be attributed to an initial burst of
5425 backbone hydrogen bonds, which takes place between antiparallel beta-
5426 strands A and B and between parallel beta-strands A' and G. Additional
5427 features of the simulations, including the position of the force peak
5428 and relative unfolding resistance of different Ig domains, can be
5429 related to experimental observations."
5433 author = HLu #" and "# KSchulten,
5434 title = "Steered molecular dynamics simulations of force-induced protein
5444 doi = "10.1002/(SICI)1097-0134(19990601)35:4<453::AID-PROT9>3.0.CO;2-M",
5445 eprint = "http://www3.interscience.wiley.com/cgi-bin/fulltext/65000328/PDFSTART",
5446 url = "http://www3.interscience.wiley.com/journal/65000328/abstract",
5447 keywords = "Computer Simulation;Fibronectins;Hydrogen Bonding;Microscopy,
5448 Atomic Force;Models, Molecular;Protein Denaturation",
5449 abstract = "Steered molecular dynamics (SMD), a computer simulation method
5450 for studying force-induced reactions in biopolymers, has been applied
5451 to investigate the response of protein domains to stretching apart of
5452 their terminal ends. The simulations mimic atomic force microscopy and
5453 optical tweezer experiments, but proceed on much shorter time scales.
5454 The simulations on different domains for 0.6 nanosecond each reveal two
5455 types of protein responses: the first type, arising in certain beta-
5456 sandwich domains, exhibits nanosecond unfolding only after a force
5457 above 1,500 pN is applied; the second type, arising in a wider class of
5458 protein domain structures, requires significantly weaker forces for
5459 nanosecond unfolding. In the first case, strong forces are needed to
5460 concertedly break a set of interstrand hydrogen bonds which protect the
5461 domains against unfolding through stretching; in the second case,
5462 stretching breaks backbone hydrogen bonds one by one, and does not
5463 require strong forces for this purpose. Stretching of beta-sandwich
5464 (immunoglobulin) domains has been investigated further revealing a
5465 specific relationship between response to mechanical strain and the
5466 architecture of beta-sandwich domains."
5469 @article { makarov01,
5470 author = DEMakarov #" and "# PHansma #" and "# HMetiu,
5471 title = "Kinetic Monte Carlo simulation of titin unfolding",
5477 pages = "9663--9673",
5479 doi = "10.1063/1.1369622",
5480 eprint = "http://hansmalab.physics.ucsb.edu/pdf/297%20-%20Makarov,%20D.E._J
5481 .Chem.Phys._2001.pdf",
5482 url = "http://link.aip.org/link/?JCP/114/9663/1",
5483 keywords = "proteins; hydrogen bonds; digital simulation; Monte Carlo
5484 methods; molecular biophysics; intramolecular mechanics;
5485 macromolecules; atomic force microscopy"
5489 author = JFMarko #" and "# EDSiggia,
5490 title = "Stretching {DNA}",
5496 pages = "8759--8770",
5498 eprint = "http://pubs.acs.org/cgi-
5499 bin/archive.cgi/mamobx/1995/28/i26/pdf/ma00130a008.pdf",
5501 "http://pubs3.acs.org/acs/journals/doilookup?in_doi=10.1021/ma00130a008
5504 note = "Derivation of the Worm-like Chain interpolation function."
5507 @article { marszalek02,
5508 author = PMarszalek #" and "# HLi #" and "# AOberhauser #" and "#
5510 title = "Chair-boat transitions in single polysaccharide molecules observed
5511 with force-ramp {AFM}",
5516 pages = "4278--4283",
5517 doi = "10.1073/pnas.072435699",
5518 eprint = "http://www.pnas.org/cgi/reprint/99/7/4278.pdf",
5519 url = "http://www.pnas.org/cgi/content/abstract/99/7/4278",
5520 abstract = "Under a stretching force, the sugar ring of polysaccharide
5521 molecules switches from the chair to the boat-like or inverted chair
5522 conformation. This conformational change can be observed by stretching
5523 single polysaccharide molecules with an atomic force microscope. In
5524 those early experiments, the molecules were stretched at a constant
5525 rate while the resulting force changed over wide ranges. However,
5526 because the rings undergo force-dependent transitions, an experimental
5527 arrangement where the force is the free variable introduces an
5528 undesirable level of complexity in the results. Here we demonstrate the
5529 use of force-ramp atomic force microscopy to capture the conformational
5530 changes in single polysaccharide molecules. Force-ramp atomic force
5531 microscopy readily captures the ring transitions under conditions where
5532 the entropic elasticity of the molecule is separated from its
5533 conformational transitions, enabling a quantitative analysis of the
5534 data with a simple two-state model. This analysis directly provides the
5535 physico-chemical characteristics of the ring transitions such as the
5536 width of the energy barrier, the relative energy of the conformers, and
5537 their enthalpic elasticity. Our experiments enhance the ability of
5538 single-molecule force spectroscopy to make high-resolution measurements
5539 of the conformations of single polysaccharide molecules under a
5540 stretching force, making an important addition to polysaccharide
5544 @article { marszalek99,
5545 author = PMarszalek #" and "# HLu #" and "# HLi #" and "# MCarrionVazquez
5546 #" and "# AOberhauser #" and "# KSchulten #" and "# JFernandez,
5547 title = "Mechanical unfolding intermediates in titin modules",
5556 doi = "10.1038/47083",
5557 eprint = "http://www.nature.com/nature/journal/v402/n6757/pdf/402100a0.pdf",
5558 url = "http://www.nature.com/nature/journal/v402/n6757/abs/402100a0.html",
5559 keywords = "Biomechanics;Computer Simulation;Humans;Hydrogen
5560 Bonding;Microscopy, Atomic Force;Models, Molecular;Muscle
5561 Proteins;Myocardium;Protein Folding;Protein Kinases;Recombinant
5563 abstract = "The modular protein titin, which is responsible for the passive
5564 elasticity of muscle, is subjected to stretching forces. Previous work
5565 on the experimental elongation of single titin molecules has suggested
5566 that force causes consecutive unfolding of each domain in an all-or-
5567 none fashion. To avoid problems associated with the heterogeneity of
5568 the modular, naturally occurring titin, we engineered single proteins
5569 to have multiple copies of single immunoglobulin domains of human
5570 cardiac titin. Here we report the elongation of these molecules using
5571 the atomic force microscope. We find an abrupt extension of each domain
5572 by approximately 7 A before the first unfolding event. This fast
5573 initial extension before a full unfolding event produces a reversible
5574 'unfolding intermediate' Steered molecular dynamics simulations show
5575 that the rupture of a pair of hydrogen bonds near the amino terminus of
5576 the protein domain causes an extension of about 6 A, which is in good
5577 agreement with our observations. Disruption of these hydrogen bonds by
5578 site-directed mutagenesis eliminates the unfolding intermediate. The
5579 unfolding intermediate extends titin domains by approximately 15\% of
5580 their slack length, and is therefore likely to be an important
5581 previously unrecognized component of titin elasticity."
5584 @article { mcpherson01,
5585 author = JDMcPherson #" and "# MMarra #" and "# LHillier #" and "#
5586 RHWaterston #" and "# AChinwalla #" and "# JWallis #" and "# MSekhon #"
5587 and "# KWylie #" and "# ERMardis #" and "# RKWilson #" and "# RFulton
5588 #" and "# TAKucaba #" and "# CWagner-McPherson #" and "# WBBarbazuk #"
5589 and "# SGGregory #" and "# SJHumphray #" and "# LFrench #" and "#
5590 RSEvans #" and "# GBethel #" and "# AWhittaker #" and "# JLHolden #"
5591 and "# OTMcCann #" and "# ADunham #" and "# CSoderlund #" and "#
5592 CEScott #" and "# DRBentley #" and "# GSchuler #" and "# HCChen #" and
5593 "# WJang #" and "# EDGreen #" and "# JRIdol #" and "# VVMaduro #" and
5594 "# KTMontgomery #" and "# ELee #" and "# AMiller #" and "# SEmerling #"
5595 and "# Kucherlapati #" and "# RGibbs #" and "# SScherer #" and "#
5596 JHGorrell #" and "# ESodergren #" and "# KClerc-Blankenburg #" and "#
5597 PTabor #" and "# SNaylor #" and "# DGarcia #" and "# PJdeJong #" and "#
5598 JJCatanese #" and "# NNowak #" and "# KOsoegawa #" and "# SQin #" and
5599 "# LRowen #" and "# AMadan #" and "# MDors #" and "# LHood #" and "#
5600 BTrask #" and "# CFriedman #" and "# HMassa #" and "# VGCheung #" and
5601 "# IRKirsch #" and "# TReid #" and "# RYonescu #" and "# JWeissenbach
5602 #" and "# TBruls #" and "# RHeilig #" and "# EBranscomb #" and "#
5603 AOlsen #" and "# NDoggett #" and "# JFCheng #" and "# THawkins #" and
5604 "# RMMyers #" and "# JShang #" and "# LRamirez #" and "# JSchmutz #"
5605 and "# OVelasquez #" and "# KDixon #" and "# NEStone #" and "# DRCox #"
5606 and "# DHaussler #" and "# WJKent #" and "# TFurey #" and "# SRogic #"
5607 and "# SKennedy #" and "# SJones #" and "# ARosenthal #" and "# GWen #"
5608 and "# MSchilhabel #" and "# GGloeckner #" and "# GNyakatura #" and "#
5609 RSiebert #" and "# BSchlegelberger #" and "# JKorenberg #" and "#
5610 XNChen #" and "# AFujiyama #" and "# MHattori #" and "# AToyoda #" and
5611 "# TYada #" and "# HSPark #" and "# YSakaki #" and "# NShimizu #" and
5612 "# SAsakawa #" and "# KKawasaki #" and "# TSasaki #" and "# AShintani
5613 #" and "# AShimizu #" and "# KShibuya #" and "# JKudoh #" and "#
5614 SMinoshima #" and "# JRamser #" and "# PSeranski #" and "# CHoff #" and
5615 "# APoustka #" and "# RReinhardt #" and "# HLehrach,
5616 title = "A physical map of the human genome.",
5625 doi = "10.1038/35057157",
5626 eprint = "http://www.nature.com/nature/journal/v409/n6822/pdf/409934a0.pdf",
5627 url = "http://www.nature.com/nature/journal/v409/n6822/full/409934a0.html",
5628 keywords = "Chromosomes, Artificial, Bacterial;Cloning, Molecular;Contig
5629 Mapping;DNA Fingerprinting;Gene Duplication;Genome, Human;Humans;In
5630 Situ Hybridization, Fluorescence;Repetitive Sequences, Nucleic Acid",
5631 abstract = "The human genome is by far the largest genome to be sequenced,
5632 and its size and complexity present many challenges for sequence
5633 assembly. The International Human Genome Sequencing Consortium
5634 constructed a map of the whole genome to enable the selection of clones
5635 for sequencing and for the accurate assembly of the genome sequence.
5636 Here we report the construction of the whole-genome bacterial
5637 artificial chromosome (BAC) map and its integration with previous
5638 landmark maps and information from mapping efforts focused on specific
5639 chromosomal regions. We also describe the integration of sequence data
5644 author = CCMello #" and "# DBarrick,
5645 title = "An experimentally determined protein folding energy landscape",
5652 pages = "14102--14107",
5654 doi = "10.1073/pnas.0403386101",
5655 keywords = "Animals; Ankyrin Repeat; Circular Dichroism; Drosophila
5656 Proteins; Drosophila melanogaster; Gene Deletion; Models, Chemical;
5657 Models, Molecular; Protein Denaturation; Protein Folding; Protein
5658 Structure, Tertiary; Spectrometry, Fluorescence; Thermodynamics; Urea",
5659 abstract = "Energy landscapes have been used to conceptually describe and
5660 model protein folding but have been difficult to measure
5661 experimentally, in large part because of the myriad of partly folded
5662 protein conformations that cannot be isolated and thermodynamically
5663 characterized. Here we experimentally determine a detailed energy
5664 landscape for protein folding. We generated a series of overlapping
5665 constructs containing subsets of the seven ankyrin repeats of the
5666 Drosophila Notch receptor, a protein domain whose linear arrangement of
5667 modular structural units can be fragmented without disrupting
5668 structure. To a good approximation, stabilities of each construct can
5669 be described as a sum of energy terms associated with each repeat. The
5670 magnitude of each energy term indicates that each repeat is
5671 intrinsically unstable but is strongly stabilized by interactions with
5672 its nearest neighbors. These linear energy terms define an equilibrium
5673 free energy landscape, which shows an early free energy barrier and
5674 suggests preferred low-energy routes for folding."
5677 @article { merkel99,
5678 author = RMerkel #" and "# PNassoy #" and "# ALeung #" and "# KRitchie #"
5680 title = "Energy landscapes of receptor-ligand bonds explored with dynamic
5681 force spectroscopy",
5690 doi = "10.1038/16219",
5691 url = "http://www.nature.com/nature/journal/v397/n6714/full/397050a0.html",
5692 keywords = "Biotin;Microscopy, Atomic Force;Protein Binding;Streptavidin",
5693 abstract = "Atomic force microscopy (AFM) has been used to measure the
5694 strength of bonds between biological receptor molecules and their
5695 ligands. But for weak noncovalent bonds, a dynamic spectrum of bond
5696 strengths is predicted as the loading rate is altered, with the
5697 measured strength being governed by the prominent barriers traversed in
5698 the energy landscape along the force-driven bond-dissociation pathway.
5699 In other words, the pioneering early AFM measurements represent only a
5700 single point in a continuous spectrum of bond strengths, because theory
5701 predicts that these will depend on the rate at which the load is
5702 applied. Here we report the strength spectra for the bonds between
5703 streptavidin (or avidin) and biotins-the prototype of receptor-ligand
5704 interactions used in earlier AFM studies, and which have been modelled
5705 by molecular dynamics. We have probed bond formation over six orders of
5706 magnitude in loading rate, and find that the bond survival time
5707 diminished from about 1 min to 0.001 s with increasing loading rate
5708 over this range. The bond strength, meanwhile, increased from about 5
5709 pN to 170 pN. Thus, although they are among the strongest noncovalent
5710 linkages in biology (affinity of 10(13) to 10(15) M(-1)), these bonds
5711 in fact appear strong or weak depending on how fast they are loaded. We
5712 are also able to relate the activation barriers derived from our
5713 strength spectra to the shape of the energy landscape derived from
5714 simulations of the biotin-avidin complex."
5717 @article { metropolis87,
5718 author = NMetropolis,
5719 title = "The Beginning of the {M}onte {C}arlo Method",
5725 url = "http://library.lanl.gov/cgi-bin/getfile?15-12.pdf"
5728 @article { mickler07,
5729 author = MMickler #" and "# RDima #" and "# HDietz #" and "# CHyeon #" and
5730 "# DThirumalai #" and "# MRief,
5731 title = "Revealing the bifurcation in the unfolding pathways of {GFP} by
5732 using single-molecule experiments and simulations",
5737 pages = "20268--20273",
5738 doi = "10.1073/pnas.0705458104",
5739 eprint = "http://www.pnas.org/cgi/reprint/104/51/20268.pdf",
5740 url = "http://www.pnas.org/cgi/content/abstract/104/51/20268",
5741 keywords = "AFM experiments, coarse-grained simulations, cross-link
5742 mutants, pathway bifurcation, plasticity of energy landscape",
5743 abstract = "Nanomanipulation of biomolecules by using single-molecule
5744 methods and computer simulations has made it possible to visualize the
5745 energy landscape of biomolecules and the structures that are sampled
5746 during the folding process. We use simulations and single-molecule
5747 force spectroscopy to map the complex energy landscape of GFP that is
5748 used as a marker in cell biology and biotechnology. By engineering
5749 internal disulfide bonds at selected positions in the GFP structure,
5750 mechanical unfolding routes are precisely controlled, thus allowing us
5751 to infer features of the energy landscape of the wild-type GFP. To
5752 elucidate the structures of the unfolding pathways and reveal the
5753 multiple unfolding routes, the experimental results are complemented
5754 with simulations of a self-organized polymer (SOP) model of GFP. The
5755 SOP representation of proteins, which is a coarse-grained description
5756 of biomolecules, allows us to perform forced-induced simulations at
5757 loading rates and time scales that closely match those used in atomic
5758 force microscopy experiments. By using the combined approach, we show
5759 that forced unfolding of GFP involves a bifurcation in the pathways to
5760 the stretched state. After detachment of an N-terminal {alpha}-helix,
5761 unfolding proceeds along two distinct pathways. In the dominant
5762 pathway, unfolding starts from the detachment of the primary N-terminal
5763 -strand, while in the minor pathway rupture of the last, C-terminal
5764 -strand initiates the unfolding process. The combined approach has
5765 allowed us to map the features of the complex energy landscape of GFP
5766 including a characterization of the structures, albeit at a coarse-
5767 grained level, of the three metastable intermediates.",
5768 note = {Hiccup in unfolding leg corresponds to unfolding
5769 intermediate (\fref{figure}{2}). The unfolding time scale in GFP
5770 is about $6\U{ms}$.},
5774 author = RNevo #" and "# CStroh #" and "# FKienberger #" and "# DKaftan #"
5775 and "# VBrumfeld #" and "# MElbaum #" and "# ZReich #" and "#
5777 title = "A molecular switch between alternative conformational states in
5778 the complex of {Ran} and importin beta1",
5786 doi = "10.1038/nsb940",
5787 eprint = "http://www.nature.com/nsmb/journal/v10/n7/pdf/nsb940.pdf",
5788 url = "http://www.nature.com/nsmb/journal/v10/n7/abs/nsb940.html",
5789 keywords = "Guanosine Diphosphate; Guanosine Triphosphate; Microscopy,
5790 Atomic Force; Protein Binding; Protein Conformation; beta Karyopherins;
5791 ran GTP-Binding Protein",
5792 abstract = "Several million macromolecules are exchanged each minute
5793 between the nucleus and cytoplasm by receptor-mediated transport. Most
5794 of this traffic is controlled by the small GTPase Ran, which regulates
5795 assembly and disassembly of the receptor-cargo complexes in the
5796 appropriate cellular compartment. Here we applied dynamic force
5797 spectroscopy to study the interaction of Ran with the nuclear import
5798 receptor importin beta1 (impbeta) at the single-molecule level. We
5799 found that the complex alternates between two distinct conformational
5800 states of different adhesion strength. The application of an external
5801 mechanical force shifts equilibrium toward one of these states by
5802 decreasing the height of the interstate activation energy barrier. The
5803 other state can be stabilized by a functional Ran mutant that increases
5804 this barrier. These results support a model whereby functional control
5805 of Ran-impbeta is achieved by a population shift between pre-existing
5806 alternative conformations."
5810 author = RNevo #" and "# VBrumfeld #" and "# MElbaum #" and "#
5811 PHinterdorfer #" and "# ZReich,
5812 title = "Direct discrimination between models of protein activation by
5813 single-molecule force measurements",
5819 pages = "2630--2634",
5821 doi = "10.1529/biophysj.104.041889",
5822 eprint = "http://www.biophysj.org/cgi/reprint/87/4/2630.pdf",
5823 url = "http://www.biophysj.org/cgi/content/abstract/87/4/2630",
5824 keywords = "Elasticity; Enzyme Activation; Micromanipulation; Microscopy,
5825 Atomic Force; Models, Chemical; Models, Molecular; Multiprotein
5826 Complexes; Nuclear Proteins; Physical Stimulation; Protein Binding;
5827 Stress, Mechanical; Structure-Activity Relationship; beta Karyopherins;
5828 ran GTP-Binding Protein",
5829 abstract = "The limitations imposed on the analyses of complex chemical and
5830 biological systems by ensemble averaging can be overcome by single-
5831 molecule experiments. Here, we used a single-molecule technique to
5832 discriminate between two generally accepted mechanisms of a key
5833 biological process--the activation of proteins by molecular effectors.
5834 The two mechanisms, namely induced-fit and population-shift, are
5835 normally difficult to discriminate by ensemble approaches. As a model,
5836 we focused on the interaction between the nuclear transport effector,
5837 RanBP1, and two related complexes consisting of the nuclear import
5838 receptor, importin beta, and the GDP- or GppNHp-bound forms of the
5839 small GTPase, Ran. We found that recognition by the effector proceeds
5840 through either an induced-fit or a population-shift mechanism,
5841 depending on the substrate, and that the two mechanisms can be
5842 differentiated by the data."
5846 author = RNevo #" and "# VBrumfeld #" and "# RKapon #" and "# PHinterdorfer
5848 title = "Direct measurement of protein energy landscape roughness",
5856 doi = "10.1038/sj.embor.7400403",
5857 eprint = "http://www.nature.com/embor/journal/v6/n5/pdf/7400403.pdf",
5858 url = "http://www.nature.com/embor/journal/v6/n5/abs/7400403.html",
5859 keywords = "Models, Molecular; Protein Binding; Protein Folding; Spectrum
5860 Analysis; Thermodynamics; beta Karyopherins; ran GTP-Binding Protein",
5861 abstract = "The energy landscape of proteins is thought to have an
5862 intricate, corrugated structure. Such roughness should have important
5863 consequences on the folding and binding kinetics of proteins, as well
5864 as on their equilibrium fluctuations. So far, no direct measurement of
5865 protein energy landscape roughness has been made. Here, we combined a
5866 recent theory with single-molecule dynamic force spectroscopy
5867 experiments to extract the overall energy scale of roughness epsilon
5868 for a complex consisting of the small GTPase Ran and the nuclear
5869 transport receptor importin-beta. The results gave epsilon > 5k(B)T,
5870 indicating a bumpy energy surface, which is consistent with the ability
5871 of importin-beta to accommodate multiple conformations and to interact
5872 with different, structurally distinct ligands.",
5873 note = "Applies \citet{hyeon03} to ligand-receptor binding.",
5874 project = "Energy Landscape Roughness"
5878 author = SNg #" and "# KBillings #" and "# TOhashi #" and "# MAllen #" and
5879 "# RBest #" and "# LRandles #" and "# HErickson #" and "# JClarke,
5880 title = "Designing an extracellular matrix protein with enhanced mechanical
5888 pages = "9633--9637",
5889 doi = "10.1073/pnas.0609901104",
5890 eprint = "http://www.pnas.org/cgi/reprint/104/23/9633.pdf",
5891 url = "http://www.pnas.org/cgi/content/abstract/104/23/9633",
5892 abstract = "The extracellular matrix proteins tenascin and fibronectin
5893 experience significant mechanical forces in vivo. Both contain a number
5894 of tandem repeating homologous fibronectin type III (fnIII) domains,
5895 and atomic force microscopy experiments have demonstrated that the
5896 mechanical strength of these domains can vary significantly. Previous
5897 work has shown that mutations in the core of an fnIII domain from human
5898 tenascin (TNfn3) reduce the unfolding force of that domain
5899 significantly: The composition of the core is apparently crucial to the
5900 mechanical stability of these proteins. Based on these results, we have
5901 used rational redesign to increase the mechanical stability of the 10th
5902 fnIII domain of human fibronectin, FNfn10, which is directly involved
5903 in integrin binding. The hydrophobic core of FNfn10 was replaced with
5904 that of the homologous, mechanically stronger TNfn3 domain. Despite the
5905 extensive substitution, FNoTNc retains both the three-dimensional
5906 structure and the cell adhesion activity of FNfn10. Atomic force
5907 microscopy experiments reveal that the unfolding forces of the
5908 engineered protein FNoTNc increase by {approx}20% to match those of
5909 TNfn3. Thus, we have specifically designed a protein with increased
5910 mechanical stability. Our results demonstrate that core engineering can
5911 be used to change the mechanical strength of proteins while retaining
5912 functional surface interactions."
5916 author = SNg #" and "# JClarke,
5917 title = "Experiments Suggest that Simulations May Overestimate
5918 Electrostatic Contributions to the Mechanical Stability of a
5919 Fibronectin Type {III} Domain",
5923 pages = "851–854",
5928 doi = "10.1016/j.jmb.2007.06.015",
5929 url = "http://www.sciencedirect.com/science/article/pii/S0022283607007966",
5931 keywords = "MD simulations",
5933 keywords = "forced unfolding",
5934 keywords = "extracellular matrix",
5935 abstract = "Steered molecular dynamics simulations have previously
5936 been used to investigate the mechanical properties of the
5937 extracellular matrix protein fibronectin. The simulations
5938 suggest that the mechanical stability of the tenth type III
5939 domain from fibronectin (FNfn10) is largely determined by a
5940 number of critical hydrogen bonds in the peripheral
5941 strands. Interestingly, the simulations predict that lowering
5942 the pH from 7 to ∼4.7 will increase the mechanical stability
5943 of FNfn10 significantly (by ∼33 %) due to the protonation of a
5944 few key acidic residues in the A and B strands. To test this
5945 simulation prediction, we used single-molecule atomic force
5946 microscopy (AFM) to investigate the mechanical stability of
5947 FNfn10 at neutral pH and at lower pH where these key residues
5948 have been shown to be protonated. Our AFM experimental results
5949 show no difference in the mechanical stability of FNfn10 at
5950 these different pH values. These results suggest that some
5951 simulations may overestimate the role played by electrostatic
5952 interactions in determining the mechanical stability of
5957 author = RNome #" and "# JZhao #" and "# WHoff #" and "# NScherer,
5958 title = "Axis-dependent anisotropy in protein unfolding from integrated
5959 nonequilibrium single-molecule experiments, analysis, and simulation",
5966 pages = "20799--20804",
5968 doi = "10.1073/pnas.0701281105",
5969 eprint = "http://www.pnas.org/cgi/reprint/104/52/20799.pdf",
5970 url = "http://www.pnas.org/cgi/content/abstract/104/52/20799",
5971 keywords = "Anisotropy; Bacterial Proteins; Biophysics; Computer
5972 Simulation; Cysteine; Halorhodospira halophila; Hydrogen Bonding;
5973 Kinetics; Luminescent Proteins; Microscopy, Atomic Force; Molecular
5974 Conformation; Protein Binding; Protein Conformation; Protein
5975 Denaturation; Protein Folding; Protein Structure, Secondary",
5976 abstract = "We present a comprehensive study that integrates experimental
5977 and theoretical nonequilibrium techniques to map energy landscapes
5978 along well defined pull-axis specific coordinates to elucidate
5979 mechanisms of protein unfolding. Single-molecule force-extension
5980 experiments along two different axes of photoactive yellow protein
5981 combined with nonequilibrium statistical mechanical analysis and
5982 atomistic simulation reveal energetic and mechanistic anisotropy.
5983 Steered molecular dynamics simulations and free-energy curves
5984 constructed from the experimental results reveal that unfolding along
5985 one axis exhibits a transition-state-like feature where six hydrogen
5986 bonds break simultaneously with weak interactions observed during
5987 further unfolding. The other axis exhibits a constant (unpeaked) force
5988 profile indicative of a noncooperative transition, with enthalpic
5989 (e.g., H-bond) interactions being broken throughout the unfolding
5990 process. Striking qualitative agreement was found between the force-
5991 extension curves derived from steered molecular dynamics calculations
5992 and the equilibrium free-energy curves obtained by JarzynskiHummerSzabo
5993 analysis of the nonequilibrium work data. The anisotropy persists
5994 beyond pulling distances of more than twice the initial dimensions of
5995 the folded protein, indicating a rich energy landscape to the
5996 mechanically fully unfolded state. Our findings challenge the notion
5997 that cooperative unfolding is a universal feature in protein
6003 title = "Handbook of Molecular Force Spectroscopy",
6005 isbn = "978-0-387-49987-1",
6006 publisher = SPRINGER,
6007 note = "The first book about force spectroscopy. Discusses the scaffold
6008 effect in section 8.4.1."
6011 @article { nummela07,
6012 author = JNummela #" and "# IAndricioaei,
6013 title = "{Exact Low-Force Kinetics from High-Force Single-Molecule
6019 pages = "3373--3381",
6020 doi = "10.1529/biophysj.107.111658",
6021 eprint = "http://www.biophysj.org/cgi/reprint/93/10/3373.pdf",
6022 url = "http://www.biophysj.org/cgi/content/abstract/93/10/3373",
6023 abstract = "Mechanical forces play a key role in crucial cellular processes
6024 involving force-bearing biomolecules, as well as in novel single-
6025 molecule pulling experiments. We present an exact method that enables
6026 one to extrapolate, to low (or zero) forces, entire time-correlation
6027 functions and kinetic rate constants from the conformational dynamics
6028 either simulated numerically or measured experimentally at a single,
6029 relatively higher, external force. The method has twofold relevance:
6030 1), to extrapolate the kinetics at physiological force conditions from
6031 molecular dynamics trajectories generated at higher forces that
6032 accelerate conformational transitions; and 2), to extrapolate unfolding
6033 rates from experimental force-extension single-molecule curves. The
6034 theoretical formalism, based on stochastic path integral weights of
6035 Langevin trajectories, is presented for the constant-force, constant
6036 loading rate, and constant-velocity modes of the pulling experiments.
6037 For the first relevance, applications are described for simulating the
6038 conformational isomerization of alanine dipeptide; and for the second
6039 relevance, the single-molecule pulling of RNA is considered. The
6040 ability to assign a weight to each trace in the single-molecule data
6041 also suggests a means to quantitatively compare unfolding pathways
6042 under different conditions."
6045 @article { oberhauser01,
6046 author = AOberhauser #" and "# PHansma #" and "# MCarrionVazquez #" and "#
6048 title = "Stepwise unfolding of titin under force-clamp atomic force
6055 doi = "10.1073/pnas.021321798",
6056 eprint = "http://www.pnas.org/cgi/reprint/98/2/468.pdf",
6057 url = "http://www.pnas.org/cgi/content/abstract/98/2/468",
6063 title = "Cantilever spring constant calibration using laser Doppler
6073 doi = "10.1063/1.2743272",
6074 url = "http://link.aip.org/link/?RSI/78/063701/1",
6075 keywords = "calibration; vibration measurement; measurement by laser beam;
6076 Doppler measurement; measurement uncertainty; atomic force microscopy",
6077 note = "Excellent review of thermal calibration to 2007, but nothing in the
6078 way of derivations. Compares thermal tune and Sader method with laser
6079 Doppler vibrometry.",
6080 project = "Cantilever Calibration"
6083 @article { olshansky97,
6084 author = SJOlshansky #" and "# BACarnes,
6085 title = "Ever since {G}ompertz",
6088 journal = Demography,
6093 url = "http://www.jstor.org/stable/2061656",
6094 keywords = "Aging;Biometry;History, 19th Century;History, 20th
6095 Century;Humans;Life Tables;Mortality;Sexual Maturation",
6096 abstract = "In 1825 British actuary Benjamin Gompertz made a simple but
6097 important observation that a law of geometrical progression pervades
6098 large portions of different tables of mortality for humans. The simple
6099 formula he derived describing the exponential rise in death rates
6100 between sexual maturity and old age is commonly, referred to as the
6101 Gompertz equation-a formula that remains a valuable tool in demography
6102 and in other scientific disciplines. Gompertz's observation of a
6103 mathematical regularity in the life table led him to believe in the
6104 presence of a low of mortality that explained why common age patterns
6105 of death exist. This law of mortality has captured the attention of
6106 scientists for the past 170 years because it was the first among what
6107 are now several reliable empirical tools for describing the dying-out
6108 process of many living organisms during a significant portion of their
6109 life spans. In this paper we review the literature on Gompertz's law of
6110 mortality and discuss the importance of his observations and insights
6111 in light of research on aging that has taken place since then.",
6112 note = "Hardly any actual math, but the references might be interesting.
6113 I'll look into them if I have the time. Available through several
6117 @article { onuchic96,
6118 author = JNOnuchic #" and "# NDSocci #" and "# ZLuthey-Schulten #" and "#
6120 title = "Protein folding funnels: the nature of the transition state
6128 keywords = "Animals; Cytochrome c Group; Humans; Infant; Protein Folding",
6129 abstract = "BACKGROUND: Energy landscape theory predicts that the folding
6130 funnel for a small fast-folding alpha-helical protein will have a
6131 transition state half-way to the native state. Estimates of the
6132 position of the transition state along an appropriate reaction
6133 coordinate can be obtained from linear free energy relationships
6134 observed for folding and unfolding rate constants as a function of
6135 denaturant concentration. The experimental results of Huang and Oas for
6136 lambda repressor, Fersht and collaborators for C12, and Gray and
6137 collaborators for cytochrome c indicate a free energy barrier midway
6138 between the folded and unfolded regions. This barrier arises from an
6139 entropic bottleneck for the folding process. RESULTS: In keeping with
6140 the experimental results, lattice simulations based on the folding
6141 funnel description show that the transition state is not just a single
6142 conformation, but rather an ensemble of a relatively large number of
6143 configurations that can be described by specific values of one or a few
6144 order parameters (e.g. the fraction of native contacts). Analysis of
6145 this transition state or bottleneck region from our lattice simulations
6146 and from atomistic models for small alpha-helical proteins by Boczko
6147 and Brooks indicates a broad distribution for native contact
6148 participation in the transition state ensemble centered around 50\%.
6149 Importantly, however, the lattice-simulated transition state ensemble
6150 does include some particularly hot contacts, as seen in the
6151 experiments, which have been termed by others a folding nucleus.
6152 CONCLUSIONS: Linear free energy relations provide a crude spectroscopy
6153 of the transition state, allowing us to infer the values of a reaction
6154 coordinate based on the fraction of native contacts. This bottleneck
6155 may be thought of as a collection of delocalized nuclei where different
6156 native contacts will have different degrees of participation. The
6157 agreement between the experimental results and the theoretical
6158 predictions provides strong support for the landscape analysis."
6162 author = COpitz #" and "# MKulke #" and "# MLeake #" and "# CNeagoe #" and
6163 "# HHinssen #" and "# RHajjar #" and "# WALinke,
6164 title = "Damped elastic recoil of the titin spring in myofibrils of human
6170 pages = "12688--12693",
6171 doi = "10.1073/pnas.2133733100",
6172 eprint = "http://www.pnas.org/cgi/reprint/100/22/12688.pdf",
6173 url = "http://www.pnas.org/cgi/content/abstract/100/22/12688",
6174 abstract = "The giant protein titin functions as a molecular spring in
6175 muscle and is responsible for most of the passive tension of
6176 myocardium. Because the titin spring is extended during diastolic
6177 stretch, it will recoil elastically during systole and potentially may
6178 influence the overall shortening behavior of cardiac muscle. Here,
6179 titin elastic recoil was quantified in single human heart myofibrils by
6180 using a high-speed charge-coupled device-line camera and a
6181 nanonewtonrange force sensor. Application of a slack-test protocol
6182 revealed that the passive shortening velocity (Vp) of nonactivated
6183 cardiomyofibrils depends on: (i) initial sarcomere length, (ii)
6184 release-step amplitude, and (iii) temperature. Selective digestion of
6185 titin, with low doses of trypsin, decelerated myofibrillar passive
6186 recoil and eventually stopped it. Selective extraction of actin
6187 filaments with a Ca2+-independent gelsolin fragment greatly reduced the
6188 dependency of Vp on release-step size and temperature. These results
6189 are explained by the presence of viscous forces opposing myofibrillar
6190 passive recoil that are caused mainly by weak actin-titin interactions.
6191 Thus, Vp is determined by two distinct factors: titin elastic recoil
6192 and internal viscous drag forces. The recoil could be modeled as that
6193 of a damped entropic spring consisting of independent worm-like chains.
6194 The functional importance of myofibrillar elastic recoil was addressed
6195 by comparing instantaneous Vp to unloaded shortening velocity, which
6196 was measured in demembranated, fully Ca2+-activated, human cardiac
6197 fibers. Titin-driven passive recoil was much faster than active
6198 unloaded shortening velocity in early phases of isotonic contraction.
6199 Damped myofibrillar elastic recoil could help accelerate active
6200 contraction speed of human myocardium during early systolic
6204 @article { oroudjev02,
6205 author = EOroudjev #" and "# JSoares #" and "# SArcidiacono #" and "#
6206 JThompson #" and "# SFossey #" and "# HHansma,
6207 title = "Segmented nanofibers of spider dragline silk: Atomic force
6208 microscopy and single-molecule force spectroscopy",
6213 pages = "6460--6465",
6214 doi = "10.1073/pnas.082526499",
6215 eprint = "http://www.pnas.org/cgi/reprint/99/suppl_2/6460.pdf",
6216 url = "http://www.pnas.org/cgi/content/abstract/99/suppl_2/6460",
6217 abstract = "Despite its remarkable materials properties, the structure of
6218 spider dragline silk has remained unsolved. Results from two probe
6219 microscopy techniques provide new insights into the structure of spider
6220 dragline silk. A soluble synthetic protein from dragline silk
6221 spontaneously forms nanofibers, as observed by atomic force microscopy.
6222 These nanofibers have a segmented substructure. The segment length and
6223 amino acid sequence are consistent with a slab-like shape for
6224 individual silk protein molecules. The height and width of nanofiber
6225 segments suggest a stacking pattern of slab-like molecules in each
6226 nanofiber segment. This stacking pattern produces nano-crystals in an
6227 amorphous matrix, as observed previously by NMR and x-ray diffraction
6228 of spider dragline silk. The possible importance of nanofiber formation
6229 to native silk production is discussed. Force spectra for single
6230 molecules of the silk protein demonstrate that this protein unfolds
6231 through a number of rupture events, indicating a modular substructure
6232 within single silk protein molecules. A minimal unfolding module size
6233 is estimated to be around 14 nm, which corresponds to the extended
6234 length of a single repeated module, 38 amino acids long. The structure
6235 of this spider silk protein is distinctly different from the structures
6236 of other proteins that have been analyzed by single-molecule force
6237 spectroscopy, and the force spectra show correspondingly novel
6242 author = EPaci #" and "# MKarplus,
6243 title = "Unfolding proteins by external forces and temperature: The
6244 importance of topology and energetics",
6249 pages = "6521--6526",
6250 doi = "10.1073/pnas.100124597",
6251 eprint = "http://www.pnas.org/cgi/reprint/97/12/6521.pdf",
6252 url = "http://www.pnas.org/cgi/content/abstract/97/12/6521"
6256 author = EPaci #" and "# MKarplus,
6257 title = "Forced unfolding of fibronectin type 3 modules: an analysis by
6258 biased molecular dynamics simulations",
6267 doi = "10.1006/jmbi.1999.2670",
6268 keywords = "Dimerization;Fibronectins;Humans;Hydrogen Bonding;Microscopy,
6269 Atomic Force;Protein Denaturation;Protein Folding",
6270 abstract = "Titin, an important constituent of vertebrate muscles, is a
6271 protein of the order of a micrometer in length in the folded state.
6272 Atomic force microscopy and laser tweezer experiments have been used to
6273 stretch titin molecules to more than ten times their folded lengths. To
6274 explain the observed relation between force and extension, it has been
6275 suggested that the immunoglobulin and fibronectin domains unfold one at
6276 a time in an all-or-none fashion. We use molecular dynamics simulations
6277 to study the forced unfolding of two different fibronectin type 3
6278 domains (the ninth, 9Fn3, and the tenth, 10Fn3, from human fibronectin)
6279 and of their heterodimer of known structure. An external biasing
6280 potential on the N to C distance is employed and the protein is treated
6281 in the polar hydrogen representation with an implicit solvation model.
6282 The latter provides an adiabatic solvent response, which is important
6283 for the nanosecond unfolding simulation method used here. A series of
6284 simulations is performed for each system to obtain meaningful results.
6285 The two different fibronectin domains are shown to unfold in the same
6286 way along two possible pathways. These involve the partial separation
6287 of the ``beta-sandwich'', an essential structural element, and the
6288 unfolding of the individual sheets in a stepwise fashion. The biasing
6289 potential results are confirmed by constant force unfolding
6290 simulations. For the two connected domains, there is complete unfolding
6291 of one domain (9Fn3) before major unfolding of the second domain
6292 (10Fn3). Comparison of different models for the potential energy
6293 function demonstrates that the dominant cohesive element in both
6294 proteins is due to the attractive van der Waals interactions;
6295 electrostatic interactions play a structural role but appear to make
6296 only a small contribution to the stabilization of the domains, in
6297 agreement with other studies of beta-sheet stability. The unfolding
6298 forces found in the simulations are of the order of those observed
6299 experimentally, even though the speed of the former is more than six
6300 orders of magnitude greater than that used in the latter."
6304 author = QPeng #" and "# HLi,
6305 title = "Atomic force microscopy reveals parallel mechanical unfolding
6306 pathways of T4 lysozyme: Evidence for a kinetic partitioning mechanism",
6311 pages = "1885--1890",
6312 doi = "10.1073/pnas.0706775105",
6313 eprint = "http://www.pnas.org/cgi/reprint/105/6/1885.pdf",
6314 url = "http://www.pnas.org/cgi/content/abstract/105/6/1885",
6315 abstract = "Kinetic partitioning is predicted to be a general mechanism for
6316 proteins to fold into their well defined native three-dimensional
6317 structure from unfolded states following multiple folding pathways.
6318 However, experimental evidence supporting this mechanism is still
6319 limited. By using single-molecule atomic force microscopy, here we
6320 report experimental evidence supporting the kinetic partitioning
6321 mechanism for mechanical unfolding of T4 lysozyme, a small protein
6322 composed of two subdomains. We observed that on stretching from its N
6323 and C termini, T4 lysozyme unfolds by multiple distinct unfolding
6324 pathways: the majority of T4 lysozymes unfold in an all-or-none fashion
6325 by overcoming a dominant unfolding kinetic barrier; and a small
6326 fraction of T4 lysozymes unfold in three-state fashion involving
6327 unfolding intermediate states. The three-state unfolding pathways do
6328 not follow well defined routes, instead they display variability and
6329 diversity in individual unfolding pathways. The unfolding intermediate
6330 states are local energy minima along the mechanical unfolding pathways
6331 and are likely to result from the residual structures present in the
6332 two subdomains after crossing the main unfolding barrier. These results
6333 provide direct evidence for the kinetic partitioning of the mechanical
6334 unfolding pathways of T4 lysozyme, and the complex unfolding behaviors
6335 reflect the stochastic nature of kinetic barrier rupture in mechanical
6336 unfolding processes. Our results demonstrate that single-molecule
6337 atomic force microscopy is an ideal tool to investigate the
6338 folding/unfolding dynamics of complex multimodule proteins that are
6339 otherwise difficult to study using traditional methods."
6343 author = WPress #" and "# STeukolsky #" and "# WVetterling #" and "#
6345 title = "Numerical Recipies in {C}: The Art of Scientific Computing",
6349 address = "New York",
6350 eprint = "http://www.nrbook.com/a/bookcpdf.php",
6351 note = "See Sections 12.0, 12.1, 12.3, and 13.4 for a good introduction to
6352 Fourier transforms and power spectrum estimation.",
6353 project = "Cantilever Calibration"
6356 @article { puchner08,
6357 author = EPuchner #" and "# GFranzen #" and "# MGautel #" and "# HEGaub,
6358 title = "Comparing proteins by their unfolding pattern.",
6366 doi = "10.1529/biophysj.108.129999",
6367 eprint = "http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2426622/pdf/426.pdf",
6368 url = "http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2426622/",
6369 keywords = "Algorithms;Computer Simulation;Microscopy, Atomic Force;Models,
6370 Chemical;Models, Molecular;Protein Denaturation;Protein
6372 abstract = "Single molecule force spectroscopy has evolved into an
6373 important and extremely powerful technique for investigating the
6374 folding potentials of biomolecules. Mechanical tension is applied to
6375 individual molecules, and the subsequent, often stepwise unfolding is
6376 recorded in force extension traces. However, because the energy
6377 barriers of the folding potentials are often close to the thermal
6378 energy, both the extensions and the forces at which these barriers are
6379 overcome are subject to marked fluctuations. Therefore, force extension
6380 traces are an inadequate representation despite widespread use
6381 particularly when large populations of proteins need to be compared and
6382 analyzed. We show in this article that contour length, which is
6383 independent of fluctuations and alterable experimental parameters, is a
6384 more appropriate variable than extension. By transforming force
6385 extension traces into contour length space, histograms are obtained
6386 that directly represent the energy barriers. In contrast to force
6387 extension traces, such barrier position histograms can be averaged to
6388 investigate details of the unfolding potential. The cross-superposition
6389 of barrier position histograms allows us to detect and visualize the
6390 order of unfolding events. We show with this approach that in contrast
6391 to the sequential unfolding of bacteriorhodopsin, two main steps in the
6392 unfolding of the enzyme titin kinase are independent of each other. The
6393 potential of this new method for accurate and automated analysis of
6394 force spectroscopy data and for novel automated screening techniques is
6395 shown with bacteriorhodopsin and with protein constructs containing GFP
6397 note = {Contour length space and barrier position fingerprinting.
6398 There are errors in \fref{equation}{3}, propagated from
6399 \citet{livadaru03}. I contacted Elias Puchner and pointed out the
6400 typos, and he revised his FRC fit parameters from $\gamma=22\dg$
6401 and $b=0.4\U{nm}$ to $\gamma=41\dg$ and $b=0.11\U{nm}$. The
6402 combined effect on \fref{figure}{3} of fixing the equation typos
6403 and adjusting the fit parameters was small, so their conclusions
6407 @article { raible04,
6408 author = MRaible #" and "# MEvstigneev #" and "# PReimann #" and "#
6409 FWBartels #" and "# RRos,
6410 title = "Theoretical analysis of dynamic force spectroscopy experiments on
6411 ligand-receptor complexes",
6420 doi = "10.1016/j.jbiotec.2004.04.017",
6421 keywords = "Binding Sites;Computer Simulation;DNA;DNA-Binding
6422 Proteins;Elasticity;Ligands;Macromolecular
6423 Substances;Micromanipulation;Microscopy, Atomic Force;Models,
6424 Chemical;Molecular Biology;Nucleic Acid Conformation;Physical
6425 Stimulation;Protein Binding;Protein Conformation;Stress, Mechanical",
6426 abstract = "The forced rupture of single chemical bonds in biomolecular
6427 compounds (e.g. ligand-receptor systems) as observed in dynamic force
6428 spectroscopy experiments is addressed. Under the assumption that the
6429 probability of bond rupture depends only on the instantaneously acting
6430 force, a data collapse onto a single master curve is predicted. For
6431 rupture data obtained experimentally by dynamic AFM force spectroscopy
6432 of a ligand-receptor bond between a DNA and a regulatory protein we do
6433 not find such a collapse. We conclude that the above mentioned,
6434 generally accepted assumption is not satisfied and we discuss possible
6438 @article { raible06,
6439 author = MRaible #" and "# MEvstigneev #" and "# FWBartels #" and "# REckel
6440 #" and "# MNguyen-Duong #" and "# RMerkel #" and "# RRos #" and "#
6441 DAnselmetti #" and "# PReimann,
6442 title = "Theoretical analysis of single-molecule force spectroscopy
6443 experiments: heterogeneity of chemical bonds",
6450 pages = "3851--3864",
6452 doi = "10.1529/biophysj.105.077099",
6453 eprint = "http://www.biophysj.org/cgi/reprint/90/11/3851.pdf",
6454 url = "http://www.biophysj.org/cgi/content/abstract/90/11/3851",
6455 keywords = "Biomechanics;Microscopy, Atomic Force;Models,
6456 Molecular;Statistical Distributions;Thermodynamics",
6457 abstract = "We show that the standard theoretical framework in single-
6458 molecule force spectroscopy has to be extended to consistently describe
6459 the experimental findings. The basic amendment is to take into account
6460 heterogeneity of the chemical bonds via random variations of the force-
6461 dependent dissociation rates. This results in a very good agreement
6462 between theory and rupture data from several different experiments."
6465 @article{ bartels03,
6466 author = FWBartels #" and "# BBaumgarth #" and "# DAnselmetti
6467 #" and "# RRos #" and "# ABecker,
6468 title = "Specific binding of the regulatory protein Exp{G} to
6469 promoter regions of the galactoglucan biosynthesis gene cluster of
6470 Sinorhizobium meliloti--a combined molecular biology and force
6471 spectroscopy investigation.",
6472 journal = JStructBiol,
6475 address = "Experimentelle Biophysik, Fakult{\"a}t f{\"u}r Physik,
6476 Universit{\"a}t Bielefeld, 33615 Bielefeld, Germany.",
6480 keywords = "Base Sequence",
6481 keywords = "Binding Sites",
6482 keywords = "Conserved Sequence",
6483 keywords = "Fungal Proteins",
6484 keywords = "Galactans",
6485 keywords = "Glucans",
6486 keywords = "Kinetics",
6487 keywords = "Microscopy, Atomic Force",
6488 keywords = "Multigene Family",
6489 keywords = "Polysaccharides, Bacterial",
6490 keywords = "Promoter Regions, Genetic",
6491 keywords = "Protein Binding",
6492 keywords = "Sinorhizobium meliloti",
6493 keywords = "Trans-Activators",
6494 abstract = "Specific protein-DNA interaction is fundamental for all
6495 aspects of gene transcription. We focus on a regulatory
6496 DNA-binding protein in the Gram-negative soil bacterium
6497 Sinorhizobium meliloti 2011, which is capable of fixing molecular
6498 nitrogen in a symbiotic interaction with alfalfa plants. The ExpG
6499 protein plays a central role in regulation of the biosynthesis of
6500 the exopolysaccharide galactoglucan, which promotes the
6501 establishment of symbiosis. ExpG is a transcriptional activator of
6502 exp gene expression. We investigated the molecular mechanism of
6503 binding of ExpG to three associated target sequences in the exp
6504 gene cluster with standard biochemical methods and single molecule
6505 force spectroscopy based on the atomic force microscope
6506 (AFM). Binding of ExpG to expA1, expG-expD1, and expE1 promoter
6507 fragments in a sequence specific manner was demonstrated, and a 28
6508 bp conserved region was found. AFM force spectroscopy experiments
6509 confirmed the specific binding of ExpG to the promoter regions,
6510 with unbinding forces ranging from 50 to 165 pN in a logarithmic
6511 dependence from the loading rates of 70-79000 pN/s. Two different
6512 regimes of loading rate-dependent behaviour were
6513 identified. Thermal off-rates in the range of k(off)=(1.2+/-1.0) x
6514 10(-3)s(-1) were derived from the lower loading rate regime for
6515 all promoter regions. In the upper loading rate regime, however,
6516 these fragments exhibited distinct differences which are
6517 attributed to the molecular binding mechanism.",
6519 URL = "http://www.ncbi.nlm.nih.gov/pubmed/12972351",
6524 author = MRief #" and "# HGrubmuller,
6525 title = "Force spectroscopy of single biomolecules",
6534 doi = "10.1002/1439-7641(20020315)3:3<255::AID-CPHC255>3.0.CO;2-M",
6535 url = "http://www3.interscience.wiley.com/journal/91016383/abstract",
6536 keywords = "Ligands;Microscopy, Atomic Force;Polysaccharides;Protein
6537 Denaturation;Proteins",
6538 abstract = "Many processes in the body are effected and regulated by highly
6539 specialized protein molecules: These molecules certainly deserve the
6540 name ``biochemical nanomachines''. Recent progress in single-molecule
6541 experiments and corresponding simulations with supercomputers enable us
6542 to watch these ``nanomachines'' at work, revealing a host of astounding
6543 mechanisms. Examples are the fine-tuned movements of the binding pocket
6544 of a receptor protein locking into its ligand molecule and the forced
6545 unfolding of titin, which acts as a molecular shock absorber to protect
6546 muscle cells. At present, we are not capable of designing such high
6547 precision machines, but we are beginning to understand their working
6548 principles and to simulate and predict their function.",
6549 note = "Nice, general review of force spectroscopy to 2002, but not much
6555 title = "Fundamentals of Statistical and Thermal Physics",
6557 publisher = McGraw-Hill,
6558 address = "New York",
6559 note = "Thermal noise for simple harmonic oscillators, in Chapter
6560 15, Sections 6 and 10.",
6561 project = "Cantilever Calibration"
6565 author = MRief #" and "# MGautel #" and "# FOesterhelt #" and "# JFernandez
6567 title = "Reversible Unfolding of Individual Titin Immunoglobulin Domains by
6573 pages = "1109--1112",
6574 doi = "10.1126/science.276.5315.1109",
6575 eprint = "http://www.sciencemag.org/cgi/reprint/276/5315/1109.pdf",
6576 url = "http://www.sciencemag.org/cgi/content/abstract/276/5315/1109",
6577 note = "Seminal paper for force spectroscopy on Titin. Cited by
6578 \citet{dietz04} (ref 9) as an example of how unfolding large proteins
6579 is easily interpreted (vs.\ confusing unfolding in bulk), but Titin is
6580 a rather simple example of that, because of its globular-chain
6582 project = "Energy Landscape Roughness"
6586 author = MRief #" and "# FOesterhelt #" and "# BHeymann #" and "# HEGaub,
6587 title = "Single Molecule Force Spectroscopy on Polysaccharides by Atomic
6595 pages = "1295--1297",
6597 doi = "10.1126/science.275.5304.1295",
6598 eprint = "http://www.sciencemag.org/cgi/reprint/275/5304/1295.pdf",
6599 url = "http://www.sciencemag.org/cgi/content/abstract/275/5304/1295",
6600 abstract = "Recent developments in piconewton instrumentation allow the
6601 manipulation of single molecules and measurements of intermolecular as
6602 well as intramolecular forces. Dextran filaments linked to a gold
6603 surface were probed with the atomic force microscope tip by vertical
6604 stretching. At low forces the deformation of dextran was found to be
6605 dominated by entropic forces and can be described by the Langevin
6606 function with a 6 angstrom Kuhn length. At elevated forces the strand
6607 elongation was governed by a twist of bond angles. At higher forces the
6608 dextran filaments underwent a distinct conformational change. The
6609 polymer stiffened and the segment elasticity was dominated by the
6610 bending of bond angles. The conformational change was found to be
6611 reversible and was corroborated by molecular dynamics calculations."
6615 author = MRief #" and "# JFernandez #" and "# HEGaub,
6616 title = "Elastically Coupled Two-Level Systems as a Model for Biopolymer
6623 pages = "4764--4767",
6626 doi = "10.1103/PhysRevLett.81.4764",
6627 eprint = "http://prola.aps.org/pdf/PRL/v81/i21/p4764_1",
6628 url = "http://prola.aps.org/abstract/PRL/v81/i21/p4764_1",
6629 note = "Original details on mechanical unfolding analysis via Monte Carlo
6634 author = MRief #" and "# HClausen-Schaumann #" and "# HEGaub,
6635 title = "Sequence-dependent mechanics of single {DNA} molecules",
6643 doi = "10.1038/7582",
6644 eprint = "http://www.nature.com/nsmb/journal/v6/n4/pdf/nsb0499_346.pdf",
6645 url = "http://www.nature.com/nsmb/journal/v6/n4/abs/nsb0499_346.html",
6646 keywords = "Bacteriophage lambda;Base Pairing;DNA;DNA, Single-Stranded;DNA,
6647 Viral;Gold;Mechanics;Microscopy, Atomic Force;Nucleotides;Spectrum
6648 Analysis;Thermodynamics",
6649 abstract = "Atomic force microscope-based single-molecule force
6650 spectroscopy was employed to measure sequence-dependent mechanical
6651 properties of DNA by stretching individual DNA double strands attached
6652 between a gold surface and an AFM tip. We discovered that in lambda-
6653 phage DNA the previously reported B-S transition, where 'S' represents
6654 an overstretched conformation, at 65 pN is followed by a nonequilibrium
6655 melting transition at 150 pN. During this transition the DNA is split
6656 into single strands that fully recombine upon relaxation. The sequence
6657 dependence was investigated in comparative studies with poly(dG-dC) and
6658 poly(dA-dT) DNA. Both the B-S and the melting transition occur at
6659 significantly lower forces in poly(dA-dT) compared to poly(dG-dC). We
6660 made use of the melting transition to prepare single poly(dG-dC) and
6661 poly(dA-dT) DNA strands that upon relaxation reannealed into hairpins
6662 as a result of their self-complementary sequence. The unzipping of
6663 these hairpins directly revealed the base pair-unbinding forces for G-C
6664 to be 20 +/- 3 pN and for A-T to be 9 +/- 3 pN."
6667 @article{ schmitt00,
6668 author = LSchmitt #" and "# MLudwig #" and "# HEGaub #" and "# RTampe,
6669 title = "A metal-chelating microscopy tip as a new toolbox for
6670 single-molecule experiments by atomic force microscopy.",
6674 address = "Institut f{\"u}r Physiologische Chemie,
6675 Philipps-Universit{\"a}t Marburg, 35033 Marburg,
6676 Germany. schmittl@mailer.uni-marburg.de",
6679 pages = "3275--3285",
6680 keywords = "Chelating Agents",
6681 keywords = "Edetic Acid",
6682 keywords = "Histidine",
6683 keywords = "Metals",
6684 keywords = "Microscopy, Atomic Force",
6685 keywords = "Nitrilotriacetic Acid",
6686 keywords = "Peptides",
6687 keywords = "Recombinant Fusion Proteins",
6688 abstract = "In recent years, the atomic force microscope (AFM) has
6689 contributed much to our understanding of the molecular forces
6690 involved in various high-affinity receptor-ligand
6691 systems. However, a universal anchor system for such measurements
6692 is still required. This would open up new possibilities for the
6693 study of biological recognition processes and for the
6694 establishment of high-throughput screening applications. One such
6695 candidate is the N-nitrilo-triacetic acid (NTA)/His-tag system,
6696 which is widely used in molecular biology to isolate and purify
6697 histidine-tagged fusion proteins. Here the histidine tag acts as a
6698 high-affinity recognition site for the NTA chelator. Accordingly,
6699 we have investigated the possibility of using this approach in
6700 single-molecule force measurements. Using a histidine-peptide as a
6701 model system, we have determined the binding force for various
6702 metal ions. At a loading rate of 0.5 microm/s, the determined
6703 forces varied from 22 +/- 4 to 58 +/- 5 pN. Most importantly, no
6704 interaction was detected for Ca(2+) and Mg(2+) up to
6705 concentrations of 10 mM. Furthermore, EDTA and a metal ion
6706 reloading step demonstrated the reversibility of the
6707 approach. Here the molecular interactions were turned off (EDTA)
6708 and on (metal reloading) in a switch-like fashion. Our results
6709 show that the NTA/His-tag system will expand the ``molecular
6710 toolboxes'' with which receptor-ligand systems can be investigated
6711 at the single-molecule level.",
6713 doi = "10.1016/S0006-3495(00)76863-9",
6714 URL = "http://www.ncbi.nlm.nih.gov/pubmed/10828003",
6718 @article { roters96,
6719 author = ARoters #" and "# DJohannsmann,
6720 title = "Distance-dependent noise measurements in scanning force
6726 pages = "7561-7577",
6727 doi = "10.1088/0953-8984",
6728 eprint = "http://www.iop.org/EJ/article/0953-8984/8/41/006/c64103.pdf",
6729 url = "http://stacks.iop.org/0953-8984/8/7561",
6730 abstract = "The changes in the thermal noise spectrum of a scanning-force-
6731 microscope cantilever upon approach of the tip to the sample were used
6732 to investigate the interactions between the cantilever and the sample.
6733 The investigation of thermal noise is the natural choice for dynamic
6734 measurements with little disturbance of the sample. In particular, the
6735 small amplitudes involved ensure linear dynamic response. It is
6736 possible to discriminate between viscous coupling, elastic coupling and
6737 changes in the effective mass. The technique is versatile in terms of
6738 substrates and environments. Hydrodynamic long-range interactions
6739 depending on the sample, the geometry and the ambient medium are
6740 observed. The dependence of hydrodynamic interaction on various
6741 parameters such as the viscosity and the density of the medium is
6742 described. For sufficiently soft surfaces, the method is sensitive to
6743 viscoelastic properties of the surface. For example, the viscous
6744 coupling to the surface is strongly increased when the surface is
6745 covered with a swollen `polymer brush'.",
6746 note = "They actually write down a Lagrangian formula and give a decent
6747 derivation of PSD, but don't show or work out the integrals.",
6748 project = "Cantilever Calibration"
6751 @article { ryckaert77,
6752 author = JPRyckaert #" and "# GCiccotti #" and "# HJCBerendsen,
6753 title = "Numerical integration of the cartesian equations of motion of a
6754 system with constraints: molecular dynamics of n-alkanes",
6761 doi = "10.1016/0021-9991(77)90098-5",
6762 url = "http://dx.doi.org/10.1016/0021-9991(77)90098-5",
6763 abstract = "A numerical algorithm integrating the 3N Cartesian equations of
6764 motion of a system of N points subject to holonomic constraints is
6765 formulated. The relations of constraint remain perfectly fulfilled at
6766 each step of the trajectory despite the approximate character of
6767 numerical integration. The method is applied to a molecular dynamics
6768 simulation of a liquid of 64 n-butane molecules and compared to a
6769 simulation using generalized coordinates. The method should be useful
6770 for molecular dynamics calculations on large molecules with internal
6771 degrees of freedom.",
6772 note = "Entry-level explaination of MD with rigid constraints. Explicit
6773 Verlet integrator example."
6776 @article { sarkar04,
6777 author = ASarkar #" and "# RRobertson #" and "# JFernandez,
6778 title = "Simultaneous atomic force microscope and fluorescence measurements
6779 of protein unfolding using a calibrated evanescent wave",
6784 pages = "12882--12886",
6785 doi = "10.1073/pnas.0403534101",
6786 eprint = "http://www.pnas.org/cgi/reprint/101/35/12882.pdf",
6787 url = "http://www.pnas.org/cgi/content/abstract/101/35/12882",
6788 abstract = "Fluorescence techniques for monitoring single-molecule dynamics
6789 in the vertical dimension currently do not exist. Here we use an atomic
6790 force microscope to calibrate the distance-dependent intensity decay of
6791 an evanescent wave. The measured evanescent wave transfer function was
6792 then used to convert the vertical motions of a fluorescent particle
6793 into displacement ($SD =< 1$ nm). We demonstrate the use of the
6794 calibrated evanescent wave to resolve the 20.1 {+/-} 0.5-nm step
6795 increases in the length of the small protein ubiquitin during forced
6796 unfolding. The experiments that we report here make an important
6797 contribution to fluorescence microscopy by demonstrating the
6798 unambiguous optical tracking of a single molecule with a resolution
6799 comparable to that of an atomic force microscope."
6803 author = TSato #" and "# MEsaki #" and "# JFernandez #" and "# TEndo,
6804 title = "{Comparison of the protein-unfolding pathways between
6805 mitochondrial protein import and atomic-force microscopy measurements}",
6810 pages = "17999--18004",
6811 doi = "10.1073/pnas.0504495102",
6812 eprint = "http://www.pnas.org/cgi/reprint/102/50/17999.pdf",
6813 url = "http://www.pnas.org/cgi/content/abstract/102/50/17999",
6814 abstract = "Many newly synthesized proteins have to become unfolded during
6815 translocation across biological membranes. We have analyzed the effects
6816 of various stabilization/destabilization mutations in the Ig-like
6817 module of the muscle protein titin upon its import from the N terminus
6818 or C terminus into mitochondria. The effects of mutations on the import
6819 of the titin module from the C terminus correlate well with those on
6820 forced mechanical unfolding in atomic-force microscopy (AFM)
6821 measurements. On the other hand, as long as turnover of the
6822 mitochondrial Hsp70 system is not rate-limiting for the import, import
6823 of the titin module from the N terminus is sensitive to mutations in
6824 the N-terminal region but not the ones in the C-terminal region that
6825 affect resistance to global unfolding in AFM experiments. We propose
6826 that the mitochondrial-import system can catalyze precursor-unfolding
6827 by reducing the stability of unfolding intermediates."
6830 @article { schlierf04,
6831 author = MSchlierf #" and "# HLi #" and "# JFernandez,
6832 title = "The unfolding kinetics of ubiquitin captured with single-molecule
6833 force-clamp techniques",
6840 pages = "7299--7304",
6842 doi = "10.1073/pnas.0400033101",
6843 eprint = "http://www.pnas.org/cgi/reprint/101/19/7299.pdf",
6844 url = "http://www.pnas.org/cgi/content/abstract/101/19/7299",
6845 keywords = "Kinetics;Microscopy, Atomic Force;Probability;Ubiquitin",
6846 abstract = "We use single-molecule force spectroscopy to study the kinetics
6847 of unfolding of the small protein ubiquitin. Upon a step increase in
6848 the stretching force, a ubiquitin polyprotein extends in discrete steps
6849 of 20.3 +/- 0.9 nm marking each unfolding event. An average of the time
6850 course of these unfolding events was well described by a single
6851 exponential, which is a necessary condition for a memoryless Markovian
6852 process. Similar ensemble averages done at different forces showed that
6853 the unfolding rate was exponentially dependent on the stretching force.
6854 Stretching a ubiquitin polyprotein with a force that increased at a
6855 constant rate (force-ramp) directly measured the distribution of
6856 unfolding forces. This distribution was accurately reproduced by the
6857 simple kinetics of an all-or-none unfolding process. Our force-clamp
6858 experiments directly demonstrate that an ensemble average of ubiquitin
6859 unfolding events is well described by a two-state Markovian process
6860 that obeys the Arrhenius equation. However, at the single-molecule
6861 level, deviant behavior that is not well represented in the ensemble
6862 average is readily observed. Our experiments make an important addition
6863 to protein spectroscopy by demonstrating an unambiguous method of
6864 analysis of the kinetics of protein unfolding by a stretching force."
6867 @article { schlierf06,
6868 author = MSchlierf #" and "# MRief,
6869 title = "Single-molecule unfolding force distributions reveal a funnel-
6870 shaped energy landscape",
6879 doi = "10.1529/biophysj.105.077982",
6880 url = "http://www.biophysj.org/cgi/content/abstract/90/4/L33",
6881 keywords = "Models, Molecular; Protein Folding; Proteins; Thermodynamics",
6882 abstract = "The protein folding process is described as diffusion on a
6883 high-dimensional energy landscape. Experimental data showing details of
6884 the underlying energy surface are essential to understanding folding.
6885 So far in single-molecule mechanical unfolding experiments a simplified
6886 model assuming a force-independent transition state has been used to
6887 extract such information. Here we show that this so-called Bell model,
6888 although fitting well to force velocity data, fails to reproduce full
6889 unfolding force distributions. We show that by applying Kramers'
6890 diffusion model, we were able to reconstruct a detailed funnel-like
6891 curvature of the underlying energy landscape and establish full
6892 agreement with the data. We demonstrate that obtaining spatially
6893 resolved details of the unfolding energy landscape from mechanical
6894 single-molecule protein unfolding experiments requires models that go
6895 beyond the Bell model.",
6896 note = {The inspiration behind my sawtooth simulation. Bell model
6897 fit to $f_{unfold}(v)$, but Kramers model fit to unfolding
6898 distribution for a given $v$. \fref{equation}{3} in the
6899 supplement is \xref{evans99}{equation}{2}, but it is just
6900 $[\text{dying percent}] \cdot [\text{surviving population}]
6902 $\nu \equiv k$ is the force/time-dependent off rate. The Kramers'
6903 rate equation (on page L34, the second equation in the paper) is
6904 \xref{hanggi90}{equation}{4.56b} (page 275) and
6905 \xref{socci96}{equation}{2} but \citet{schlierf06} gets the minus
6906 sign wrong in the exponent. $U_F(x=0)\gg 0$ and
6907 $U_F(x_\text{max})\ll 0$ (\cf~\xref{schlierf06}{figure}{1}).
6908 Schlierf's integral (as written) contains
6909 $\exp{-U_F(x_\text{max})}\cdot\exp{U_F(0)}$, which is huge, when
6910 it should contain $\exp{U_F(x_\text{max})}\cdot\exp{-U_F(0)}$,
6911 which is tiny. For more details and a picture of the peak that
6912 forms the bulk of the integrand, see
6913 \cref{eq:kramers,fig:kramers:integrand}. I pointed out this
6914 problem to Michael Schlierf, but he was unconvinced.},
6917 @article { schwaiger04,
6918 author = ISchwaiger #" and "# AKardinal #" and "# MSchleicher #" and "#
6919 AANoegel #" and "# MRief,
6920 title = "A mechanical unfolding intermediate in an actin-crosslinking
6930 doi = "10.1038/nsmb705",
6931 eprint = "http://www.nature.com/nsmb/journal/v11/n1/pdf/nsmb705.pdf",
6932 url = "http://www.nature.com/nsmb/journal/v11/n1/full/nsmb705.html",
6933 keywords = "Actins; Animals; Contractile Proteins; Cross-Linking Reagents;
6934 Dictyostelium; Dimerization; Microfilament Proteins; Microscopy, Atomic
6935 Force; Mutagenesis, Site-Directed; Protein Denaturation; Protein
6936 Folding; Protein Structure, Tertiary; Protozoan Proteins",
6937 abstract = "Many F-actin crosslinking proteins consist of two actin-binding
6938 domains separated by a rod domain that can vary considerably in length
6939 and structure. In this study, we used single-molecule force
6940 spectroscopy to investigate the mechanics of the immunoglobulin (Ig)
6941 rod domains of filamin from Dictyostelium discoideum (ddFLN). We find
6942 that one of the six Ig domains unfolds at lower forces than do those of
6943 all other domains and exhibits a stable unfolding intermediate on its
6944 mechanical unfolding pathway. Amino acid inserts into various loops of
6945 this domain lead to contour length changes in the single-molecule
6946 unfolding pattern. These changes allowed us to map the stable core of
6947 approximately 60 amino acids that constitutes the unfolding
6948 intermediate. Fast refolding in combination with low unfolding forces
6949 suggest a potential in vivo role for this domain as a mechanically
6950 extensible element within the ddFLN rod.",
6951 note = "ddFLN unfolding with WLC params for sacrificial domains. Gives
6952 persistence length $p = 0.5\mbox{ nm}$ in ``high force regime'', $p =
6953 0.9\mbox{ nm}$ in ``low force regime'', with a transition at $F =
6955 project = "sawtooth simulation"
6958 @article { schwaiger05,
6959 author = ISchwaiger #" and "# MSchleicher #" and "# AANoegel #" and "#
6961 title = "The folding pathway of a fast-folding immunoglobulin domain
6962 revealed by single-molecule mechanical experiments",
6970 doi = "10.1038/sj.embor.7400317",
6971 eprint = "http://www.nature.com/embor/journal/v6/n1/pdf/7400317.pdf",
6972 url = "http://www.nature.com/embor/journal/v6/n1/index.html",
6973 keywords = "Animals; Contractile Proteins; Dictyostelium; Immunoglobulins;
6974 Kinetics; Microfilament Proteins; Models, Molecular; Protein Folding;
6975 Protein Structure, Tertiary",
6976 abstract = "The F-actin crosslinker filamin from Dictyostelium discoideum
6977 (ddFLN) has a rod domain consisting of six structurally similar
6978 immunoglobulin domains. When subjected to a stretching force, domain 4
6979 unfolds at a lower force than all the other domains in the chain.
6980 Moreover, this domain shows a stable intermediate along its mechanical
6981 unfolding pathway. We have developed a mechanical single-molecule
6982 analogue to a double-jump stopped-flow experiment to investigate the
6983 folding kinetics and pathway of this domain. We show that an obligatory
6984 and productive intermediate also occurs on the folding pathway of the
6985 domain. Identical mechanical properties suggest that the unfolding and
6986 refolding intermediates are closely related. The folding process can be
6987 divided into two consecutive steps: in the first step 60 C-terminal
6988 amino acids form an intermediate at the rate of 55 s(-1); and in the
6989 second step the remaining 40 amino acids are packed on this core at the
6990 rate of 179 s(-1). This division increases the overall folding rate of
6991 this domain by a factor of ten compared with all other homologous
6992 domains of ddFLN that lack the folding intermediate."
6995 @article { sharma07,
6996 author = DSharma #" and "# OPerisic #" and "# QPeng #" and "# YCao #" and
6997 "# CLam #" and "# HLu #" and "# HLi,
6998 title = "Single-molecule force spectroscopy reveals a mechanically stable
6999 protein fold and the rational tuning of its mechanical stability",
7004 pages = "9278--9283",
7005 doi = "10.1073/pnas.0700351104",
7006 eprint = "http://www.pnas.org/cgi/reprint/104/22/9278.pdf",
7007 url = "http://www.pnas.org/cgi/content/abstract/104/22/9278",
7008 abstract = "It is recognized that shear topology of two directly connected
7009 force-bearing terminal [beta]-strands is a common feature among the
7010 vast majority of mechanically stable proteins known so far. However,
7011 these proteins belong to only two distinct protein folds, Ig-like
7012 [beta] sandwich fold and [beta]-grasp fold, significantly hindering
7013 delineating molecular determinants of mechanical stability and rational
7014 tuning of mechanical properties. Here we combine single-molecule atomic
7015 force microscopy and steered molecular dynamics simulation to reveal
7016 that the de novo designed Top7 fold [Kuhlman B, Dantas G, Ireton GC,
7017 Varani G, Stoddard BL, Baker D (2003) Science 302:13641368] represents
7018 a mechanically stable protein fold that is distinct from Ig-like [beta]
7019 sandwich and [beta]-grasp folds. Although the two force-bearing [beta]
7020 strands of Top7 are not directly connected, Top7 displays significant
7021 mechanical stability, demonstrating that the direct connectivity of
7022 force-bearing [beta] strands in shear topology is not mandatory for
7023 mechanical stability. This finding broadens our understanding of the
7024 design of mechanically stable proteins and expands the protein fold
7025 space where mechanically stable proteins can be screened. Moreover, our
7026 results revealed a substructure-sliding mechanism for the mechanical
7027 unfolding of Top7 and the existence of two possible unfolding pathways
7028 with different height of energy barrier. Such insights enabled us to
7029 rationally tune the mechanical stability of Top7 by redesigning its
7030 mechanical unfolding pathway. Our study demonstrates that computational
7031 biology methods (including de novo design) offer great potential for
7032 designing proteins of defined topology to achieve significant and
7033 tunable mechanical properties in a rational and systematic fashion."
7037 author = YJSheng #" and "# SJiang #" and "# HKTsao,
7038 title = "Forced Kramers escape in single-molecule pulling experiments",
7048 doi = "10.1063/1.2046632",
7049 url = "http://link.aip.org/link/?JCP/123/091102/1",
7050 keywords = "molecular biophysics; bonds (chemical); proteins",
7051 note = "Gives appropriate Einstein-S... relation for diffusion to damping",
7052 project = "sawtooth simulation"
7055 @article { shillcock98,
7056 author = JShillcock #" and "# USeifert,
7057 title = "Escape from a metastable well under a time-ramped force",
7063 pages = "7301--7304",
7066 doi = "10.1103/PhysRevE.57.7301",
7067 eprint = "http://prola.aps.org/pdf/PRE/v57/i6/p7301_1",
7068 url = "http://link.aps.org/abstract/PRE/v57/p7301",
7069 project = "sawtooth simulation"
7073 author = GESims #" and "# SRJun #" and "# GAWu #" and "# SHKim,
7074 title = "Alignment-free genome comparison with feature frequency profiles
7075 ({FFP}) and optimal resolutions",
7082 pages = "2677--2682",
7084 doi = "10.1073/pnas.0813249106",
7085 eprint = "http://www.pnas.org/cgi/reprint/106/31/12826",
7086 url = "http://www.pnas.org/content/106/8/2677",
7087 keywords = "Genome;Introns;Phylogeny",
7088 abstract = "For comparison of whole-genome (genic + nongenic) sequences,
7089 multiple sequence alignment of a few selected genes is not appropriate.
7090 One approach is to use an alignment-free method in which feature (or
7091 l-mer) frequency profiles (FFP) of whole genomes are used for
7092 comparison-a variation of a text or book comparison method, using word
7093 frequency profiles. In this approach it is critical to identify the
7094 optimal resolution range of l-mers for the given set of genomes
7095 compared. The optimum FFP method is applicable for comparing whole
7096 genomes or large genomic regions even when there are no common genes
7097 with high homology. We outline the method in 3 stages: (i) We first
7098 show how the optimal resolution range can be determined with English
7099 books which have been transformed into long character strings by
7100 removing all punctuation and spaces. (ii) Next, we test the robustness
7101 of the optimized FFP method at the nucleotide level, using a mutation
7102 model with a wide range of base substitutions and rearrangements. (iii)
7103 Finally, to illustrate the utility of the method, phylogenies are
7104 reconstructed from concatenated mammalian intronic genomes; the FFP
7105 derived intronic genome topologies for each l within the optimal range
7106 are all very similar. The topology agrees with the established
7107 mammalian phylogeny revealing that intron regions contain a similar
7108 level of phylogenic signal as do coding regions."
7112 author = SBSmith #" and "# LFinzi #" and "# CBustamante,
7113 title = "Direct mechanical measurements of the elasticity of single {DNA}
7114 molecules by using magnetic beads",
7121 pages = "1122--1126",
7123 doi = "10.1126/science.1439819",
7124 eprint = "http://www.sciencemag.org/cgi/reprint/258/5085/1122.pdf",
7125 url = "http://www.sciencemag.org/cgi/content/abstract/258/5085/1122",
7126 keywords = "Chemistry,
7127 Physical;Cisplatin;DNA;Elasticity;Ethidium;Glass;Indoles;Intercalating
7128 Agents;Magnetics;Mathematics;Microspheres",
7129 abstract = "Single DNA molecules were chemically attached by one end to a
7130 glass surface and by their other end to a magnetic bead. Equilibrium
7131 positions of the beads were observed in an optical microscope while the
7132 beads were acted on by known magnetic and hydrodynamic forces.
7133 Extension versus force curves were obtained for individual DNA
7134 molecules at three different salt concentrations with forces between
7135 10(-14) and 10(-11) newtons. Deviations from the force curves predicted
7136 by the freely jointed chain model suggest that DNA has significant
7137 local curvature in solution. Ethidium bromide and
7138 4',6-diamidino-2-phenylindole had little effect on the elastic response
7139 of the molecules, but their extent of intercalation was directly
7140 measured. Conversely, the effect of bend-inducing cis-
7141 diamminedichloroplatinum (II) was large and supports the hypothesis of
7142 natural curvature in DNA."
7146 author = SBSmith #" and "# YCui #" and "# CBustamante,
7147 title = "Overstretching {B}-{DNA}: the elastic response of individual
7148 double-stranded and single-stranded {DNA} molecules",
7157 keywords = "Base Composition;Chemistry, Physical;DNA;DNA, Single-
7158 Stranded;Elasticity;Nucleic Acid Conformation;Osmolar
7159 Concentration;Thermodynamics",
7160 abstract = "Single molecules of double-stranded DNA (dsDNA) were stretched
7161 with force-measuring laser tweezers. Under a longitudinal stress of
7162 approximately 65 piconewtons (pN), dsDNA molecules in aqueous buffer
7163 undergo a highly cooperative transition into a stable form with 5.8
7164 angstroms rise per base pair, that is, 70\% longer than B form dsDNA.
7165 When the stress was relaxed below 65 pN, the molecules rapidly and
7166 reversibly contracted to their normal contour lengths. This transition
7167 was affected by changes in the ionic strength of the medium and the
7168 water activity or by cross-linking of the two strands of dsDNA.
7169 Individual molecules of single-stranded DNA were also stretched giving
7170 a persistence length of 7.5 angstroms and a stretch modulus of 800 pN.
7171 The overstretched form may play a significant role in the energetics of
7176 author = NDSocci #" and "# JNOnuchic #" and "# PGWolynes,
7177 title = "Diffusive dynamics of the reaction coordinate for protein folding
7184 pages = "5860--5868",
7186 doi = "10.1063/1.471317",
7187 eprint = "http://arxiv.org/pdf/cond-mat/9601091",
7188 url = "http://link.aip.org/link/?JCP/104/5860/1",
7189 keywords = "PROTEINS; FOLDS; DIFFUSION; MONTE CARLO METHOD; SIMULATION;
7191 abstract = "The quantitative description of model protein folding kinetics
7192 using a diffusive collective reaction coordinate is examined. Direct
7193 folding kinetics, diffusional coefficients and free energy profiles are
7194 determined from Monte Carlo simulations of a 27-mer, 3 letter code
7195 lattice model, which corresponds roughly to a small helical protein.
7196 Analytic folding calculations, using simple diffusive rate theory,
7197 agree extremely well with the full simulation results. Folding in this
7198 system is best seen as a diffusive, funnel-like process.",
7199 note = "A nice introduction to some quantitative ramifications of the
7200 funnel energy landscape. There's also a bit of Kramers' theory and
7201 graph theory thrown in for good measure."
7205 author = NDSocci #" and "# JNOnuchic #" and "# PGWolynes,
7206 title = "Stretching lattice models of protein folding",
7213 pages = "2031--2035",
7215 keywords = "Amino Acid Sequence;Drug Stability;Kinetics;Models,
7216 Theoretical;Molecular Sequence Data;Peptides;Protein
7217 Denaturation;Protein Folding",
7218 abstract = "A new class of experiments that probe folding of individual
7219 protein domains uses mechanical stretching to cause the transition. We
7220 show how stretching forces can be incorporated in lattice models of
7221 folding. For fast folding proteins, the analysis suggests a complex
7222 relation between the force dependence and the reaction coordinate for
7226 @article { staple08,
7227 author = DBStaple #" and "# SHPayne #" and "# ALCReddin #" and "# HJKreuzer,
7228 title = "Model for stretching and unfolding the giant multidomain muscle
7229 protein using single-molecule force spectroscopy.",
7238 doi = "10.1103/PhysRevLett.101.248301",
7239 url = "http://dx.doi.org/10.1103/PhysRevLett.101.248301",
7240 keywords = "Kinetics;Microscopy, Atomic Force;Models, Chemical;Muscle
7241 Proteins;Protein Conformation;Protein Folding;Protein Kinases;Protein
7242 Structure, Tertiary;Thermodynamics",
7243 abstract = "Single-molecule manipulation has allowed the forced unfolding
7244 of multidomain proteins. Here we outline a theory that not only
7245 explains these experiments but also points out a number of difficulties
7246 in their interpretation and makes suggestions for further experiments.
7247 For titin we reproduce force-extension curves, the dependence of break
7248 force on pulling speed, and break-force distributions and also validate
7249 two common experimental views: Unfolding titin Ig domains can be
7250 explained as stepwise increases in contour length, and increasing force
7251 peaks in native Ig sequences represent a hierarchy of bond strengths.
7252 Our theory is valid for essentially any molecule that can be unfolded
7253 in atomic force microscopy; as a further example, we present force-
7254 extension curves for the unfolding of RNA hairpins."
7258 author = RStark #" and "# TDrobek #" and "# WHeckl,
7259 title = "Thermomechanical noise of a free v-shaped cantilever for atomic-
7268 doi = "http://dx.doi.org/10.1016/S0304-3991(00)00077-2",
7269 abstract = "We have calculated the thermal noise of a v-shaped AFM
7270 cantilever (Microlever, Type E, Thermomicroscopes) by means of a finite
7271 element analysis. The modal shapes of the first 10 eigenmodes are
7272 displayed as well as the numerical constants, which are needed for the
7273 calibration using the thermal noise method. In the first eigenmode,
7274 values for the thermomechanical noise of the z-displacement at 22
7275 degrees C temperature of square root of u2(1) = A/square root of
7276 c(cant) and the photodiode signal (normal-force) of S2(1) = A/square
7277 root of c(cant) were obtained. The results also indicate a systematic
7278 deviation ofthe spectral density of the thermomechanical noise of
7279 v-shaped cantilevers as compared to rectangular beam-shaped
7281 note = "Higher mode adjustments for v-shaped cantilevers from simulation.",
7282 project = "Cantilever Calibration"
7285 @article { strick96,
7286 author = TRStrick #" and "# JFAllemand #" and "# DBensimon #" and "#
7287 ABensimon #" and "# VCroquette,
7288 title = "The elasticity of a single supercoiled {DNA} molecule",
7295 pages = "1835--1837",
7297 keywords = "Bacteriophage lambda;DNA, Superhelical;DNA,
7298 Viral;Elasticity;Magnetics;Nucleic Acid Conformation;Temperature",
7299 abstract = "Single linear DNA molecules were bound at multiple sites at one
7300 extremity to a treated glass cover slip and at the other to a magnetic
7301 bead. The DNA was therefore torsionally constrained. A magnetic field
7302 was used to rotate the beads and thus to coil and pull the DNA. The
7303 stretching force was determined by analysis of the Brownian
7304 fluctuations of the bead. Here the elastic behavior of individual
7305 lambda DNA molecules over- and underwound by up to 500 turns was
7306 studied. A sharp transition was discovered from a low to a high
7307 extension state at a force of approximately 0.45 piconewtons for
7308 underwound molecules and at a force of approximately 3 piconewtons for
7309 overwound ones. These transitions, probably reflecting the formation of
7310 alternative structures in stretched coiled DNA molecules, might be
7311 relevant for DNA transcription and replication."
7314 @article { strunz99,
7315 author = TStrunz #" and "# KOroszlan #" and "# RSchafer #" and "#
7317 title = "Dynamic force spectroscopy of single {DNA} molecules",
7322 pages = "11277--11282",
7323 doi = "10.1073/pnas.96.20.11277",
7324 eprint = "http://www.pnas.org/cgi/reprint/96/20/11277.pdf",
7325 url = "http://www.pnas.org/cgi/content/abstract/96/20/11277"
7329 author = ASzabo #" and "# KSchulten #" and "# ZSchulten,
7330 title = "First passage time approach to diffusion controlled reactions",
7336 pages = "4350--4357",
7338 doi = "10.1063/1.439715",
7339 url = "http://link.aip.org/link/?JCP/72/4350/1",
7340 keywords = "DIFFUSION; CHEMICAL REACTIONS; CHEMICAL REACTION KINETICS;
7341 PROBABILITY; DIFFERENTIAL EQUATIONS"
7344 @article { talaga00,
7345 author = DTalaga #" and "# WLau #" and "# HRoder #" and "# JTang #" and "#
7346 YJia #" and "# WDeGrado #" and "# RHochstrasser,
7347 title = "Dynamics and folding of single two-stranded coiled-coil peptides
7348 studied by fluorescent energy transfer confocal microscopy",
7353 pages = "13021--13026",
7354 doi = "10.1073/pnas.97.24.13021",
7355 eprint = "http://www.pnas.org/cgi/reprint/97/24/13021.pdf",
7356 url = "http://www.pnas.org/cgi/content/abstract/97/24/13021"
7359 @article { thirumalai05,
7360 author = DThirumalai #" and "# CHyeon,
7361 title = "{RNA} and Protein Folding: Common Themes and Variations",
7362 affiliation = "Biophysics Program, and Department of Chemistry and
7363 Biochemistry, Institute for Physical Science and Technology, University
7364 of Maryland, College Park, Maryland 20742",
7369 pages = "4957--4970",
7372 "http://pubs3.acs.org/acs/journals/doilookup?in_doi=10.1021/bi047314+",
7373 abstract = "Visualizing the navigation of an ensemble of unfolded molecules
7374 through the bumpy energy landscape in search of the native state gives
7375 a pictorial view of biomolecular folding. This picture, when combined
7376 with concepts in polymer theory, provides a unified theory of RNA and
7377 protein folding. Just as for proteins, the major folding free energy
7378 barrier for RNA scales sublinearly with the number of nucleotides,
7379 which allows us to extract the elusive prefactor for RNA folding.
7380 Several folding scenarios can be anticipated by considering variations
7381 in the energy landscape that depend on sequence, native topology, and
7382 external conditions. RNA and protein folding mechanism can be described
7383 by the kinetic partitioning mechanism (KPM) according to which a
7384 fraction () of molecules reaches the native state directly, whereas the
7385 remaining fraction gets kinetically trapped in metastable
7386 conformations. For two-state folders 1. Molecular chaperones are
7387 recruited to assist protein folding whenever is small. We show that the
7388 iterative annealing mechanism, introduced to describe chaperonin-
7389 mediated folding, can be generalized to understand protein-assisted RNA
7390 folding. The major differences between the folding of proteins and RNA
7391 arise in the early stages of folding. For RNA, folding can only begin
7392 after the polyelectrolyte problem is solved, whereas protein collapse
7393 requires burial of hydrophobic residues. Cross-fertilization of ideas
7394 between the two fields should lead to an understanding of how RNA and
7395 proteins solve their folding problems.",
7396 note = "unfolding-refolding"
7400 author = SThornton #" and "# JMarion,
7401 title = "Classical Dynamics of Particles and Systems",
7404 isbn = "0-534-40896-6",
7405 publisher = BrooksCole,
7406 address = "Belmont, CA"
7409 @article { tlusty98,
7410 author = TTlusty #" and "# AMeller #" and "# RBar-Ziv,
7411 title = "Optical Gradient Forces of Strongly Localized Fields",
7417 pages = "1738--1741",
7420 doi = "10.1103/PhysRevLett.81.1738",
7421 eprint = "http://prola.aps.org/pdf/PRL/v81/i8/p1738_1",
7423 \url{http://nanoscience.bu.edu/papers/p1738_1_Meller.pdf}.
7424 Cited by \citet{grossman05} for derivation of thermal response
7425 functions. However, I only see a referenced thermal energy when
7426 they list the likelyhood of a small partical (radius $<R_c$)
7427 escaping due to thermal energy, where $R_c$ is roughly $R_c \sim
7428 (k_B T / \alpha I_0)^{1/3}$, $\alpha$ is a dielectric scaling
7429 term, and $I_0$ is the maximum beam energy density. I imagine
7430 Grossman and Stout mixed up this reference.",
7431 project = "Cantilever Calibration"
7434 @article { tshiprut08,
7435 author = ZTshiprut #" and "# JKlafter #" and "# MUrbakh,
7436 title = "Single-molecule pulling experiments: when the stiffness of the
7437 pulling device matters",
7446 doi = "10.1529/biophysj.108.141580",
7447 eprint = "http://www.biophysj.org/cgi/reprint/95/6/L42.pdf",
7448 abstract = "Using Langevin modeling, we investigate the role of the
7449 experimental setup on the unbinding forces measured in single-molecule
7450 pulling experiments. We demonstrate that the stiffness of the pulling
7451 device, K(eff), may influence the unbinding forces through its effect
7452 on the barrier heights for both unbinding and rebinding processes.
7453 Under realistic conditions the effect of K(eff) on the rebinding
7454 barrier is shown to play the most important role. This results in a
7455 significant increase of the mean unbinding force with the stiffness for
7456 a given loading rate. Thus, in contrast to the phenomenological Bell
7457 model, we find that the loading rate (the multiplicative value K(eff)V,
7458 V being the pulling velocity) is not the only control parameter that
7459 determines the mean unbinding force. If interested in intrinsic
7460 properties of a molecular system, we recommend probing the system in
7461 the parameter range corresponding to a weak spring and relatively high
7462 loading rates where rebinding is negligible.",
7463 note = "Cites \citet{dudko03} for Kramers' description of irreversible
7464 rupture, and claims it is required to explain the deviations in
7465 $\avg{F}$ at the same loading rate. Proposes Moese equation as an
7466 example potential. Cites \citet{walton08} for experimental evidence of
7467 $\avg{F}$ increasing with linker stiffness."
7470 @article { uniprot10,
7471 author = UniProtConsort,
7473 title = "The Universal Protein Resource (UniProt) in 2010.",
7479 number = "Database issue",
7480 pages = "D142--D148",
7482 doi = "10.1093/nar/gkp846",
7483 url = "http://nar.oxfordjournals.org/cgi/content/abstract/38/suppl_1/D142",
7484 keywords = "Algorithms;Animals;Computational Biology;Databases, Nucleic
7485 Acid;Databases, Protein;Europe;Genome, Fungal;Genome,
7486 Viral;Humans;Information Storage and Retrieval;Internet;Protein
7487 Isoforms;Proteome;Proteomics;Software",
7488 abstract = "The primary mission of UniProt is to support biological
7489 research by maintaining a stable, comprehensive, fully classified,
7490 richly and accurately annotated protein sequence knowledgebase, with
7491 extensive cross-references and querying interfaces freely accessible to
7492 the scientific community. UniProt is produced by the UniProt Consortium
7493 which consists of groups from the European Bioinformatics Institute
7494 (EBI), the Swiss Institute of Bioinformatics (SIB) and the Protein
7495 Information Resource (PIR). UniProt is comprised of four major
7496 components, each optimized for different uses: the UniProt Archive, the
7497 UniProt Knowledgebase, the UniProt Reference Clusters and the UniProt
7498 Metagenomic and Environmental Sequence Database. UniProt is updated and
7499 distributed every 3 weeks and can be accessed online for searches or
7500 download at http://www.uniprot.org."
7503 @misc { uniprot:STRAV,
7504 key = "uniprot:STRAV",
7505 url = "http://www.uniprot.org/uniprot/P22629"
7508 @book { vanKampen07,
7509 author = NGvanKampen,
7510 title = "Stochastic Processes in Physics and Chemistry",
7514 address = "Amsterdam",
7516 project = "sawtooth simulation"
7519 @article { venter01,
7520 author = JCVenter #" and "# MDAdams #" and "# EWMyers #" and "# PWLi #" and
7521 "# RJMural #" and "# GGSutton #" and "# HOSmith #" and "# MYandell #"
7522 and "# CAEvans #" and "# RAHolt #" and "# JDGocayne #" and "#
7523 PAmanatides #" and "# RMBallew #" and "# DHHuson #" and "# JRWortman #"
7524 and "# QZhang #" and "# CDKodira #" and "# XHZheng #" and "# LChen #"
7525 and "# MSkupski #" and "# GSubramanian #" and "# PDThomas #" and "#
7526 JZhang #" and "# GLGaborMiklos #" and "# CNelson #" and "# SBroder #"
7527 and "# AGClark #" and "# JNadeau #" and "# VAMcKusick #" and "# NZinder
7528 #" and "# AJLevine #" and "# RJRoberts #" and "# MSimon #" and "#
7529 CSlayman #" and "# MHunkapiller #" and "# RBolanos #" and "# ADelcher
7530 #" and "# IDew #" and "# DFasulo #" and "# MFlanigan #" and "# LFlorea
7531 #" and "# AHalpern #" and "# SHannenhalli #" and "# SKravitz #" and "#
7532 SLevy #" and "# CMobarry #" and "# KReinert #" and "# KRemington #" and
7533 "# JAbu-Threideh #" and "# EBeasley #" and "# KBiddick #" and "#
7534 VBonazzi #" and "# RBrandon #" and "# MCargill #" and "#
7535 IChandramouliswaran #" and "# RCharlab #" and "# KChaturvedi #" and "#
7536 ZDeng #" and "# VDiFrancesco #" and "# PDunn #" and "# KEilbeck #" and
7537 "# CEvangelista #" and "# AEGabrielian #" and "# WGan #" and "# WGe #"
7538 and "# FGong #" and "# ZGu #" and "# PGuan #" and "# TJHeiman #" and "#
7539 MEHiggins #" and "# RRJi #" and "# ZKe #" and "# KAKetchum #" and "#
7540 ZLai #" and "# YLei #" and "# ZLi #" and "# JLi #" and "# YLiang #" and
7541 "# XLin #" and "# FLu #" and "# GVMerkulov #" and "# NMilshina #" and
7542 "# HMMoore #" and "# AKNaik #" and "# VANarayan #" and "# BNeelam #"
7543 and "# DNusskern #" and "# DBRusch #" and "# SSalzberg #" and "# WShao
7544 #" and "# BShue #" and "# JSun #" and "# ZWang #" and "# AWang #" and
7545 "# XWang #" and "# JWang #" and "# MWei #" and "# RWides #" and "#
7546 CXiao #" and "# CYan #" and "# AYao #" and "# JYe #" and "# MZhan #"
7547 and "# WZhang #" and "# HZhang #" and "# QZhao #" and "# LZheng #" and
7548 "# FZhong #" and "# WZhong #" and "# SZhu #" and "# SZhao #" and "#
7549 DGilbert #" and "# SBaumhueter #" and "# GSpier #" and "# CCarter #"
7550 and "# ACravchik #" and "# TWoodage #" and "# FAli #" and "# HAn #" and
7551 "# AAwe #" and "# DBaldwin #" and "# HBaden #" and "# MBarnstead #" and
7552 "# IBarrow #" and "# KBeeson #" and "# DBusam #" and "# ACarver #" and
7553 "# ACenter #" and "# MLCheng #" and "# LCurry #" and "# SDanaher #" and
7554 "# LDavenport #" and "# RDesilets #" and "# SDietz #" and "# KDodson #"
7555 and "# LDoup #" and "# SFerriera #" and "# NGarg #" and "# AGluecksmann
7556 #" and "# BHart #" and "# JHaynes #" and "# CHaynes #" and "# CHeiner
7557 #" and "# SHladun #" and "# DHostin #" and "# JHouck #" and "# THowland
7558 #" and "# CIbegwam #" and "# JJohnson #" and "# FKalush #" and "#
7559 LKline #" and "# SKoduru #" and "# ALove #" and "# FMann #" and "# DMay
7560 #" and "# SMcCawley #" and "# TMcIntosh #" and "# IMcMullen #" and "#
7561 MMoy #" and "# LMoy #" and "# BMurphy #" and "# KNelson #" and "#
7562 CPfannkoch #" and "# EPratts #" and "# VPuri #" and "# HQureshi #" and
7563 "# MReardon #" and "# RRodriguez #" and "# YHRogers #" and "# DRomblad
7564 #" and "# BRuhfel #" and "# RScott #" and "# CSitter #" and "#
7565 MSmallwood #" and "# EStewart #" and "# RStrong #" and "# ESuh #" and
7566 "# RThomas #" and "# NNTint #" and "# STse #" and "# CVech #" and "#
7567 GWang #" and "# JWetter #" and "# SWilliams #" and "# MWilliams #" and
7568 "# SWindsor #" and "# EWinn-Deen #" and "# KWolfe #" and "# JZaveri #"
7569 and "# KZaveri #" and "# JFAbril #" and "# RGuigo #" and "# MJCampbell
7570 #" and "# KVSjolander #" and "# BKarlak #" and "# AKejariwal #" and "#
7571 HMi #" and "# BLazareva #" and "# THatton #" and "# ANarechania #" and
7572 "# KDiemer #" and "# AMuruganujan #" and "# NGuo #" and "# SSato #" and
7573 "# VBafna #" and "# SIstrail #" and "# RLippert #" and "# RSchwartz #"
7574 and "# BWalenz #" and "# SYooseph #" and "# DAllen #" and "# ABasu #"
7575 and "# JBaxendale #" and "# LBlick #" and "# MCaminha #" and "#
7576 JCarnes-Stine #" and "# PCaulk #" and "# YHChiang #" and "# MCoyne #"
7577 and "# CDahlke #" and "# AMays #" and "# MDombroski #" and "# MDonnelly
7578 #" and "# DEly #" and "# SEsparham #" and "# CFosler #" and "# HGire #"
7579 and "# SGlanowski #" and "# KGlasser #" and "# AGlodek #" and "#
7580 MGorokhov #" and "# KGraham #" and "# BGropman #" and "# MHarris #" and
7581 "# JHeil #" and "# SHenderson #" and "# JHoover #" and "# DJennings #"
7582 and "# CJordan #" and "# JJordan #" and "# JKasha #" and "# LKagan #"
7583 and "# CKraft #" and "# ALevitsky #" and "# MLewis #" and "# XLiu #"
7584 and "# JLopez #" and "# DMa #" and "# WMajoros #" and "# JMcDaniel #"
7585 and "# SMurphy #" and "# MNewman #" and "# TNguyen #" and "# NNguyen #"
7586 and "# MNodell #" and "# SPan #" and "# JPeck #" and "# MPeterson #"
7587 and "# WRowe #" and "# RSanders #" and "# JScott #" and "# MSimpson #"
7588 and "# TSmith #" and "# ASprague #" and "# TStockwell #" and "# RTurner
7589 #" and "# EVenter #" and "# MWang #" and "# MWen #" and "# DWu #" and
7590 "# MWu #" and "# AXia #" and "# AZandieh #" and "# XZhu,
7591 title = "The sequence of the human genome.",
7598 pages = "1304--1351",
7600 doi = "10.1126/science.1058040",
7601 eprint = "http://www.sciencemag.org/cgi/content/pdf/291/5507/1304",
7602 url = "http://www.sciencemag.org/cgi/content/short/291/5507/1304",
7603 keywords = "Algorithms;Animals;Chromosome Banding;Chromosome
7604 Mapping;Chromosomes, Artificial, Bacterial;Computational
7605 Biology;Consensus Sequence;CpG Islands;DNA, Intergenic;Databases,
7606 Factual;Evolution, Molecular;Exons;Female;Gene
7607 Duplication;Genes;Genetic Variation;Genome, Human;Human Genome
7608 Project;Humans;Introns;Male;Phenotype;Physical Chromosome
7609 Mapping;Polymorphism, Single Nucleotide;Proteins;Pseudogenes;Repetitive
7610 Sequences, Nucleic Acid;Retroelements;Sequence Analysis, DNA;Species
7612 abstract = "A 2.91-billion base pair (bp) consensus sequence of the
7613 euchromatic portion of the human genome was generated by the whole-
7614 genome shotgun sequencing method. The 14.8-billion bp DNA sequence was
7615 generated over 9 months from 27,271,853 high-quality sequence reads
7616 (5.11-fold coverage of the genome) from both ends of plasmid clones
7617 made from the DNA of five individuals. Two assembly strategies-a whole-
7618 genome assembly and a regional chromosome assembly-were used, each
7619 combining sequence data from Celera and the publicly funded genome
7620 effort. The public data were shredded into 550-bp segments to create a
7621 2.9-fold coverage of those genome regions that had been sequenced,
7622 without including biases inherent in the cloning and assembly procedure
7623 used by the publicly funded group. This brought the effective coverage
7624 in the assemblies to eightfold, reducing the number and size of gaps in
7625 the final assembly over what would be obtained with 5.11-fold coverage.
7626 The two assembly strategies yielded very similar results that largely
7627 agree with independent mapping data. The assemblies effectively cover
7628 the euchromatic regions of the human chromosomes. More than 90\% of the
7629 genome is in scaffold assemblies of 100,000 bp or more, and 25\% of the
7630 genome is in scaffolds of 10 million bp or larger. Analysis of the
7631 genome sequence revealed 26,588 protein-encoding transcripts for which
7632 there was strong corroborating evidence and an additional approximately
7633 12,000 computationally derived genes with mouse matches or other weak
7634 supporting evidence. Although gene-dense clusters are obvious, almost
7635 half the genes are dispersed in low G+C sequence separated by large
7636 tracts of apparently noncoding sequence. Only 1.1\% of the genome is
7637 spanned by exons, whereas 24\% is in introns, with 75\% of the genome
7638 being intergenic DNA. Duplications of segmental blocks, ranging in size
7639 up to chromosomal lengths, are abundant throughout the genome and
7640 reveal a complex evolutionary history. Comparative genomic analysis
7641 indicates vertebrate expansions of genes associated with neuronal
7642 function, with tissue-specific developmental regulation, and with the
7643 hemostasis and immune systems. DNA sequence comparisons between the
7644 consensus sequence and publicly funded genome data provided locations
7645 of 2.1 million single-nucleotide polymorphisms (SNPs). A random pair of
7646 human haploid genomes differed at a rate of 1 bp per 1250 on average,
7647 but there was marked heterogeneity in the level of polymorphism across
7648 the genome. Less than 1\% of all SNPs resulted in variation in
7649 proteins, but the task of determining which SNPs have functional
7650 consequences remains an open challenge."
7653 @article { verdier70,
7655 title = "Relaxation Behavior of the Freely Jointed Chain",
7661 pages = "5512--5517",
7663 doi = "10.1063/1.1672818",
7664 url = "http://link.aip.org/link/?JCP/52/5512/1"
7667 @article { walther07,
7668 author = KWalther #" and "# FGrater #" and "# LDougan #" and "# CBadilla #"
7669 and "# BBerne #" and "# JFernandez,
7670 title = "Signatures of hydrophobic collapse in extended proteins captured
7671 with force spectroscopy",
7676 pages = "7916--7921",
7677 doi = "10.1073/pnas.0702179104",
7678 eprint = "http://www.pnas.org/cgi/reprint/104/19/7916.pdf",
7679 url = "http://www.pnas.org/cgi/content/abstract/104/19/7916",
7680 abstract = "We unfold and extend single proteins at a high force and then
7681 linearly relax the force to probe their collapse mechanisms. We observe
7682 a large variability in the extent of their recoil. Although chain
7683 entropy makes a small contribution, we show that the observed
7684 variability results from hydrophobic interactions with randomly varying
7685 magnitude from protein to protein. This collapse mechanism is common to
7686 highly extended proteins, including nonfolding elastomeric proteins
7687 like PEVK from titin. Our observations explain the puzzling differences
7688 between the folding behavior of highly extended proteins, from those
7689 folding after chemical or thermal denaturation. Probing the collapse of
7690 highly extended proteins with force spectroscopy allows separation of
7691 the different driving forces in protein folding."
7694 @article { walton08,
7695 author = EBWalton #" and "# SLee #" and "# KJVanVliet,
7696 title = "Extending {B}ell's model: How force transducer stiffness alters
7697 measured unbinding forces and kinetics of molecular complexes",
7704 pages = "2621--2630",
7706 doi = "10.1529/biophysj.107.114454",
7707 keywords = "Biotin;Computer
7708 Simulation;Elasticity;Kinetics;Mechanotransduction, Cellular;Models,
7709 Chemical;Models, Molecular;Molecular Motor
7710 Proteins;Motion;Streptavidin;Stress, Mechanical;Transducers",
7711 abstract = "Forced unbinding of complementary macromolecules such as
7712 ligand-receptor complexes can reveal energetic and kinetic details
7713 governing physiological processes ranging from cellular adhesion to
7714 drug metabolism. Although molecular-level experiments have enabled
7715 sampling of individual ligand-receptor complex dissociation events,
7716 disparities in measured unbinding force F(R) among these methods lead
7717 to marked variation in inferred binding energetics and kinetics at
7718 equilibrium. These discrepancies are documented for even the ubiquitous
7719 ligand-receptor pair, biotin-streptavidin. We investigated these
7720 disparities and examined atomic-level unbinding trajectories via
7721 steered molecular dynamics simulations, as well as via molecular force
7722 spectroscopy experiments on biotin-streptavidin. In addition to the
7723 well-known loading rate dependence of F(R) predicted by Bell's model,
7724 we find that experimentally accessible parameters such as the effective
7725 stiffness of the force transducer k can significantly perturb the
7726 energy landscape and the apparent unbinding force of the complex for
7727 sufficiently stiff force transducers. Additionally, at least 20\%
7728 variation in unbinding force can be attributed to minute differences in
7729 initial atomic positions among energetically and structurally
7730 comparable complexes. For force transducers typical of molecular force
7731 spectroscopy experiments and atomistic simulations, this energy barrier
7732 perturbation results in extrapolated energetic and kinetic parameters
7733 of the complex that depend strongly on k. We present a model that
7734 explicitly includes the effect of k on apparent unbinding force of the
7735 ligand-receptor complex, and demonstrate that this correction enables
7736 prediction of unbinding distances and dissociation rates that are
7737 decoupled from the stiffness of actual or simulated molecular linkers.",
7738 note = "Some detailed estimates at U(x)."
7741 @article { walton86,
7743 title = "The Abbe theory of imaging: an alternative derivation of the
7750 url = "http://stacks.iop.org/0143-0807/7/62"
7753 @article { watanabe05,
7754 author = HWatanabe #" and "# TInoue,
7755 title = "Conformational dynamics of Rouse chains during creep/recovery
7756 processes: a review",
7761 pages = "R607--R636",
7762 doi = "10.1088/0953-8984/17/19/R01",
7763 eprint = "http://www.iop.org/EJ/article/0953-8984/17/19/R01/cm5_19_R01.pdf",
7764 url = "http://stacks.iop.org/0953-8984/17/R607",
7765 abstract = "The Rouse model is a well-established model for non-entangled
7766 polymer chains and also serves as a fundamental model for entangled
7767 chains. The dynamic behaviour of this model under strain-controlled
7768 conditions has been fully analysed in the literature. However, despite
7769 the importance of the Rouse model, no analysis has been made so far of
7770 the orientational anisotropy of the Rouse eigenmodes during the stress-
7771 controlled, creep and recovery processes. For completeness of the
7772 analysis of the model, the Rouse equation of motion is solved to
7773 calculate this anisotropy for monodisperse chains and their binary
7774 blends during the creep/recovery processes. The calculation is simple
7775 and straightforward, but the result is intriguing in the sense that
7776 each Rouse eigenmode during these processes has a distribution in the
7777 retardation times. This behaviour, reflecting the interplay/correlation
7778 among the Rouse eigenmodes of different orders (and for different
7779 chains in the blends) under the constant stress condition, is quite
7780 different from the behaviour under rate-controlled flow (where each
7781 eigenmode exhibits retardation/relaxation associated with a single
7782 characteristic time). Furthermore, the calculation indicates that the
7783 Rouse chains exhibit affine deformation on sudden imposition/removal of
7784 the stress and the magnitude of this deformation is inversely
7785 proportional to the number of bond vectors per chain. In relation to
7786 these results, a difference between the creep and relaxation properties
7787 is also discussed for chains obeying multiple relaxation mechanisms
7788 (Rouse and reptation mechanisms).",
7789 note = "Middly-detailed Rouse model review."
7793 author = AWiita #" and "# SAinavarapu #" and "# HHuang #" and "# JFernandez,
7794 title = "From the Cover: Force-dependent chemical kinetics of disulfide
7795 bond reduction observed with single-molecule techniques",
7800 pages = "7222--7227",
7801 doi = "10.1073/pnas.0511035103",
7802 eprint = "http://www.pnas.org/cgi/reprint/103/19/7222.pdf",
7803 url = "http://www.pnas.org/cgi/content/abstract/103/19/7222",
7804 abstract = "The mechanism by which mechanical force regulates the kinetics
7805 of a chemical reaction is unknown. Here, we use single-molecule force-
7806 clamp spectroscopy and protein engineering to study the effect of force
7807 on the kinetics of thiol/disulfide exchange. Reduction of disulfide
7808 bonds through the thiol/disulfide exchange chemical reaction is crucial
7809 in regulating protein function and is known to occur in mechanically
7810 stressed proteins. We apply a constant stretching force to single
7811 engineered disulfide bonds and measure their rate of reduction by DTT.
7812 Although the reduction rate is linearly dependent on the concentration
7813 of DTT, it is exponentially dependent on the applied force, increasing
7814 10-fold over a 300-pN range. This result predicts that the disulfide
7815 bond lengthens by 0.34 A at the transition state of the thiol/disulfide
7816 exchange reaction. Our work at the single bond level directly
7817 demonstrates that thiol/disulfide exchange in proteins is a force-
7818 dependent chemical reaction. Our findings suggest that mechanical force
7819 plays a role in disulfide reduction in vivo, a property that has never
7820 been explored by traditional biochemistry. Furthermore, our work also
7821 indicates that the kinetics of any chemical reaction that results in
7822 bond lengthening will be force-dependent."
7825 @article { wilcox05,
7826 author = AWilcox #" and "# JChoy #" and "# CBustamante #" and "#
7828 title = "Effect of protein structure on mitochondrial import",
7833 pages = "15435--15440",
7834 doi = "10.1073/pnas.0507324102",
7835 eprint = "http://www.pnas.org/cgi/reprint/102/43/15435.pdf",
7836 url = "http://www.pnas.org/cgi/content/abstract/102/43/15435",
7837 abstract = "Most proteins that are to be imported into the mitochondrial
7838 matrix are synthesized as precursors, each composed of an N-terminal
7839 targeting sequence followed by a mature domain. Precursors are
7840 recognized through their targeting sequences by receptors at the
7841 mitochondrial surface and are then threaded through import channels
7842 into the matrix. Both the targeting sequence and the mature domain
7843 contribute to the efficiency with which proteins are imported into
7844 mitochondria. Precursors must be in an unfolded conformation during
7845 translocation. Mitochondria can unfold some proteins by changing their
7846 unfolding pathways. The effectiveness of this unfolding mechanism
7847 depends on the local structure of the mature domain adjacent to the
7848 targeting sequence. This local structure determines the extent to which
7849 the unfolding pathway can be changed and, therefore, the unfolding rate
7850 increased. Atomic force microscopy studies find that the local
7851 structures of proteins near their N and C termini also influence their
7852 resistance to mechanical unfolding. Thus, protein unfolding during
7853 import resembles mechanical unfolding, and the specificity of import is
7854 determined by the resistance of the mature domain to unfolding as well
7855 as by the properties of the targeting sequence."
7858 @article { wolfsberg01,
7859 author = TGWolfsberg #" and "# JMcEntyre #" and "# GDSchuler,
7860 title = "Guide to the draft human genome.",
7869 doi = "10.1038/35057000",
7870 eprint = "http://www.nature.com/nature/journal/v409/n6822/pdf/409824a0.pdf",
7871 url = "http://www.nature.com/nature/journal/v409/n6822/full/409824a0.html",
7872 keywords = "Amino Acid Sequence;Chromosome Mapping;Computational
7873 Biology;Genes;Genetic Variation;Genome, Human;Human Genome
7874 Project;Humans;Internet;Molecular Sequence Data;Sequence Analysis, DNA",
7875 abstract = "There are a number of ways to investigate the structure,
7876 function and evolution of the human genome. These include examining the
7877 morphology of normal and abnormal chromosomes, constructing maps of
7878 genomic landmarks, following the genetic transmission of phenotypes and
7879 DNA sequence variations, and characterizing thousands of individual
7880 genes. To this list we can now add the elucidation of the genomic DNA
7881 sequence, albeit at 'working draft' accuracy. The current challenge is
7882 to weave together these disparate types of data to produce the
7883 information infrastructure needed to support the next generation of
7884 biomedical research. Here we provide an overview of the different
7885 sources of information about the human genome and how modern
7886 information technology, in particular the internet, allows us to link
7891 author = JWWu #" and "# WLHung #" and "# CHTsai,
7892 title = "Estimation of parameters of the {G}ompertz distribution using the
7893 least squares method",
7902 doi = "10.1016/j.amc.2003.08.086",
7903 url = "http://dx.doi.org/10.1016/j.amc.2003.08.086",
7904 keywords = "Gompertz distribution; Least squares estimate; Maximum
7905 likelihood estimate; First failure-censored; Series system",
7906 abstract = "The Gompertz distribution has been used to describe human
7907 mortality and establish actuarial tables. Recently, this distribution
7908 has been again studied by some authors. The maximum likelihood
7909 estimates for the parameters of the Gompertz distribution has been
7910 discussed by Garg et al. [J. R. Statist. Soc. C 19 (1970) 152]. The
7911 purpose of this paper is to propose unweighted and weighted least
7912 squares estimates for parameters of the Gompertz distribution under the
7913 complete data and the first failure-censored data (series systems; see
7914 [J. Statist. Comput. Simulat. 52 (1995) 337]). A simulation study is
7915 carried out to compare the proposed estimators and the maximum
7916 likelihood estimators. Results of the simulation studies show that the
7917 performance of the weighted least squares estimators is acceptable."
7921 author = GYang #" and "# CCecconi #" and "# WBaase #" and "# IVetter #" and
7922 "# WBreyer #" and "# JHaack #" and "# BMatthews #" and "# FDahlquist #"
7924 title = "Solid-state synthesis and mechanical unfolding of polymers of {T4}
7931 doi = "10.1073/pnas.97.1.139",
7932 eprint = "http://www.pnas.org/cgi/reprint/97/1/139.pdf",
7933 url = "http://www.pnas.org/cgi/content/abstract/97/1/139"
7937 author = YYang #" and "# FCLin #" and "# GYang,
7938 title = "Temperature control device for single molecule measurements using
7939 the atomic force microscope",
7949 doi = "10.1063/1.2204580",
7950 url = "http://link.aip.org/link/?RSI/77/063701/1",
7951 keywords = "temperature control; atomic force microscopy; thermocouples;
7953 note = "Introduces our temperature control system",
7954 project = "Energy Landscape Roughness"
7958 author = WYu #" and "# JLamb #" and "# FHan #" and "# JBirchler,
7959 title = "Telomere-mediated chromosomal truncation in maize",
7964 pages = "17331--17336",
7965 doi = "10.1073/pnas.0605750103",
7966 eprint = "http://www.pnas.org/cgi/reprint/103/46/17331.pdf",
7967 url = "http://www.pnas.org/cgi/content/abstract/103/46/17331",
7968 abstract = "Direct repeats of Arabidopsis telomeric sequence were
7969 constructed to test telomere-mediated chromosomal truncation in maize.
7970 Two constructs with 2.6 kb of telomeric sequence were used to transform
7971 maize immature embryos by Agrobacterium-mediated transformation. One
7972 hundred seventy-six transgenic lines were recovered in which 231
7973 transgene loci were revealed by a FISH analysis. To analyze chromosomal
7974 truncations that result in transgenes located near chromosomal termini,
7975 Southern hybridization analyses were performed. A pattern of smear in
7976 truncated lines was seen as compared with discrete bands for internal
7977 integrations, because telomeres in different cells are elongated
7978 differently by telomerase. When multiple restriction enzymes were used
7979 to map the transgene positions, the size of the smears shifted in
7980 accordance with the locations of restriction sites on the construct.
7981 This result demonstrated that the transgene was present at the end of
7982 the chromosome immediately before the integrated telomere sequence.
7983 Direct evidence for chromosomal truncation came from the results of
7984 FISH karyotyping, which revealed broken chromosomes with transgene
7985 signals at the ends. These results demonstrate that telomere-mediated
7986 chromosomal truncation operates in plant species. This technology will
7987 be useful for chromosomal engineering in maize as well as other plant
7992 author = JZhao #" and "# HLee #" and "# RNome #" and "# SMajid #" and "#
7993 NScherer #" and "# WHoff,
7994 title = "Single-molecule detection of structural changes during
7995 {P}er-{A}rnt-{S}im ({PAS}) domain activation",
8000 pages = "11561--11566",
8001 doi = "10.1073/pnas.0601567103",
8002 eprint = "http://www.pnas.org/cgi/reprint/103/31/11561.pdf",
8003 url = "http://www.pnas.org/cgi/content/abstract/103/31/11561",
8004 abstract = "The Per-Arnt-Sim (PAS) domain is a ubiquitous protein module
8005 with a common three-dimensional fold involved in a wide range of
8006 regulatory and sensory functions in all domains of life. The activation
8007 of these functions is thought to involve partial unfolding of N- or
8008 C-terminal helices attached to the PAS domain. Here we use atomic force
8009 microscopy to probe receptor activation in single molecules of
8010 photoactive yellow protein (PYP), a prototype of the PAS domain family.
8011 Mechanical unfolding of Cys-linked PYP multimers in the presence and
8012 absence of illumination reveals that, in contrast to previous studies,
8013 the PAS domain itself is extended by {approx}3 nm (at the 10-pN
8014 detection limit of the measurement) and destabilized by {approx}30% in
8015 the light-activated state of PYP. Comparative measurements and steered
8016 molecular dynamics simulations of two double-Cys PYP mutants that probe
8017 different regions of the PAS domain quantify the anisotropy in
8018 stability and changes in local structure, thereby demonstrating the
8019 partial unfolding of their PAS domain upon activation. These results
8020 establish a generally applicable single-molecule approach for mapping
8021 functional conformational changes to selected regions of a protein. In
8022 addition, the results have profound implications for the molecular
8023 mechanism of PAS domain activation and indicate that stimulus-induced
8024 partial protein unfolding can be used as a signaling mechanism."
8027 @article { zhuang06,
8028 author = WZhuang #" and "# DAbramavicius #" and "# SMukamel,
8029 title = "Two-dimensional vibrational optical probes for peptide fast
8030 folding investigation",
8035 pages = "18934--18938",
8036 doi = "10.1073/pnas.0606912103",
8037 eprint = "http://www.pnas.org/cgi/reprint/103/50/18934.pdf",
8038 url = "http://www.pnas.org/cgi/content/abstract/103/50/18934",
8039 abstract = "A simulation study shows that early protein folding events may
8040 be investigated by using a recently developed family of nonlinear
8041 infrared techniques that combine the high temporal and spatial
8042 resolution of multidimensional spectroscopy with the chirality-specific
8043 sensitivity of amide vibrations to structure. We demonstrate how the
8044 structural sensitivity of cross-peaks in two-dimensional correlation
8045 plots of chiral signals of an {alpha} helix and a [beta] hairpin may be
8046 used to clearly resolve structural and dynamical details undetectable
8047 by one-dimensional techniques (e.g. circular dichroism) and identify
8048 structures indistinguishable by NMR."
8051 @article { zinober02,
8052 author = RCZinober #" and "# DJBrockwell #" and "# GSBeddard #" and "#
8053 AWBlake #" and "# PDOlmsted #" and "# SERadford #" and "# DASmith,
8054 title = "Mechanically unfolding proteins: the effect of unfolding history
8055 and the supramolecular scaffold",
8061 pages = "2759--2765",
8063 doi = "10.1110/ps.0224602",
8064 eprint = "http://www.proteinscience.org/cgi/reprint/11/12/2759.pdf",
8065 url = "http://www.proteinscience.org/cgi/content/abstract/11/12/2759",
8066 keywords = "Computer Simulation; Models, Molecular; Monte Carlo Method;
8067 Protein Folding; Protein Structure, Tertiary; Proteins",
8068 abstract = "The mechanical resistance of a folded domain in a polyprotein
8069 of five mutant I27 domains (C47S, C63S I27)(5)is shown to depend on the
8070 unfolding history of the protein. This observation can be understood on
8071 the basis of competition between two effects, that of the changing
8072 number of domains attempting to unfold, and the progressive increase in
8073 the compliance of the polyprotein as domains unfold. We present Monte
8074 Carlo simulations that show the effect and experimental data that
8075 verify these observations. The results are confirmed using an
8076 analytical model based on transition state theory. The model and
8077 simulations also predict that the mechanical resistance of a domain
8078 depends on the stiffness of the surrounding scaffold that holds the
8079 domain in vivo, and on the length of the unfolded domain. Together,
8080 these additional factors that influence the mechanical resistance of
8081 proteins have important consequences for our understanding of natural
8082 proteins that have evolved to withstand force.",
8083 note = "Introduces unfolding-order \emph{scaffold effect} on average
8085 project = "sawtooth simulation"
8088 @article { zwanzig92,
8089 author = RZwanzig #" and "# ASzabo #" and "# BBagchi,
8090 title = "Levinthal's paradox.",
8100 "http://www.ncbi.nlm.nih.gov/pmc/articles/PMC48166/pdf/pnas01075-0036.p
8102 url = "http://www.ncbi.nlm.nih.gov/pmc/articles/PMC48166/",
8103 keywords = "Mathematics;Models, Theoretical;Protein Conformation;Proteins",
8104 abstract = "Levinthal's paradox is that finding the native folded state of
8105 a protein by a random search among all possible configurations can take
8106 an enormously long time. Yet proteins can fold in seconds or less.
8107 Mathematical analysis of a simple model shows that a small and
8108 physically reasonable energy bias against locally unfavorable
8109 configurations, of the order of a few kT, can reduce Levinthal's time
8110 to a biologically significant size."
8114 author = XHong #" and "# XChu #" and "# PZou #" and "# YLiu
8116 title = "Magnetic-field-assisted rapid ultrasensitive
8117 immunoassays using Fe3{O4}/Zn{O}/Au nanorices as Raman
8123 address = "Centre for Advanced Optoelectronic Functional
8124 Materials Research, Key Laboratory for UV
8125 Light-Emitting Materials and Technology of Ministry of
8126 Education, Northeast Normal University, Changchun
8131 keywords = "Biosensing Techniques",
8132 keywords = "Electromagnetic Fields",
8133 keywords = "Equipment Design",
8134 keywords = "Equipment Failure Analysis",
8135 keywords = "Immunoassay",
8136 keywords = "Magnetite Nanoparticles",
8137 keywords = "Spectrum Analysis, Raman",
8138 keywords = "Zinc Oxide",
8139 abstract = "Rapid and ultrasensitive immunoassays were developed
8140 by using biofunctional Fe3O4/ZnO/Au nanorices as Raman
8141 probes. Taking advantage of the superparamagnetic
8142 property of the nanorices, the labeled proteins can
8143 rapidly be separated and purified with a commercial
8144 permanent magnet. The unsusceptible multiphonon
8145 resonant Raman scattering of the nanorices provided a
8146 characteristic spectroscopic fingerprint function,
8147 which allowed an accurate detection of the analyte.
8148 High specificity and selectivity of the assay were
8149 demonstrated. It was found that the diffusion barriers
8150 and the boundary layer effects had a great influence on
8151 the detection limit. Manipulation of the nanorice
8152 probes using an external magnetic field can enhance the
8153 assay sensitivity by several orders of magnitude, and
8154 reduce the detection time from 1 h to 3 min. This
8155 magnetic-field-assisted rapid and ultrasensitive
8156 immunoassay based on the resonant Raman scatting of
8157 semiconductor shows significant value for potential
8158 applications in biomedicine, food safety, and
8159 environmental defence.",
8161 doi = "10.1016/j.bios.2010.06.066",
8162 URL = "http://www.ncbi.nlm.nih.gov/pubmed/20667438",
8167 author = LZhao #" and "# ABulhassan #" and "# GYang #" and "#
8169 title = "Real-time detection of the morphological change in
8170 cellulose by a nanomechanical sensor.",
8175 address = "Department of Physics, Drexel University,
8176 Philadelphia, Pennsylvania, USA.",
8180 keywords = "Cellulose",
8181 keywords = "Computer Systems",
8182 keywords = "Equipment Design",
8183 keywords = "Equipment Failure Analysis",
8184 keywords = "Micro-Electrical-Mechanical Systems",
8185 keywords = "Molecular Conformation",
8186 keywords = "Nanotechnology",
8187 keywords = "Transducers",
8188 abstract = "Up to now, experimental limitations have prevented
8189 researchers from achieving the molecular-level
8190 understanding for the initial steps of the enzymatic
8191 hydrolysis of cellulose, where cellulase breaks down
8192 the crystal structure on the surface region of
8193 cellulose and exposes cellulose chains for the
8194 subsequent hydrolysis by cellulase. Because one of
8195 these non-hydrolytic enzymatic steps could be the
8196 rate-limiting step for the entire enzymatic hydrolysis
8197 of crystalline cellulose by cellulase, being able to
8198 analyze and understand these steps is instrumental in
8199 uncovering novel leads for improving the efficiency of
8200 cellulase. In this communication, we report an
8201 innovative application of the microcantilever technique
8202 for a real-time assessment of the morphological change
8203 of cellulose induced by a treatment of sodium chloride.
8204 This sensitive nanomechanical approach to define
8205 changes in surface structure of cellulose has the
8206 potential to permit a real-time assessment of the
8207 effect of the non-hydrolytic activities of cellulase on
8208 cellulose and thereby to provide a comprehensive
8209 understanding of the initial steps of the enzymatic
8210 hydrolysis of cellulose.",
8212 doi = "10.1002/bit.22754",
8213 URL = "http://www.ncbi.nlm.nih.gov/pubmed/20653025",
8218 author = RLiu #" and "# MRoman #" and "# GYang,
8219 title = "Correction of the viscous drag induced errors in
8220 macromolecular manipulation experiments using atomic
8225 address = "Department of Physics, Drexel University,
8226 Philadelphia, Pennsylvania 19104, USA.",
8230 keywords = "Algorithms",
8231 keywords = "Artifacts",
8232 keywords = "Macromolecular Substances",
8233 keywords = "Mechanical Processes",
8234 keywords = "Microscopy, Atomic Force",
8235 keywords = "Models, Theoretical",
8236 keywords = "Motion",
8237 keywords = "Protein Folding",
8238 keywords = "Signal Processing, Computer-Assisted",
8239 keywords = "Viscosity",
8240 abstract = "We describe a method to correct the errors induced by
8241 viscous drag on the cantilever in macromolecular
8242 manipulation experiments using the atomic force
8243 microscope. The cantilever experiences a viscous drag
8244 force in these experiments because of its motion
8245 relative to the surrounding liquid. This viscous force
8246 superimposes onto the force generated by the
8247 macromolecule under study, causing ambiguity in the
8248 experimental data. To remove this artifact, we analyzed
8249 the motions of the cantilever and the liquid in
8250 macromolecular manipulation experiments, and developed
8251 a novel model to treat the viscous drag on the
8252 cantilever as the superposition of the viscous force on
8253 a static cantilever in a moving liquid and that on a
8254 bending cantilever in a static liquid. The viscous
8255 force was measured under both conditions and the
8256 results were used to correct the viscous drag induced
8257 errors from the experimental data. The method will be
8258 useful for many other cantilever based techniques,
8259 especially when high viscosity and high cantilever
8260 speed are involved.",
8262 doi = "10.1063/1.3436646",
8263 URL = "http://www.ncbi.nlm.nih.gov/pubmed/20590242",
8267 @phdthesis { roman12,
8269 title = "Macromolecular crowding effects in the mechanical unfolding
8270 forces of proteins",
8274 url = "http://hdl.handle.net/1860/3854",
8275 eprint = "http://idea.library.drexel.edu/bitstream/1860/3854/1/Roman_Marisa.pdf",
8276 keywords = "Physics",
8277 keywords = "Biophysics",
8278 keywords = "Protein folding",
8279 abstract = "Macromolecules can occupy a large fraction of the volume
8280 of a cell and this crowded environment influences the behavior and
8281 properties of the proteins, such as mechanical unfolding forces,
8282 thermal stability and rates of folding and diffusion. Although
8283 much is already known about molecular crowding, it is not well
8284 understood how it affects a protein’s resistance to mechanical
8285 stress in a crowded environment and how the size of the crowders
8286 affect those changes. An atomic force microscope-based single
8287 molecule method was used to measure the effects of the crowding on
8288 the mechanical stability of a model protein, in this case I-27. As
8289 proteins tend to aggregate, single molecule methods provided a way
8290 to prevent aggregation because of the very low concentration of
8291 proteins in the solution under study. Dextran was used as the
8292 crowding agent with three different molecular weights 6kDa, 10 kDa
8293 and 40 kDa, with concentrations varying from zero to 300 grams per
8294 liter in a pH neutral buffer solution at room temperature. Results
8295 showed that the forces required to unfold biomolecules were
8296 increased when a high concentration of crowder molecules were
8297 added to the buffer solution and that the maximum force required
8298 to unfold a domain was when the crowder size was 10 kDa, which is
8299 comparable to the protein size. Unfolding rates obtained from
8300 Monte Carlo simulations showed that they were also affected in the
8301 presence of crowders. As a consequence, the energy barrier was
8302 also affected. These effects were most notable when the size of
8303 the crowder was 10 kDa, comparable to the size of the protein. On
8304 the other hand, distances to the transition state did not seem to
8305 change when crowders were added to the solution. The effect of
8306 Dextran on the energy barrier was modeled by using established
8307 theories such as Ogston’s and scaled particle theory, neither of
8308 which was completely convincing at describing the results. It can
8309 be hypothesized that the composition of Dextran plays a role in
8310 the deviation of the predicted behavior with respect to the
8311 experimental data.",
8315 @article { measey09,
8316 author = TMeasey #" and "# KBSmith #" and "# SDecatur #" and "#
8317 LZhao #" and "# GYang #" and "# RSchweitzerStenner,
8318 title = "Self-aggregation of a polyalanine octamer promoted by
8319 its {C}-terminal tyrosine and probed by a strongly
8320 enhanced vibrational circular dichroism signal.",
8325 address = "Department of Chemistry, Drexel University, 3141
8326 Chestnut Street, Philadelphia, Pennsylvania 19104,
8330 pages = "18218--18219",
8331 keywords = "Amyloid",
8332 keywords = "Circular Dichroism",
8333 keywords = "Dimerization",
8334 keywords = "Oligopeptides",
8335 keywords = "Peptides",
8336 keywords = "Protein Conformation",
8337 keywords = "Tyrosine",
8338 abstract = "The eight-residue alanine oligopeptide
8339 Ac-A(4)KA(2)Y-NH(2) (AKY8) was found to form
8340 amyloid-like fibrils upon incubation at room
8341 temperature in acidified aqueous solution at peptide
8342 concentrations >10 mM. The fibril solution exhibits an
8343 enhanced vibrational circular dichroism (VCD) couplet
8344 in the amide I' band region that is nearly 2 orders of
8345 magnitude larger than typical polypeptide/protein
8346 signals in this region. The UV-CD spectrum of the
8347 fibril solution shows CD in the region associated with
8348 the tyrosine side chain absorption. A similar peptide,
8349 Ac-A(4)KA(2)-NH(2) (AK7), which lacks a terminal
8350 tyrosine residue, does not aggregate. These results
8351 suggest a pivotal role for the C-terminal tyrosine
8352 residue in stabilizing the aggregation state of this
8353 peptide. It is speculated that interactions between the
8354 lysine and tyrosine side chains of consecutive strands
8355 in an antiparallel arrangement (e.g., cation-pi
8356 interactions) are responsible for the stabilization of
8357 the resulting fibrils. These results offer
8358 considerations and insight regarding the de novo design
8359 of self-assembling oligopeptides for biomedical and
8360 biotechnological applications and highlight the
8361 usefulness of VCD as a tool for probing amyloid fibril
8364 doi = "10.1021/ja908324m",
8365 URL = "http://www.ncbi.nlm.nih.gov/pubmed/19958029",
8370 author = GShan #" and "# SWang #" and "# XFei #" and "# YLiu
8372 title = "Heterostructured Zn{O}/Au nanoparticles-based resonant
8373 Raman scattering for protein detection.",
8378 address = "Center for Advanced Optoelectronic Functional
8379 Materials Research, Northeast Normal University,
8380 Changchun 130024, P. R. China.",
8383 pages = "1468--1472",
8384 keywords = "Animals",
8386 keywords = "Humans",
8387 keywords = "Immunoglobulin G",
8388 keywords = "Metal Nanoparticles",
8389 keywords = "Microscopy, Electron, Transmission",
8390 keywords = "Spectrum Analysis, Raman",
8391 keywords = "Zinc Oxide",
8392 abstract = "A new method of protein detection was explored on the
8393 resonant Raman scattering signal of ZnO nanoparticles.
8394 A probe for the target protein was constructed by
8395 binding the ZnO/Au nanoparticles to secondary protein
8396 by eletrostatic interaction. The detection of proteins
8397 was achieved by an antibody-based sandwich assay. A
8398 first antibody, which could be specifically recognized
8399 by target protein, was attached to a solid silicon
8400 surface. The ZnO/Au protein probe could specifically
8401 recognize and bind to the complex of the target protein
8402 and first antibody. This method on the resonant Raman
8403 scattering signal of ZnO nanoparticles showed good
8404 selectivity and sensitivity for the target protein.",
8406 doi = "10.1021/jp8046032",
8407 URL = "http://www.ncbi.nlm.nih.gov/pubmed/19138135",
8412 author = JMYuan #" and "# CLChyan #" and "# HXZhou #" and "#
8413 TYChung #" and "# HPeng #" and "# GPing #" and "#
8415 title = "The effects of macromolecular crowding on the
8416 mechanical stability of protein molecules.",
8421 address = "Department of Physics, Drexel University,
8422 Philadelphia, Pennsylvania 19104, USA.",
8425 pages = "2156--2166",
8426 keywords = "Circular Dichroism",
8427 keywords = "Dextrans",
8428 keywords = "Kinetics",
8429 keywords = "Microscopy, Atomic Force",
8430 keywords = "Microscopy, Scanning Probe",
8431 keywords = "Protein Folding",
8432 keywords = "Protein Stability",
8433 keywords = "Protein Structure, Secondary",
8434 keywords = "Thermodynamics",
8435 keywords = "Ubiquitin",
8436 abstract = "Macromolecular crowding, a common phenomenon in the
8437 cellular environments, can significantly affect the
8438 thermodynamic and kinetic properties of proteins. A
8439 single-molecule method based on atomic force microscopy
8440 (AFM) was used to investigate the effects of
8441 macromolecular crowding on the forces required to
8442 unfold individual protein molecules. It was found that
8443 the mechanical stability of ubiquitin molecules was
8444 enhanced by macromolecular crowding from added dextran
8445 molecules. The average unfolding force increased from
8446 210 pN in the absence of dextran to 234 pN in the
8447 presence of 300 g/L dextran at a pulling speed of 0.25
8448 microm/sec. A theoretical model, accounting for the
8449 effects of macromolecular crowding on the native and
8450 transition states of the protein molecule by applying
8451 the scaled-particle theory, was used to quantitatively
8452 explain the crowding-induced increase in the unfolding
8453 force. The experimental results and interpretation
8454 presented could have wide implications for the many
8455 proteins that experience mechanical stresses and
8456 perform mechanical functions in the crowded environment
8459 doi = "10.1110/ps.037325.108",
8460 URL = "http://www.ncbi.nlm.nih.gov/pubmed/18780817",
8465 author = YLiu #" and "# MZhong #" and "# GShan #" and "# YLi
8466 #" and "# BHuang #" and "# GYang,
8467 title = "Biocompatible Zn{O}/Au nanocomposites for
8468 ultrasensitive {DNA} detection using resonance Raman
8474 address = "Centre for Advanced Optoelectronic Functional
8475 Materials Research, Institute of Genetics and Cytology,
8476 Northeast Normal University, Changchun, People's
8477 Republic of China. ycliu@nenu.edu.cn",
8480 pages = "6484--6489",
8481 keywords = "Base Sequence",
8484 keywords = "Microscopy, Electron, Transmission",
8485 keywords = "Nanocomposites",
8486 keywords = "Sensitivity and Specificity",
8487 keywords = "Spectrum Analysis, Raman",
8488 keywords = "Zinc Oxide",
8489 abstract = "A novel method for identifying DNA microarrays based
8490 on ZnO/Au nanocomposites functionalized with
8491 thiol-oligonucleotide as probes is descried here. DNA
8492 labeled with ZnO/Au nanocomposites has a strong Raman
8493 signal even without silver acting as a surface-enhanced
8494 Raman scattering promoter. X-ray photoelectron spectra
8495 confirmed the formation of a three-component sandwich
8496 assay, i.e., constituted DNA and ZnO/Au nanocomposites.
8497 The resonance multiple-phonon Raman signal of the
8498 ZnO/Au nanocomposites as a spectroscopic fingerprint is
8499 used to detect a target sequence of oligonucleotide.
8500 This method exhibits extraordinary sensitivity and the
8501 detection limit is at least 1 fM.",
8503 doi = "10.1021/jp710399d",
8504 URL = "http://www.ncbi.nlm.nih.gov/pubmed/18444675",
8509 author = YGuo #" and "# AMylonakis #" and "# ZZhang #" and "#
8510 GYang #" and "# PLelkes #" and "# SChe #" and "#
8512 title = "Templated synthesis of electroactive periodic
8513 mesoporous organosilica bridged with oligoaniline.",
8516 address = "Department of Chemistry, Drexel University,
8517 Philadelphia, Pennsylvania 19104, USA.",
8520 pages = "2909--2917",
8521 keywords = "Aniline Compounds",
8522 keywords = "Cetrimonium Compounds",
8523 keywords = "Electrochemistry",
8524 keywords = "Hydrolysis",
8525 keywords = "Microscopy, Electron, Transmission",
8526 keywords = "Molecular Structure",
8527 keywords = "Organosilicon Compounds",
8528 keywords = "Particle Size",
8529 keywords = "Porosity",
8530 keywords = "Spectroscopy, Fourier Transform Infrared",
8531 keywords = "Surface Properties",
8532 keywords = "Thermogravimetry",
8533 keywords = "X-Ray Diffraction",
8534 abstract = "The synthesis and characterization of novel
8535 electroactive periodic mesoporous organosilica (PMO)
8536 are reported. The silsesquioxane precursor,
8537 N,N'-bis(4'-(3-triethoxysilylpropylureido)phenyl)-1,4-quinonene-diimine
8538 (TSUPQD), was prepared from the emeraldine base of
8539 amino-capped aniline trimer (EBAT) using a one-step
8540 coupling reaction and was used as an organic silicon
8541 source in the co-condensation with tetraethyl
8542 orthosilicate (TEOS) in proper ratios. By means of a
8543 hydrothermal sol-gel approach with the cationic
8544 surfactant cetyltrimethyl-ammonium bromide (CTAB) as
8545 the structure-directing template and acetone as the
8546 co-solvent for the dissolution of TSUPQD, a series of
8547 novel MCM-41 type siliceous materials (TSU-PMOs) were
8548 successfully prepared under mild alkaline conditions.
8549 The resultant mesoporous organosilica were
8550 characterized by Fourier transform infrared (FT-IR)
8551 spectroscopy, thermogravimetry, X-ray diffraction,
8552 nitrogen sorption, and transmission electron microscopy
8553 (TEM) and showed that this series of TSU-PMOs exhibited
8554 hexagonally patterned mesostructures with pore
8555 diameters of 2.1-2.8 nm. Although the structural
8556 regularity and pore parameters gradually deteriorated
8557 with increasing loading of organic bridges, the
8558 electrochemical behavior of TSU-PMOs monitored by
8559 cyclic voltammetry demonstrated greater
8560 electroactivities for samples with higher concentration
8561 of the incorporated TSU units.",
8563 doi = "10.1002/chem.200701605",
8564 URL = "http://www.ncbi.nlm.nih.gov/pubmed/18224650",
8569 author = LiLi #" and "# BLi #" and "# GYang #" and "# CYLi,
8570 title = "Polymer decoration on carbon nanotubes via physical
8576 address = "A. J. Drexel Nanotechnology Institute and Department
8577 of Materials Science and Engineering, Drexel
8578 University, Philadelphia, Pennsylvania 19104, USA.",
8581 pages = "8522--8525",
8582 keywords = "Microscopy, Atomic Force",
8583 keywords = "Microscopy, Electron, Transmission",
8584 keywords = "Nanotubes, Carbon",
8585 keywords = "Polymers",
8586 keywords = "Surface Properties",
8587 keywords = "Volatilization",
8588 abstract = "The polymer decoration technique has been widely used
8589 to study the chain folding behavior of polymer single
8590 crystals. In this article, we demonstrate that this
8591 method can be successfully adopted to pattern a variety
8592 of polymers on carbon nanotubes (CNTs). The resulting
8593 structure is a two-dimensional nanohybrid shish kebab
8594 (2D NHSK), wherein the CNT forms the shish and the
8595 polymer crystals form the kebabs. 2D NHSKs consisting
8596 of CNTs and polymers such as polyethylene, nylon 66,
8597 polyvinylidene fluoride and poly(L-lysine) have been
8598 achieved. Transmission electron microscopy and atomic
8599 force microscopy were used to study the nanoscale
8600 morphology of these hybrid materials. Relatively
8601 periodic decoration of polymers on both single-walled
8602 and multi-walled CNTs was observed. It is envisaged
8603 that this unique method offers a facile means to
8604 achieve patterned CNTs for nanodevice applications.",
8606 doi = "10.1021/la700480z",
8607 URL = "http://www.ncbi.nlm.nih.gov/pubmed/17602575",
8612 author = MSu #" and "# YYang #" and "# GYang,
8613 title = "Quantitative measurement of hydroxyl radical induced
8614 {DNA} double-strand breaks and the effect of
8615 {N}-acetyl-{L}-cysteine.",
8620 address = "Department of Physics, Drexel University,
8621 Philadelphia, PA 19104, USA.",
8624 pages = "4136--4142",
8625 keywords = "Acetylcysteine",
8626 keywords = "Animals",
8627 keywords = "DNA Damage",
8628 keywords = "Humans",
8629 keywords = "Hydroxyl Radical",
8630 keywords = "Microscopy, Atomic Force",
8631 keywords = "Nucleic Acid Conformation",
8632 keywords = "Plasmids",
8633 abstract = "Reactive oxygen species, such as hydroxyl or
8634 superoxide radicals, can be generated by exogenous
8635 agents as well as from normal cellular metabolism.
8636 Those radicals are known to induce various lesions in
8637 DNA, including strand breaks and base modifications.
8638 These lesions have been implicated in a variety of
8639 diseases such as cancer, arteriosclerosis, arthritis,
8640 neurodegenerative disorders and others. To assess these
8641 oxidative DNA damages and to evaluate the effects of
8642 the antioxidant N-acetyl-L-cysteine (NAC), atomic force
8643 microscopy (AFM) was used to image DNA molecules
8644 exposed to hydroxyl radicals generated via Fenton
8645 chemistry. AFM images showed that the circular DNA
8646 molecules became linear after incubation with hydroxyl
8647 radicals, indicating the development of double-strand
8648 breaks. The occurrence of the double-strand breaks was
8649 found to depend on the concentration of the hydroxyl
8650 radicals and the duration of the reaction. Under the
8651 conditions of the experiments, NAC was found to
8652 exacerbate the free radical-induced DNA damage.",
8654 doi = "10.1016/j.febslet.2006.06.060",
8655 URL = "http://www.ncbi.nlm.nih.gov/pubmed/16828758",
8660 author = LiLi #" and "# YYang #" and "# GYang #" and "# XuChen
8661 #" and "# BHsiao #" and "# BChu #" and "#
8662 JSpanier #" and "# CYLi,
8663 title = "Patterning polyethylene oligomers on carbon nanotubes
8664 using physical vapor deposition.",
8668 address = "A. J. Drexel Nanotechnology Institute and Department
8669 of Materials Science and Engineering, Drexel
8670 University, Philadelphia, Pennsylvania 19104, USA.",
8673 pages = "1007--1012",
8674 keywords = "Microscopy, Atomic Force",
8675 keywords = "Nanotechnology",
8676 keywords = "Nanotubes, Carbon",
8677 keywords = "Polyethylenes",
8678 keywords = "Volatilization",
8679 abstract = "Periodic patterning on one-dimensional (1D) carbon
8680 nanotubes (CNTs) is of great interest from both
8681 scientific and technological points of view. In this
8682 letter, we report using a facile physical vapor
8683 deposition method to achieve periodic polyethylene (PE)
8684 oligomer patterning on individual CNTs. Upon heating
8685 under vacuum, PE degraded into oligomers and
8686 crystallized into rod-shaped single crystals. These PE
8687 rods periodically decorate on CNTs with their long axes
8688 perpendicular to the CNT axes. The formation mechanism
8689 was attributed to ``soft epitaxy'' growth of PE
8690 oligomer crystals on CNTs. Both SWNTs and MWNTs were
8691 decorated successfully with PE rods. The intermediate
8692 state of this hybrid structure, MWNTs absorbed with a
8693 thin layer of PE, was captured successfully by
8694 depositing PE vapor on MWNTs detached from the solid
8695 substrate, and was observed using high-resolution
8696 transmission electron microscopy. Furthermore, this
8697 hybrid structure formation depends critically on CNT
8698 surface chemistry: alkane-modification of the MWNT
8699 surface prohibited the PE single-crystal growth on the
8700 CNTs. We anticipate that this work could open a gateway
8701 for creating complex CNT-based nanoarchitectures for
8702 nanodevice applications.",
8704 doi = "10.1021/nl060276q",
8705 URL = "http://www.ncbi.nlm.nih.gov/pubmed/16683841",
8710 author = MKuhn #" and "# HJanovjak #" and "# MHubain #" and "# DJMuller,
8711 title = {Automated alignment and pattern recognition of
8712 single-molecule force spectroscopy data.},
8715 address = {Division of Computer Science, California Institute of
8716 Technology, Pasadena, California 91125, USA.},
8722 doi = {10.1111/j.1365-2818.2005.01478.x},
8723 URL = {http://www.ncbi.nlm.nih.gov/pubmed/15857374},
8725 keywords = {Algorithms},
8726 keywords = {Bacteriorhodopsins},
8727 keywords = {Data Interpretation, Statistical},
8728 keywords = {Escherichia coli Proteins},
8729 keywords = {Microscopy, Atomic Force},
8730 keywords = {Protein Folding},
8731 keywords = {Sodium-Hydrogen Antiporter},
8732 keywords = {Software},
8733 abstract = {Recently, direct measurements of forces stabilizing
8734 single proteins or individual receptor-ligand bonds became
8735 possible with ultra-sensitive force probe methods like the atomic
8736 force microscope (AFM). In force spectroscopy experiments using
8737 AFM, a single molecule or receptor-ligand pair is tethered between
8738 the tip of a micromachined cantilever and a supporting
8739 surface. While the molecule is stretched, forces are measured by
8740 the deflection of the cantilever and plotted against extension,
8741 yielding a force spectrum characteristic for each biomolecular
8742 system. In order to obtain statistically relevant results, several
8743 hundred to thousand single-molecule experiments have to be
8744 performed, each resulting in a unique force spectrum. We developed
8745 software and algorithms to analyse large numbers of force
8746 spectra. Our algorithms include the fitting polymer extension
8747 models to force peaks as well as the automatic alignment of
8748 spectra. The aligned spectra allowed recognition of patterns of
8749 peaks across different spectra. We demonstrate the capabilities of
8750 our software by analysing force spectra that were recorded by
8751 unfolding single transmembrane proteins such as bacteriorhodopsin
8752 and NhaA. Different unfolding pathways were detected by
8753 classifying peak patterns. Deviant spectra, e.g. those with no
8754 attachment or erratic peaks, can be easily identified. The
8755 software is based on the programming language C++, the GNU
8756 Scientific Library (GSL), the software WaveMetrics IGOR Pro and
8757 available open-source at http://bioinformatics.org/fskit/.},
8758 note = {Development stalled in 2005 after Michael graduated.},
8761 @article{ janovjak05,
8762 author = HJanovjak #" and "# JStruckmeier #" and "# DJMuller,
8763 title = {Hydrodynamic effects in fast {AFM} single-molecule
8764 force measurements.},
8768 address = {BioTechnological Center, University of Technology
8769 Dresden, 01307 Dresden, Germany.},
8775 doi = {10.1007/s00249-004-0430-3},
8776 url = {http://www.ncbi.nlm.nih.gov/pubmed/15257425},
8778 keywords = {Algorithms},
8779 keywords = {Computer Simulation},
8780 keywords = {Elasticity},
8781 keywords = {Microfluidics},
8782 keywords = {Microscopy, Atomic Force},
8783 keywords = {Models, Chemical},
8784 keywords = {Models, Molecular},
8785 keywords = {Physical Stimulation},
8786 keywords = {Protein Binding},
8787 keywords = {Proteins},
8788 keywords = {Stress, Mechanical},
8789 keywords = {Viscosity},
8790 abstract = {Atomic force microscopy (AFM) allows the critical forces
8791 that unfold single proteins and rupture individual receptor-ligand
8792 bonds to be measured. To derive the shape of the energy landscape,
8793 the dynamic strength of the system is probed at different force
8794 loading rates. This is usually achieved by varying the pulling
8795 speed between a few nm/s and a few $\mu$m/s, although for a more
8796 complete investigation of the kinetic properties higher speeds are
8797 desirable. Above 10 $\mu$m/s, the hydrodynamic drag force acting
8798 on the AFM cantilever reaches the same order of magnitude as the
8799 molecular forces. This has limited the maximum pulling speed in
8800 AFM single-molecule force spectroscopy experiments. Here, we
8801 present an approach for considering these hydrodynamic effects,
8802 thereby allowing a correct evaluation of AFM force measurements
8803 recorded over an extended range of pulling speeds (and thus
8804 loading rates). To support and illustrate our theoretical
8805 considerations, we experimentally evaluated the mechanical
8806 unfolding of a multi-domain protein recorded at $30\U{$mu$m/s}$
8811 author = MSandal #" and "# FValle #" and "# ITessari #" and "#
8812 SMammi #" and "# EBergantino #" and "# FMusiani #" and "#
8813 MBrucale #" and "# LBubacco #" and "# BSamori,
8814 title = {Conformational Equilibria in Monomeric $\alpha$-Synuclein
8815 at the Single-Molecule Level},
8818 address = {Department of Biochemistry G. Moruzzi,
8819 University of Bologna, Bologna, Italy.},
8825 doi = {10.1371/journal.pbio.0060006},
8826 url = {http://www.ncbi.nlm.nih.gov/pubmed/18198943},
8828 keywords = {Buffers},
8829 keywords = {Circular Dichroism},
8830 keywords = {Copper},
8831 keywords = {Entropy},
8832 keywords = {Models, Molecular},
8833 keywords = {Molecular Sequence Data},
8834 keywords = {Mutation},
8835 keywords = {Protein Structure, Secondary},
8836 keywords = {Protein Structure, Tertiary},
8837 keywords = {alpha-Synuclein},
8838 abstract = {Human $\alpha$-Synuclein ($\alpha$Syn) is a natively
8839 unfolded protein whose aggregation into amyloid fibrils is
8840 involved in the pathology of Parkinson disease. A full
8841 comprehension of the structure and dynamics of early intermediates
8842 leading to the aggregated states is an unsolved problem of
8843 essential importance to researchers attempting to decipher the
8844 molecular mechanisms of $\alpha$Syn aggregation and formation of
8845 fibrils. Traditional bulk techniques used so far to solve this
8846 problem point to a direct correlation between $\alpha$Syn's unique
8847 conformational properties and its propensity to aggregate, but
8848 these techniques can only provide ensemble-averaged information
8849 for monomers and oligomers alike. They therefore cannot
8850 characterize the full complexity of the conformational equilibria
8851 that trigger the aggregation process. We applied atomic force
8852 microscopy-based single-molecule mechanical unfolding methodology
8853 to study the conformational equilibrium of human wild-type and
8854 mutant $\alpha$Syn. The conformational heterogeneity of monomeric
8855 $\alpha$Syn was characterized at the single-molecule level. Three
8856 main classes of conformations, including disordered and
8857 ``$\beta$-like'' structures, were directly observed and quantified
8858 without any interference from oligomeric soluble forms. The
8859 relative abundance of the ``$\beta$-like'' structures
8860 significantly increased in different conditions promoting the
8861 aggregation of $\alpha$Syn: the presence of \Cu, the pathogenic
8862 A30P mutation, and high ionic strength. This methodology can
8863 explore the full conformational space of a protein at the
8864 single-molecule level, detecting even poorly populated conformers
8865 and measuring their distribution in a variety of biologically
8866 important conditions. To the best of our knowledge, we present
8867 for the first time evidence of a conformational equilibrium that
8868 controls the population of a specific class of monomeric
8869 $\alpha$Syn conformers, positively correlated with conditions
8870 known to promote the formation of aggregates. A new tool is thus
8871 made available to test directly the influence of mutations and
8872 pharmacological strategies on the conformational equilibrium of
8873 monomeric $\alpha$Syn.},
8877 author = MSandal #" and "# FBenedetti #" and "# MBrucale #" and "#
8878 AGomezCasado #" and "# BSamori,
8879 title = "Hooke: An open software platform for force spectroscopy.",
8884 address = "Department of Biochemistry, University of Bologna,
8885 Bologna, Italy. massimo.sandal@unibo.it",
8888 pages = "1428--1430",
8889 keywords = "Algorithms",
8890 keywords = "Computational Biology",
8891 keywords = "Internet",
8892 keywords = "Microscopy, Atomic Force",
8893 keywords = "Proteome",
8894 keywords = "Proteomics",
8895 keywords = "Software",
8896 abstract = "SUMMARY: Hooke is an open source, extensible software
8897 intended for analysis of atomic force microscope (AFM)-based
8898 single molecule force spectroscopy (SMFS) data. We propose it as a
8899 platform on which published and new algorithms for SMFS analysis
8900 can be integrated in a standard, open fashion, as a general
8901 solution to the current lack of a standard software for SMFS data
8902 analysis. Specific features and support for file formats are coded
8903 as independent plugins. Any user can code new plugins, extending
8904 the software capabilities. Basic automated dataset filtering and
8905 semi-automatic analysis facilities are included. AVAILABILITY:
8906 Software and documentation are available at
8907 (http://code.google.com/p/hooke). Hooke is a free software under
8908 the GNU Lesser General Public License.",
8910 doi = "10.1093/bioinformatics/btp180",
8911 URL = "http://www.ncbi.nlm.nih.gov/pubmed/19336443",
8915 @article{ materassi09,
8916 author = DMaterassi #" and "# PBaschieri #" and "# BTiribilli #" and "#
8917 GZuccheri #" and "# BSamori,
8918 title = {An open source/real-time atomic force microscope
8919 architecture to perform customizable force spectroscopy
8923 address = {Department of Electrical and Computer Engineering,
8924 University of Minnesota, 200 Union St. SE, Minneapolis,
8925 Minnesota 55455, USA. mater013@umn.edu},
8931 doi = "10.1063/1.3194046",
8932 url = "http://www.ncbi.nlm.nih.gov/pubmed/19725671",
8934 keywords = {Algorithms},
8935 keywords = {Animals},
8936 keywords = {Calibration},
8938 keywords = {Microscopy, Atomic Force},
8939 keywords = {Muscle Proteins},
8940 keywords = {Myocardium},
8941 keywords = {Optics and Photonics},
8942 keywords = {Ownership},
8943 keywords = {Protein Kinases},
8944 keywords = {Software},
8945 keywords = {Spectrum Analysis},
8946 keywords = {Time Factors},
8947 abstract = {We describe the realization of an atomic force
8948 microscope architecture designed to perform customizable
8949 experiments in a flexible and automatic way. Novel technological
8950 contributions are given by the software implementation platform
8951 (RTAI-LINUX), which is free and open source, and from a functional
8952 point of view, by the implementation of hard real-time control
8953 algorithms. Some other technical solutions such as a new way to
8954 estimate the optical lever constant are described as well. The
8955 adoption of this architecture provides many degrees of freedom in
8956 the device behavior and, furthermore, allows one to obtain a
8957 flexible experimental instrument at a relatively low cost. In
8958 particular, we show how such a system has been employed to obtain
8959 measures in sophisticated single-molecule force spectroscopy
8960 experiments\citep{fernandez04}. Experimental results on proteins
8961 already studied using the same methodologies are provided in order
8962 to show the reliability of the measure system.},
8963 note = {Although this paper claims to present an open source
8964 experiment control framework (on Linux!), it doesn't actually link
8965 to any source code. This is puzzling and frusterating.},
8968 @article{ aioanei11,
8969 author = DAioanei #" and "# MBrucale #" and "# BSamori,
8970 title = {Open source platform for the execution and analysis of
8971 mechanical refolding experiments.},
8975 address = {Department of Biochemistry G.~Moruzzi,
8976 University of Bologna, Via Irnerio 48, 40126 Bologna, Italy.
8977 aioaneid@gmail.com},
8983 doi = {10.1093/bioinformatics/btq663},
8984 url = {http://www.ncbi.nlm.nih.gov/pubmed/21123222},
8986 keywords = {Computational Biology},
8987 keywords = {Kinetics},
8988 keywords = {Protein Denaturation},
8989 keywords = {Protein Refolding},
8990 keywords = {Software},
8991 abstract = {Single-molecule force spectroscopy has facilitated the
8992 experimental investigation of biomolecular force-coupled kinetics,
8993 from which the kinetics at zero force can be extrapolated via
8994 explicit theoretical models. The atomic force microscope (AFM) in
8995 particular is routinely used to study protein unfolding kinetics,
8996 but only rarely protein folding kinetics. The discrepancy arises
8997 because mechanical protein refolding studies are more technically
8999 note = {\href{http://code.google.com/p/refolding/}{Refolding} is a
9000 suite for performing and analyzing double-pulse refolding
9001 experiments. The experiment-driver is mostly written in Java with
9002 the analysis code in Python. The driver is curious; it uses the
9003 NanoScope scripting interface to drive the experiment through the
9004 NanoScope software by impersonating a mouse-wielding user (like
9005 Selenium does for web browsers). See the
9006 \imint{sh}|RobotNanoDriver.java| code for details. There is also
9007 support for automatic velocity clamp analysis.},
9010 @article{ benedetti11,
9011 author = FBenedetti #" and "# CMicheletti #" and "# GBussi #" and "#
9012 SKSekatskii #" and "# GDietler,
9013 title = {Nonkinetic modeling of the mechanical unfolding of
9014 multimodular proteins: theory and experiments.},
9018 address = {Laboratory of Physics of Living Matter,
9019 Ecole Polytechnique F{\'e}d{\'e}rale de Lausanne,
9020 Lausanne, Switzerland.},
9024 pages = {1504--1512},
9026 doi = {10.1016/j.bpj.2011.07.047},
9027 url = {http://www.ncbi.nlm.nih.gov/pubmed/21943432},
9029 keywords = {Kinetics},
9030 keywords = {Microscopy, Atomic Force},
9031 keywords = {Models, Molecular},
9032 keywords = {Monte Carlo Method},
9033 keywords = {Protein Unfolding},
9034 keywords = {Stochastic Processes},
9035 abstract = {We introduce and discuss a novel approach called
9036 back-calculation for analyzing force spectroscopy experiments on
9037 multimodular proteins. The relationship between the histograms of
9038 the unfolding forces for different peaks, corresponding to a
9039 different number of not-yet-unfolded protein modules, is exploited
9040 in such a manner that the sole distribution of the forces for one
9041 unfolding peak can be used to predict the unfolding forces for
9042 other peaks. The scheme is based on a bootstrap prediction method
9043 and does not rely on any specific kinetic model for multimodular
9044 unfolding. It is tested and validated in both
9045 theoretical/computational contexts (based on stochastic
9046 simulations) and atomic force microscopy experiments on (GB1)(8)
9047 multimodular protein constructs. The prediction accuracy is so
9048 high that the predicted average unfolding forces corresponding to
9049 each peak for the GB1 construct are within only 5 pN of the
9050 averaged directly-measured values. Experimental data are also used
9051 to illustrate how the limitations of standard kinetic models can
9052 be aptly circumvented by the proposed approach.},
9055 @phdthesis{ benedetti12,
9056 author = FBenedetti,
9057 title = {Statistical Study of the Unfolding of Multimodular Proteins
9058 and their Energy Landscape by Atomic Force Microscopy},
9060 address = {Lausanne},
9061 affiliation = {EPFL},
9064 doi = {10.5075/epfl-thesis-5440},
9065 url = {http://infoscience.epfl.ch/record/181215},
9066 eprint = {http://infoscience.epfl.ch/record/181215/files/EPFL_TH5440.pdf},
9067 keywords = {atomic force microscope (AFM); single molecule force
9068 spectrosopy; velocity clamp AFM; Monte carlo simulations; force
9069 modulation spectroscopy; energy barrier model; non kinetic methods
9070 for force spectroscopy},
9071 abstract = {The aim of the present thesis is to investigate several
9072 aspects of: the proteins mechanics, interprotein interactions and
9073 to study also new techniques, theoretical and technical, to obtain
9074 and analyze the force spectroscopy experiments. The first section
9075 is dedicated to the statistical properties of the unfolding forces
9076 in a chain of homomeric multimodular proteins. The basic idea of
9077 this kind of statistic is to divide the peaks observed in a force
9078 extension curve in separate groups and then analyze these groups
9079 considering their position in the force curves. In fact in a
9080 multimodular homomeric protein the unfolding force is related to
9081 the number of not yet unfolded modules (we call it "N"). Such
9082 effect yields to a linear dependence of the most probable
9083 unfolding force of a peak on ln(N). We demonstrate how such
9084 dependence can be used to extract the kinetic parameters and how,
9085 ignoring it, could lead to significant errors. Following this
9086 topic we continue with non kinetic methods that, using the
9087 resampling from the rupture forces of any peak, could reconstruct
9088 the rupture forces for all the other peaks in a chain. Then a
9089 discussion about the Monte Carlo simulation for protein pulling is
9090 present. In fact a theoretical framework for such methodology has
9091 to be introduced to understand the various simulations done. In
9092 this chapter we also introduce a methodology to study the ligand
9093 receptor interactions when we directly functionalize the AFM tip
9094 and the substrate. In fact, in many of our experiments, we see a
9095 "cloud of points" in the force vs loading rate graph. We have
9096 modeled a system composed by "N" parallel springs, and studying
9097 the distribution of forces obtained in the force vs loading rate
9098 graph we have establish a procedure to restore the kinetic
9099 parameters used. Such procedure has then been used to discuss real
9100 experiments similar to biotin-avidin interaction. In the following
9101 chapter we discuss a first order approximation of the Bell-Evans
9102 model where a more explicit form of the potential is
9103 considered. In particular the dependence of the curvature of the
9104 potential on the applied force at the minimum and at the
9105 metastable state is considered. In the well known Bell-Evans model
9106 the prefactors of the transition rate are fixed at any force,
9107 however this is not what happen in nature, where the prefactors
9108 (that are the second local derivative of the interacting energy
9109 with respect to the reaction coordinate in its minimum and
9110 maximum) depend on the force applied. The results obtained with
9111 the force spectroscopy of the Laminin-binding-protein are
9112 discussed, in particular this protein showed a phase transition
9113 when the pH was changed. The behavior of this protein changes,
9114 from a normal WLC behavior to a plateau behavior. The analysis of
9115 the force spectroscopy curves shows a distribution of length where
9116 the maximum of the first prominent peak correspond to the full
9117 length of the protein. However, length that could be associated
9118 with dimers and trymers are also present in this
9119 distribution. Later a new approach to study the lock and key
9120 mechanism, using "handles" with a specific force extension
9121 pattern, is introduced. In particular handles of (I27)3 and
9122 (I27–SNase)3 were biochemically attached to: strept-actin
9123 molecules, biotin molecules, RNase and Angiogenin. The main idea
9124 is to have a system composed by "handle-(molecule A)-(molecule
9125 B)-handle" where the handles are covalently attached to the
9126 respective molecules and the two molecules "A and B" are attached
9127 by secondary bonds. This approach allows a better recognition of
9128 the protein-protein interaction enabling us to filter out spurious
9129 events. Doing a statistic on the rupture forces and comparing this
9130 with the statistic of the detachments of the system of the bare
9131 handles, we are able to extract the information of the interaction
9132 between the molecule A and B. The two last chapters are of more
9133 preliminary character that the previous part of the thesis. A
9134 section is dedicated to the estimation of effective mass and
9135 viscous drag of the cantilevers studied by autocorrelation and
9136 noise power spectrum. Usually the noise power spectrum method is
9137 the most used, however the autocorrelation should give
9138 approximately the same information. The parameters obtained are
9139 important in high frequency modulation techniques. In fact, they
9140 are needed to interpret the results. The results of these two
9141 methods show a good agreement in the estimation of the mass and
9142 the viscous drag of the various cantilever used. Afterwards a
9143 chapter is dedicated to the discussion of the force spectroscopy
9144 experiments using a low frequency modulation of the cantilever
9145 base. Such experiments allow us to record the phase and the
9146 amplitude shift of the modulation signal used. Using the amplitude
9147 channel we managed to restore the static force signal with a lower
9148 level of noise. Moreover these signals give us direct information
9149 about the dynamic stiffness and the lose of energy in the system,
9150 information that, using the standard technique would be difficult
9151 (or even impossible) to obtain.},
9155 author = TKempe #" and "# SBHKent #" and "# FChow #" and "# SMPeterson
9156 #" and "# WSundquist #" and "# JLItalien #" and "# DHarbrecht
9157 #" and "# DPlunkett #" and "# WDeLorbe,
9158 title = "Multiple-copy genes: Production and modification of
9159 monomeric peptides from large multimeric fusion proteins.",
9165 keywords = "Cloning, Molecular",
9166 keywords = "Cyanogen Bromide",
9167 keywords = "DNA, Recombinant",
9168 keywords = "Escherichia coli",
9169 keywords = "Gene Expression Regulation",
9170 keywords = "Genetic Vectors",
9171 keywords = "Humans",
9172 keywords = "Molecular Weight",
9173 keywords = "Peptide Fragments",
9174 keywords = "Plasmids",
9175 keywords = "Substance P",
9176 keywords = "beta-Galactosidase",
9177 abstract = "A vector system has been designed for obtaining high
9178 yields of polypeptides synthesized in Escherichia coli. Multiple
9179 copies of a synthetic gene encoding the neuropeptide substance P
9180 (SP) (Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2) have been
9181 linked and fused to the lacZ gene. Each copy of the SP gene was
9182 flanked by codons for methionine to create sites for cleavage by
9183 cyanogen bromide (CNBr). The isolated multimeric SP fusion
9184 protein was converted to monomers of SP analog, each containing a
9185 carboxyl-terminal homoserine lactone (Hse-lactone) residue
9186 (Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Hse-lactone), upon
9187 treatment with CNBr in formic acid. The Hse-lactone moiety was
9188 subjected to chemical modifications to produce an SP Hse
9189 amide. This method permits synthesis of peptide amide analogs and
9190 other peptide derivatives by combining recombinant DNA techniques
9191 and chemical methods.",
9193 URL = "http://www.ncbi.nlm.nih.gov/pubmed/2419204",
9198 author = MHonda #" and "# YBaba #" and "# NHiaro #" and "# TSekiguchi,
9199 title = "Metal-molecular interface of sulfur-containing amino acid
9200 and thiophene on gold surface",
9205 url = "http://dx.doi.org/10.1088/1742-6596/100/5/052071",
9207 abstract = "Chemical-bonding states of metal-molecular interface
9208 have been investigated for L-cysteine and thiophene on gold by
9209 x-ray photoelectron spectroscopy (XPS) and near edge x-ray
9210 adsorption fine structure (NEXAFS). A remarkable difference in
9211 Au-S bonding states was found between L-cysteine and
9212 thiophene. For mono-layered L-cysteine on gold, the binding energy
9213 of S 1s in XPS and the resonance energy at the S K-edge in NEXAFS
9214 are higher by 8–9 eV than those for multi-layered film (molecular
9215 L-cysteine). In contrast, the S K-edge resonance energy for
9216 mono-layered thiophene on gold was 2475.0 eV, which is the same as
9217 that for molecular L-cysteine. In S 1s XPS for mono-layered
9218 thiophene, two peaks were observed. The higher binging-energy and
9219 more intense peak at 2473.4 eV are identified as gold sulfide. The
9220 binding energy of smaller peak, whose intensity is less than 1/3
9221 of the higher binding energy peak, is 2472.2 eV, which is the same
9222 as that for molecular thiophene. These observations indicate that
9223 Au-S interface behavior shows characteristic chemical bond only
9224 for the Au-S interface of L-cysteine monolayer on gold
9230 title = "Formation and Structure of Self-Assembled Monolayers.",
9235 address = "Department of Chemical Engineering, Chemistry and
9236 Materials Science, and the Herman F. Mark Polymer Research
9237 Institute, Polytechnic University, Six MetroTech Center, Brooklyn,
9241 pages = "1533--1554",
9243 URL = "http://www.ncbi.nlm.nih.gov/pubmed/11848802",
9248 author = GHager #" and "# ABrolo,
9249 title = "Adsorption/desorption behaviour of cysteine and cystine in
9250 neutral and basic media: electrochemical evidence for differing
9251 thiol and disulfide adsorption to a {Au(111)} single crystal
9254 volume = "550--551",
9259 doi = "10.1016/S0022-0728(03)00052-4",
9260 url = "http://www.sciencedirect.com/science/article/pii/S0022072803000524",
9262 keywords = "Disulfide",
9263 keywords = "Thiol adsorption",
9264 keywords = "Self-assembled monolayers",
9265 keywords = "Au(111) single crystal electrode",
9266 keywords = "Cysteine",
9267 keywords = "Cystine",
9268 abstract = "The adsorption/desorption behaviour of the
9269 thiol/disulfide redox couple, cysteine/cystine, was monitored at a
9270 Au(111) single crystal electrode. The monolayers were formed
9271 electrochemically from 0.1 M KClO4 and 0.1 M NaOH solutions
9272 containing either the thiol or the disulfide. Distinct features in
9273 the adsorption potential were noted. An adsorption peak was
9274 observed in the cyclic voltammograms (CVs) from Au(111) in 0.1 M
9275 KClO4 solutions containing cystine at $-0.57$ V vs. saturated
9276 calomel electrode. Under the same conditions, the CVs from
9277 solutions containing cysteine showed an adsorption peak at $-0.43$
9278 V (0.14 V more positive than the corresponding peak from disulfide
9279 solutions). This showed that the thiol and disulfide species have
9280 different adsorption properties. Similar behaviour was observed in
9281 0.1 M NaOH. Cyclic voltammetric and chronocoulometric data were
9282 employed to determine the surface coverage of the different
9283 monolayers. Cysteine solutions prepared in 0.1 M KClO4 provided
9284 coverages of $3.0\times10^{-10}$ and $2.5\times10^{-10}$
9285 mol~cm$^{-2}$ for the L and the D--L species, respectively as
9286 evaluated from the desorption peaks. Desorption of cystine in the
9287 same medium yielded coverages of $1.2\times10^{-10}$ mol~cm$^{-2}$
9288 for both L and D--L solutions (or $2.4\times10^{-10}$
9289 mol~cm$^{-2}$ in cysteine equivalents). Surface coverages obtained
9290 from Au(111) in 0.1 M NaOH corresponded to $3.9\times10^{10}$
9291 mol~cm$^{-2}$ for L-cysteine, and $1.2\times10^{-10}$
9292 mol~cm$^{-2}$ (or $2.4\times10^{-10}$ mol~cm$^{-2}$ cysteine
9293 equivalents) for L and D--L cystine.",
9298 title = "The Nanomechanics of Polycystin-1: A Kidney Mechanosensor",
9302 url = "http://etd.utmb.edu/theses/available/etd-07072010-132038/",
9304 keywords = "Polycystin-1",
9305 keywords = "Missense mutations",
9306 keywords = "Atomic Force Microscopy",
9307 keywords = "Osmolyte",
9308 keywords = "Mechanosensor",
9309 abstract = "Mutations in polycystin-1 (PC1) can cause Autosomal
9310 Dominant Polycystic Kidney Disease (ADPKD), which is a leading
9311 cause of renal failure. The available evidence suggests that PC1
9312 acts as a mechanosensor, receiving signals from the primary cilia,
9313 neighboring cells, and extracellular matrix. PC1 is a large
9314 membrane protein that has a long N-terminal extracellular region
9315 (about 3000 aa) with a multimodular structure including sixteen
9316 Ig-like PKD domains, which are targeted by many naturally
9317 occurring missense mutations. Nothing is known about the effects
9318 of these mutations on the biophysical properties of PKD
9319 domains. In addition, PC1 is expressed along the renal tubule,
9320 where it is exposed to a wide range of concentration of urea. Urea
9321 is known to destabilize proteins. Other osmolytes found in the
9322 kidney such as sorbitol, betaine and TMAO are known to counteract
9323 urea's negative effects on proteins. Nothing is known about how
9324 the mechanical properties of PC1 are affected by these
9325 osmolytes. Here I use nano-mechanical techniques to study the
9326 effects of missense mutations and effects of denaturants and
9327 various osmolytes on the mechanical properties of PKD
9328 domains. Several missense mutations were found to alter the
9329 mechanical stability of PKD domains resulting in distinct
9330 mechanical phenotypes. Based on these findings, I hypothesize that
9331 missense mutations may cause ADPKD by altering the stability of
9332 the PC1 ectodomain, thereby perturbing its ability to sense
9333 mechanical signals. I also found that urea has a significant
9334 impact on both the mechanical stability and refolding rate of PKD
9335 domains. It not only lowers their mechanical stability, but also
9336 slows down their refolding rate. Moreover, several osmolytes were
9337 found to effectively counteract the effects of urea. Our data
9338 provide the evidence that naturally occurring osmolytes can help
9339 to maintain Polycystin-1 mechanical stability and folding
9340 kinetics. This study has the potential to provide new therapeutic
9341 approaches (e.g. through the use of osmolytes or chemical
9342 chaperones) for rescuing destabilized and misfolded PKD domains.",
9346 @article{ sundberg03,
9347 author = MSundberg #" and "# JRosengren #" and "# RBunk
9348 #" and "# JLindahl #" and "# INicholls #" and "# STagerud
9349 #" and "# POmling #" and "# LMontelius #" and "# AMansson,
9350 title = "Silanized surfaces for in vitro studies of actomyosin
9351 function and nanotechnology applications.",
9356 address = "Department of Chemistry and Biomedical Sciences,
9357 University of Kalmar, SE-391 82 Kalmar, Sweden.",
9361 keywords = "Actomyosin",
9362 keywords = "Adsorption",
9363 keywords = "Animals",
9364 keywords = "Collodion",
9365 keywords = "Kinetics",
9366 keywords = "Methods",
9367 keywords = "Movement",
9368 keywords = "Nanotechnology",
9369 keywords = "Rabbits",
9370 keywords = "Silicon",
9371 keywords = "Surface Properties",
9372 keywords = "Trimethylsilyl Compounds",
9373 abstract = "We have previously shown that selective heavy meromyosin
9374 (HMM) adsorption to predefined regions of nanostructured polymer
9375 resist surfaces may be used to produce a nanostructured in vitro
9376 motility assay. However, actomyosin function was of lower quality
9377 than on conventional nitrocellulose films. We have therefore
9378 studied actomyosin function on differently derivatized glass
9379 surfaces with the aim to find a substitute for the polymer
9380 resists. We have found that surfaces derivatized with
9381 trimethylchlorosilane (TMCS) were superior to all other surfaces
9382 tested, including nitrocellulose. High-quality actin filament
9383 motility was observed up to 6 days after incubation with HMM and
9384 the fraction of motile actin filaments and the velocity of smooth
9385 sliding were generally higher on TMCS than on nitrocellulose. The
9386 actomyosin function on TMCS-derivatized glass and nitrocellulose
9387 is considered in relation to roughness and hydrophobicity of these
9388 surfaces. The results suggest that TMCS is an ideal substitute for
9389 polymer resists in the nanostructured in vitro motility
9390 assay. Furthermore, TMCS derivatized glass also seems to offer
9391 several advantages over nitrocellulose for HMM adsorption in the
9392 ordinary in /vitro motility assay.",
9394 URL = "http://www.ncbi.nlm.nih.gov/pubmed/14622967",
9395 doi = "10.1016/j.ab.2003.07.022",
9400 author = HItoh #" and "# ATakahashi #" and "# KAdachi #" and "#
9401 HNoji #" and "# RYasuda #" and "# MYoshida #" and "#
9403 title = "Mechanically driven {ATP} synthesis by {F1}-{ATP}ase.",
9408 address = "Tsukuba Research Laboratory, Hamamatsu Photonics KK,
9409 Joko, Hamamatsu 431-3103, Japan.
9410 hiritoh@hpk.trc-net.co.jp",
9414 keywords = "Adenosine Diphosphate",
9415 keywords = "Adenosine Triphosphate",
9416 keywords = "Bacillus",
9417 keywords = "Catalysis",
9419 keywords = "Magnetics",
9420 keywords = "Microchemistry",
9421 keywords = "Microspheres",
9422 keywords = "Molecular Motor Proteins",
9423 keywords = "Proton-Translocating ATPases",
9424 keywords = "Rotation",
9425 keywords = "Torque",
9426 abstract = "ATP, the main biological energy currency, is synthesized
9427 from ADP and inorganic phosphate by ATP synthase in an
9428 energy-requiring reaction. The F1 portion of ATP synthase, also
9429 known as F1-ATPase, functions as a rotary molecular motor: in
9430 vitro its gamma-subunit rotates against the surrounding
9431 alpha3beta3 subunits, hydrolysing ATP in three separate catalytic
9432 sites on the beta-subunits. It is widely believed that reverse
9433 rotation of the gamma-subunit, driven by proton flow through the
9434 associated F(o) portion of ATP synthase, leads to ATP synthesis in
9435 biological systems. Here we present direct evidence for the
9436 chemical synthesis of ATP driven by mechanical energy. We attached
9437 a magnetic bead to the gamma-subunit of isolated F1 on a glass
9438 surface, and rotated the bead using electrical magnets. Rotation
9439 in the appropriate direction resulted in the appearance of ATP in
9440 the medium as detected by the luciferase-luciferin reaction. This
9441 shows that a vectorial force (torque) working at one particular
9442 point on a protein machine can influence a chemical reaction
9443 occurring in physically remote catalytic sites, driving the
9444 reaction far from equilibrium.",
9446 doi = "10.1038/nature02212",
9447 URL = "http://www.ncbi.nlm.nih.gov/pubmed/14749837",
9452 author = NSakaki #" and "# RShimoKon #" and "# KAdachi
9453 #" and "# HItoh #" and "# SFuruike #" and "# EMuneyuki
9454 #" and "# MYoshida #" and "# KKinosita,
9455 title = "One rotary mechanism for {F1}-{ATP}ase over {ATP}
9456 concentrations from millimolar down to nanomolar.",
9461 address = "Department of Functional Molecular Science, The Graduate
9462 University for Advanced Studies, Nishigonaka 38, Myodaiji, Okazaki
9466 pages = "2047--2056",
9467 keywords = "Adenosine Triphosphate",
9468 keywords = "Hydrolysis",
9469 keywords = "Kinetics",
9470 keywords = "Microchemistry",
9471 keywords = "Molecular Motor Proteins",
9472 keywords = "Nanostructures",
9473 keywords = "Protein Binding",
9474 keywords = "Protein Conformation",
9475 keywords = "Proton-Translocating ATPases",
9476 keywords = "Rotation",
9477 keywords = "Torque",
9478 abstract = "F(1)-ATPase is a rotary molecular motor in which the
9479 central gamma-subunit rotates inside a cylinder made of
9480 alpha(3)beta(3)-subunits. The rotation is driven by ATP hydrolysis
9481 in three catalytic sites on the beta-subunits. How many of the
9482 three catalytic sites are filled with a nucleotide during the
9483 course of rotation is an important yet unsettled question. Here we
9484 inquire whether F(1) rotates at extremely low ATP concentrations
9485 where the site occupancy is expected to be low. We observed under
9486 an optical microscope rotation of individual F(1) molecules that
9487 carried a bead duplex on the gamma-subunit. Time-averaged rotation
9488 rate was proportional to the ATP concentration down to 200 pM,
9489 giving an apparent rate constant for ATP binding of 2 x 10(7)
9490 M(-1)s(-1). A similar rate constant characterized bulk ATP
9491 hydrolysis in solution, which obeyed a simple Michaelis-Menten
9492 scheme between 6 mM and 60 nM ATP. F(1) produced the same torque
9493 of approximately 40 pN.nm at 2 mM, 60 nM, and 2 nM ATP. These
9494 results point to one rotary mechanism governing the entire range
9495 of nanomolar to millimolar ATP, although a switchover between two
9496 mechanisms cannot be dismissed. Below 1 nM ATP, we observed less
9497 regular rotations, indicative of the appearance of another
9500 doi = "10.1529/biophysj.104.054668",
9501 URL = "http://www.ncbi.nlm.nih.gov/pubmed/15626703",
9505 @article{ schmidt02,
9506 author = JSchmidt #" and "# XJiang #" and "# CMontemagno,
9507 title = "Force Tolerances of Hybrid Nanodevices",
9511 pages = "1229--1233",
9513 doi = "10.1021/nl025773v",
9514 URL = "http://pubs.acs.org/doi/abs/10.1021/nl025773v",
9515 eprint = "http://pubs.acs.org/doi/pdf/10.1021/nl025773v",
9516 abstract = "We have created hybrid devices consisting of nanoscale
9517 fabricated inorganic components integrated with and powered by a
9518 genetically engineered motor protein. We wish to increase the
9519 assembly yield and lifetime of these devices through
9520 identification, measurement, and improvement of weak internal
9521 bonds. Using dynamic force spectroscopy, we have measured the bond
9522 rupture force of (histidine)\textsubscript{6} on a number of
9523 different surfaces as a function of loading rate. The bond sizes,
9524 lifetimes, and energy barrier heights were derived from these
9525 measurements. We compare the (His)\textsubscript{6}--nickel bonds
9526 to other bonds composing the hybrid device and describe
9527 preliminary measurements of the force tolerances of the protein
9528 itself. Pathways for improvement of device longevity and
9529 robustness are discussed.",
9533 author = YSLo #" and "# YJZhu #" and "# TBeebe,
9534 title = "Loading-Rate Dependence of Individual Ligand−Receptor
9535 Bond-Rupture Forces Studied by Atomic Force Microscopy",
9539 pages = "3741--3748",
9541 doi = "10.1021/la001569g",
9542 URL = "http://pubs.acs.org/doi/abs/10.1021/la001569g",
9543 eprint = "http://pubs.acs.org/doi/pdf/10.1021/la001569g",
9544 abstract = "It is known that bond strength is a dynamic property
9545 that is dependent upon the force loading rate applied during the
9546 rupturing of a bond. For biotin--avidin and biotin--streptavidin
9547 systems, dynamic force spectra, which are plots of bond strength
9548 vs loge(loading rate), have been acquired in a recent biomembrane
9549 force probe (BFP) study at force loading rates in the range
9550 0.05--60 000 pN/s. In the present study, the dynamic force spectrum
9551 of the biotin--streptavidin bond strength in solution was extended
9552 from loading rates of ∼104 to ∼107 pN/s with the atomic force
9553 microscope (AFM). A Poisson statistical analysis method was
9554 applied to extract the magnitude of individual bond-rupture forces
9555 and nonspecific interactions from the AFM force--distance curve
9556 measurements. The bond strengths were found to scale linearly with
9557 the logarithm of the loading rate. The nonspecific interactions
9558 also exhibited a linear dependence on the logarithm of loading
9559 rate, although not increasing as rapidly as the specific
9560 interactions. The dynamic force spectra acquired here with the AFM
9561 combined well with BFP measurements by Merkel et al. The combined
9562 spectrum exhibited two linear regimes, consistent with the view
9563 that multiple energy barriers are present along the unbinding
9564 coordinate of the biotin--streptavidin complex. This study
9565 demonstrated that unbinding forces measured by different
9566 techniques are in agreement and can be used together to obtain a
9567 dynamic force spectrum covering 9 orders of magnitude in loading
9569 note = "These guys seem to be pretty thorough, give this one another read.",
9573 author = ABaljon #" and "# MRobbins,
9574 title = "Energy Dissipation During Rupture of Adhesive Bonds",
9581 doi = "10.1126/science.271.5248.482",
9582 URL = "http://www.sciencemag.org/content/271/5248/482.abstract",
9583 eprint = "http://www.sciencemag.org/content/271/5248/482.full.pdf",
9584 abstract = "Molecular dynamics simulations were used to study
9585 energy-dissipation mechanisms during the rupture of a thin
9586 adhesive bond formed by short chain molecules. The degree of
9587 dissipation and its velocity dependence varied with the state of
9588 the film. When the adhesive was in a liquid phase, dissipation was
9589 caused by viscous loss. In glassy films, dissipation occurred
9590 during a sequence of rapid structural rearrangements. Roughly
9591 equal amounts of energy were dissipated in each of three types of
9592 rapid motion: cavitation, plastic yield, and bridge rupture. These
9593 mechanisms have similarities to nucleation, plastic flow, and
9594 crazing in commercial polymeric adhesives.",
9597 @article{ fisher99a,
9598 author = TEFisher #" and "# PMarszalek #" and "# AOberhauser
9599 #" and "# MCarrionVazquez #" and "# JFernandez,
9600 title = "The micro-mechanics of single molecules studied with
9601 atomic force microscopy.",
9606 address = "Department of Physiology and Biophysics, Mayo Foundation,
9607 1-117 Medical Sciences Building, Rochester, MN 55905, USA.",
9608 volume = "520 Pt 1",
9610 keywords = "Animals",
9611 keywords = "Extracellular Matrix",
9612 keywords = "Extracellular Matrix Proteins",
9613 keywords = "Humans",
9614 keywords = "Microscopy, Atomic Force",
9615 keywords = "Polysaccharides",
9616 abstract = "The atomic force microscope (AFM) in its force-measuring
9617 mode is capable of effecting displacements on an angstrom scale
9618 (10 A = 1 nm) and measuring forces of a few piconewtons. Recent
9619 experiments have applied AFM techniques to study the mechanical
9620 properties of single biological polymers. These properties
9621 contribute to the function of many proteins exposed to mechanical
9622 strain, including components of the extracellular matrix
9623 (ECM). The force-bearing proteins of the ECM typically contain
9624 multiple tandem repeats of independently folded domains, a common
9625 feature of proteins with structural and mechanical
9626 roles. Polysaccharide moieties of adhesion glycoproteins such as
9627 the selectins are also subject to strain. Force-induced extension
9628 of both types of molecules with the AFM results in conformational
9629 changes that could contribute to their mechanical function. The
9630 force-extension curve for amylose exhibits a transition in
9631 elasticity caused by the conversion of its glucopyranose rings
9632 from the chair to the boat conformation. Extension of multi-domain
9633 proteins causes sequential unraveling of domains, resulting in a
9634 force-extension curve displaying a saw tooth pattern of peaks. The
9635 engineering of multimeric proteins consisting of repeats of
9636 identical domains has allowed detailed analysis of the mechanical
9637 properties of single protein domains. Repetitive extension and
9638 relaxation has enabled direct measurement of rates of domain
9639 unfolding and refolding. The combination of site-directed
9640 mutagenesis with AFM can be used to elucidate the amino acid
9641 sequences that determine mechanical stability. The AFM thus offers
9642 a novel way to explore the mechanical functions of proteins and
9643 will be a useful tool for studying the micro-mechanics of
9646 URL = "http://www.ncbi.nlm.nih.gov/pubmed/10517795",
9650 @article{ fisher99b,
9651 author = TEFisher #" and "# AOberhauser #" and "# MCarrionVazquez
9652 #" and "# PMarszalek #" and "# JFernandez,
9653 title = "The study of protein mechanics with the atomic force microscope.",
9654 journal = "Trends in biochemical sciences",
9657 address = "Dept of Physiology and Biophysics, Mayo Foundation, 1-117
9658 Medical Sciences Building, Rochester, MN 55905, USA.",
9662 keywords = "Entropy",
9663 keywords = "Kinetics",
9664 keywords = "Microscopy, Atomic Force",
9665 keywords = "Protein Binding",
9666 keywords = "Protein Folding",
9667 keywords = "Proteins",
9668 abstract = "The unfolding and folding of single protein molecules
9669 can be studied with an atomic force microscope (AFM). Many
9670 proteins with mechanical functions contain multiple, individually
9671 folded domains with similar structures. Protein engineering
9672 techniques have enabled the construction and expression of
9673 recombinant proteins that contain multiple copies of identical
9674 domains. Thus, the AFM in combination with protein engineering
9675 has enabled the kinetic analysis of the force-induced unfolding
9676 and refolding of individual domains as well as the study of the
9677 determinants of mechanical stability.",
9679 URL = "http://www.ncbi.nlm.nih.gov/pubmed/10500301",
9683 @article{ zlatanova00,
9684 author = JZlatanova #" and "# SLindsay #" and "# SLeuba,
9685 title = "Single molecule force spectroscopy in biology using the
9686 atomic force microscope.",
9689 address = "Biochip Technology Center, Argonne National Laboratory,
9690 9700 South Cass Avenue, Bldg. 202-A253, Argonne, IL 60439,
9691 USA. jzlatano@duke.poly.edu",
9695 keywords = "Biophysics",
9696 keywords = "Cell Adhesion",
9698 keywords = "Elasticity",
9699 keywords = "Microscopy, Atomic Force",
9700 keywords = "Polysaccharides",
9701 keywords = "Proteins",
9702 keywords = "Signal Processing, Computer-Assisted",
9703 keywords = "Viscosity",
9704 abstract = "The importance of forces in biology has been recognized
9705 for quite a while but only in the past decade have we acquired
9706 instrumentation and methodology to directly measure interactive
9707 forces at the level of single biological macromolecules and/or
9708 their complexes. This review focuses on force measurements
9709 performed with the atomic force microscope. A general introduction
9710 to the principle of action is followed by review of the types of
9711 interactions being studied, describing the main results and
9712 discussing the biological implications.",
9714 URL = "http://www.ncbi.nlm.nih.gov/pubmed/11106806",
9716 note = "Lots of great force-clamp cartoons explaining different
9717 approach/retract features.",
9721 author = MViani #" and "# TESchafer #" and "# AChand #" and "# MRief
9722 #" and "# HEGaub #" and "# HHansma,
9723 title = "Small cantilevers for force spectroscopy of single molecules",
9728 pages = "2258--2262",
9729 abstract = "We have used a simple process to fabricate small
9730 rectangular cantilevers out of silicon nitride. They have lengths
9731 of 9--50 $\mu$m, widths of 3--5 $\mu$m, and thicknesses of 86 and
9732 102 nm. We have added metallic reflector pads to some of the
9733 cantilever ends to maximize reflectivity while minimizing
9734 sensitivity to temperature changes. We have characterized small
9735 cantilevers through their thermal spectra and show that they can
9736 measure smaller forces than larger cantilevers with the same
9737 spring constant because they have lower coefficients of viscous
9738 damping. Finally, we show that small cantilevers can be used for
9739 experiments requiring large measurement bandwidths, and have used
9740 them to unfold single titin molecules over an order of magnitude
9741 faster than previously reported with conventional cantilevers.",
9743 issn_online = "1089-7550",
9744 doi = "10.1063/1.371039",
9745 URL = "http://jap.aip.org/resource/1/japiau/v86/i4/p2258_s1",
9749 @article{ capitanio02,
9750 author = MCapitanio #" and "# GRomano #" and "# RBallerini #" and "#
9751 MGiuntini #" and "# FPavone #" and "# DDunlap #" and "# LFinzi,
9752 title = "Calibration of optical tweezers with differential
9753 interference contrast signals",
9758 pages = "1687--1696",
9759 abstract = "A comparison of different calibration methods for
9760 optical tweezers with the differential interference contrast (DIC)
9761 technique was performed to establish the uses and the advantages
9762 of each method. A detailed experimental and theoretical analysis
9763 of each method was performed with emphasis on the anisotropy
9764 involved in the DIC technique and the noise components in the
9765 detection. Finally, a time of flight method that permits the
9766 reconstruction of the optical potential well was demonstrated.",
9768 issn_online = "1089-7623",
9769 doi = "10.1063/1.1460929",
9770 URL = "http://rsi.aip.org/resource/1/rsinak/v73/i4/p1687_s1",
9775 author = GBinnig #" and "# CQuate #" and "# CGerber,
9776 title = "Atomic force microscope",
9784 abstract = "The scanning tunneling microscope is proposed as a
9785 method to measure forces as small as $10^{-18}$ N. As one
9786 application for this concept, we introduce a new type of
9787 microscope capable of investigating surfaces of insulators on an
9788 atomic scale. The atomic force microscope is a combination of the
9789 principles of the scanning tunneling microscope and the stylus
9790 profilometer. It incorporates a probe that does not damage the
9791 surface. Our preliminary results in air demonstrate a lateral
9792 resolution of 30 \AA and a vertical resolution less than 1 \AA.",
9794 doi = "10.1103/PhysRevLett.56.930",
9795 URL = "http://www.ncbi.nlm.nih.gov/pubmed/10033323",
9796 eprint = {http://prl.aps.org/pdf/PRL/v56/i9/p930_1},
9798 note = "Original AFM paper.",
9802 author = BDrake #" and "# CBPrater #" and "# ALWeisenhorn #" and "#
9803 SAGould #" and "# TRAlbrecht #" and "# CQuate #" and "#
9804 DSCannell #" and "# HHansma #" and "# PHansma,
9805 title = {Imaging crystals, polymers, and processes in water with the
9806 atomic force microscope},
9813 pages = {1586--1589},
9814 doi = {10.1126/science.2928794},
9815 url = {http://www.sciencemag.org/content/243/4898/1586.abstract},
9816 eprint = {http://www.sciencemag.org/content/243/4898/1586.full.pdf},
9817 abstract ={The atomic force microscope (AFM) can be used to image
9818 the surface of both conductors and nonconductors even if they are
9819 covered with water or aqueous solutions. An AFM was used that
9820 combines microfabricated cantilevers with a previously described
9821 optical lever system to monitor deflection. Images of mica
9822 demonstrate that atomic resolution is possible on rigid materials,
9823 thus opening the possibility of atomic-scale corrosion experiments
9824 on nonconductors. Images of polyalanine, an amino acid polymer,
9825 show the potential of the AFM for revealing the structure of
9826 molecules important in biology and medicine. Finally, a series of
9827 ten images of the polymerization of fibrin, the basic component of
9828 blood clots, illustrate the potential of the AFM for revealing
9829 subtle details of biological processes as they occur in real
9833 @article{ radmacher92,
9834 author = MRadmacher #" and "# RWTillmann #" and "# MFritz #" and "# HEGaub,
9835 title = {From molecules to cells: imaging soft samples with the
9836 atomic force microscope},
9843 pages = {1900--1905},
9844 doi = {10.1126/science.1411505},
9845 url = {http://www.sciencemag.org/content/257/5078/1900.abstract},
9846 eprint = {http://www.sciencemag.org/content/257/5078/1900.full.pdf},
9847 abstract ={Since its invention a few years ago, the atomic force microscope has become one of the most widely used near-field microscopes. Surfaces of hard sample are imaged routinely with atomic resolution. Soft samples, however, remain challenging. An overview is presented on the application of atomic force microscopy to organic samples ranging from thin ordered films at molecular resolution to living cells. Fundamental mechanisms of the image formation are discussed, and novel imaging modes are introduced that exploit different aspects of the tip-sample interaction for local measurements of the micromechanical properties of the sample. As examples, images of Langmuir-Blodgett films, which map the local viscoelasticity as well as the friction coefficient, are presented.},
9850 @article{ williams86,
9851 author = CCWilliams #" and "# HKWickramasinghe,
9852 title = "Scanning thermal profiler",
9859 pages = "1587--1589",
9860 abstract = "A new high-resolution profilometer has been demonstrated
9861 based upon a noncontacting near-field thermal probe. The thermal
9862 probe consists of a thermocouple sensor with dimensions
9863 approaching 100 nm. Profiling is achieved by scanning the heated
9864 sensor above but close to the surface of a solid. The conduction
9865 of heat between tip and sample via the air provides a means for
9866 maintaining the sample spacing constant during the lateral
9867 scan. The large difference in thermal properties between air and
9868 solids makes the profiling technique essentially independent of
9869 the material properties of the solid. Noncontact profiling of
9870 resist and metal films has shown a lateral resolution of 100 nm
9871 and a depth solution of 3 nm. The basic theory of the new probe is
9872 described and the results presented.",
9874 issn_online = "1077-3118",
9875 doi = "10.1063/1.97288",
9876 URL = "http://apl.aip.org/resource/1/applab/v49/i23/p1587_s1",
9881 author = GMeyer #" and "# NMAmer,
9882 title = "Novel optical approach to atomic force microscopy",
9889 pages = "1045--1047",
9890 abstract = "A sensitive and simple optical method for detecting the
9891 cantilever deflection in atomic force microscopy is described. The
9892 method was incorporated in an atomic force microscope, and imaging
9893 and force measurements, in ultrahigh vacuum, were successfully
9896 issn_online = "1077-3118",
9897 doi = "10.1063/1.100061",
9898 URL = "http://apl.aip.org/resource/1/applab/v53/i12/p1045_s1",
9904 title = {Notes on Structured Programming},
9907 url = {http://www.cs.utexas.edu/users/EWD/ewd02xx/EWD249.PDF},
9908 publisher = THEMath,
9909 note = {T.H. Report 70-WSK-03},
9914 title = {On the Composition of Well-Structured Programs},
9923 doi = {10.1145/356635.356639},
9924 url = {http://doi.acm.org/10.1145/356635.356639},
9926 address = {New York, NY, USA},
9929 @article{ shneiderman79,
9930 author = BShneiderman #" and "# RMayer,
9931 title = {Syntactic/semantic interactions in programmer behavior: A
9932 model and experimental results},
9939 doi = {10.1007/BF00977789},
9940 url = {http://dx.doi.org/10.1007/BF00977789},
9942 keywords = {Programming; programming languages; cognitive models;
9943 program composition; program comprehension; debugging;
9944 modification; learning; education; information processing},
9945 language = {English},
9950 title = {Why Functional Programming Matters},
9956 doi = {10.1093/comjnl/32.2.98},
9957 URL = {http://comjnl.oxfordjournals.org/content/32/2/98.abstract},
9958 eprint = {http://comjnl.oxfordjournals.org/content/32/2/98.full.pdf+html},
9959 abstract ={As software becomes more and more complex, it is more and
9960 more important to structure it well. Well-structured software is
9961 easy to write, easy to debug, and provides a collection of modules
9962 that can be re-used to reduce future programming
9963 costs. Conventional languages place conceptual limits on the way
9964 problems can be modularised. Functional languages push those
9965 limits back. In this paper we show that two features of functional
9966 languages in particular, higher-order functions and lazy
9967 evaluation, can contribute greatly to modularity. As examples, we
9968 manipulate lists and trees, program several numerical algorithms,
9969 and implement the alpha-beta heuristics (an Artificial
9970 Intelligence algorithm used in game-playing programs). Since
9971 modularity is the key to successful programming, functional
9972 languages are vitally important to the real world.},
9975 @article{ hilburn93,
9977 title = {A top-down approach to teaching an introductory computer science course},
9978 journal = ACM:SIGCSE,
9986 doi = {10.1145/169073.169349},
9987 url = {http://doi.acm.org/10.1145/169073.169349},
9990 address = {New York, NY, USA},
9995 title = {The mythical man-month},
9996 edition = {20$^\text{th}$ anniversary},
9998 isbn = {0-201-83595-9},
10000 address = {Boston, MA, USA},
10001 url = {http://dl.acm.org/citation.cfm?id=207583},
10002 note = {First published in 1975},
10005 @inproceedings{ claerbout92,
10006 author = JClaerbout #" and "# MKarrenbach,
10007 title = {Electronic documents give reproducible research a new meaning},
10008 booktitle = {SEG Technical Program Expanded Abstracts 1992},
10011 pages = {601--604},
10012 doi = {10.1190/1.1822162},
10013 issn = {1052-3812},
10015 url = {http://library.seg.org/doi/abs/10.1190/1.1822162},
10016 eprint = {http://sepwww.stanford.edu/doku.php?id=sep:research:reproducible:seg92},
10019 @incollection{ buckheit95,
10020 author = JBuckheit #" and "# DDonoho,
10021 title = {WaveLab and Reproducible Research},
10022 booktitle = {Wavelets and Statistics},
10023 series = {Lecture Notes in Statistics},
10024 editor = AAntoniadis #" and "# GOppenheim,
10028 isbn = {978-0-387-94564-4},
10029 doi = {10.1007/978-1-4612-2544-7_5},
10030 url = {http://dx.doi.org/10.1007/978-1-4612-2544-7_5},
10031 eprint = {http://www-stat.stanford.edu/~wavelab/Wavelab_850/wavelab.pdf},
10032 publisher = SPRINGER,
10033 language = {English},
10036 @article{ schwab00,
10037 author = MSchwab #" and "# MKarrenbach #" and "# JClaerbout,
10038 title = {Making scientific computations reproducible},
10041 month = {November--December},
10045 doi = {10.1109/5992.881708},
10046 ISSN = {1521-9615},
10047 keywords = {document handling;file organisation;natural sciences
10048 computing;research and development
10049 management;ReDoc;authors;computational results;reproducible
10050 scientific computations;research paper;software filing
10051 system;standardized rules;Computer
10052 interfaces;Documentation;Electronic
10053 publishing;Laboratories;Organizing;Reproducibility of
10054 results;Software maintenance;Software systems;Software
10055 testing;Technological innovation},
10056 abstract = {To verify a research paper's computational results,
10057 readers typically have to recreate them from scratch. ReDoc is a
10058 simple software filing system for authors that lets readers easily
10059 reproduce computational results using standardized rules and
10063 @article{ wilson06a,
10065 title = {Where's the Real Bottleneck in Scientific Computing?},
10068 month = {January--February},
10071 @article{ wilson06b,
10073 title = {Software Carpentry: Getting Scientists to Write Better
10074 Code by Making Them More Productive},
10077 month = {November--December},
10080 @article{ vandewalle09,
10081 author = PVandewalle #" and "# JKovacevic #" and "# MVetterli ,
10082 title = {Reproducible Research in Signal Processing - What, why, and how},
10083 journal = IEEE:SPM,
10089 doi = {10.1109/MSP.2009.932122},
10090 issn = {1053-5888},
10091 url = {http://rr.epfl.ch/17/},
10092 eprint = {http://rr.epfl.ch/17/1/VandewalleKV09.pdf},
10093 keywords={research and development;signal processing;high-quality
10094 reviewing process;large data set;reproducible research;signal
10095 processing;win-win situation;Advertising;Digital signal
10096 processing;Education;Programming;Reproducibility of
10097 results;Scholarships;Signal processing;Signal processing
10098 algorithms;Testing;Wikipedia},
10099 abstract = {Have you ever tried to reproduce the results presented
10100 in a research paper? For many of our current publications, this
10101 would unfortunately be a challenging task. For a computational
10102 algorithm, details such as the exact data set, initialization or
10103 termination procedures, and precise parameter values are often
10104 omitted in the publication for various reasons, such as a lack of
10105 space, a lack of self-discipline, or an apparent lack of interest
10106 to the readers, to name a few. This makes it difficult, if not
10107 impossible, for someone else to obtain the same results. In our
10108 experience, it is often even worse as even we are not always able
10109 to reproduce our own experiments, making it difficult to answer
10110 questions from colleagues about details. Following are some
10111 examples of e-mails we have received: ``I just read your paper
10112 X. It is very completely described, however I am confused by
10113 Y. Could you provide the implementation code to me for reference
10114 if possible?'' ``Hi! I am also working on a project related to
10115 X. I have implemented your algorithm but cannot get the same
10116 results as described in your paper. Which values should I use for
10117 parameters Y and Z?''},
10120 @article{ aruliah12,
10121 author = DAruliah #" and "# CTBrown #" and "# MPCHong #" and "#
10122 MDavis #" and "# RTGuy #" and "# SHaddock #" and "# KHuff #" and "#
10123 IMitchell #" and "# MPlumbley #" and "# BWaugh #" and "#
10124 EPWhite #" and "# GWilson #" and "# PWilson,
10125 title = {Best Practices for Scientific Computing},
10127 volume = {abs/1210.0530},
10132 url = {http://arxiv.org/abs/1210.0530},
10133 eprint = {http://arxiv.org/pdf/1210.0530v3},
10134 note = {v3: Thu, 29 Nov 2012 19:28:27 GMT},
10137 @article{ ziegler42,
10138 author = JZiegler #" and "# NNichols,
10139 title = {Optimum Settings for Automatic Controllers},
10144 pages = {759--765},
10145 url = {http://www.driedger.ca/Z-N/Z-N.html},
10146 eprint = {http://www.driedger.ca/Z-N/Z-n.pdf},
10150 author = GHCohen #" and "# GACoon,
10151 title = {Theoretical considerations of retarded control},
10155 pages = {827--834},
10159 author = FSWang #" and "# WSJuang #" and "# CTChan,
10160 title = {Optimal tuning of {PID} controllers for single and
10161 cascade control loops},
10167 publisher = GordonBreach,
10168 issn = {0098-6445},
10169 doi = {10.1080/00986449508936294},
10170 url = {http://www.tandfonline.com/doi/abs/10.1080/00986449508936294},
10171 keywords = {process control; cascade control; controller tuning},
10172 abstract = {Design of one parameter tuning of three-mode PID
10173 controller was developed in this present study. The integral time
10174 and the derivative time of the controller were expressed in terms
10175 of the time constant and dead time of the process. Only the
10176 proportional gain was observed to be dependent on the implemented
10177 tunable parameter in which the stable region could be
10178 predetermined by the Routh test. Extension of the concept towards
10179 designing cascade PID controllers was straightforward such that
10180 only two parameters for the inner and outer PID controllers
10181 required to be tuned, respectively. The optimal tuning correlative
10182 formulas of the proportional gain for single and cascade control
10183 systems were obtained by the least square regression method.},
10186 @article{ astrom93,
10187 author = KAstrom #" and "# THagglund #" and "# CCHang #" and "# WKHo,
10188 title = {Automatic tuning and adaptation for {PID} controllers---a survey},
10193 pages = {699--714},
10194 issn = "0967-0661",
10195 doi = "10.1016/0967-0661(93)91394-C",
10196 url = "http://www.sciencedirect.com/science/article/pii/096706619391394C",
10197 keywords = {Adaptive control},
10198 keywords = {automatic tuning},
10199 keywords = {gain scheduling},
10200 keywords = {{PID} control},
10201 abstract = {Adaptive techniques such as gain scheduling, automatic
10202 tuning and continuous adaptation have been used in industrial
10203 single-loop controllers for about ten years. This paper gives a
10204 survey of the different adaptive techniques, the underlying
10205 process models and control designs. An overview of industrial
10206 products is also presented, which includes a fairly detailed
10207 investigation of four different adaptive single-loop
10213 title = {Notes on the use of propagation of error formulas},
10219 pages = {263--273},
10221 issn = {0022-4316},
10222 url = {http://nistdigitalarchives.contentdm.oclc.org/cdm/compoundobject/collection/p13011coll6/id/78003/rec/5},
10223 eprint = {http://nistdigitalarchives.contentdm.oclc.org/utils/getfile/collection/p13011coll6/id/78003/filename/print/page/download},
10224 keywords = {Approximation; error; formula; imprecision; law of
10225 error; products; propagation of error; random; ratio; systematic;
10227 abstract = {The ``law of propagation of error'' is a tool that
10228 physical scientists have conveniently and frequently used in their
10229 work for many years, yet an adequate reference is difficult to
10230 find. In this paper an expository review of this topic is
10231 presented, particularly in the light of current practices and
10232 interpretations. Examples on the accuracy of the approximations
10233 are given. The reporting of the uncertainties of final results is
10237 @article{ livadaru03,
10238 author = LLivadaru #" and "# RRNetz #" and "# HJKreuzer,
10239 title = {Stretching Response of Discrete Semiflexible Polymers},
10243 journal = Macromol,
10246 pages = {3732--3744},
10247 doi = {10.1021/ma020751g},
10248 URL = {http://pubs.acs.org/doi/abs/10.1021/ma020751g},
10249 eprint = {http://pubs.acs.org/doi/pdf/10.1021/ma020751g},
10250 abstract = {We demonstrate that semiflexible polymer chains
10251 (characterized by a persistence length $l$) made up of discrete
10252 segments or bonds of length $b$ show at large stretching forces a
10253 crossover from the standard wormlike chain (WLC) behavior to a
10254 discrete-chain (DC) behavior. In the DC regime, the stretching
10255 response is independent of the persistence length and shows a
10256 different force dependence than in the WLC regime. We perform
10257 extensive transfer-matrix calculations for the force-response of a
10258 freely rotating chain (FRC) model as a function of varying bond
10259 angle $\gamma$ (and thus varying persistence length) and chain
10260 length. The FRC model is a first step toward the understanding of
10261 the stretching behavior of synthetic polymers, denatured proteins,
10262 and single-stranded DNA under large tensile forces. We also
10263 present scaling results for the force response of the elastically
10264 jointed chain (EJC) model, that is, a chain made up of freely
10265 jointed bonds that are connected by joints with some bending
10266 stiffness; this is the discretized version of the continuum WLC
10267 model. The EJC model might be applicable to stiff biopolymers such
10268 as double-stranded DNA or Actin. Both models show a similar
10269 crossover from the WLC to the DC behavior, which occurs at a force
10270 $f/k_BT\sim l/b^2$ and is thus (for polymers with a moderately
10271 large persistence length) in the piconewton range probed in many
10272 AFM experiments. We also give a heuristic simple function for the
10273 force--distance relation of a FRC, valid in the global force
10274 range, which can be used to fit experimental data. Our findings
10275 might help to resolve the discrepancies encountered when trying to
10276 fit experimental data for the stretching response of polymers in a
10277 broad force range with a single effective persistence length.},
10278 note = {There are two typos in \fref{equation}{46}.
10279 \citet{livadaru03} have
10281 \frac{R_z}{L} = \begin{cases}
10282 \frac{fa}{3k_BT} & \frac{fb}{k_BT} < \frac{b}{l} \\
10283 1 - \p({\frac{fl}{4k_BT}})^{-0.5}
10284 & \frac{b}{l} < \frac{fb}{k_BT} < \frac{l}{b} \\
10285 1 - \p({\frac{fb}{ck_BT}})^{-1} & \frac{1}{b} < \frac{fb}{k_BT} \;,
10288 but the correct formula is
10290 \frac{R_z}{L} = \begin{cases}
10291 \frac{fa}{3k_BT} & \frac{fb}{k_BT} < \frac{b}{l} \\
10292 1 - \p({\frac{4fl}{k_BT}})^{-0.5}
10293 & \frac{b}{l} < \frac{fb}{k_BT} < \frac{l}{b} \\
10294 1 - \p({\frac{cfb}{k_BT}})^{-1} & \frac{1}{b} < \frac{fb}{k_BT} \;,
10297 with both the $4$ and the $c$ moved into their respective
10298 numerators. I pointed these errors out to Roland Netz in 2012,
10299 along with the fact that even with the corrected formula there is
10300 a discontinuity between the low- and moderate-force regimes. Netz
10301 confirmed the errors, and pointed out that the discontinuity is
10302 because \fref{equation}{46} only accounts for the scaling (without
10303 prefactors). Unfortunately, there does not seem to be a published
10304 erratum pointing out the error and at least \citet{puchner08} have
10305 quoted the incorrect form.},
10309 author = PCarl #" and "# PDalhaimer,
10310 title = {{PUNIAS}: Protein Unfolding and Nano-indentation Analysis
10315 note = {4 Int. Workshop, Scanning Probe Microscopy in Life Sciences},
10316 address = {Berlin},
10317 url = {http://punias.voila.net/},
10321 author = PCarl #" and "# HSchillers,
10322 title = {Elasticity measurement of living cells with an atomic force
10323 microscope: data acquisition and processing.},
10327 address = {Institute of Physiology II, University of M{\"u}nster,
10328 Robert-Koch-Str. 27b, 48149, M{\"u}nster, Germany.},
10332 pages = {551--559},
10333 issn = {0031-6768},
10334 doi = {10.1007/s00424-008-0524-3},
10335 url = {http://www.ncbi.nlm.nih.gov/pubmed/18481081},
10337 keywords = {Animals},
10338 keywords = {Biomechanics},
10339 keywords = {CHO Cells},
10340 keywords = {Cricetinae},
10341 keywords = {Cricetulus},
10342 keywords = {Cystic Fibrosis Transmembrane Conductance Regulator},
10343 keywords = {Elastic Modulus},
10344 keywords = {Equipment Design},
10345 keywords = {Microscopy, Atomic Force},
10346 keywords = {Models, Biological},
10347 keywords = {Reproducibility of Results},
10348 keywords = {Signal Processing, Computer-Assisted},
10349 keywords = {Transfection},
10350 abstract = {Elasticity of living cells is a parameter of increasing
10351 importance in cellular physiology, and the atomic force microscope
10352 is a suitable instrument to quantitatively measure it. The
10353 principle of an elasticity measurement is to physically indent a
10354 cell with a probe, to measure the applied force, and to process
10355 this force-indentation data using an appropriate model. It is
10356 crucial to know what extent the geometry of the indenting probe
10357 influences the result. Therefore, we indented living Chinese
10358 hamster ovary cells at 37 degrees C with sharp tips and colloidal
10359 probes (spherical particle tips) of different sizes and
10360 materials. We furthermore developed an implementation of the Hertz
10361 model, which simplifies the data processing. Our results show (a)
10362 that the size of the colloidal probe does not influence the result
10363 over a wide range (radii $0.5$-$26\U{$\mu$m}$) and (b) indenting
10364 cells with sharp tips results in higher Young's moduli
10365 (approximately $1,300\U{Pa}$) than using colloidal probes
10366 (approximately $400\U{Pa}$).},
10367 note = {Mentions \citetalias{punias} as if it was in-house software,
10368 which makes sense because Philippe Carl seems to be a major author.},
10371 @article{ struckmeier08,
10372 author = JStruckmeier #" and "# RWahl #" and "# MLeuschner #" and "#
10373 JNunes #" and "# HJanovjak #" and "# UGeisler #" and "#
10374 GHofmann #" and "# TJahnke #" and "# DJMuller,
10375 title = {Fully automated single-molecule force spectroscopy for
10376 screening applications},
10380 address = {Cellular Machines, Biotechnology Center,
10381 Technische Universit{\"a}t Dresden, Tatzberg 47, D-01307
10387 issn = {0957-4484},
10388 doi = {10.1088/0957-4484/19/38/384020},
10389 url = {http://www.ncbi.nlm.nih.gov/pubmed/21832579},
10391 abstract = {With the introduction of single-molecule force
10392 spectroscopy (SMFS) it has become possible to directly access the
10393 interactions of various molecular systems. A bottleneck in
10394 conventional SMFS is collecting the large amount of data required
10395 for statistically meaningful analysis. Currently, atomic force
10396 microscopy (AFM)-based SMFS requires the user to tediously `fish'
10397 for single molecules. In addition, most experimental and
10398 environmental conditions must be manually adjusted. Here, we
10399 developed a fully automated single-molecule force
10400 spectroscope. The instrument is able to perform SMFS while
10401 monitoring and regulating experimental conditions such as buffer
10402 composition and temperature. Cantilever alignment and calibration
10403 can also be automatically performed during experiments. This,
10404 combined with in-line data analysis, enables the instrument, once
10405 set up, to perform complete SMFS experiments autonomously.},
10406 note = {An advertisement for JPK's \citetalias{force-robot}.},
10409 @article{ andreopoulos11,
10410 author = BAndreopoulos #" and "# DLabudde,
10411 title = {Efficient unfolding pattern recognition in single molecule
10412 force spectroscopy data},
10416 address = {Department of Bioinformatics, Biotechnological Center,
10417 University of Technology Dresden, Dresden, Germany.
10418 williama@biotec.tu-dresden.de},
10423 issn = {1748-7188},
10424 doi = {10.1186/1748-7188-6-16},
10425 url = {http://www.ncbi.nlm.nih.gov/pubmed/21645400},
10427 abstract = {Single-molecule force spectroscopy (SMFS) is a technique
10428 that measures the force necessary to unfold a protein. SMFS
10429 experiments generate Force-Distance (F-D) curves. A statistical
10430 analysis of a set of F-D curves reveals different unfolding
10431 pathways. Information on protein structure, conformation,
10432 functional states, and inter- and intra-molecular interactions can
10437 editor = HWTurnbull,
10439 title = {The correspondence of Isaac Newton},
10444 url = {http://books.google.com/books?id=pr8WAQAAMAAJ},
10445 note = {The ``Giants'' quote is on page 416, in a letter to Robert
10446 Hooke dated February 5, 1676.},
10449 @book{ whitehead11,
10450 author = ANWhitehead,
10451 title = {An introduction to mathematics},
10455 address = {London},
10456 url = {http://archive.org/details/introductiontoma00whitiala},
10457 note = {The ``civilization'' quote is on page 61.},
10461 author = NJMlot #" and "# CATovey #" and "# DLHu,
10462 title = {Fire ants self-assemble into waterproof rafts to survive floods},
10466 address = {Schools of Mechanical Engineering, Industrial and
10467 Systems Engineering, and Biology,
10468 Georgia Institute of Technology, Atlanta, GA 30318, USA.},
10472 pages = {7669--7673},
10473 issn = {1091-6490},
10474 doi = {10.1073/pnas.1016658108},
10475 url = {http://www.ncbi.nlm.nih.gov/pubmed/21518911},
10477 keywords = {Animals},
10479 keywords = {Behavior, Animal},
10480 keywords = {Biophysical Phenomena},
10481 keywords = {Floods},
10482 keywords = {Hydrophobic and Hydrophilic Interactions},
10483 keywords = {Microscopy, Electron, Scanning},
10484 keywords = {Models, Biological},
10485 keywords = {Social Behavior},
10486 keywords = {Surface Properties},
10487 keywords = {Time-Lapse Imaging},
10488 keywords = {Video Recording},
10489 keywords = {Water},
10490 abstract = {Why does a single fire ant \species{Solenopsis invicta}
10491 struggle in water, whereas a group can float effortlessly for
10492 days? We use time-lapse photography to investigate how fire ants
10493 \species{S.~invicta} link their bodies together to build
10494 waterproof rafts. Although water repellency in nature has been
10495 previously viewed as a static material property of plant leaves
10496 and insect cuticles, we here demonstrate a self-assembled
10497 hydrophobic surface. We find that ants can considerably enhance
10498 their water repellency by linking their bodies together, a process
10499 analogous to the weaving of a waterproof fabric. We present a
10500 model for the rate of raft construction based on observations of
10501 ant trajectories atop the raft. Central to the construction
10502 process is the trapping of ants at the raft edge by their
10503 neighbors, suggesting that some ``cooperative'' behaviors may rely
10505 note = {Higher resolution pictures are available at
10506 \url{http://antlab.gatech.edu/antlab/The_Ant_Raft.html}.},
10509 @article{ chauhan97,
10510 author = VPChauhan #" and "# IRay #" and "# AChauhan #" and "#
10511 JWegiel #" and "# HMWisniewski,
10512 title = {Metal cations defibrillize the amyloid beta-protein fibrils.},
10515 address = {New York State Institute for Basic Research in
10516 Developmental Disabilities, Staten Island 10314-6399,
10521 pages = {805--809},
10522 issn = {0364-3190},
10523 url = {http://www.ncbi.nlm.nih.gov/pubmed/9232632},
10524 doi = {10.1023/A:1022079709085},
10526 keywords = {Alzheimer Disease},
10527 keywords = {Amyloid beta-Peptides},
10528 keywords = {Drug Evaluation, Preclinical},
10529 keywords = {Humans},
10530 keywords = {Metals},
10531 keywords = {Peptide Fragments},
10532 keywords = {Solubility},
10533 abstract = {Amyloid beta-protein (A beta) is the major constituent
10534 of amyloid fibrils composing beta-amyloid plaques and
10535 cerebrovascular amyloid in Alzheimer's disease (AD). We studied
10536 the effect of metal cations on preformed fibrils of synthetic A
10537 beta by Thioflavin T (ThT) fluorescence spectroscopy and
10538 electronmicroscopy (EM) in negative staining. The amount of cross
10539 beta-pleated sheet structure of A beta 1-40 fibrils was found to
10540 decrease by metal cations in a concentration-dependent manner as
10541 measured by ThT fluorescence spectroscopy. The order of
10542 defibrillization of A beta 1-40 fibrils by metal cations was: Ca2+
10543 and Zn2+ (IC50 = 100 microM) > Mg3+ (IC50 = 300 microM) > Al3+
10544 (IC50 = 1.1 mM). EM analysis in negative staining showed that A
10545 beta 1-40 fibrils in the absence of cations were organized in a
10546 fine network with a little or no amorphous material. The addition
10547 of Ca2+, Mg2+, and Zn2+ to preformed A beta 1-40 fibrils
10548 defibrillized the fibrils or converted them into short rods or to
10549 amorphous material. Al3+ was less effective, and reduced the
10550 fibril network by about 80\% of that in the absence of any metal
10551 cation. Studies with A beta 1-42 showed that this peptide forms
10552 more dense network of fibrils as compared to A beta 1-40. Both ThT
10553 fluorescence spectroscopy and EM showed that similar to A beta
10554 1-40, A beta 1-42 fibrils are also defibrillized in the presence
10555 of millimolar concentrations of Ca2+. These studies suggest that
10556 metal cations can defibrillize the fibrils of synthetic A beta.},
10557 note = {From page 806, ``The exact mechanism by which these metal
10558 ions affect the fibrillization of A$\beta$ is not known.''},
10561 @article{ friedman05,
10562 author = RFriedman #" and "# ENachliel #" and "# MGutman,
10563 title = {Molecular dynamics of a protein surface: ion-residues
10568 address = {Laser Laboratory for Fast Reactions in Biology,
10569 Department of Biochemistry, The George S. Wise Faculty
10570 for Life Sciences, Tel Aviv University, Israel.},
10574 pages = {768--781},
10575 issn = {0006-3495},
10576 doi = {10.1529/biophysj.105.058917},
10577 url = {http://www.ncbi.nlm.nih.gov/pubmed/15894639},
10579 keywords = {Amino Acids},
10580 keywords = {Binding Sites},
10581 keywords = {Chlorine},
10582 keywords = {Computer Simulation},
10584 keywords = {Models, Chemical},
10585 keywords = {Models, Molecular},
10586 keywords = {Motion},
10587 keywords = {Protein Binding},
10588 keywords = {Protein Conformation},
10589 keywords = {Ribosomal Protein S6},
10590 keywords = {Sodium},
10591 keywords = {Solutions},
10592 keywords = {Static Electricity},
10593 keywords = {Surface Properties},
10594 keywords = {Water},
10595 abstract = {Time-resolved measurements indicated that protons could
10596 propagate on the surface of a protein or a membrane by a special
10597 mechanism that enhanced the shuttle of the proton toward a
10598 specific site. It was proposed that a suitable location of
10599 residues on the surface contributes to the proton shuttling
10600 function. In this study, this notion was further investigated by
10601 the use of molecular dynamics simulations, where Na(+) and Cl(-)
10602 are the ions under study, thus avoiding the necessity for quantum
10603 mechanical calculations. Molecular dynamics simulations were
10604 carried out using as a model a few Na(+) and Cl(-) ions enclosed
10605 in a fully hydrated simulation box with a small globular protein
10606 (the S6 of the bacterial ribosome). Three independent 10-ns-long
10607 simulations indicated that the ions and the protein's surface were
10608 in equilibrium, with rapid passage of the ions between the
10609 protein's surface and the bulk. However, it was noted that close
10610 to some domains the ions extended their duration near the surface,
10611 thus suggesting that the local electrostatic potential hindered
10612 their diffusion to the bulk. During the time frame in which the
10613 ions were detained next to the surface, they could rapidly shuttle
10614 between various attractor sites located under the electrostatic
10615 umbrella. Statistical analysis of the molecular dynamics and
10616 electrostatic potential/entropy consideration indicated that the
10617 detainment state is an energetic compromise between attractive
10618 forces and entropy of dilution. The similarity between the motion
10619 of free ions next to a protein and the proton transfer on the
10620 protein's surface are discussed.},
10623 @article{ friedman11,
10624 author = RFriedman,
10625 title = {Ions and the protein surface revisited: extensive molecular
10626 dynamics simulations and analysis of protein structures in
10627 alkali-chloride solutions.},
10631 address = {School of Natural Sciences, Linn{\ae}us University,
10632 391 82 Kalmar, Sweden. ran.friedman@lnu.se},
10636 pages = {9213--9223},
10637 issn = {1520-5207},
10638 doi = {10.1021/jp112155m},
10639 URL = {http://www.ncbi.nlm.nih.gov/pubmed/21688775},
10641 keywords = {Alkalies},
10642 keywords = {Amyloid},
10643 keywords = {Chlorides},
10644 keywords = {Databases, Protein},
10645 keywords = {Fungal Proteins},
10646 keywords = {HIV Protease},
10647 keywords = {Humans},
10648 keywords = {Molecular Dynamics Simulation},
10649 keywords = {Protein Multimerization},
10650 keywords = {Protein Structure, Secondary},
10651 keywords = {Proteins},
10652 keywords = {Ribosomal Protein S6},
10653 keywords = {Solutions},
10654 keywords = {Solvents},
10655 keywords = {Surface Properties},
10656 abstract = {Proteins interact with ions in various ways. The surface
10657 of proteins has an innate capability to bind ions, and it is also
10658 influenced by the screening of the electrostatic potential owing
10659 to the presence of salts in the bulk solution. Alkali metal ions
10660 and chlorides interact with the protein surface, but such
10661 interactions are relatively weak and often transient. In this
10662 paper, computer simulations and analysis of protein structures are
10663 used to characterize the interactions between ions and the protein
10664 surface. The results show that the ion-binding properties of
10665 protein residues are highly variable. For example, alkali metal
10666 ions are more often associated with aspartate residues than with
10667 glutamates, whereas chlorides are most likely to be located near
10668 arginines. When comparing NaCl and KCl solutions, it was found
10669 that certain surface residues attract the anion more strongly in
10670 NaCl. This study demonstrates that protein-salt interactions
10671 should be accounted for in the planning and execution of
10672 experiments and simulations involving proteins, particularly if
10673 subtle structural details are sought after.},
10677 author = YZhang #" and "# PSCremer,
10678 title = {Interactions between macromolecules and ions: The
10679 {H}ofmeister series.},
10683 address = {Department of Chemistry, Texas A\&M University,
10684 College Station, TX 77843, USA.},
10688 pages = {658--663},
10689 issn = {1367-5931},
10690 doi = {10.1016/j.cbpa.2006.09.020},
10691 url = {http://www.ncbi.nlm.nih.gov/pubmed/17035073},
10693 keywords = {Acrylamides},
10694 keywords = {Biopolymers},
10695 keywords = {Solubility},
10696 keywords = {Thermodynamics},
10697 keywords = {Water},
10698 abstract = {The Hofmeister series, first noted in 1888, ranks the
10699 relative influence of ions on the physical behavior of a wide
10700 variety of aqueous processes ranging from colloidal assembly to
10701 protein folding. Originally, it was thought that an ion's
10702 influence on macromolecular properties was caused at least in part
10703 by `making' or `breaking' bulk water structure. Recent
10704 time-resolved and thermodynamic studies of water molecules in salt
10705 solutions, however, demonstrate that bulk water structure is not
10706 central to the Hofmeister effect. Instead, models are being
10707 developed that depend upon direct ion-macromolecule interactions
10708 as well as interactions with water molecules in the first
10709 hydration shell of the macromolecule.},
10710 note = {A quick pass through Hofmeister history, but no discussion
10711 of cations (``A complete picture will inevitably involve an
10712 integrated understanding of the role of cations (including
10713 guanidinium ions) and osmolytes (such as urea and tri-methylamine
10714 N-oxide) as well. There has been some progress in these fields,
10715 although such subjects are generally beyond the scope of this
10716 short review.'').},
10719 @article{ isaacs06,
10720 author = AMIsaacs #" and "# DBSenn #" and "# MYuan #" and "#
10721 JPShine #" and "# BAYankner,
10722 title = {Acceleration of amyloid beta-peptide aggregation by
10723 physiological concentrations of calcium.},
10727 address = {Department of Neurology and Division of Neuroscience,
10728 The Children's Hospital, Harvard Medical School,
10729 Boston, Massachusetts 02115, USA.},
10733 pages = {27916--27923},
10734 issn = {0021-9258},
10735 doi = {10.1074/jbc.M602061200},
10736 url = {http://www.ncbi.nlm.nih.gov/pubmed/16870617},
10738 keywords = {Alzheimer Disease},
10739 keywords = {Amyloid},
10740 keywords = {Amyloid beta-Peptides},
10741 keywords = {Animals},
10742 keywords = {Calcium},
10743 keywords = {Cells, Cultured},
10744 keywords = {Copper},
10745 keywords = {Neurons},
10748 abstract = {Alzheimer disease is characterized by the accumulation
10749 of aggregated amyloid beta-peptide (Abeta) in the brain. The
10750 physiological mechanisms and factors that predispose to Abeta
10751 aggregation and deposition are not well understood. In this
10752 report, we show that calcium can predispose to Abeta aggregation
10753 and fibril formation. Calcium increased the aggregation of early
10754 forming protofibrillar structures and markedly increased
10755 conversion of protofibrils to mature amyloid fibrils. This
10756 occurred at levels 20-fold below the calcium concentration in the
10757 extracellular space of the brain, the site at which amyloid plaque
10758 deposition occurs. In the absence of calcium, protofibrils can
10759 remain stable in vitro for several days. Using this approach, we
10760 directly compared the neurotoxicity of protofibrils and mature
10761 amyloid fibrils and demonstrate that both species are inherently
10762 toxic to neurons in culture. Thus, calcium may be an important
10763 predisposing factor for Abeta aggregation and toxicity. The high
10764 extracellular concentration of calcium in the brain, together with
10765 impaired intraneuronal calcium regulation in the aging brain and
10766 Alzheimer disease, may play an important role in the onset of
10767 amyloid-related pathology.},
10768 note = {Physiological levels of \NaCl\ are $\sim 150\U{mM}$. \Ca\
10769 is $\sim 2\U{mM}$.},
10773 author = AItkin #" and "# VDupres #" and "# YFDufrene #" and "#
10774 BBechinger #" and "# JMRuysschaert #" and "# VRaussens,
10775 title = {Calcium ions promote formation of amyloid $\beta$-peptide
10776 (1-40) oligomers causally implicated in neuronal toxicity of
10777 {A}lzheimer's disease.},
10781 address = {Laboratory of Structure and Function of Biological
10782 Membranes, Center for Structural Biology and
10783 Bioinformatics, Universit{\'e} Libre de Bruxelles,
10784 Brussels, Belgium.},
10785 journal = PLOS:ONE,
10789 keywords = {Alzheimer Disease},
10790 keywords = {Amyloid beta-Peptides},
10791 keywords = {Blotting, Western},
10792 keywords = {Calcium},
10793 keywords = {Fluorescence},
10794 keywords = {Humans},
10796 keywords = {Models, Biological},
10797 keywords = {Mutant Proteins},
10798 keywords = {Neurons},
10799 keywords = {Protein Structure, Quaternary},
10800 keywords = {Protein Structure, Secondary},
10801 keywords = {Spectroscopy, Fourier Transform Infrared},
10802 keywords = {Thiazoles},
10803 ISSN = {1932-6203},
10804 doi = {10.1371/journal.pone.0018250},
10805 URL = {http://www.ncbi.nlm.nih.gov/pubmed/21464905},
10807 abstract = {Amyloid $\beta$-peptide (A$\beta$) is directly linked to
10808 Alzheimer's disease (AD). In its monomeric form, A$\beta$
10809 aggregates to produce fibrils and a range of oligomers, the latter
10810 being the most neurotoxic. Dysregulation of Ca(2+) homeostasis in
10811 aging brains and in neurodegenerative disorders plays a crucial
10812 role in numerous processes and contributes to cell dysfunction and
10813 death. Here we postulated that calcium may enable or accelerate
10814 the aggregation of A$\beta$. We compared the aggregation pattern
10815 of A$\beta$(1-40) and that of A$\beta$(1-40)E22G, an amyloid
10816 peptide carrying the Arctic mutation that causes early onset of
10817 the disease. We found that in the presence of Ca(2+),
10818 A$\beta$(1-40) preferentially formed oligomers similar to those
10819 formed by A$\beta$(1-40)E22G with or without added Ca(2+), whereas
10820 in the absence of added Ca(2+) the A$\beta$(1-40) aggregated to
10821 form fibrils. Morphological similarities of the oligomers were
10822 confirmed by contact mode atomic force microscopy imaging. The
10823 distribution of oligomeric and fibrillar species in different
10824 samples was detected by gel electrophoresis and Western blot
10825 analysis, the results of which were further supported by
10826 thioflavin T fluorescence experiments. In the samples without
10827 Ca(2+), Fourier transform infrared spectroscopy revealed
10828 conversion of oligomers from an anti-parallel $\beta$-sheet to the
10829 parallel $\beta$-sheet conformation characteristic of
10830 fibrils. Overall, these results led us to conclude that calcium
10831 ions stimulate the formation of oligomers of A$\beta$(1-40), that
10832 have been implicated in the pathogenesis of AD.},
10833 note = {$2\U{mM}$ of \Ca\ is the \emph{extracellular} concentration.
10834 Cytosol concetrations are in the $\mu$M range.},
10838 author = JZidar #" and "# FMerzel,
10839 title = {Probing amyloid-beta fibril stability by increasing ionic
10844 address = {National Institute of Chemistry, Hajdrihova 19,
10845 SI-1000 Ljubljana, Slovenia.},
10849 pages = {2075--2081},
10850 issn = {1520-5207},
10851 doi = {10.1021/jp109025b},
10852 URL = {http://www.ncbi.nlm.nih.gov/pubmed/21329333},
10854 keywords = {Amyloid beta-Peptides},
10855 keywords = {Entropy},
10856 keywords = {Hydrogen Bonding},
10857 keywords = {Molecular Dynamics Simulation},
10858 keywords = {Osmolar Concentration},
10859 keywords = {Protein Multimerization},
10860 keywords = {Protein Stability},
10861 keywords = {Protein Structure, Secondary},
10862 keywords = {Solvents},
10863 keywords = {Vibration},
10864 abstract = {Previous experimental studies have demonstrated changing
10865 the ionic strength of the solvent to have a great impact on the
10866 mechanism of aggregation of amyloid-beta (A$\beta$) protein
10867 leading to distinct fibril morphology at high and low ionic
10868 strength. Here, we use molecular dynamics simulations to elucidate
10869 the ionic strength-dependent effects on the structure and dynamics
10870 of the model A$\beta$ fibril. The change in ionic strength was
10871 brought forth by varying the NaCl concentration in the environment
10872 surrounding the A$\beta$ fibril. Comparison of the calculated
10873 vibrational spectra of A$\beta$ derived from 40 ns all-atom
10874 molecular dynamics simulations at different ionic strength reveals
10875 the fibril structure to be stiffer with increasing ionic
10876 strength. This finding is further corroborated by the calculation
10877 of the stretching force constants. Decomposition of binding and
10878 dynamical properties into contributions from different structural
10879 segments indicates the elongation of the fibril at low ionic
10880 strength is most likely promoted by hydrogen bonding between
10881 N-terminal parts of the fibril, whereas aggregation at higher
10882 ionic strength is suggested to be driven by the hydrophobic
10884 note = {Only study \NaCl\ over the range to $308\U{mM}$, but show a
10885 general decreased hydrogen bonding as concentration increases.},
10889 author = LMiao #" and "# HQin #" and "# PKoehl #" and "# JSong,
10890 title = {Selective and specific ion binding on proteins at
10891 physiologically-relevant concentrations.},
10895 address = {Department of Biological Sciences, Faculty of Science,
10896 National University of Singapore, Singapore.},
10900 pages = {3126--3132},
10901 issn = {1873-3468},
10902 doi = {10.1016/j.febslet.2011.08.048},
10903 url = {http://www.ncbi.nlm.nih.gov/pubmed/21907714},
10905 keywords = {Amino Acid Sequence},
10906 keywords = {Ephrin-B2},
10908 keywords = {Models, Molecular},
10909 keywords = {Molecular Sequence Data},
10910 keywords = {Nuclear Magnetic Resonance, Biomolecular},
10911 keywords = {Protein Binding},
10912 keywords = {Protein Folding},
10913 keywords = {Protein Structure, Tertiary},
10914 keywords = {Salts},
10915 keywords = {Solutions},
10916 keywords = {Thermodynamics},
10917 keywords = {Water},
10918 abstract = {Insoluble proteins dissolved in unsalted water appear to
10919 have no well-folded tertiary structures. This raises a fundamental
10920 question as to whether being unstructured is due to the absence of
10921 salt ions. To address this issue, we solubilized the insoluble
10922 ephrin-B2 cytoplasmic domain in unsalted water and first confirmed
10923 using NMR spectroscopy that it is only partially folded. Using NMR
10924 HSQC titrations with 14 different salts, we further demonstrate
10925 that the addition of salt triggers no significant folding of the
10926 protein within physiologically relevant ion concentrations. We
10927 reveal however that their 8 anions bind to the ephrin-B2 protein
10928 with high affinity and specificity at biologically-relevant
10929 concentrations. Interestingly, the binding is found to be both
10930 salt- and residue-specific.},
10931 note = {They suggest that for low concentrations ($<100\U{mM}$),
10932 protein-ion interactions are mostly electrostatic. The Hofmeister
10933 effects only kick in at higher consentrations.},
10937 author = HJDyson #" and "# PEWright,
10938 title = {Intrinsically unstructured proteins and their functions.},
10942 address = {Department of Molecular Biology and Skaggs Institute
10943 for Chemical Biology, The Scripps Research Institute,
10944 10550 North Torrey Pines Road, La Jolla, California
10945 92037, USA. dyson@scripps.edu},
10948 pages = {197--208},
10949 issn = {1471-0072},
10950 doi = {10.1038/nrm1589},
10951 url = {http://www.ncbi.nlm.nih.gov/pubmed/15738986},
10953 keywords = {CREB-Binding Protein},
10954 keywords = {Humans},
10955 keywords = {Nuclear Proteins},
10956 keywords = {Nucleic Acids},
10957 keywords = {Protein Binding},
10958 keywords = {Protein Processing, Post-Translational},
10959 keywords = {Protein Structure, Tertiary},
10960 keywords = {Proteins},
10961 keywords = {Trans-Activators},
10962 keywords = {Tumor Suppressor Protein p53},
10963 abstract = {Many gene sequences in eukaryotic genomes encode entire
10964 proteins or large segments of proteins that lack a well-structured
10965 three-dimensional fold. Disordered regions can be highly conserved
10966 between species in both composition and sequence and, contrary to
10967 the traditional view that protein function equates with a stable
10968 three-dimensional structure, disordered regions are often
10969 functional, in ways that we are only beginning to discover. Many
10970 disordered segments fold on binding to their biological targets
10971 (coupled folding and binding), whereas others constitute flexible
10972 linkers that have a role in the assembly of macromolecular
10976 @article{ cleland64,
10977 author = WWCleland,
10978 title = {Dithiothreitol, a New Protective Reagent for SH Groups},
10984 pages = {480--482},
10985 keywords = {Alcohols},
10986 keywords = {Chromatography},
10987 keywords = {Coenzyme A},
10988 keywords = {Oxidation-Reduction},
10989 keywords = {Research},
10990 keywords = {Sulfhydryl Compounds},
10991 keywords = {Sulfides},
10992 keywords = {Ultraviolet Rays},
10993 issn = {0006-2960},
10994 doi = {10.1021/bi00892a002},
10995 url = {http://www.ncbi.nlm.nih.gov/pubmed/14192894},
10996 eprint = {http://pubs.acs.org/doi/pdf/10.1021/bi00892a002},