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{DBerk = "Berk, D."}
95 @string{FBerkemeier = "Berkemeier, Felix"}
96 @string{BBerne = "Berne, Bruce J."}
97 @string{MBertz = "Bertz, Morten"}
98 @string{RBest = "Best, Robert B."}
99 @string{GBethel = "Bethel, G."}
100 @string{NBhasin = "Bhasin, Nishant"}
101 @string{KBiddick = "Biddick, K."}
102 @string{KBillings = "Billings, Kate S."}
103 @string{GBinnig = "Binnig, Gerd"}
104 @string{BCBPRC = "Biochemical and Biophysical Research Communications"}
105 @string{Biochem = "Biochemistry"}
106 @string{BBABE = "Biochimica et Biophysica Acta (BBA) - Bioenergetics"}
107 @string{BIOINFO = "Bioinformatics (Oxford, England)"}
108 @string{Biomet = "Biometrika"}
109 @string{BPJ = "Biophysical Journal"}
110 %string{BPJ = "Biophys. J."}
111 @string{BIOSENSE = "Biosensors and Bioelectronics"}
112 @string{BIOTECH = "Biotechnology and Bioengineering"}
113 @string{JBirchler = "Birchler, James A."}
114 @string{AWBlake = "Blake, Anthony W."}
115 @string{JBlawzdziewicz = "Blawzdziewicz, Jerzy"}
116 @string{LBlick = "Blick, L."}
117 @string{RBolanos = "Bolanos, R."}
118 @string{VBonazzi = "Bonazzi, V."}
119 @string{Borgia = "Borgia"}
120 @string{MBorkovec = "Borkovec, Michal"}
121 @string{RBrandon = "Brandon, R."}
122 @string{EBranscomb = "Branscomb, E."}
123 @string{EBraverman = "Braverman, Elena"}
124 @string{WBreyer = "Breyer, Wendy A."}
125 @string{FBrochard-Wyart = "Brochard-Wyart, F."}
126 @string{DJBrockwell = "Brockwell, David J."}
127 @string{SBroder = "Broder, S."}
128 @string{SBroedel = "Broedel, Sheldon E."}
129 @string{ABrolo = "Brolo, Alexandre G."}
130 @string{FBrooks = "Brooks, Jr., Frederick P."}
131 @string{BrooksCole = "Brooks/Cole"}
132 @string{BDBrowerToland = "Brower-Toland, Brent D."}
133 @string{CTBrown = "Brown, C. Titus"}
134 @string{MBrucale = "Brucale, Marco"}
135 @string{TBruls = "Bruls, T."}
136 @string{VBrumfeld = "Brumfeld, Vlad"}
137 @string{JDBryngelson = "Bryngelson, J. D."}
138 @string{JBuckheit = "Buckheit, Jonathan B."}
139 @string{ABuguin = "Buguin, A."}
140 @string{ABulhassan = "Bulhassan, Ahmed"}
141 @string{BBullard = "Bullard, Belinda"}
142 @string{RBunk = "Bunk, Richard"}
143 @string{NABurnham = "Burnham, N.~A."}
144 @string{DBusam = "Busam, D."}
145 @string{GBussi = "Bussi, Giovanni"}
146 @string{CBustamante = "Bustamante, Carlos"}
147 @string{YBustanji = "Bustanji, Yasser"}
148 @string{HJButt = {Butt, Hans-J\"urgen}}
149 @string{CUP = "Cambridge University Press"}
150 @string{MCaminha = "Caminha, M."}
151 @string{ICampbell = "Campbell, Iain D."}
152 @string{MJCampbell = "Campbell, M. J."}
153 @string{DSCannell = "Cannell, D.~S."}
154 @string{YCao = "Cao, Yi"}
155 @string{MCapitanio = "Capitanio, M."}
156 @string{MCargill = "Cargill, M."}
157 @string{PCarl = "Carl, Philippe"}
158 @string{BACarnes = "Carnes, B. A."}
159 @string{JCarnes-Stine = "Carnes-Stine, J."}
160 @string{MCarrionVazquez = "Carrion-Vazquez, Mariano"}
161 @string{CCarter = "Carter, C."}
162 @string{ACarver = "Carver, A."}
163 @string{JJCatanese = "Catanese, J.~J."}
164 @string{PCaulk = "Caulk, P."}
165 @string{CCecconi = "Cecconi, Ciro"}
166 @string{ACenter = "Center, A."}
167 @string{CTChan = "Chan, C.~T."}
168 @string{HSChan = "Chan, H.~S."}
169 @string{AChand = "Chand, Ami"}
170 @string{IChandramouliswaran = "Chandramouliswaran, I."}
171 @string{CHChang = "Chang, Chung-Hung"}
172 @string{EChapman = "Chapman, Edwin R."}
173 @string{RCharlab = "Charlab, R."}
174 @string{KChaturvedi = "Chaturvedi, K."}
175 @string{AChauhan = "Chauhan, A."}
176 @string{VPChauhan = "Chauhan, V.~P."}
177 @string{CChauzy = "Chauzy, C."}
178 @string{SChe = "Che, Shunai"}
179 @string{CEC = "Chemical Engineering Communications"}
180 @string{CHEMREV = "Chemical reviews"}
181 @string{CHEM = "Chemistry (Weinheim an der Bergstrasse, Germany)"}
182 @string{CPC = "Chemphyschem"}
183 @string{HCChen = "Chen, H. C."}
184 @string{LChen = "Chen, L."}
185 @string{XNChen = "Chen, X. N."}
186 @string{XiChen = "Chen, Xinyong"}
187 @string{XuChen = "Chen, Xuming"}
188 @string{JFCheng = "Cheng, J. F."}
189 @string{MLCheng = "Cheng, M. L."}
190 @string{VGCheung = "Cheung, V. G."}
191 @string{YHChiang = "Chiang, Y. H."}
192 @string{AChinwalla = "Chinwalla, A."}
193 @string{FChow = "Chow, Flora"}
194 @string{JChoy = "Choy, Jason"}
195 @string{BChu = "Chu, Benjamin"}
196 @string{XChu = "Chu, Xueying"}
197 @string{TYChung = "Chung, Tse-Yu"}
198 @string{CLChyan = "Chyan, Chia-Lin"}
199 @string{GCiccotti = "Ciccotti, Giovanni"}
200 @string{JClaerbout = "Claerbout, Jon F."}
201 @string{AGClark = "Clark, A. G."}
202 @string{Clarke = "Clarke"}
203 @string{JClarke = "Clarke, Jane"}
204 @string{JClarkson = "Clarkson, John"}
205 @string{HClausen-Schaumann = "Clausen-Schaumann, H."}
206 @string{JMClaverie = "Claverie, J. M."}
207 @string{WWCleland = "Cleland, W.~W."}
208 @string{KClerc-Blankenburg = "Clerc-Blankenburg, K."}
209 @string{NJCobb = "Cobb, Nathan J."}
210 @string{GHCohen = "Cohen, G.~H."}
211 @string{FSCollins = "Collins, Francis S."}
212 @string{CUP = "Columbia University Press"}
213 @string{CPR = "Computer Physics Reports"}
214 @string{CSE = "Computing in Science \& Engineering"}
215 @string{UniProtConsort = "Consortium, The UniProt"}
216 @string{MConti = "Conti, Matteo"}
217 @string{CEP = "Control Engineering Practice"}
218 @string{GACoon = "Coon, G.~A."}
219 @string{PVCornish = "Cornish, Peter V."}
220 @string{MNCourel = "Courel, M. N."}
221 @string{GCowan = "Cowan, Glen"}
222 @string{DRCox = "Cox, D. R."}
223 @string{MCoyne = "Coyne, M."}
224 @string{DCraig = "Craig, David"}
225 @string{ACravchik = "Cravchik, A."}
226 @string{PSCremer = "Cremer, Paul S."}
227 @string{CCroarkin = "Croarkin, Carroll"}
228 @string{VCroquette = "Croquette, Vincent"}
229 @string{YCui = "Cui, Y."}
230 @string{COSB = "Current Opinion in Structural Biology"}
231 @string{COCB = "Current Opinion in Chemical Biology"}
232 @string{LCurry = "Curry, L."}
233 @string{CDahlke = "Dahlke, C."}
234 @string{FDahlquist = "Dahlquist, Frederick W."}
235 @string{PDalhaimer = "Dalhaimer, Paul"}
236 @string{SDanaher = "Danaher, S."}
237 @string{LDavenport = "Davenport, L."}
238 @string{MCDavies = "Davies, M.~C."}
239 @string{MDavis = "Davis, Matt"}
240 @string{SDecatur = "Decatur, Sean M."}
241 @string{WDeGrado = "DeGrado, William F."}
242 @string{PDebrunner = "Debrunner, P."}
243 @string{ADelcher = "Delcher, A."}
244 @string{WDeLorbe = "DeLorbe, William J."}
245 @string{BDelpech = "Delpech, B."}
246 @string{Demography = "Demography"}
247 @string{ZDeng = "Deng, Z."}
248 @string{RDesilets = "Desilets, R."}
249 @string{IDew = "Dew, I."}
250 @string{CDewhurst = "Dewhurst, Charles"}
251 @string{VDiFrancesco = "Di Francesco, V."}
252 @string{KDiemer = "Diemer, K."}
253 @string{GDietler = "Dietler, Giovanni"}
254 @string{HDietz = "Dietz, Hendrik"}
255 @string{SDietz = "Dietz, S."}
256 @string{EDijkstra = "Dijkstra, Edsger Wybe"}
257 @string{KADill = "Dill, K. A."}
258 @string{RDima = "Dima, Ruxandra I."}
259 @string{DDischer = "Discher, Dennis E."}
260 @string{KDixon = "Dixon, K."}
261 @string{KDodson = "Dodson, K."}
262 @string{NDoggett = "Doggett, N."}
263 @string{MDombroski = "Dombroski, M."}
264 @string{MDonnelly = "Donnelly, M."}
265 @string{DDonoho = "Donoho, David L."}
266 @string{CDornmair = "Dornmair, C."}
267 @string{MDors = "Dors, M."}
268 @string{LDougan = "Dougan, Lorna"}
269 @string{LDoup = "Doup, L."}
270 @string{BDrake = "Drake, B."}
271 @string{TDrobek = "Drobek, T."}
272 @string{Drexel = "Drexel University"}
273 @string{OKDudko = "Dudko, Olga K."}
274 @string{YFDufrene = "Dufr{\^e}ne, Yves F."}
275 @string{ADunham = "Dunham, A."}
276 @string{DDunlap = "Dunlap, D."}
277 @string{PDunn = "Dunn, P."}
278 @string{VDupres = "Dupres, Vincent"}
279 @string{HJDyson = "Dyson, H.~Jane"}
280 @string{EMBORep = "EMBO Rep"}
281 @string{EMBO = "EMBO Rep."}
282 @string{REckel = "Eckel, R."}
283 @string{KEilbeck = "Eilbeck, K."}
284 @string{MElbaum = "Elbaum, Michael"}
285 @string{E:NHPL = "Elsevier, North-Holland Personal Library"}
286 @string{DEly = "Ely, D."}
287 @string{SEmerling = "Emerling, S."}
288 @string{TEndo = "Endo, Toshiya"}
289 @string{SWEnglander = "Englander, S. Walter"}
290 @string{HErickson = "Erickson, Harold P."}
291 @string{MEsaki = "Esaki, Masatoshi"}
292 @string{SEsparham = "Esparham, S."}
293 @string{EBJ = "European biophysics journal: EBJ"}
294 @string{EJP = "European Journal of Physics"}
295 @string{EPL = "Europhysics Letters"}
296 @string{CEvangelista = "Evangelista, C."}
297 @string{CAEvans = "Evans, C. A."}
298 @string{EEvans = "Evans, E."}
299 @string{RSEvans = "Evans, R. S."}
300 @string{MEvstigneev = "Evstigneev, M."}
301 @string{DFasulo = "Fasulo, D."}
302 @string{FEBS = "FEBS letters"}
303 @string{XFei = "Fei, Xiaofang"}
304 @string{JFernandez = "Fernandez, Julio M."}
305 @string{SFerriera = "Ferriera, S."}
306 @string{AEFilippov = "Filippov, A. E."}
307 @string{LFinzi = "Finzi, L."}
308 @string{TEFisher = "Fisher, T. E."}
309 @string{MFlanigan = "Flanigan, M."}
310 @string{BFlannery = "Flannery, B."}
311 @string{LFlorea = "Florea, L."}
312 @string{ELFlorin = "Florin, Ernst-Ludwig"}
313 @string{FoldDes = "Fold Des"}
314 @string{NRForde = "Forde, Nancy R."}
315 @string{CFosler = "Fosler, C."}
316 @string{SFossey = "Fossey, S. A."}
317 @string{SFowler = "Fowler, Susan B."}
318 @string{GFranzen = "Franzen, Gereon"}
319 @string{SFreitag = "Freitag, S."}
320 @string{LFrench = "French, L."}
321 @string{RWFriddle = "Friddle, Raymond W."}
322 @string{CFriedman = "Friedman, C."}
323 @string{RFriedman = "Friedman, Ran"}
324 @string{MFritz = "Fritz, M."}
325 @string{HFuchs = "Fuchs, Harald"}
326 @string{TFujii = "Fujii, Tadashi"}
327 @string{HFujita = "Fujita, Hideaki"}
328 @string{AFujiyama = "Fujiyama, A."}
329 @string{RFulton = "Fulton, R."}
330 @string{TFunck = "Funck, Theodor"}
331 @string{TFurey = "Furey, T."}
332 @string{SFuruike = "Furuike, Shou"}
333 @string{GLGaborMiklos = "Gabor Miklos, G. L."}
334 @string{AEGabrielian = "Gabrielian, A. E."}
335 @string{WGan = "Gan, W."}
336 @string{DNGanchev = "Ganchev, Dragomir N."}
337 @string{MGao = "Gao, Mu"}
338 @string{DGarcia = "Garcia, D."}
339 @string{TGarcia = "Garcia, Tzintzuni"}
340 @string{NGarg = "Garg, N."}
341 @string{HEGaub = "Gaub, Hermann E."}
342 @string{MGautel = "Gautel, Mathias"}
343 @string{LAGavrilov = "Gavrilov, L. A."}
344 @string{NSGavrilova = "Gavrilova, N. S."}
345 @string{WGe = "Ge, W."}
346 @string{UGeisler = "Geisler, Ulrich"}
347 @string{GENE = "Gene"}
348 @string{CGerber = "Gerber, Christoph"}
349 @string{CGergely = "Gergely, C."}
350 @string{RGibbs = "Gibbs, R."}
351 @string{DGilbert = "Gilbert, D."}
352 @string{HGire = "Gire, H."}
353 @string{MGiuntini = "Giuntini, M."}
354 @string{SGlanowski = "Glanowski, S."}
355 @string{JGlaser = "Glaser, Jens"}
356 @string{KGlasser = "Glasser, K."}
357 @string{AGlodek = "Glodek, A."}
358 @string{GGloeckner = "Gloeckner, G."}
359 @string{AGluecksmann = "Gluecksmann, A."}
360 @string{JDGocayne = "Gocayne, J. D."}
361 @string{AGomezCasado = "Gomez-Casado, Alberto"}
362 @string{BGompertz = "Gompertz, Benjamin"}
363 @string{FGong = "Gong, F."}
364 @string{GordonBreach = "Gordon Breach Scientific Publishing Ltd."}
365 @string{MGorokhov = "Gorokhov, M."}
366 @string{JHGorrell = "Gorrell, J. H."}
367 @string{SAGould = "Gould, S.~A."}
368 @string{KGraham = "Graham, K."}
369 @string{HLGranzier = "Granzier, Henk L."}
370 @string{FGrater = "Gr{\"a}ter, Frauke"}
371 @string{EDGreen = "Green, E. D."}
372 @string{SGGregory = "Gregory, S. G."}
373 @string{BGropman = "Gropman, B."}
374 @string{CGrossman = "Grossman, C."}
375 @string{HGrubmuller = {Grubm\"uller, Helmut}}
376 @string{AGrutzner = {Gr\"utzner, Anika}}
377 @string{ZGu = "Gu, Z."}
378 @string{PGuan = "Guan, P."}
379 @string{RGuigo = "Guig\'o, R."}
380 @string{EJGumbel = "Gumbel, Emil Julius"}
381 @string{HJGuntherodt = "Guntherodt, Hans-Joachim"}
382 @string{NGuo = "Guo, N."}
383 @string{YGuo = "Guo, Yi"}
384 @string{MGutman = "Gutman, Menachem"}
385 @string{RTGuy = "Guy, Richard T."}
386 @string{PHanggi = {H\"anggi, Peter}}
387 @string{THa = "Ha, Taekjip"}
388 @string{JHaack = "Haack, Julie A."}
389 @string{SHaddock = "Haddock, Steven H.~D."}
390 @string{GHager = "Hager, Gabriele"}
391 @string{THagglund = "H{\"a}gglund, T."}
392 @string{RHajjar = "Hajjar, Roger J."}
393 @string{AHalpern = "Halpern, A."}
394 @string{KHalvorsen = "Halvorsen, Ken"}
395 @string{FHan = "Han, Fangpu"}
396 @string{CCHang = "Hang, C.~C."}
397 @string{SHannenhalli = "Hannenhalli, S."}
398 @string{HHansma = "Hansma, H. G."}
399 @string{PHansma = "Hansma, Paul K."}
400 @string{DHarbrecht = "Harbrecht, Douglas"}
401 @string{SHarper = "Harper, Sandy"}
402 @string{MHarris = "Harris, M."}
403 @string{BHart = "Hart, B."}
404 @string{DPHart = "Hart, D.P."}
405 @string{JWHatfield = "Hatfield, John William"}
406 @string{THatton = "Hatton, T."}
407 @string{MHattori = "Hattori, M."}
408 @string{DHaussler = "Haussler, D."}
409 @string{THawkins = "Hawkins, T."}
410 @string{CHaynes = "Haynes, C."}
411 @string{JHaynes = "Haynes, J."}
412 @string{WHeckl = "Heckl, W. M."}
413 @string{CVHeer = "Heer, C.~V."}
414 @string{JHeil = "Heil, J."}
415 @string{RHeilig = "Heilig, R."}
416 @string{TJHeiman = "Heiman, T. J."}
417 @string{CHeiner = "Heiner, C."}
418 @string{MHelmes = "Helmes, M."}
419 @string{JHemmerle = "Hemmerle, J."}
420 @string{SHenderson = "Henderson, S."}
421 @string{BHeymann = "Heymann, Berthold"}
422 @string{NHiaro = "Hiaro, N."}
423 @string{MEHiggins = "Higgins, M. E."}
424 @string{THilburn = "Hilburn, Thomas B."}
425 @string{LHillier = "Hillier, L."}
426 @string{HHinssen = "Hinssen, Horst"}
427 @string{PHinterdorfer = "Hinterdorfer, Peter"}
428 @string{HistochemJ = "Histochem J"}
429 @string{SHladun = "Hladun, S."}
430 @string{WKHo = "Ho, W.~K."}
431 @string{RHochstrasser = "Hochstrasser, Robin M."}
432 @string{CSHodges = "Hodges, C.~S."}
433 @string{CHoff = "Hoff, C."}
434 @string{WHoff = "Hoff, Wouter D."}
435 @string{JLHolden = "Holden, J. L."}
436 @string{RAHolt = "Holt, R. A."}
437 @string{GHofmann = "Hofmann, Gerd"}
438 @string{MHonda = "Honda, M."}
439 @string{NPCHong = "Hong, Neil P. Chue"}
440 @string{XHong = "Hong, Xia"}
441 @string{LHood = "Hood, L."}
442 @string{JHoover = "Hoover, J."}
443 @string{JHorber = "Horber, J. K. H."}
444 @string{HHosser = "Hosser, H."}
445 @string{DHostin = "Hostin, D."}
446 @string{JHouck = "Houck, J."}
447 @string{AHoumeida = "Houmeida, Ahmed"}
448 @string{JHoward = "Howard, J."}
449 @string{THowland = "Howland, T."}
450 @string{BHsiao = "Hsiao, Benjamin S."}
451 @string{CKHu = "Hu, Chin-Kun"}
452 @string{DLHu = "Hu, David L."}
453 @string{BHuang = "Huang, Baiqu"}
454 @string{HHuang = "Huang, Hector Han-Li"}
455 @string{MHubain = "Hubain, Maurice"}
456 @string{AJHudspeth = "Hudspeth, A.~J."}
457 @string{KHuff = "Huff, Katy"}
458 @string{JHughes = "Hughes, John"}
459 @string{GHummer = "Hummer, Gerhard"}
460 @string{SJHumphray = "Humphray, S. J."}
461 @string{WLHung = "Hung, Wen-Liang"}
462 @string{MHunkapiller = "Hunkapiller, M."}
463 @string{DHHuson = "Huson, D. H."}
464 @string{JHutter = "Hutter, Jeffrey L."}
465 @string{CHyeon = "Hyeon, Changbong"}
466 @string{IEEE:TIT = "IEEE Transactions on Information Theory"}
467 @string{IEEE:SPM = "IEEE Signal Processing Magazine"}
468 @string{CIbegwam = "Ibegwam, C."}
469 @string{JRIdol = "Idol, J. R."}
470 @string{SImprota = "Improta, S."}
471 @string{TInoue = "Inoue, Tadashi"}
472 @string{IJBMM = "International Journal of Biological Macromolecules"}
473 @string{IJCIS = "International Journal of Computer \& Information Sciences"}
474 @string{AItkin = "Itkin, Anna"}
475 @string{HItoh = "Itoh, Hiroyasu"}
476 @string{AIrback = "Irback, Anders"}
477 @string{AMIsaacs = "Isaacs, Adrian M."}
478 @string{BIsralewitz = "Isralewitz, B."}
479 @string{SIstrail = "Istrail, S."}
480 @string{MIvemeyer = "Ivemeyer, M."}
481 @string{DIzhaky = "Izhaky, David"}
482 @string{SIzrailev = "Izrailev, S."}
483 @string{TJahnke = "J{\"a}hnke, Torsten"}
484 @string{WJang = "Jang, W."}
485 @string{HJanovjak = "Janovjak, Harald"}
486 @string{LJanosi = "Janosi, Lorant"}
487 @string{AJanshoff = "Janshoff, Andreas"}
488 @string{JJAP = "Japanese Journal of Applied Physics"}
489 @string{MJaschke = "Jaschke, Manfred"}
490 @string{DJennings = "Jennings, D."}
491 @string{HFJi = "Ji, Hai-Feng"}
492 @string{RRJi = "Ji, R. R."}
493 @string{YJia = "Jia, Yiwei"}
494 @string{SJiang = "Jiang, Shaoyi"}
495 @string{XJiang = "Jiang, Xingqun"}
496 @string{DJohannsmann = "Johannsmann, Diethelm"}
497 @string{CJohnson = "Johnson, Colin P."}
498 @string{JJohnson = "Johnson, J."}
499 @string{AJollymore = "Jollymore, Ashlee"}
500 @string{REJones = "Jones, R.E."}
501 @string{SJones = "Jones, S."}
502 @string{CJordan = "Jordan, C."}
503 @string{JJordan = "Jordan, J."}
504 %string{JACS = "J Am Chem Soc"}
505 @string{JACS = "Journal of the American Chemical Society"}
506 @string{JASA = "Journal of the American Statistical Association"}
507 @string{JAP = "Journal of Applied Physics"}
508 @string{JBM = "J Biomech"}
509 @string{JBT = "J Biotechnol"}
510 @string{JCPPCB = "Journal de Chimie Physique et de Physico-Chimie Biologique"}
511 @string{JCS = "Journal of Cell Science"}
512 @string{JCompP = "Journal of Computational Physics"}
513 @string{JEChem = "Journal of Electroanalytical Chemistry"}
514 @string{JMathBiol = "J Math Biol"}
515 @string{JMicro = "Journal of Microscopy"}
516 @string{JPhysio = "Journal of Physiology"}
517 @string{JStructBiol = "Journal of Structural Biology"}
518 @string{JTB = "J Theor Biol"}
519 @string{JMB = "Journal of Molecular Biology"}
520 @string{JP:CM = "Journal of Physics: Condensed Matter"}
521 @string{JP:CON = "Journal of Physics: Conference Series"}
522 @string{JRNBS:C = "Journal of Research of the National Bureau of Standards. Section C: Engineering and Instrumentation"}
523 @string{WSJuang = "Juang, F.~S."}
524 @string{DAJuckett = "Juckett, D. A."}
525 @string{SRJun = "Jun, Se-Ran"}
526 @string{DKaftan = "Kaftan, David"}
527 @string{LKagan = "Kagan, L."}
528 @string{FKalush = "Kalush, F."}
529 @string{ELKaplan = "Kaplan, E. L."}
530 @string{RKapon = "Kapon, Ruti"}
531 @string{AKardinal = "Kardinal, Angelika"}
532 @string{BKarlak = "Karlak, B."}
533 @string{MKarplus = "Karplus, Martin"}
534 @string{MKarrenbach = "Karrenbach, Martin"}
535 @string{JKasha = "Kasha, J."}
536 @string{KKawasaki = "Kawasaki, K."}
537 @string{ZKe = "Ke, Z."}
538 @string{AKejariwal = "Kejariwal, A."}
539 @string{MSKellermayer = "Kellermayer, Mikl\'os S. Z."}
540 @string{TKempe = "Kempe, Thomas"}
541 @string{SKennedy = "Kennedy, S."}
542 @string{SBHKent = "Kent, Stephen B. H."}
543 @string{WJKent = "Kent, W. J."}
544 @string{KAKetchum = "Ketchum, K. A."}
545 @string{FKienberger = "Kienberger, Ferry"}
546 @string{SHKim = "Kim, Sung-Hou"}
547 @string{WKing = "King, William Trevor"}
548 @string{KKinosita = "{Kinosita Jr.}, Kazuhiko"}
549 @string{IRKirsch = "Kirsch, I. R."}
550 @string{JKlafter = "Klafter, J."}
551 @string{AKleiner = "Kleiner, Ariel"}
552 @string{DKlimov = "Klimov, Dmitri K."}
553 @string{LKline = "Kline, L."}
554 @string{LKlumb = "Klumb, L."}
555 @string{KAPPP = "Kluwer Academic Publishers--Plenum Publishers"}
556 @string{CDKodira = "Kodira, C. D."}
557 @string{SKoduru = "Koduru, S."}
558 @string{PKoehl = "Koehl, Patrice"}
559 @string{BKolmerer = "Kolmerer, B."}
560 @string{JKorenberg = "Korenberg, J."}
561 @string{IKosztin = "Kosztin, Ioan"}
562 @string{JKovacevic = "Kovacevic, Jelena"}
563 @string{CKraft = "Kraft, C."}
564 @string{HAKramers = "Kramers, H. A."}
565 @string{AKrammer = "Krammer, Andre"}
566 @string{SKravitz = "Kravitz, S."}
567 @string{HJKreuzer = {Kreuzer, Hans J\"urgen}}
568 @string{MMGKrishna = "Krishna, Mallela M. G."}
569 @string{KKroy = "Kroy, Klaus"}
570 @string{HHKu = "Ku, H.~H."}
571 @string{TAKucaba = "Kucaba, T. A."}
572 @string{Kucherlapati = "Kucherlapati"}
573 @string{JKudoh = "Kudoh, J."}
574 @string{MKuhn = "Kuhn, Michael"}
575 @string{MKulke = "Kulke, Michael"}
576 @string{CKwok = "Kwok, Carol H."}
577 @string{RLevy = "L\'evy, R"}
578 @string{DLabeit = "Labeit, Dietmar"}
579 @string{SLabeit = "Labeit, Siegfried"}
580 @string{DLabudde = "Labudde, Dirk"}
581 @string{SLahmers = "Lahmers, Sunshine"}
582 @string{ZLai = "Lai, Z."}
583 @string{CLam = "Lam, Canaan"}
584 @string{JLamb = "Lamb, Jonathan C."}
585 @string{LANG = "Langmuir"}
586 % "Langmuir : the ACS journal of surfaces and colloids",
587 @string{WLau = "Lau, Wai Leung"}
588 @string{RLaw = "Law, Richard"}
589 @string{BLazareva = "Lazareva, B."}
590 @string{MLeake = "Leake, Mark C."}
591 @string{ELee = "Lee, E."}
592 @string{HLee = "Lee, Haeshin"}
593 @string{SLee = "Lee, Sunyoung"}
594 @string{HLehmann = "Lehmann, H."}
595 @string{HLehrach = "Lehrach, H."}
596 @string{YLei = "Lei, Y."}
597 @string{PLelkes = "Lelkes, Peter I."}
598 @string{OLequin = "Lequin, Olivier"}
599 @string{CLethias = "Lethias, Claire"}
600 @string{SLeuba = "Leuba, Sanford H."}
601 @string{ALeung = "Leung, A."}
602 @string{MLeuschner = "Leuschner, Mirko"}
603 @string{AJLevine = "Levine, A. J."}
604 @string{CLevinthal = "Levinthal, Cyrus"}
605 @string{ALevitsky = "Levitsky, A."}
606 @string{SLevy = "Levy, S."}
607 @string{MLewis = "Lewis, M."}
608 @string{JLItalien = "L'Italien, James J."}
609 @string{BLi = "Li, Bing"}
610 @string{CYLi = "Li, Christopher Y."}
611 @string{HLi = "Li, Hongbin"}
612 @string{JLi = "Li, J."}
613 @string{LeLi = "Li, Lewyn"}
614 @string{LiLi = "Li, Lingyu"}
615 @string{MSLi = "Li, Mai Suan"}
616 @string{PWLi = "Li, P. W."}
617 @string{YLi = "Li, Yajun"}
618 @string{ZLi = "Li, Z."}
619 @string{YLiang = "Liang, Y."}
620 @string{GLiao = "Liao, George"}
621 @string{FCLin = "Lin, Fan-Chi"}
622 @string{JLin = "Lin, Jianhua"}
623 @string{SHLin = "Lin, Sheng-Hsien"}
624 @string{XLin = "Lin, X."}
625 @string{JLindahl = "Lindahl, Joakim"}
626 @string{SLindsay = "Lindsay, Stuart M."}
627 @string{WALinke = "Linke, Wolfgang A."}
628 @string{RLippert = "Lippert, R."}
629 @string{JLis = "Lis, John T."}
630 @string{RLiu = "Liu, Runcong"}
631 @string{WLiu = "Liu, W."}
632 @string{XLiu = "Liu, X."}
633 @string{YLiu = "Liu, Yichun"}
634 @string{LLivadaru = "Livadaru, L."}
635 @string{YSLo = "Lo, Yu-Shiu"}
636 @string{GLois = "Lois, Gregg"}
637 @string{JLopez = "Lopez, J."}
638 @string{LANL = "Los Alamos National Laboratory"}
639 @string{LAS = "Los Alamos Science"}
640 @string{ALove = "Love, A."}
641 @string{FLu = "Lu, F."}
642 @string{HLu = "Lu, Hui"}
643 @string{QLu = "Lu, Qinghua"}
644 @string{MLudwig = "Ludwig, Markus"}
645 @string{ZPLuo = "Luo, Zong-Ping"}
646 @string{ZLuthey-Schulten = "Luthey-Schulten, Z."}
647 @string{EMunck = {M\"unck, E.}}
648 @string{DMa = "Ma, D."}
649 @string{LMa = "Ma, Liang"}
650 @string{MMaaloum = "Maaloum, Mounir"}
651 @string{Macromol = "Macromolecules"}
652 @string{AMadan = "Madan, A."}
653 @string{VVMaduro = "Maduro, V. V."}
654 @string{CMaingonnat = "Maingonnat, C."}
655 @string{SMajid = "Majid, Sophia"}
656 @string{WMajoros = "Majoros, W."}
657 @string{DEMakarov = "Makarov, Dmitrii E."}
658 @string{RMamdani = "Mamdani, Reneeta"}
659 @string{EMandello = "Mandello, Enrico"}
660 @string{GManderson = "Manderson, Gavin"}
661 @string{FMann = "Mann, F."}
662 @string{AMansson = "M{\aa}nsson, Alf"}
663 @string{ERMardis = "Mardis, E. R."}
664 @string{JMarion = "Marion, J."}
665 @string{JFMarko = "Marko, John F."}
666 @string{MMarra = "Marra, M."}
667 @string{PMarszalek = "Marszalek, Piotr E."}
668 @string{MMartin = "Martin, M. J."}
669 @string{YMartin = "Martin, Y."}
670 @string{HMassa = "Massa, H."}
671 @string{GAMatei = "Matei, G.~A."}
672 @string{DMaterassi = "Materassi, Donatello"}
673 @string{JMathe = "Math\'e, J\'er\^ome"}
674 @string{AMatouschek = "Matouschek, Andreas"}
675 @string{BMatthews = "Matthews, Brian W."}
676 @string{DMay = "May, D."}
677 @string{RMayer = "Mayer, Richard"}
678 @string{LMayne = "Mayne, Leland"}
679 @string{AMays = "Mays, A."}
680 @string{OTMcCann = "McCann, O. T."}
681 @string{SMcCawley = "McCawley, S."}
682 @string{JMcDaniel = "McDaniel, J."}
683 @string{JMcEntyre = "McEntyre, J."}
684 @string{McGraw-Hill = "McGraw-Hill"}
685 @string{TMcIntosh = "McIntosh, T."}
686 @string{VAMcKusick = "McKusick, V. A."}
687 @string{IMcMullen = "McMullen, I."}
688 @string{JDMcPherson = "McPherson, J. D."}
689 @string{TMeasey = "Measey, Thomas J."}
690 @string{MAD = "Mech Ageing Dev"}
691 @string{PMeier = "Meier, Paul"}
692 @string{AMeller = "Meller, Amit"}
693 @string{CCMello = "Mello, Cecilia C."}
694 @string{RMerkel = "Merkel, R."}
695 @string{GVMerkulov = "Merkulov, G. V."}
696 @string{FMerzel = "Merzel, Franci"}
697 @string{HMetiu = "Metiu, Horia"}
698 @string{NMetropolis = "Metropolis, Nicholas"}
699 @string{GMeyer = "Meyer, Gerhard"}
700 @string{HMi = "Mi, H."}
701 @string{LMiao = "Miao, Linlin"}
702 @string{CMicheletti = "Micheletti, Cristian"}
703 @string{MMickler = "Mickler, Moritz"}
704 @string{AMiller = "Miller, A."}
705 @string{NMilshina = "Milshina, N."}
706 @string{SMinoshima = "Minoshima, S."}
707 @string{IMitchell = "Mitchell, Ian"}
708 @string{SMitternacht = "Mitternacht, Simon"}
709 @string{NJMlot = "Mlot, Nathan J."}
710 @string{CMobarry = "Mobarry, C."}
711 @string{NMohandas = "Mohandas, N."}
712 @string{SMohanty = "Mohanty, Sandipan"}
713 @string{UMohideen = "Mohideen, U."}
714 @string{PJMohr = "Mohr, Peter J."}
715 @string{VMontana = "Montana, Vedrana"}
716 @string{LMontanaro = "Montanaro, Lucio"}
717 @string{LMontelius = "Montelius, Lars"}
718 @string{CMontemagno = "Montemagno, Carlo D."}
719 @string{KTMontgomery = "Montgomery, K. T."}
720 @string{HMMoore = "Moore, H. M."}
721 @string{MMorgan = "Morgan, Michael"}
722 @string{LMoy = "Moy, L."}
723 @string{MMoy = "Moy, M."}
724 @string{VMoy = "Moy, Vincent T."}
725 @string{SMukamel = "Mukamel, Shaul"}
726 @string{DJMuller = "M{\"u}ller, Daniel J."}
727 @string{PMundel = "Mundeol, P."}
728 @string{EMuneyuki = "Muneyuki, Eiro"}
729 @string{RJMural = "Mural, R. J."}
730 @string{BMurphy = "Murphy, B."}
731 @string{SMurphy = "Murphy, S."}
732 @string{AMuruganujan = "Muruganujan, A."}
733 @string{EWMyers = "Myers, E. W."}
734 @string{RMMyers = "Myers, R. M."}
735 @string{AMylonakis = "Mylonakis, Andreas"}
736 @string{ENachliel = "Nachliel, Esther"}
737 @string{JNadeau = "Nadeau, J."}
738 @string{AKNaik = "Naik, A. K."}
739 @string{NANO = "Nano letters"}
740 @string{NT = "Nanotechnology"}
741 @string{VANarayan = "Narayan, V. A."}
742 @string{ANarechania = "Narechania, A."}
743 @string{PNassoy = "Nassoy, P."}
744 @string{NBS = "National Bureau of Standards"}
745 @string{NAT = "Nature"}
746 @string{NSB = "Nature Structural Biology"}
747 @string{NSMB = "Nature Structural Molecular Biology"}
748 @string{NRMCB = "Nature Reviews Molecular Cell Biology"}
749 @string{SNaylor = "Naylor, S."}
750 @string{CNeagoe = "Neagoe, Ciprian"}
751 @string{BNeelam = "Neelam, B."}
752 @string{MNeitzert = "Neitzert, Marcus"}
753 @string{CNelson = "Nelson, C."}
754 @string{KNelson = "Nelson, K."}
755 @string{RRNetz = "Netz, R.~R."}
756 @string{NR = "Neurochemical research"}
757 @string{NEURON = "Neuron"}
758 @string{RNevo = "Nevo, Reinat"}
759 @string{NJP = "New Journal of Physics"}
760 @string{DBNewell = "Newell, David B."}
761 @string{MNewman = "Newman, M."}
762 @string{INewton = "Newton, Isaac"}
763 @string{SNg = "Ng, Sean P."}
764 @string{NNguyen = "Nguyen, N."}
765 @string{TNguyen = "Nguyen, T."}
766 @string{MNguyen-Duong = "Nguyen-Duong, M."}
767 @string{INicholls = "Nicholls, Ian A."}
768 @string{NNichols = "Nichols, N.~B."}
769 @string{SNie = "Nie, S."}
770 @string{MNodell = "Nodell, M."}
771 @string{AANoegel = "Noegel, Angelika A."}
772 @string{HNoji = "Noji, Hiroyuki"}
773 @string{RNome = "Nome, Rene A."}
774 @string{NNowak = "Nowak, N."}
775 @string{ANoy = "Noy, Aleksandr"}
776 @string{NAR = "Nucleic Acids Research"}
777 @string{JNummela = "Nummela, Jeremiah"}
778 @string{JNunes = "Nunes, Joao"}
779 @string{DNusskern = "Nusskern, D."}
780 @string{GNyakatura = "Nyakatura, G."}
781 @string{CSOHern = "O'Hern, Corey S."}
782 @string{YOberdorfer = {Oberd\"orfer, York}}
783 @string{AOberhauser = "Oberhauser, Andres F."}
784 @string{FOesterhelt = "Oesterhelt, Filipp"}
785 @string{TOhashi = "Ohashi, Tomoo"}
786 @string{BOhler = "Ohler, Benjamin"}
787 @string{PDOlmsted = "Olmsted, Peter D."}
788 @string{AOlsen = "Olsen, A."}
789 @string{SJOlshansky = "Olshansky, S. J."}
790 @string{POmling = {Omlink, P{\"a}r}}
791 @string{JNOnuchic = "Onuchic, J. N."}
792 @string{YOono = "Oono, Y."}
793 @string{GOppenheim = "Oppenheim, Georges"}
794 @string{COpitz = "Optiz, Christiane A."}
795 @string{KOroszlan = "Oroszlan, Krisztina"}
796 @string{EOroudjev = "Oroudjev, E."}
797 @string{KOsoegawa = "Osoegawa, K."}
798 @string{OUP = "Oxford University Press"}
799 @string{EPaci = "Paci, Emanuele"}
800 @string{SPan = "Pan, S."}
801 @string{HSPark = "Park, H. S."}
802 @string{VParpura = "Parpura, Vladimir"}
803 @string{APastore = "Pastore, A."}
804 @string{APatrinos = "Patrinos, Aristides"}
805 @string{FPavone = "Pavone, F. S."}
806 @string{SHPayne = "Payne, Stephen H."}
807 @string{JPeck = "Peck, J."}
808 @string{HPeng = "Peng, Haibo"}
809 @string{QPeng = "Peng, Qing"}
810 @string{RNPerham = "Perham, Richard N."}
811 @string{OPerisic = "Perisic, Ognjen"}
812 @string{CPeterson = "Peterson, Craig L."}
813 @string{MPeterson = "Peterson, M."}
814 @string{SMPeterson = "Peterson, Susan M."}
815 @string{CPfannkoch = "Pfannkoch, C."}
816 @string{PA = "Pfl{\"u}gers Archiv: European journal of physiology"}
817 @string{PTRSL = "Philosophical Transactions of the Royal Society of London"}
818 @string{PR:E = "Phys Rev E Stat Nonlin Soft Matter Phys"}
819 @string{PRL = "Physical Review Letters"}
820 %string{PRL = "Phys Rev Lett"}
821 @string{Physica = "Physica"}
822 @string{GPing = "Ping, Guanghui"}
823 @string{NPinotsis = "Pinotsis, Nikos"}
824 @string{MPlumbley = "Plumbley, Mark"}
825 @string{PLOS:ONE = "PLOS ONE"}
826 %string{PLOS:ONE = "Public Library of Science ONE"}
827 @string{DPlunkett = "Plunkett, David"}
828 @string{PPodsiadlo = "Podsiadlo, Paul"}
829 @string{ASPolitou = "Politou, A. S."}
830 @string{APoustka = "Poustka, A."}
831 @string{CBPrater = "Prater, C.~B."}
832 @string{GPratesi = "Pratesi, G."}
833 @string{EPratts = "Pratts, E."}
834 @string{WPress = "Press, W."}
835 @string{PNAS = "Proceedings of the National Academy of Sciences of the
836 United States of America"}
837 @string{PBPMB = "Progress in Biophysics and Molecular Biology"}
838 @string{PS = "Protein Science"}
839 @string{PROT = "Proteins"}
840 @string{RSUP = "Published for the Royal Society at the University Press"}
841 @string{EPuchner = "Puchner, Elias M."}
842 @string{VPuri = "Puri, V."}
843 @string{WPyckhout-Hintzen = "Pyckhout-Hintzen, Wim"}
844 @string{HQin = "Qin, Haina"}
845 @string{SQin = "Qin, S."}
846 @string{SRQuake = "Quake, Stephen R."}
847 @string{CQuate = "Quate, Calvin F."}
848 @string{HQureshi = "Qureshi, H."}
849 @string{SERadford = "Radford, Sheena E."}
850 @string{MRadmacher = "Radmacher, M."}
851 @string{MRaible = "Raible, M."}
852 @string{LRamirez = "Ramirez, L."}
853 @string{JRamser = "Ramser, J."}
854 @string{LRandles = "Randles, Lucy G."}
855 @string{VRaussens = "Raussens, Vincent"}
856 @string{IRay = "Ray, I."}
857 @string{MReardon = "Reardon, M."}
858 @string{ALCReddin = "Reddin, Andrew L. C."}
859 @string{SRedick = "Redick, Sambra D."}
860 @string{ZReich = "Reich, Ziv"}
861 @string{TReid = "Reid, T."}
862 @string{PReimann = "Reimann, P."}
863 @string{KReinert = "Reinert, K."}
864 @string{RReinhardt = "Reinhardt, R."}
865 @string{KRemington = "Remington, K."}
866 @string{RMP = "Rev. Mod. Phys."}
867 @string{RSI = "Review of Scientific Instruments"}
868 @string{FRief = "Rief, Frederick"}
869 @string{MRief = "Rief, Matthias"}
870 @string{KRitchie = "Ritchie, K."}
871 @string{MRobbins = "Robbins, Mark O."}
872 @string{CJRoberts = "Roberts, C.~J."}
873 @string{RJRoberts = "Roberts, R. J."}
874 @string{RRobertson = "Robertson, Ragan B."}
875 @string{HRoder = "Roder, Heinrich"}
876 @string{RRodriguez = "Rodriguez, R."}
877 @string{YHRogers = "Rogers, Y. H."}
878 @string{SRogic = "Rogic, S."}
879 @string{MRoman = "Roman, Marisa B."}
880 @string{GRomano = "Romano, G."}
881 @string{DRomblad = "Romblad, D."}
882 @string{RRos = "Ros, Robert"}
883 @string{BRosenberg = "Rosenberg, B."}
884 @string{JRosengren = "Rosengren, Jenny P."}
885 @string{ARosenthal = "Rosenthal, A."}
886 @string{ARoters = "Roters, Andreas"}
887 @string{WRowe = "Rowe, W."}
888 @string{LRowen = "Rowen, L."}
889 @string{BRuhfel = "Ruhfel, B."}
890 @string{DBRusch = "Rusch, D. B."}
891 @string{JMRuysschaert = "Ruysschaert, Jean-Marie"}
892 @string{JPRyckaert = "Ryckaert, Jean-Paul"}
893 @string{NSakaki = "Sakaki, Naoyoshi"}
894 @string{YSakaki = "Sakaki, Y."}
895 @string{SSalzberg = "Salzberg, S."}
896 @string{BSamori = "Samor{\`i}, Bruno"}
897 @string{MSandal = "Sandal, Massimo"}
898 @string{RSanders = "Sanders, R."}
899 @string{ASarkar = "Sarkar, Atom"}
900 @string{TSasaki = "Sasaki, T."}
901 @string{SSato = "Sato, S."}
902 @string{TSato = "Sato, Takehiro"}
903 @string{PSchaaf = "Schaaf, P."}
904 @string{RSchafer = "Schafer, Rolf"}
905 @string{TESchafer = "Sch{\"a}fer, Tilman E."}
906 @string{NScherer = "Scherer, Norbert F."}
907 @string{SScherer = "Scherer, S."}
908 @string{MSchilhabel = "Schilhabel, M."}
909 @string{HSchillers = "Schillers, Hermann"}
910 @string{BSchlegelberger = "Schlegelberger, B."}
911 @string{MSchleicher = "Schleicher, Michael"}
912 @string{MSchlierf = "Schlierf, Michael"}
913 @string{JSchmidt = "Schmidt, Jacob J."}
914 @string{LSchmitt = "Schmitt, Lutz"}
915 @string{JSchmutz = "Schmutz, J."}
916 @string{GSchuler = "Schuler, G."}
917 @string{GDSchuler = "Schuler, G. D."}
918 @string{KSchulten = "Schulten, Klaus"}
919 @string{ZSchulten = "Schulten, Zan"}
920 @string{MSchwab = "Schwab, M."}
921 @string{ISchwaiger = "Schwaiger, Ingo"}
922 @string{RSchwartz = "Schwartz, R."}
923 @string{RSchweitzerStenner = "Scheitzer-Stenner, Reinhard"}
924 @string{SCI = "Science"}
925 @string{CEScott = "Scott, C. E."}
926 @string{JScott = "Scott, J."}
927 @string{RScott = "Scott, R."}
928 @string{USeifert = "Seifert, Udo"}
929 @string{SKSekatskii = "Sekatskii, Sergey K."}
930 @string{MSekhon = "Sekhon, M."}
931 @string{TSekiguchi = "Sekiguchi, T."}
932 @string{BSenger = "Senger, B."}
933 @string{DBSenn = "Senn, David B."}
934 @string{PSeranski = "Seranski, P."}
935 @string{RSesboue = {Sesbo\"u\'e, R.}}
936 @string{EShakhnovich = "Shakhnovich, Eugene"}
937 @string{GShan = "Shan, Guiye"}
938 @string{JShang = "Shang, J."}
939 @string{WShao = "Shao, W."}
940 @string{DSharma = "Sharma, Deepak"}
941 @string{YJSheng = "Sheng, Yu-Jane"}
942 @string{KShibuya = "Shibuya, K."}
943 @string{JShillcock = "Shillcock, Julian"}
944 @string{AShimizu = "Shimizu, A."}
945 @string{NShimizu = "Shimizu, N."}
946 @string{RShimoKon = "Shimo-Kon, Rieko"}
947 @string{JPShine = "Shine, James P."}
948 @string{AShintani = "Shintani, A."}
949 @string{BShneiderman = "Shneiderman, Ben"}
950 @string{BShue = "Shue, B."}
951 @string{RSiebert = "Siebert, R."}
952 @string{EDSiggia = "Siggia, Eric D."}
953 @string{MSimon = "Simon, M."}
954 @string{MSimpson = "Simpson, M."}
955 @string{GESims = "Sims, Gregory E."}
956 @string{CSitter = "Sitter, C."}
957 @string{KVSjolander = "Sjolander, K. V."}
958 @string{MSkupski = "Skupski, M."}
959 @string{CSlayman = "Slayman, C."}
960 @string{MSmallwood = "Smallwood, M."}
961 @string{CSmith = "Smith, Corey L."}
962 @string{DASmith = "Smith, D. Alastair"}
963 @string{HOSmith = "Smith, H. O."}
964 @string{KBSmith = "Smith, Kathryn B."}
965 @string{SSmith = "Smith, S."}
966 @string{SBSmith = "Smith, S. B."}
967 @string{TSmith = "Smith, T."}
968 @string{JSoares = "Soares, J."}
969 @string{NDSocci = "Socci, N. D."}
970 @string{SEG = "Society of Exploration Geophysicists"}
971 @string{ESodergren = "Sodergren, E."}
972 @string{CSoderlund = "Soderlund, C."}
973 @string{JSong = "Song, Jianxing"}
974 @string{JSpanier = "Spanier, Jonathan E."}
975 @string{DSpeicher = "Speicher, David W."}
976 @string{GSpier = "Spier, G."}
977 @string{ASprague = "Sprague, A."}
978 @string{SPRINGER = "Springer Science + Business Media, LLC"}
979 @string{DBStaple = "Staple, Douglas B."}
980 @string{RStark = "Stark, R. W."}
981 @string{PSStayton = "Stayton, P. S."}
982 @string{REStenkamp = "Stenkamp, R. E."}
983 @string{SStepaniants = "Stepaniants, S."}
984 @string{EStewart = "Stewart, E."}
985 @string{MRStockmeier = "Stockmeier, M. R."}
986 @string{TStockwell = "Stockwell, T."}
987 @string{NEStone = "Stone, N. E."}
988 @string{AStout = "Stout, A."}
989 @string{TRStrick = "Strick, T. R."}
990 @string{CStroh = "Stroh, Cordula"}
991 @string{RStrong = "Strong, R."}
992 @string{JStruckmeier = "Struckmeier, Jens"}
993 @string{STR = "Structure"}
994 @string{TStrunz = "Strunz, Torsten"}
995 @string{MSu = "Su, Meihong"}
996 @string{GSubramanian = "Subramanian, G."}
997 @string{ESuh = "Suh, E."}
998 @string{JSun = "Sun, J."}
999 @string{YLSun = "Sun, Yu-Long"}
1000 @string{MSundberg = "Sundberg, Mark"}
1001 @string{WSundquist = "Sundquist, Wesley I."}
1002 @string{KSurewicz = "Surewicz, Krystyna"}
1003 @string{WKSurewicz = "Surewicz, Witold K."}
1004 @string{GGSutton = "Sutton, G. G."}
1005 @string{ASzabo = "Szabo, Attila"}
1006 @string{STagerud = "T{\aa}gerud, Sven"}
1007 @string{PTabor = "Tabor, P."}
1008 @string{ATakahashi = "Takahashi, Akiri"}
1009 @string{DTalaga = "Talaga, David S."}
1010 @string{PTalkner = "Talkner, Peter"}
1011 @string{RTampe = "Tamp{\'e}, Robert"}
1012 @string{JTang = "Tang, Jianyong"}
1013 @string{PTavan = "Tavan, P."}
1014 @string{BNTaylor = "Taylor, Barry N."}
1015 @string{THEMath = "Technische Hogeschool Eindhoven, Nederland,
1016 Onderafdeling der Wiskunde"}
1017 @string{SJBTendler = "Tendler, S.~J.~B."}
1018 @string{STeukolsky = "Teukolsky, S."}
1019 @string{CJ = "The Computer Journal"}
1020 @string{JBC = "The Journal of Biological Chemistry"}
1021 @string{JCP = "The Journal of Chemical Physics"}
1022 @string{JPC:B = "The Journal of Physical Chemistry B"}
1023 @string{JPC:C = "The Journal of Physical Chemistry C"}
1024 @string{RS = "The Royal Society"}
1025 @string{DThirumalai = "Thirumalai, Devarajan"}
1026 @string{PDThomas = "Thomas, P. D."}
1027 @string{RThomas = "Thomas, R."}
1028 @string{JThompson = "Thompson, J. B."}
1029 @string{EJThoreson = "Thoreson, E.~J."}
1030 @string{SThornton = "Thornton, S."}
1031 @string{RWTillmann = "Tillmann, R.~W."}
1032 @string{NNTint = "Tint, N. N."}
1033 @string{BTiribilli = "Tiribilli, Bruno"}
1034 @string{TTlusty = "Tlusty, Tsvi"}
1035 @string{PTobias = "Tobias, Paul"}
1036 @string{JTocaHerrera = "Toca-Herrera, Jose L."}
1037 @string{CATovey = "Tovey, Craig A."}
1038 @string{AToyoda = "Toyoda, A."}
1039 @string{TASME = "Transactions of the American Society of Mechanical Engineers"}
1040 @string{BTrask = "Trask, B."}
1041 @string{TBI = "Tribology International"}
1042 @string{JTrinick = "Trinick, John"}
1043 @string{KTrombitas = "Trombit\'as, K."}
1044 @string{ILTrong = "Trong, I. Le"}
1045 @string{CHTsai = "Tsai, Chih-Hui"}
1046 @string{HKTsao = "Tsao, Heng-Kwong"}
1047 @string{STse = "Tse, S."}
1048 @string{ZTshiprut = "Tshiprut, Z."}
1049 @string{JCMTsibris = "Tsibris, J.C.M."}
1050 @string{LTskhovrebova = "Tskhovrebova, Larissa"}
1051 @string{HWTurnbull = "Turnbull, Herbert Westren"}
1052 @string{RTurner = "Turner, R."}
1053 @string{AUlman = "Ulman, Abraham"}
1054 @string{UltraMic = "Ultramicroscopy"}
1055 @string{UIP:Urbana = "University of Illinois Press, Urbana"}
1056 @string{UTMB = "University of Texas Medical Branch"}
1057 @string{MUrbakh = "Urbakh, M."}
1058 @string{KJVanVliet = "Van Vliet, Krystyn J."}
1059 @string{PVandewalle = "Vandewalle, Patrick"}
1060 @string{CVech = "Vech, C."}
1061 @string{OVelasquez = "Velasquez, O."}
1062 @string{EVenter = "Venter, E."}
1063 @string{JCVenter = "Venter, J. C."}
1064 @string{PHVerdier = "Verdier, Peter H."}
1065 @string{IVetter = "Vetter, Ingrid R."}
1066 @string{MVetterli = "Vetterli, Martin"}
1067 @string{WVetterling = "Vetterling, W."}
1068 @string{MViani = "Viani, Mario B."}
1069 @string{JCVoegel = "Voegel, J.-C."}
1070 @string{VVogel = "Vogel, Viola"}
1071 @string{CWagner-McPherson = "Wagner-McPherson, C."}
1072 @string{RWahl = "Wahl, Reiner"}
1073 @string{TAWaigh = "Waigh, Thomas A."}
1074 @string{BWalenz = "Walenz, B."}
1075 @string{JWallis = "Wallis, J."}
1076 @string{KWalther = "Walther, Kirstin A."}
1077 @string{AJWalton = "Walton, Alan J"}
1078 @string{EBWalton = "Walton, Emily B."}
1079 @string{AWang = "Wang, A."}
1080 @string{FSWang = "Wang, F.~S."}
1081 @string{GWang = "Wang, G."}
1082 @string{JWang = "Wang, J."}
1083 @string{MWang = "Wang, M."}
1084 @string{MDWang = "Wang, Michelle D."}
1085 @string{SWang = "Wang, Shuang"}
1086 @string{XWang = "Wang, X."}
1087 @string{ZWang = "Wang, Z."}
1088 @string{HWatanabe = "Watanabe, Hiroshi"}
1089 @string{KWatanabe = "Watanabe, Kaori"}
1090 @string{RHWaterston = "Waterston, R. H."}
1091 @string{BWaugh = "Waugh, Ben"}
1092 @string{JWegiel = "Wegiel, J."}
1093 @string{MWei = "Wei, M."}
1094 @string{YWei = "Wei, Yen"}
1095 @string{ALWeisenhorn = "Weisenhorn, A.~L."}
1096 @string{JWeissenbach = "Weissenbach, J."}
1097 @string{BLWelch = "Welch, Bernard Lewis"}
1098 @string{GWen = "Wen, G."}
1099 @string{MWen = "Wen, M."}
1100 @string{JWetter = "Wetter, J."}
1101 @string{EPWhite = "White, Ethan P."}
1102 @string{ANWhitehead = "Whitehead, Alfred North"}
1103 @string{AWhittaker = "Whittaker, A."}
1104 @string{HKWickramasinghe = "Wickramasinghe, H. K."}
1105 @string{RWides = "Wides, R."}
1106 @string{AWiita = "Wiita, Arun P."}
1107 @string{MWilchek = "Wilchek, Meir"}
1108 @string{AWilcox = "Wilcox, Alexander J."}
1109 @string{Williams = "Williams"}
1110 @string{CCWilliams = "Williams, C. C."}
1111 @string{MWilliams = "Williams, M."}
1112 @string{SWilliams = "Williams, S."}
1113 @string{WN = "Williams \& Norgate"}
1114 @string{MWilmanns = "Wilmanns, Matthias"}
1115 @string{GWilson = "Wilson, Greg"}
1116 @string{PWilson = "Wilson, Paul"}
1117 @string{RKWilson = "Wilson, R. K."}
1118 @string{SWilson = "Wilson, Scott"}
1119 @string{SWindsor = "Windsor, S."}
1120 @string{EWinn-Deen = "Winn-Deen, E."}
1121 @string{NWirth = "Wirth, Niklaus"}
1122 @string{HMWisniewski = "Wisniewski, H.~M."}
1123 @string{CWitt = "Witt, Christian"}
1124 @string{KWolfe = "Wolfe, K."}
1125 @string{TGWolfsberg = "Wolfsberg, T. G."}
1126 @string{PGWolynes = "Wolynes, P. G."}
1127 @string{WPWong = "Wong, Wesley P."}
1128 @string{TWoodage = "Woodage, T."}
1129 @string{GRWoodcock = "Woodcock, Glenna R."}
1130 @string{JRWortman = "Wortman, J. R."}
1131 @string{PEWright = "Wright, Peter E."}
1132 @string{DWu = "Wu, D."}
1133 @string{GAWu = "Wu, Guohong A."}
1134 @string{JWWu = "Wu, Jong-Wuu"}
1135 @string{MWu = "Wu, M."}
1136 @string{YWu = "Wu, Yiming"}
1137 @string{GJLWuite = "Wuite, Gijs J. L."}
1138 @string{KWylie = "Wylie, K."}
1139 @string{JXi = "Xi, Jun"}
1140 @string{AXia = "Xia, A."}
1141 @string{CXiao = "Xiao, C."}
1142 @string{SXiao = "Xiao, Senbo"}
1143 @string{TYada = "Yada, T."}
1144 @string{CYan = "Yan, C."}
1145 @string{MYandell = "Yandell, M."}
1146 @string{GYang = "Yang, Guoliang"}
1147 @string{YYang = "Yang, Yao"}
1148 @string{BAYankner = "Yankner, Bruce A."}
1149 @string{AYao = "Yao, A."}
1150 @string{RYasuda = "Yaduso, Ryohei"}
1151 @string{JYe = "Ye, J."}
1152 @string{RYeh = "Yeh, Richard C."}
1153 @string{RYonescu = "Yonescu, R."}
1154 @string{SYooseph = "Yooseph, S."}
1155 @string{MYoshida = "Yoshida, Masasuke"}
1156 @string{WYu = "Yu, Weichang"}
1157 @string{JMYuan = "Yuan, Jian-Min"}
1158 @string{MYuan = "Yuan, Menglan"}
1159 @string{AZandieh = "Zandieh, A."}
1160 @string{JZaveri = "Zaveri, J."}
1161 @string{KZaveri = "Zaveri, K."}
1162 @string{MZhan = "Zhan, M."}
1163 @string{HZhang = "Zhang, H."}
1164 @string{JZhang = "Zhang, J."}
1165 @string{QZhang = "Zhang, Q."}
1166 @string{WZhang = "Zhang, W."}
1167 @string{YZhang = "Zhang, Yanjie"}
1168 @string{ZZhang = "Zhang, Zongtao"}
1169 @string{JZhao = "Zhao, Jason Ming"}
1170 @string{LZhao = "Zhao, Liming"}
1171 @string{QZhao = "Zhao, Q."}
1172 @string{SZhao = "Zhao, S."}
1173 @string{LZheng = "Zheng, L."}
1174 @string{XHZheng = "Zheng, X. H."}
1175 @string{FZhong = "Zhong, F."}
1176 @string{MZhong = "Zhong, Mingya"}
1177 @string{WZhong = "Zhong, W."}
1178 @string{HXZhou = "Zhou, Huan-Xiang"}
1179 @string{SZhu = "Zhu, S."}
1180 @string{XZhu = "Zhu, X."}
1181 @string{YJZhu = "Zhu, Ying-Jie"}
1182 @string{WZhuang = "Zhuang, Wei"}
1183 @string{JZidar = "Zidar, Jernej"}
1184 @string{JZiegler = "Ziegler, J.G."}
1185 @string{NZinder = "Zinder, N."}
1186 @string{RCZinober = "Zinober, Rebecca C."}
1187 @string{JZlatanova = "Zlatanova, Jordanka"}
1188 @string{PZou = "Zou, Peng"}
1189 @string{GZuccheri = "Zuccheri, Giampaolo"}
1190 @string{RZwanzig = "Zwanzig, R."}
1191 @string{arXiv = "arXiv"}
1192 @string{PGdeGennes = "de Gennes, P. G."}
1193 @string{PJdeJong = "de Jong, P. J."}
1194 @string{NGvanKampen = "van Kampen, N.G."}
1195 @string{NIST:SEMATECH = "{NIST/SEMATECH}"}
1196 @string{EDCola = "{\uppercase{d}}i Cola, Emanuela"}
1198 @inbook{ NIST:chi-square,
1199 crossref = {NIST:ESH},
1200 chapter = {1.3.5.15: Chi-Square Goodness-of-Fit Test},
1204 url = {http://www.itl.nist.gov/div898/handbook/eda/section3/eda35f.htm},
1207 @inbook{ NIST:gumbel,
1208 crossref = {NIST:ESH},
1209 chapter = {1.3.6.6.16: Extreme Value Type {I} Distribution},
1213 url = {http://www.itl.nist.gov/div898/handbook/eda/section3/eda366g.htm},
1217 editor = CCroarkin #" and "# PTobias,
1218 author = NIST:SEMATECH,
1219 title = {e-{H}andbook of Statistical Methods},
1222 publisher = NIST:SEMATECH,
1223 address = {Boulder, Colorado},
1224 url = {http://www.itl.nist.gov/div898/handbook/},
1225 note = {This manual was developed from seed material produced by
1229 @misc{ wikipedia:gumbel,
1230 author = "Wikipedia",
1231 title = "Gumbel distribution --- {W}ikipedia{,} The Free Encyclopedia",
1233 url = "http://en.wikipedia.org/wiki/Gumbel_distribution",
1238 title = "Statistics of Extremes",
1241 address = "New York",
1242 note = "TODO: read",
1245 @misc{ wikipedia:GEV,
1246 author = "Wikipedia",
1247 title = "Generalized extreme value distribution --- {W}ikipedia{,}
1248 The Free Encyclopedia",
1250 url = "http://en.wikipedia.org/wiki/Generalized_extreme_value_distribution",
1253 @misc{ wikipedia:gompertz,
1254 author = "Wikipedia",
1255 title = "Gompertz distribution --- {W}ikipedia{,} The Free Encyclopedia",
1257 url = "http://en.wikipedia.org/wiki/Gompertz_distribution",
1260 @misc{ wikipedia:gumbel-t1,
1261 author = "Wikipedia",
1262 title = "Type-1 Gumbel distribution --- {W}ikipedia{,} The Free
1265 url = "http://en.wikipedia.org/wiki/Type-1_Gumbel_distribution",
1268 @misc{ wikipedia:gumbel-t2,
1269 author = "Wikipedia",
1270 title = "Type-2 Gumbel distribution --- {W}ikipedia{,} The Free
1273 url = "http://en.wikipedia.org/wiki/Type-2_Gumbel_distribution",
1276 @article { allemand03,
1277 author = JFAllemand #" and "# DBensimon #" and "# VCroquette,
1278 title = "Stretching {DNA} and {RNA} to probe their interactions with
1287 keywords = "DNA;DNA-Binding
1288 Proteins;Isomerases;Micromanipulation;Microscopy, Atomic Force;Nucleic
1289 Acid Conformation;Nucleotidyltransferases",
1290 abstract = "When interacting with a single stretched DNA, many proteins
1291 modify its end-to-end distance. This distance can be monitored in real
1292 time using various micromanipulation techniques that were initially
1293 used to determine the elastic properties of bare nucleic acids and
1294 their mechanically induced structural transitions. These methods are
1295 currently being applied to the study of DNA enzymes such as DNA and RNA
1296 polymerases, topoisomerases and structural proteins such as RecA. They
1297 permit the measurement of the probability distributions of the rate,
1298 processivity, on-time, affinity and efficiency for a large variety of
1299 DNA-based molecular motors."
1303 author = RAlon #" and "# EABayer #" and "# MWilchek,
1304 title = "Streptavidin contains an {RYD} sequence which mimics the {RGD}
1305 receptor domain of fibronectin",
1312 pages = "1236--1241",
1314 doi = "DOI: 10.1016/0006-291X(90)90526-S",
1315 url = "http://www.sciencedirect.com/science/article/B6WBK-
1316 4F5M7K3-3C/2/c94b612e06efc8534ee24bb1da889811",
1317 keywords = "Amino Acid Sequence;Animals;Bacterial Proteins;Binding
1318 Sites;Cell Line;Cell Membrane;Cricetinae;Fibronectins;Molecular
1319 Sequence Data;Streptavidin",
1320 abstract = "Streptavidin binds at low levels and high affinity to cell
1321 surfaces, the cause of which can be traced to the occurrence of a
1322 sequence containing RYD (Arg-Tyr-Asp) in the protein molecule. This
1323 binding is enhanced in the presence of biotin. Cell-bound streptavidin
1324 can be displaced by fibronectin, as well as by RGD- and RYD-containing
1325 peptides. In addition, streptavidin can displace fibronectin from cell
1326 surfaces. The RYD sequence of streptavidin thus mimics RGD (Arg-Gly-
1327 Asp), the universal recognition domain present in fibronectin and other
1328 adhesion-related molecules. The observed adhesion to cells has no
1329 relevance to biotin-binding since the RYD sequence is not part of the
1330 biotin-binding site of streptavidin. Since the use of streptavidin in
1331 avidin-biotin technology is based on its biotin-binding properties,
1332 researchers are hereby warned against its indiscriminate use in
1333 histochemical and cytochemical studies.",
1334 note = "Biological role of streptavidin."
1337 @article { balsera97,
1338 author = MBalsera #" and "# SStepaniants #" and "# SIzrailev #" and "#
1339 YOono #" and "# KSchulten,
1340 title = "Reconstructing potential energy functions from simulated force-
1341 induced unbinding processes",
1347 pages = "1281--1287",
1349 eprint = "http://www.biophysj.org/cgi/reprint/73/3/1281.pdf",
1350 url = "http://www.biophysj.org/cgi/content/abstract/73/3/1281",
1351 keywords = "Binding Sites;Biopolymers;Kinetics;Ligands;Microscopy, Atomic
1352 Force;Models, Chemical;Molecular Conformation;Protein
1353 Conformation;Proteins;Reproducibility of Results;Stochastic
1354 Processes;Thermodynamics",
1355 abstract = "One-dimensional stochastic models demonstrate that molecular
1356 dynamics simulations of a few nanoseconds can be used to reconstruct
1357 the essential features of the binding potential of macromolecules. This
1358 can be accomplished by inducing the unbinding with the help of external
1359 forces applied to the molecules, and discounting the irreversible work
1360 performed on the system by these forces. The fluctuation-dissipation
1361 theorem sets a fundamental limit on the precision with which the
1362 binding potential can be reconstructed by this method. The uncertainty
1363 in the resulting potential is linearly proportional to the irreversible
1364 component of work performed on the system during the simulation. These
1365 results provide an a priori estimate of the energy barriers observable
1366 in molecular dynamics simulations."
1369 @article { baneyx02,
1370 author = GBaneyx #" and "# LBaugh #" and "# VVogel,
1371 title = "Supramolecular Chemistry And Self-assembly Special Feature:
1372 Fibronectin extension and unfolding within cell matrix fibrils
1373 controlled by cytoskeletal tension",
1378 pages = "5139--5143",
1379 doi = "10.1073/pnas.072650799",
1380 eprint = "http://www.pnas.org/cgi/reprint/99/8/5139.pdf",
1381 url = "http://www.pnas.org/cgi/content/abstract/99/8/5139",
1382 abstract = "Evidence is emerging that mechanical stretching can alter the
1383 functional states of proteins. Fibronectin (Fn) is a large,
1384 extracellular matrix protein that is assembled by cells into elastic
1385 fibrils and subjected to contractile forces. Assembly into fibrils
1386 coincides with expression of biological recognition sites that are
1387 buried in Fn's soluble state. To investigate how supramolecular
1388 assembly of Fn into fibrillar matrix enables cells to mechanically
1389 regulate its structure, we used fluorescence resonance energy transfer
1390 (FRET) as an indicator of Fn conformation in the fibrillar matrix of
1391 NIH 3T3 fibroblasts. Fn was randomly labeled on amine residues with
1392 donor fluorophores and site-specifically labeled on cysteine residues
1393 in modules FnIII7 and FnIII15 with acceptor fluorophores.
1394 Intramolecular FRET was correlated with known structural changes of Fn
1395 in denaturing solution, then applied in cell culture as an indicator of
1396 Fn conformation within the matrix fibrils of NIH 3T3 fibroblasts. Based
1397 on the level of FRET, Fn in many fibrils was stretched by cells so that
1398 its dimer arms were extended and at least one FnIII module unfolded.
1399 When cytoskeletal tension was disrupted using cytochalasin D, FRET
1400 increased, indicating refolding of Fn within fibrils. These results
1401 suggest that cell-generated force is required to maintain Fn in
1402 partially unfolded conformations. The results support a model of Fn
1403 fibril elasticity based on unraveling and refolding of FnIII modules.
1404 We also observed variation of FRET between and along single fibrils,
1405 indicating variation in the degree of unfolding of Fn in fibrils.
1406 Molecular mechanisms by which mechanical force can alter the structure
1407 of Fn, converting tensile forces into biochemical cues, are discussed."
1410 @article { basche01,
1411 author = TBasche #" and "# SNie #" and "# JFernandez,
1412 title = "Single molecules",
1417 pages = "10527--10528",
1418 doi = "10.1073/pnas.191365898",
1419 eprint = "http://www.pnas.org/cgi/reprint/98/19/10527.pdf",
1420 url = "http://www.pnas.org/cgi/content/abstract/98/19/10527",
1421 note = "Mini summary of single-molecule techniques and look to future.
1422 Focuses on AFM, but mentions others."
1425 @article { bechhoefer02,
1426 author = JBechhoefer #" and "# SWilson,
1427 title = "Faster, cheaper, safer optical tweezers for the undergraduate
1436 doi = "10.1119/1.1445403",
1437 url = "http://link.aip.org/link/?AJP/70/393/1",
1438 keywords = "student experiments; safety; radiation pressure; laser beam
1440 note = {Good discussion of the effect of correlation time on
1441 calibration. References work on deconvolving thermal noise from
1442 other noise\citep{cowan98}. Excellent detail on power spectrum
1443 derivation and thermal noise for extremely overdamped
1444 oscillators in Appendix A (references \citet{rief65}), except
1445 that their equation A12 is missing a factor of $1/\pi$. I
1446 pointed this out to John Bechhoefer and he confirmed the
1448 project = "Cantilever Calibration"
1451 @article{ berg-sorensen05,
1452 author = KBergSorensen #" and "# HFlyvbjerg,
1453 title = {The colour of thermal noise in classical Brownian motion: a
1454 feasibility study of direct experimental observation},
1462 doi = {10.1088/1367-2630/7/1/038},
1463 url = {http://stacks.iop.org/1367-2630/7/i=1/a=038},
1464 eprint = {http://iopscience.iop.org/1367-2630/7/1/038/pdf/1367-2630_7_1_038.pdf},
1465 abstract = {One hundred years after Einstein modelled Brownian
1466 motion, a central aspect of this motion in incompressible fluids
1467 has not been verified experimentally: the thermal noise that
1468 drives the Brownian particle, is not white, as in Einstein's
1469 simple theory. It is slightly coloured, due to hydrodynamics and
1470 the fluctuation--dissipation theorem. This theoretical result from
1471 the 1970s was prompted by computer simulation results in apparent
1472 violation of Einstein's theory. We discuss how a direct
1473 experimental observation of this colour might be carried out by
1474 using optical tweezers to separate the thermal noise from the
1475 particle's dynamic response to it. Since the thermal noise is
1476 almost white, very good statistics is necessary to resolve its
1477 colour. That requires stable equipment and long recording times,
1478 possibly making this experiment one for the future only. We give
1479 results for experimental requirements and for stochastic errors as
1480 functions of experimental window and measurement time, and discuss
1481 some potential sources of systematic errors.},
1484 @article { bedard08,
1485 author = SBedard #" and "# MMGKrishna #" and "# LMayne #" and "#
1487 title = "Protein folding: Independent unrelated pathways or predetermined
1488 pathway with optional errors.",
1495 pages = "7182--7187",
1497 doi = "10.1073/pnas.0801864105",
1498 eprint = "http://www.pnas.org/content/105/20/7182.full.pdf",
1499 url = "http://www.pnas.org/content/105/20/7182.full",
1500 keywords = "Biochemistry;Guanidine;Kinetics;Micrococcal Nuclease;Models,
1501 Biological;Models, Chemical;Models, Theoretical;Protein
1502 Conformation;Protein Denaturation;Protein Folding;Protein Structure,
1503 Secondary;Proteins;Proteomics;Reproducibility of
1504 Results;Thermodynamics",
1505 abstract = "The observation of heterogeneous protein folding kinetics has
1506 been widely interpreted in terms of multiple independent unrelated
1507 pathways (IUP model), both experimentally and in theoretical
1508 calculations. However, direct structural information on folding
1509 intermediates and their properties now indicates that all of a protein
1510 population folds through essentially the same stepwise pathway,
1511 determined by cooperative native-like foldon units and the way that the
1512 foldons fit together in the native protein. It is essential to decide
1513 between these fundamentally different folding mechanisms. This article
1514 shows, contrary to previous supposition, that the heterogeneous folding
1515 kinetics observed for the staphylococcal nuclease protein (SNase) does
1516 not require alternative parallel pathways. SNase folding kinetics can
1517 be fit equally well by a single predetermined pathway that allows for
1518 optional misfolding errors, which are known to occur ubiquitously in
1519 protein folding. Structural, kinetic, and thermodynamic information for
1520 the folding intermediates and pathways of many proteins is consistent
1521 with the predetermined pathway-optional error (PPOE) model but contrary
1522 to the properties implied in IUP models."
1527 title = "Models for the specific adhesion of cells to cells",
1536 url = "http://www.jstor.org/stable/1746930",
1537 keywords = "Antigen-Antibody Reactions; Cell Adhesion; Cell Membrane;
1538 Chemistry, Physical; Electrophysiology; Enzymes; Glycoproteins;
1539 Kinetics; Ligands; Membrane Proteins; Models, Biological; Receptors,
1541 abstract = "A theoretical framework is proposed for the analysis of
1542 adhesion between cells or of cells to surfaces when the adhesion is
1543 mediated by reversible bonds between specific molecules such as antigen
1544 and antibody, lectin and carbohydrate, or enzyme and substrate. From a
1545 knowledge of the reaction rates for reactants in solution and of their
1546 diffusion constants both in solution and on membranes, it is possible
1547 to estimate reaction rates for membrane-bound reactants. Two models are
1548 developed for predicting the rate of bond formation between cells and
1549 are compared with experiments. The force required to separate two cells
1550 is shown to be greater than the expected electrical forces between
1551 cells, and of the same order of magnitude as the forces required to
1552 pull gangliosides and perhaps some integral membrane proteins out of
1553 the cell membrane.",
1554 note = "The Bell model and a fair bit of cell bonding background.",
1555 project = "sawtooth simulation"
1559 author = DBerk #" and "# EEvans,
1560 title = "Detachment of agglutinin-bonded red blood cells. {III}. Mechanical
1561 analysis for large contact areas",
1569 keywords = "Cell Adhesion;Erythrocyte Membrane;Erythrocytes;Hemagglutinatio
1570 n;Hemagglutinins;Humans;Kinetics;Mathematics;Models,
1571 Biological;Pressure",
1572 abstract = "An experimental method and analysis are introduced which
1573 provide direct quantitation of the strength of adhesive contact for
1574 large agglutinin-bonded regions between macroscopically smooth membrane
1575 capsules (e.g., red blood cells). The approach yields intrinsic
1576 properties for separation of adherent regions independent of mechanical
1577 deformation of the membrane capsules during detachment. Conceptually,
1578 the micromechanical method involves one rigid test-capsule surface (in
1579 the form of a perfect sphere) held fixed by a micropipette and a second
1580 deformable capsule maneuvered with another micropipette to force
1581 contact with the test capsule. Only the test capsule is bound with
1582 agglutinin so that the maximum number of cross-bridges can be formed
1583 without steric interference. Following formation of a large adhesion
1584 region by mechanical impingement, the deformable capsule is detached
1585 from the rigid capsule surface by progressive aspiration into the
1586 micropipette. For the particular case modeled here, the deformable
1587 capsule is assumed to be a red blood cell which is preswollen by slight
1588 osmotic hydration before the test. The caliber of the detachment
1589 pipette is chosen so that the capsule will form a smooth cylindrical
1590 ``piston'' inside the pipette as it is aspirated. Because of the high
1591 flexibility of the membrane, the capsule naturally seals against the
1592 tube wall by pressurization even though it does not adhere to the
1593 glass. This arrangement maintains perfect axial symmetry and prevents
1594 the membrane from folding or buckling. Hence, it is possible to
1595 rigorously analyze the mechanics of deformation of the cell body to
1596 obtain the crucial ``transducer'' relation between pipette suction
1597 force and the membrane tension applied directly at the perimeter of the
1598 adhesive contact. Further, the geometry of the cell throughout the
1599 detachment process is predicted which provides accurate specification
1600 of the contact angle theta c between surfaces at the perimeter of the
1601 contact. A full analysis of red cell capsules during detachment has
1602 been carried out; however, it is shown that the shear rigidity of the
1603 red cell membrane can often be neglected so that the red cell can be
1604 treated as if it were an underfilled lipid bilayer vesicle. From the
1605 analysis, the mechanical leverage factor (1-cos theta c) and the
1606 membrane tension at the contact perimeter are determined to provide a
1607 complete description of the local mechanics of membrane separation as
1608 functions of large-scale experimental variables (e.g., suction force,
1609 contact diameter, overall cell length).(ABSTRACT TRUNCATED AT 400
1614 author = RBest #" and "# SFowler #" and "# JTocaHerrera #" and "# JClarke,
1615 title = "A simple method for probing the mechanical unfolding pathway of
1616 proteins in detail",
1621 pages = "12143--12148",
1622 doi = "10.1073/pnas.192351899",
1623 eprint = "http://www.pnas.org/cgi/reprint/99/19/12143.pdf",
1624 url = "http://www.pnas.org/cgi/content/abstract/99/19/12143",
1625 abstract = "Atomic force microscopy is an exciting new single-molecule
1626 technique to add to the toolbox of protein (un)folding methods.
1627 However, detailed analysis of the unfolding of proteins on application
1628 of force has, to date, relied on protein molecular dynamics simulations
1629 or a qualitative interpretation of mutant data. Here we describe how
1630 protein engineering {Phi} value analysis can be adapted to characterize
1631 the transition states for mechanical unfolding of proteins. Single-
1632 molecule studies also have an advantage over bulk experiments, in that
1633 partial {Phi} values arising from partial structure in the transition
1634 state can be clearly distinguished from those averaged over alternate
1635 pathways. We show that unfolding rate constants derived in the standard
1636 way by using Monte Carlo simulations are not reliable because of the
1637 errors involved. However, it is possible to circumvent these problems,
1638 providing the unfolding mechanism is not changed by mutation, either by
1639 a modification of the Monte Carlo procedure or by comparing mutant and
1640 wild-type data directly. The applicability of the method is tested on
1641 simulated data sets and experimental data for mutants of titin I27.",
1642 note = "Points out order-of-magnitude errors in $k_{u0}$ estimation from
1643 fitting Monte Carlo simulations."
1647 author = RBest #" and "# GHummer,
1648 title = "Protein folding kinetics under force from molecular simulation.",
1655 pages = "3706--3707",
1657 doi = "10.1021/ja0762691",
1658 keywords = "Computer Simulation;Kinetics;Models, Chemical;Protein
1659 Folding;Stress, Mechanical;Ubiquitin",
1660 abstract = "Despite a large number of studies on the mechanical unfolding
1661 of proteins, there are still relatively few successful attempts to
1662 refold proteins in the presence of a stretching force. We explore
1663 refolding kinetics under force using simulations of a coarse-grained
1664 model of ubiquitin. The effects of force on the folding kinetics can be
1665 fitted by a one-dimensional Kramers theory of diffusive barrier
1666 crossing, resulting in physically meaningful parameters for the height
1667 and location of the folding activation barrier. By comparing parameters
1668 obtained from pulling in different directions, we find that the
1669 unfolded state plays a dominant role in the refolding kinetics. Our
1670 findings explain why refolding becomes very slow at even moderate
1671 pulling forces and suggest how it could be practically observed in
1672 experiments at higher forces."
1676 author = RBest #" and "# EPaci #" and "# GHummer #" and "# OKDudko,
1677 title = "Pulling direction as a reaction coordinate for the mechanical
1678 unfolding of single molecules.",
1685 pages = "5968--5976",
1687 doi = "10.1021/jp075955j",
1688 keywords = "Computer Simulation;Kinetics;Models, Molecular;Protein
1689 Folding;Protein Structure, Tertiary;Time Factors;Ubiquitin",
1690 abstract = "The folding and unfolding kinetics of single molecules, such as
1691 proteins or nucleic acids, can be explored by mechanical pulling
1692 experiments. Determining intrinsic kinetic information, at zero
1693 stretching force, usually requires an extrapolation by fitting a
1694 theoretical model. Here, we apply a recent theoretical approach
1695 describing molecular rupture in the presence of force to unfolding
1696 kinetic data obtained from coarse-grained simulations of ubiquitin.
1697 Unfolding rates calculated from simulations over a broad range of
1698 stretching forces, for different pulling directions, reveal a
1699 remarkable ``turnover'' from a force-independent process at low force
1700 to a force-dependent process at high force, akin to the ``roll-over''
1701 in unfolding rates sometimes seen in studies using chemical denaturant.
1702 While such a turnover in rates is unexpected in one dimension, we
1703 demonstrate that it can occur for dynamics in just two dimensions. We
1704 relate the turnover to the quality of the pulling direction as a
1705 reaction coordinate for the intrinsic folding mechanism. A novel
1706 pulling direction, designed to be the most relevant to the intrinsic
1707 folding pathway, results in the smallest turnover. Our results are in
1708 accord with protein engineering experiments and simulations which
1709 indicate that the unfolding mechanism at high force can differ from the
1710 intrinsic mechanism. The apparent similarity between extrapolated and
1711 intrinsic rates in experiments, unexpected for different unfolding
1712 barriers, can be explained if the turnover occurs at low forces."
1715 @article { borgia08,
1716 author = Borgia #" and "# Williams #" and "# Clarke,
1717 title = "Single-Molecule Studies of Protein Folding",
1725 doi = "10.1146/annurev.biochem.77.060706.093102",
1726 eprint = "http://arjournals.annualreviews.org/doi/pdf/10.1146/annurev.bioch
1727 em.77.060706.093102",
1728 url = "http://arjournals.annualreviews.org/doi/abs/10.1146/annurev.biochem.
1730 abstract = "Although protein-folding studies began several decades ago, it
1731 is only recently that the tools to analyze protein folding at the
1732 single-molecule level have been developed. Advances in single-molecule
1733 fluorescence and force spectroscopy techniques allow investigation of
1734 the folding and dynamics of single protein molecules, both at
1735 equilibrium and as they fold and unfold. The experiments are far from
1736 simple, however, both in execution and in interpretation of the
1737 results. In this review, we discuss some of the highlights of the work
1738 so far and concentrate on cases where comparisons with the classical
1739 experiments can be made. We conclude that, although there have been
1740 relatively few startling insights from single-molecule studies, the
1741 rapid progress that has been made suggests that these experiments have
1742 significant potential to advance our understanding of protein folding.
1743 In particular, new techniques offer the possibility to explore regions
1744 of the energy landscape that are inaccessible to classical ensemble
1745 measurements and, perhaps, to observe rare events undetectable by other
1749 @article { braverman08,
1750 author = EBraverman #" and "# RMamdani,
1751 title = "Continuous versus pulse harvesting for population models in
1752 constant and variable environment",
1756 journal = JMathBiol,
1761 doi = "10.1007/s00285-008-0169-z",
1763 "http://www.springerlink.com/content/a1m23v50201m2401/fulltext.pdf",
1764 url = "http://www.springerlink.com/content/a1m23v50201m2401/",
1765 abstract = "We consider both autonomous and nonautonomous population models
1766 subject to either impulsive or continuous harvesting. It is
1767 demonstrated in the paper that the impulsive strategy can be as good as
1768 the continuous one, but cannot outperform it. We introduce a model,
1769 where certain harm to the population is incorporated in each harvesting
1770 event, and study it for the logistic and the Gompertz laws of growth.
1771 In this case, impulsive harvesting is not only the optimal strategy but
1772 is the only possible one.",
1773 note = "An example of non-exponential Gomperz law."
1776 @article { brochard-wyart99,
1777 author = FBrochard-Wyart #" and "# ABuguin #" and "# PGdeGennes,
1778 title = "Dynamics of taut {DNA} chains",
1785 "http://www.iop.org/EJ/article/0295-5075/47/2/171/epl_47_2_171.pdf",
1786 url = "http://stacks.iop.org/0295-5075/47/171",
1787 abstract = {We discuss the dynamics of stretched DNA chains, subjected to a
1788 tension force f, in a "taut" regime where ph = flp0/kBT $>$ 1 (lp0
1789 being the unperturbed persistence length). We deal with two variables:
1790 the local transverse displacements u, and the longitudinal position of
1791 a monomer u[?]. The variables u and u[?] follow two distinct Rouse
1792 equations, with diffusion coefficients D[?] = f/e (where e is the
1793 solvent viscosity) and D[?] = 4ph1/2D[?]. We apply these ideas to a
1794 discussion of various transient regimes.},
1795 note = "Theory for weakly bending relaxation modes in WLCs and FJCs."
1798 @article { brockwell02,
1799 author = DJBrockwell #" and "# GSBeddard #" and "# JClarkson #" and "#
1800 RCZinober #" and "# AWBlake #" and "# JTrinick #" and "# PDOlmsted #"
1801 and "# DASmith #" and "# SERadford,
1802 title = "The effect of core destabilization on the mechanical resistance of
1811 doi = "10.1016/S0006-3495(02)75182-5",
1812 eprint = "http://www.biophysj.org/cgi/reprint/83/1/458.pdf",
1813 url = "http://www.biophysj.org/cgi/content/abstract/83/1/458",
1814 keywords = "Amino Acid Sequence; Dose-Response Relationship, Drug;
1815 Kinetics; Magnetic Resonance Spectroscopy; Models, Molecular; Molecular
1816 Sequence Data; Monte Carlo Method; Muscle Proteins; Mutation; Peptide
1817 Fragments; Protein Denaturation; Protein Folding; Protein Kinases;
1818 Protein Structure, Secondary; Protein Structure, Tertiary; Proteins;
1820 abstract = "It is still unclear whether mechanical unfolding probes the
1821 same pathways as chemical denaturation. To address this point, we have
1822 constructed a concatamer of five mutant I27 domains (denoted (I27)(5)*)
1823 and used it for mechanical unfolding studies. This protein consists of
1824 four copies of the mutant C47S, C63S I27 and a single copy of C63S I27.
1825 These mutations severely destabilize I27 (DeltaDeltaG(UN) = 8.7 and
1826 17.9 kJ mol(-1) for C63S I27 and C47S, C63S I27, respectively). Both
1827 mutations maintain the hydrogen bond network between the A' and G
1828 strands postulated to be the major region of mechanical resistance for
1829 I27. Measuring the speed dependence of the force required to unfold
1830 (I27)(5)* in triplicate using the atomic force microscope allowed a
1831 reliable assessment of the intrinsic unfolding rate constant of the
1832 protein to be obtained (2.0 x 10(-3) s(-1)). The rate constant of
1833 unfolding measured by chemical denaturation is over fivefold faster
1834 (1.1 x 10(-2) s(-1)), suggesting that these techniques probe different
1835 unfolding pathways. Also, by comparing the parameters obtained from the
1836 mechanical unfolding of a wild-type I27 concatamer with that of
1837 (I27)(5)*, we show that although the observed forces are considerably
1838 lower, core destabilization has little effect on determining the
1839 mechanical sensitivity of this domain."
1842 @article { brockwell03,
1843 author = DJBrockwell #" and "# EPaci #" and "# RCZinober #" and "#
1844 GSBeddard #" and "# PDOlmsted #" and "# DASmith #" and "# RNPerham #"
1846 title = "Pulling geometry defines the mechanical resistance of a beta-sheet
1856 doi = "10.1038/nsb968",
1857 eprint = "http://www.nature.com/nsmb/journal/v10/n9/pdf/nsb968.pdf",
1858 url = "http://www.nature.com/nsmb/journal/v10/n9/abs/nsb968.html",
1859 keywords = "Anisotropy;Escherichia coli;Kinetics;Models, Molecular;Monte
1860 Carlo Method;Protein Folding;Protein Structure, Secondary;Protein
1861 Structure, Tertiary;Proteins;Software;Temperature;Thermodynamics",
1862 abstract = "Proteins show diverse responses when placed under mechanical
1863 stress. The molecular origins of their differing mechanical resistance
1864 are still unclear, although the orientation of secondary structural
1865 elements relative to the applied force vector is thought to have an
1866 important function. Here, by using a method of protein immobilization
1867 that allows force to be applied to the same all-beta protein, E2lip3,
1868 in two different directions, we show that the energy landscape for
1869 mechanical unfolding is markedly anisotropic. These results, in
1870 combination with molecular dynamics (MD) simulations, reveal that the
1871 unfolding pathway depends on the pulling geometry and is associated
1872 with unfolding forces that differ by an order of magnitude. Thus, the
1873 mechanical resistance of a protein is not dictated solely by amino acid
1874 sequence, topology or unfolding rate constant, but depends critically
1875 on the direction of the applied extension.",
1876 note = "Another scaffold effect paper. TODO: details"
1879 @article { brower-toland02,
1880 author = BDBrowerToland #" and "# CSmith #" and "# RYeh #" and "# JLis #"
1881 and "# CPeterson #" and "# MDWang,
1882 title = "From the Cover: Mechanical disruption of individual nucleosomes
1883 reveals a reversible multistage release of {DNA}",
1888 pages = "1960--1965",
1889 doi = "10.1073/pnas.022638399",
1890 eprint = "http://www.pnas.org/cgi/reprint/99/4/1960.pdf",
1891 url = "http://www.pnas.org/cgi/content/abstract/99/4/1960",
1892 abstract = "The dynamic structure of individual nucleosomes was examined by
1893 stretching nucleosomal arrays with a feedback-enhanced optical trap.
1894 Forced disassembly of each nucleosome occurred in three stages.
1895 Analysis of the data using a simple worm-like chain model yields 76 bp
1896 of DNA released from the histone core at low stretching force.
1897 Subsequently, 80 bp are released at higher forces in two stages: full
1898 extension of DNA with histones bound, followed by detachment of
1899 histones. When arrays were relaxed before the dissociated state was
1900 reached, nucleosomes were able to reassemble and to repeat the
1901 disassembly process. The kinetic parameters for nucleosome disassembly
1902 also have been determined."
1905 @article { bryngelson87,
1906 author = JDBryngelson #" and "# PGWolynes,
1907 title = "Spin glasses and the statistical mechanics of protein folding",
1913 pages = "7524--7528",
1915 keywords = "Kinetics; Mathematics; Models, Theoretical; Protein
1916 Conformation; Proteins; Stochastic Processes",
1917 abstract = "The theory of spin glasses was used to study a simple model of
1918 protein folding. The phase diagram of the model was calculated, and the
1919 results of dynamics calculations are briefly reported. The relation of
1920 these results to folding experiments, the relation of these hypotheses
1921 to previous protein folding theories, and the implication of these
1922 hypotheses for protein folding prediction schemes are discussed.",
1923 note = "Seminal protein folding via energy landscape paper."
1926 @article { bryngelson95,
1927 author = JDBryngelson #" and "# JNOnuchic #" and "# NDSocci #" and "#
1929 title = "Funnels, pathways, and the energy landscape of protein folding: a
1938 doi = "10.1002/prot.340210302",
1939 keywords = "Amino Acid Sequence; Chemistry, Physical; Computer Simulation;
1940 Data Interpretation, Statistical; Kinetics; Models, Chemical; Molecular
1941 Sequence Data; Protein Biosynthesis; Protein Conformation; Protein
1942 Folding; Proteins; Thermodynamics",
1943 abstract = "The understanding, and even the description of protein folding
1944 is impeded by the complexity of the process. Much of this complexity
1945 can be described and understood by taking a statistical approach to the
1946 energetics of protein conformation, that is, to the energy landscape.
1947 The statistical energy landscape approach explains when and why unique
1948 behaviors, such as specific folding pathways, occur in some proteins
1949 and more generally explains the distinction between folding processes
1950 common to all sequences and those peculiar to individual sequences.
1951 This approach also gives new, quantitative insights into the
1952 interpretation of experiments and simulations of protein folding
1953 thermodynamics and kinetics. Specifically, the picture provides simple
1954 explanations for folding as a two-state first-order phase transition,
1955 for the origin of metastable collapsed unfolded states and for the
1956 curved Arrhenius plots observed in both laboratory experiments and
1957 discrete lattice simulations. The relation of these quantitative ideas
1958 to folding pathways, to uniexponential vs. multiexponential behavior in
1959 protein folding experiments and to the effect of mutations on folding
1960 is also discussed. The success of energy landscape ideas in protein
1961 structure prediction is also described. The use of the energy landscape
1962 approach for analyzing data is illustrated with a quantitative analysis
1963 of some recent simulations, and a qualitative analysis of experiments
1964 on the folding of three proteins. The work unifies several previously
1965 proposed ideas concerning the mechanism protein folding and delimits
1966 the regions of validity of these ideas under different thermodynamic
1970 @article { bullard06,
1971 author = BBullard #" and "# TGarcia #" and "# VBenes #" and "# MLeake #"
1972 and "# WALinke #" and "# AOberhauser,
1973 title = "The molecular elasticity of the insect flight muscle proteins
1974 projectin and kettin",
1979 pages = "4451--4456",
1980 doi = "10.1073/pnas.0509016103",
1981 eprint = "http://www.pnas.org/cgi/reprint/103/12/4451.pdf",
1982 url = "http://www.pnas.org/cgi/content/abstract/103/12/4451",
1983 abstract = "Projectin and kettin are titin-like proteins mainly responsible
1984 for the high passive stiffness of insect indirect flight muscles, which
1985 is needed to generate oscillatory work during flight. Here we report
1986 the mechanical properties of kettin and projectin by single-molecule
1987 force spectroscopy. Force-extension and force-clamp curves obtained
1988 from Lethocerus projectin and Drosophila recombinant projectin or
1989 kettin fragments revealed that fibronectin type III domains in
1990 projectin are mechanically weaker (unfolding force, Fu {approx} 50-150
1991 pN) than Ig-domains (Fu {approx} 150-250 pN). Among Ig domains in
1992 Sls/kettin, the domains near the N terminus are less stable than those
1993 near the C terminus. Projectin domains refolded very fast [85% at 15
1994 s-1 (25{degrees}C)] and even under high forces (15-30 pN). Temperature
1995 affected the unfolding forces with a Q10 of 1.3, whereas the refolding
1996 speed had a Q10 of 2-3, probably reflecting the cooperative nature of
1997 the folding mechanism. High bending rigidities of projectin and kettin
1998 indicated that straightening the proteins requires low forces. Our
1999 results suggest that titin-like proteins in indirect flight muscles
2000 could function according to a folding-based-spring mechanism."
2003 @article { bustamante08,
2004 author = CBustamante,
2005 title = "In singulo Biochemistry: When Less Is More",
2011 doi = "10.1146/annurev.biochem.012108.120952",
2012 eprint = "http://arjournals.annualreviews.org/doi/pdf/10.1146/annurev.bioch
2014 url = "http://arjournals.annualreviews.org/doi/abs/10.1146/annurev.biochem.
2016 abstract = "It has been over one-and-a-half decades since methods of
2017 single-molecule detection and manipulation were first introduced in
2018 biochemical research. Since then, the application of these methods to
2019 an expanding variety of problems has grown at a vertiginous pace. While
2020 initially many of these experiments led more to confirmatory results
2021 than to new discoveries, today single-molecule methods are often the
2022 methods of choice to establish new mechanism-based results in
2023 biochemical research. Throughout this process, improvements in the
2024 sensitivity, versatility, and both spatial and temporal resolution of
2025 these techniques has occurred hand in hand with their applications. We
2026 discuss here some of the advantages of single-molecule methods over
2027 their bulk counterparts and argue that these advantages should help
2028 establish them as essential tools in the technical arsenal of the
2032 @article { bustamante94,
2033 author = CBustamante #" and "# JFMarko #" and "# EDSiggia #" and "# SSmith,
2034 title = "Entropic elasticity of lambda-phage {DNA}",
2041 pages = "1599--1600",
2043 doi = "10.1126/science.8079175",
2044 eprint = "http://www.sciencemag.org/cgi/reprint/265/5178/1599.pdf",
2045 url = "http://www.sciencemag.org/cgi/content/abstract/265/5178/1599",
2046 keywords = "Bacteriophage lambda; DNA, Viral; Least-Squares Analysis;
2048 note = "WLC interpolation formula."
2051 @article { bustanji03,
2052 author = YBustanji #" and "# CArciola #" and "# MConti #" and "# EMandello
2053 #" and "# LMontanaro #" and "# BSamori,
2054 title = "Dynamics of the interaction between a fibronectin molecule and a
2055 living bacterium under mechanical force",
2060 pages = "13292--13297",
2061 doi = "10.1073/pnas.1735343100",
2062 eprint = "http://www.pnas.org/cgi/reprint/100/23/13292.pdf",
2063 url = "http://www.pnas.org/cgi/content/abstract/100/23/13292",
2064 abstract = "Fibronectin (Fn) is an important mediator of bacterial
2065 invasions and of persistent infections like that of Staphylococcus
2066 epidermis. Similar to many other types of cell-protein adhesion, the
2067 binding between Fn and S. epidermidis takes place under physiological
2068 shear rates. We investigated the dynamics of the interaction between
2069 individual living S. epidermidis cells and single Fn molecules under
2070 mechanical force by using the scanning force microscope. The mechanical
2071 strength of this interaction and the binding site in the Fn molecule
2072 were determined. The energy landscape of the binding/unbinding process
2073 was mapped, and the force spectrum and the association and dissociation
2074 rate constants of the binding pair were measured. The interaction
2075 between S. epidermidis cells and Fn molecules is compared with those of
2076 two other protein/ligand pairs known to mediate different dynamic
2077 states of adhesion of cells under a hydrodynamic flow: the firm
2078 adhesion mediated by biotin/avidin interactions, and the rolling
2079 adhesion, mediated by L-selectin/P-selectin glycoprotein ligand-1
2080 interactions. The inner barrier in the energy landscape of the Fn case
2081 characterizes a high-energy binding mode that can sustain larger
2082 deformations and for significantly longer times than the correspondent
2083 high-strength L-selectin/P-selectin glycoprotein ligand-1 binding mode.
2084 The association kinetics of the former interaction is much slower to
2085 settle than the latter. On this basis, the observations made at the
2086 macroscopic scale by other authors of a strong lability of the
2087 bacterial adhesions mediated by Fn under high turbulent flow are
2088 rationalized at the molecular level."
2092 author = YMartin #" and "# CCWilliams #" and "# HKWickramasinghe,
2093 title = {Atomic force microscope---force mapping and profiling on a
2101 pages = {4723--4729},
2103 issn_online = "1089-7550",
2104 doi = {10.1063/1.338807},
2105 url = {http://jap.aip.org/resource/1/japiau/v61/i10/p4723_s1},
2107 abstract = {A modified version of the atomic force microscope is
2108 introduced that enables a precise measurement of the force between
2109 a tip and a sample over a tip-sample distance range of 30--150
2110 \AA. As an application, the force signal is used to maintain the
2111 tip-sample spacing constant, so that profiling can be achieved
2112 with a spatial resolution of 50 \AA. A second scheme allows the
2113 simultaneous measurement of force and surface profile; this scheme
2114 has been used to obtain material-dependent information from
2115 surfaces of electronic materials.},
2119 author = HJButt #" and "# MJaschke,
2120 title = "Calculation of thermal noise in atomic force microscopy",
2126 doi = "10.1088/0957-4484/6/1/001",
2127 url = "http://stacks.iop.org/0957-4484/6/1",
2128 abstract = "Thermal fluctuations of the cantilever are a fundamental source
2129 of noise in atomic force microscopy. We calculated thermal noise using
2130 the equipartition theorem and considering all possible vibration modes
2131 of the cantilever. The measurable amplitude of thermal noise depends on
2132 the temperature, the spring constant K of the cantilever and on the
2133 method by which the cantilever defletion is detected. If the deflection
2134 is measured directly, e.g. with an interferometer or a scanning
2135 tunneling microscope, the thermal noise of a cantilever with a free end
2136 can be calculated from square root kT/K. If the end of the cantilever
2137 is supported by a hard surface no thermal fluctuations of the
2138 deflection are possible. If the optical lever technique is applied to
2139 measure the deflection, the thermal noise of a cantilever with a free
2140 end is square root 4kT/3K. When the cantilever is supported thermal
2141 noise decreases to square root kT/3K, but it does not vanish.",
2142 note = "Corrections to basic $kx^2 = kB T$ due to higher order modes in
2143 rectangular cantilevers.",
2144 project = "Cantilever Calibration"
2147 @article{ jaschke95,
2148 author = MJaschke #" and "# HJButt,
2149 title = {Height calibration of optical lever atomic force
2150 microscopes by simple laser interferometry},
2155 pages = {1258--1259},
2157 url = {http://rsi.aip.org/resource/1/rsinak/v66/i2/p1258_s1},
2158 doi = {10.1063/1.1146018},
2160 keywords = {atomic force microscopy;calibration;interferometry;laser
2161 beam applications;mirrors;spatial resolution},
2162 abstract = {A new and simple interferometric method for height
2163 calibration of AFM piezo scanners is presented. Except for a small
2164 mirror no additional equipment is required since the fixed
2165 wavelength of the laser diode is used as a calibration
2166 standard. The calibration is appliable in the range between
2167 several ten nm and several μm. Besides vertical calibration many
2168 problems of piezo elements like hysteresis, nonlinearity, creep,
2169 derating, etc. and their dependence on scan parameters or
2170 temperature can be investigated.},
2174 author = YCao #" and "# MBalamurali #" and "# DSharma #" and "# HLi,
2175 title = "A functional single-molecule binding assay via force spectroscopy",
2180 pages = "15677--15681",
2181 doi = "10.1073/pnas.0705367104",
2182 eprint = "http://www.pnas.org/cgi/reprint/104/40/15677.pdf",
2183 url = "http://www.pnas.org/cgi/content/abstract/104/40/15677",
2184 abstract = "Protein-ligand interactions, including protein-protein
2185 interactions, are ubiquitously essential in biological processes and
2186 also have important applications in biotechnology. A wide range of
2187 methodologies have been developed for quantitative analysis of protein-
2188 ligand interactions. However, most of them do not report direct
2189 functional/structural consequence of ligand binding. Instead they only
2190 detect the change of physical properties, such as fluorescence and
2191 refractive index, because of the colocalization of protein and ligand,
2192 and are susceptible to false positives. Thus, important information
2193 about the functional state of proteinligand complexes cannot be
2194 obtained directly. Here we report a functional single-molecule binding
2195 assay that uses force spectroscopy to directly probe the functional
2196 consequence of ligand binding and report the functional state of
2197 protein-ligand complexes. As a proof of principle, we used protein G
2198 and the Fc fragment of IgG as a model system in this study. Binding of
2199 Fc to protein G does not induce major structural changes in protein G
2200 but results in significant enhancement of its mechanical stability.
2201 Using mechanical stability of protein G as an intrinsic functional
2202 reporter, we directly distinguished and quantified Fc-bound and Fc-free
2203 forms of protein G on a single-molecule basis and accurately determined
2204 their dissociation constant. This single-molecule functional binding
2205 assay is label-free, nearly background-free, and can detect functional
2206 heterogeneity, if any, among proteinligand interactions. This
2207 methodology opens up avenues for studying protein-ligand interactions
2208 in a functional context, and we anticipate that it will find broad
2209 application in diverse protein-ligand systems."
2213 author = PCarl #" and "# CKwok #" and "# GManderson #" and "# DSpeicher #"
2215 title = "Forced unfolding modulated by disulfide bonds in the Ig domains of
2216 a cell adhesion molecule",
2221 pages = "1565--1570",
2222 doi = "10.1073/pnas.031409698",
2223 eprint = "http://www.pnas.org/cgi/reprint/98/4/1565.pdf",
2224 url = "http://www.pnas.org/cgi/content/abstract/98/4/1565",
2228 @article { carrion-vazquez00,
2229 author = MCarrionVazquez #" and "# AOberhauser #" and "# TEFisher #" and "#
2230 PMarszalek #" and "# HLi #" and "# JFernandez,
2231 title = "Mechanical design of proteins studied by single-molecule force
2232 spectroscopy and protein engineering",
2238 doi = "10.1016/S0079-6107(00)00017-1",
2240 eprint = "http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1302160&blo
2242 url = "http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1302160",
2243 keywords = "Elasticity;Hydrogen Bonding;Microscopy, Atomic Force;Protein
2244 Denaturation;Protein Engineering;Protein Folding;Recombinant
2245 Proteins;Signal Processing, Computer-Assisted",
2246 abstract = "Mechanical unfolding and refolding may regulate the molecular
2247 elasticity of modular proteins with mechanical functions. The
2248 development of the atomic force microscopy (AFM) has recently enabled
2249 the dynamic measurement of these processes at the single-molecule
2250 level. Protein engineering techniques allow the construction of
2251 homomeric polyproteins for the precise analysis of the mechanical
2252 unfolding of single domains. alpha-Helical domains are mechanically
2253 compliant, whereas beta-sandwich domains, particularly those that
2254 resist unfolding with backbone hydrogen bonds between strands
2255 perpendicular to the applied force, are more stable and appear
2256 frequently in proteins subject to mechanical forces. The mechanical
2257 stability of a domain seems to be determined by its hydrogen bonding
2258 pattern and is correlated with its kinetic stability rather than its
2259 thermodynamic stability. Force spectroscopy using AFM promises to
2260 elucidate the dynamic mechanical properties of a wide variety of
2261 proteins at the single molecule level and provide an important
2262 complement to other structural and dynamic techniques (e.g., X-ray
2263 crystallography, NMR spectroscopy, patch-clamp).",
2264 note = {Surface contact \fref{figure}{2} is a modified version of
2265 \xref{baljon96}{figure}{1}. They are both good pictures for
2266 explaining that the tip's radius of curvature ($\sim 20\U{nm}$) is
2267 larger than the I27 domains\citet{improta96} ($\sim 2\U{nm}$).},
2270 @article { carrion-vazquez03,
2271 author = MCarrionVazquez #" and "# HLi #" and "# HLu #" and "# PMarszalek
2272 #" and "# AOberhauser #" and "# JFernandez,
2273 title = "The mechanical stability of ubiquitin is linkage dependent",
2282 doi = "10.1038/nsb965",
2283 eprint = "http://www.nature.com/nsmb/journal/v10/n9/pdf/nsb965.pdf",
2284 url = "http://www.nature.com/nsmb/journal/v10/n9/abs/nsb965.html",
2285 keywords = "Humans;Hydrogen Bonding;Kinetics;Lysine;Microscopy, Atomic
2286 Force;Models, Molecular;Polyubiquitin;Protein Binding;Protein
2287 Folding;Protein Structure, Tertiary;Ubiquitin",
2288 abstract = "Ubiquitin chains are formed through the action of a set of
2289 enzymes that covalently link ubiquitin either through peptide bonds or
2290 through isopeptide bonds between their C terminus and any of four
2291 lysine residues. These naturally occurring polyproteins allow one to
2292 study the mechanical stability of a protein, when force is applied
2293 through different linkages. Here we used single-molecule force
2294 spectroscopy techniques to examine the mechanical stability of
2295 N-C-linked and Lys48-C-linked ubiquitin chains. We combined these
2296 experiments with steered molecular dynamics (SMD) simulations and found
2297 that the mechanical stability and unfolding pathway of ubiquitin
2298 strongly depend on the linkage through which the mechanical force is
2299 applied to the protein. Hence, a protein that is otherwise very stable
2300 may be easily unfolded by a relatively weak mechanical force applied
2301 through the right linkage. This may be a widespread mechanism in
2302 biological systems."
2305 @article { carrion-vazquez99a,
2306 author = MCarrionVazquez #" and "# PMarszalek #" and "# AOberhauser #" and
2308 title = "Atomic force microscopy captures length phenotypes in single
2314 pages = "11288--11292",
2315 doi = "10.1073/pnas.96.20.11288",
2316 eprint = "http://www.pnas.org/cgi/reprint/96/20/11288.pdf",
2317 url = "http://www.pnas.org/cgi/content/abstract/96/20/11288",
2321 @article { carrion-vazquez99b,
2322 author = MCarrionVazquez #" and "# AOberhauser #" and "# SFowler #" and "#
2323 PMarszalek #" and "# SBroedel #" and "# JClarke #" and "# JFernandez,
2324 title = "Mechanical and chemical unfolding of a single protein: A
2330 pages = "3694--3699",
2331 doi = "10.1073/pnas.96.7.3694",
2332 eprint = "http://www.pnas.org/cgi/reprint/96/7/3694.pdf",
2333 url = "http://www.pnas.org/cgi/content/abstract/96/7/3694"
2337 author = CLChyan #" and "# FCLin #" and "# HPeng #" and "# JMYuan #" and "#
2338 CHChang #" and "# SHLin #" and "# GYang,
2339 title = "Reversible mechanical unfolding of single ubiquitin molecules",
2343 address = "Department of Chemistry, National Dong Hwa University,
2348 pages = "3995--4006",
2350 doi = "10.1529/biophysj.104.042754",
2351 eprint = "http://download.cell.com/biophysj/pdf/PIIS0006349504738643.pdf",
2352 url = "http://www.cell.com/biophysj/abstract/S0006-3495(04)73864-3",
2354 keywords = "Computer
2355 Simulation;Elasticity;Mechanics;Micromanipulation;Microscopy, Atomic
2356 Force;Models, Chemical;Models, Molecular;Protein Conformation;Protein
2357 Denaturation;Protein Folding;Stress, Mechanical;Structure-Activity
2358 Relationship;Ubiquitin",
2359 abstract = "Single-molecule manipulation techniques have enabled the
2360 characterization of the unfolding and refolding process of individual
2361 protein molecules, using mechanical forces to initiate the unfolding
2362 transition. Experimental and computational results following this
2363 approach have shed new light on the mechanisms of the mechanical
2364 functions of proteins involved in several cellular processes, as well
2365 as revealed new information on the protein folding/unfolding free-
2366 energy landscapes. To investigate how protein molecules of different
2367 folds respond to a stretching force, and to elucidate the effects of
2368 solution conditions on the mechanical stability of a protein, we
2369 synthesized polymers of the protein ubiquitin and characterized the
2370 force-induced unfolding and refolding of individual ubiquitin molecules
2371 using an atomic-force-microscope-based single-molecule manipulation
2372 technique. The ubiquitin molecule was highly resistant to a stretching
2373 force, and the mechanical unfolding process was reversible. A model
2374 calculation based on the hydrogen-bonding pattern in the native
2375 structure was performed to explain the origin of this high mechanical
2376 stability. Furthermore, pH effects were studied and it was found that
2377 the forces required to unfold the protein remained constant within a pH
2378 range around the neutral value, and forces decreased as the solution pH
2379 was lowered to more acidic values.",
2380 note = "includes pH effects",
2383 @article { ciccotti86,
2384 author = GCiccotti #" and "# JPRyckaert,
2385 title = "Molecular dynamics simulation of rigid molecules",
2392 doi = "10.1016/0167-7977(86)90022-5",
2393 url = "http://dx.doi.org/10.1016/0167-7977(86)90022-5",
2394 note = "I haven't read this, but it looks like a nice review of MD with
2398 @article { claverie01,
2399 author = JMClaverie,
2400 title = "Gene number. What if there are only 30,000 human genes?",
2407 pages = "1255--1257",
2409 url = "http://www.sciencemag.org/cgi/content/full/291/5507/1255",
2410 keywords = "Animals;Computational Biology;Drug Industry;Expressed Sequence
2411 Tags;Gene Expression;Gene Expression Regulation;Genes;Genetic
2412 Techniques;Genome, Human;Genomics;Human Genome Project;Humans;Models,
2413 Genetic;Polymorphism, Single Nucleotide;Proteins;RNA, Messenger"
2416 @misc { codata-boltzmann,
2417 key = "codata-boltzmann",
2418 crossref = "codata06",
2419 url = "http://physics.nist.gov/cgi-bin/cuu/Value?k"
2422 @article { codata06,
2423 author = PJMohr #" and "# BNTaylor #" and "# DBNewell,
2425 title = "{CODATA} recommended values of the fundamental physical constants:
2435 doi = "10.1103/RevModPhys.80.633"
2438 @article { collins03,
2439 author = FSCollins #" and "# MMorgan #" and "# APatrinos,
2440 title = "The Human Genome Project: Lessons from large-scale biology.",
2449 doi = "10.1126/science.1084564",
2450 eprint = "http://www.sciencemag.org/cgi/reprint/300/5617/286.pdf",
2451 url = "http://www.sciencemag.org/cgi/content/summary/300/5617/277",
2452 keywords = "Access to Information;Computational Biology;Databases, Nucleic
2453 Acid;Genome, Human;Genomics;Government Agencies;History, 20th
2454 Century;Human Genome Project;Humans;International Cooperation;National
2455 Institutes of Health (U.S.);Private Sector;Public Policy;Public
2456 Sector;Publishing;Quality Control;Sequence Analysis, DNA;United States",
2457 note = "See also: \href{http://www.ornl.gov/sci/techresources/Human_Genome/
2458 project/journals/journals.shtml}{Landmark HPG Papers}"
2461 @article { cornish07,
2462 author = PVCornish #" and "# THa,
2463 title = "A survey of single-molecule techniques in chemical biology",
2467 journal = ACS:ChemBiol,
2472 doi = "10.1021/cb600342a",
2473 keywords = "Animals;Data Collection;Humans;Microscopy, Atomic
2474 Force;Microscopy, Fluorescence;Molecular Biology",
2475 abstract = "Single-molecule methods have revolutionized scientific research
2476 by rendering the investigation of once-inaccessible biological
2477 processes amenable to scientific inquiry. Several of the more
2478 established techniques will be emphasized in this Review, including
2479 single-molecule fluorescence microscopy, optical tweezers, and atomic
2480 force microscopy, which have been applied to many diverse biological
2481 processes. Serving as a taste of all the exciting research currently
2482 underway, recent examples will be discussed of translocation of RNA
2483 polymerase, myosin VI walking, protein folding, and enzyme activity. We
2484 will end by providing an assessment of what the future holds, including
2485 techniques that are currently in development."
2490 title = "Statistical Data Analysis",
2493 address = "New York",
2494 note = "Noise deconvolution in Chapter 11",
2495 project = "Cantilever Calibration"
2499 author = DCraig #" and "# AKrammer #" and "# KSchulten #" and "# VVogel,
2500 title = "Comparison of the early stages of forced unfolding for fibronectin
2501 type {III} modules",
2506 pages = "5590--5595",
2507 doi = "10.1073/pnas.101582198",
2508 eprint = "http://www.pnas.org/cgi/reprint/98/10/5590.pdf",
2509 url = "http://www.pnas.org/cgi/content/abstract/98/10/5590",
2513 @article { delpech01,
2514 author = BDelpech #" and "# MNCourel #" and "# CMaingonnat #" and "#
2515 CChauzy #" and "# RSesboue #" and "# GPratesi,
2516 title = "Hyaluronan digestion and synthesis in an experimental model of
2519 month = "September/October",
2520 journal = HistochemJ,
2525 keywords = "Animals;Culture Media;Humans;Hyaluronic
2526 Acid;Hyaluronoglucosaminidase;Mice;Mice, Nude;Neoplasm
2527 Metastasis;Neoplasm Transplantation;Neoplasms, Experimental;Tumor
2529 abstract = "To approach the question of hyaluronan catabolism in tumours,
2530 we have selected the cancer cell line H460M, a highly metastatic cell
2531 line in the nude mouse. H460M cells release hyaluronidase in culture
2532 media at a high rate of 57 pU/cell/h, without producing hyaluronan.
2533 Hyaluronidase was measured in the H460M cell culture medium at the
2534 optimum pH 3.8, and was not found above pH 4.5, with the enzyme-linked
2535 sorbent assay technique and zymography. Tritiated hyaluronan was
2536 digested at pH 3.8 by cells or cell membranes as shown by gel
2537 permeation chromatography, but no activity was recorded at pH 7 with
2538 this technique. Hyaluronan was digested in culture medium by tumour
2539 slices, prepared from tumours developed in nude mice grafted with H460M
2540 cells, showing that hyaluronan could be digested in complex tissue at
2541 physiological pH. Culture of tumour slices with tritiated acetate
2542 resulted in the accumulation within 2 days of radioactive
2543 macromolecules in the culture medium. The radioactive macromolecular
2544 material was mostly digested by Streptomyces hyaluronidase, showing
2545 that hyaluronan was its main component and that hyaluronan synthesis
2546 occurred together with its digestion. These results demonstrate that
2547 the membrane-associated hyaluronidase of H460M cells can act in vivo,
2548 and that hyaluronan, which is synthesised by the tumour stroma, can be
2549 made soluble and reduced to a smaller size by tumour cells before being
2550 internalised and further digested."
2553 @article { diCola05,
2554 author = EDCola #" and "# TAWaigh #" and "# JTrinick #" and "#
2555 LTskhovrebova #" and "# AHoumeida #" and "# WPyckhout-Hintzen #" and "#
2558 title = "Persistence length of titin from rabbit skeletal muscles measured
2559 with scattering and microrheology techniques",
2566 pages = "4095--4106",
2568 doi = "10.1529/biophysj.104.054908",
2569 eprint = "http://download.cell.com/biophysj/pdf/PIIS0006349505734603.pdf",
2570 url = "http://www.cell.com/biophysj/retrieve/pii/S0006349505734603",
2571 keywords = "Animals;Biophysics;Elasticity;Light;Muscle Proteins;Muscle,
2572 Skeletal;Neutrons;Protein Conformation;Protein
2573 Kinases;Rabbits;Rheology;Scattering, Radiation;Temperature",
2574 abstract = "The persistence length of titin from rabbit skeletal muscles
2575 was measured using a combination of static and dynamic light
2576 scattering, and neutron small angle scattering. Values of persistence
2577 length in the range 9-16 nm were found for titin-II, which corresponds
2578 to mainly physiologically inelastic A-band part of the protein, and for
2579 a proteolytic fragment with 100-nm contour length from the
2580 physiologically elastic I-band part. The ratio of the hydrodynamic
2581 radius to the static radius of gyration indicates that the proteins
2582 obey Gaussian statistics typical of a flexible polymer in a -solvent.
2583 Furthermore, measurements of the flexibility as a function of
2584 temperature demonstrate that titin-II and the I-band titin fragment
2585 experience a similar denaturation process; unfolding begins at 318 K
2586 and proceeds in two stages: an initial gradual 50\% change in
2587 persistence length is followed by a sharp unwinding transition at 338
2588 K. Complementary microrheology (video particle tracking) measurements
2589 indicate that the viscoelasticity in dilute solution behaves according
2590 to the Flory/Fox model, providing a value of the radius of gyration for
2591 titin-II (63 +/- 1 nm) in agreement with static light scattering and
2592 small angle neutron scattering results."
2596 author = HDietz #" and "# MRief,
2597 title = "Exploring the energy landscape of {GFP} by single-molecule
2598 mechanical experiments",
2603 pages = "16192--16197",
2604 doi = "10.1073/pnas.0404549101",
2605 eprint = "http://www.pnas.org/cgi/reprint/101/46/16192.pdf",
2606 url = "http://www.pnas.org/cgi/content/abstract/101/46/16192",
2607 abstract = "We use single-molecule force spectroscopy to drive
2608 single GFP molecules from the native state through their
2609 complex energy landscape into the completely unfolded
2610 state. Unlike many smaller proteins, mechanical GFP unfolding
2611 proceeds by means of two subsequent intermediate states. The
2612 transition from the native state to the first intermediate
2613 state occurs near thermal equilibrium at $\approx35\U{pN}$ and
2614 is characterized by detachment of a seven-residue N-terminal
2615 $\alpha$-helix from the beta barrel. We measure the
2616 equilibrium free energy cost associated with this transition
2617 as 22 kBT. Detachment of this small $\alpha$-helix completely
2618 destabilizes GFP thermodynamically even though the
2619 $\beta$-barrel is still intact and can bear load. Mechanical
2620 stability of the protein on the millisecond timescale,
2621 however, is determined by the activation barrier of unfolding
2622 the $\beta$-barrel out of this thermodynamically unstable
2623 intermediate state. High bandwidth, time-resolved measurements
2624 of the cantilever relaxation phase upon unfolding of the
2625 $\beta$-barrel revealed a second metastable mechanical
2626 intermediate with one complete $\beta$-strand detached from
2627 the barrel. Quantitative analysis of force distributions and
2628 lifetimes lead to a detailed picture of the complex mechanical
2629 unfolding pathway through a rough energy landscape.",
2630 note = "Towards use of Green Flourescent Protein (GFP) as an
2631 embedded force probe. Nice energy-landscape-to-one-dimension
2632 compression graphic.",
2633 project = "Energy landscape roughness"
2636 @article { dietz06a,
2637 author = HDietz #" and "# MRief,
2638 title = "Protein structure by mechanical triangulation",
2645 pages = "1244--1247",
2646 doi = "10.1073/pnas.0509217103",
2647 eprint = "http://www.pnas.org/cgi/reprint/103/5/1244.pdf",
2648 url = "http://www.pnas.org/cgi/content/abstract/103/5/1244",
2649 abstract = "Knowledge of protein structure is essential to understand
2650 protein function. High-resolution protein structure has so far been the
2651 domain of ensemble methods. Here, we develop a simple single-molecule
2652 technique to measure spatial position of selected residues within a
2653 folded and functional protein structure in solution. Construction and
2654 mechanical unfolding of cysteine-engineered polyproteins with
2655 controlled linkage topology allows measuring intramolecular distance
2656 with angstrom precision. We demonstrate the potential of this technique
2657 by determining the position of three residues in the structure of green
2658 fluorescent protein (GFP). Our results perfectly agree with the GFP
2659 crystal structure. Mechanical triangulation can find many applications
2660 where current bulk structural methods fail."
2663 @article { dietz06b,
2664 author = HDietz #" and "# FBerkemeier #" and "# MBertz #" and "# MRief,
2665 title = "Anisotropic deformation response of single protein molecules",
2672 pages = "12724--12728",
2673 doi = "10.1073/pnas.0602995103",
2674 eprint = "http://www.pnas.org/cgi/reprint/103/34/12724.pdf",
2675 url = "http://www.pnas.org/cgi/content/abstract/103/34/12724",
2676 abstract = "Single-molecule methods have given experimental access to the
2677 mechanical properties of single protein molecules. So far, access has
2678 been limited to mostly one spatial direction of force application.
2679 Here, we report single-molecule experiments that explore the mechanical
2680 properties of a folded protein structure in precisely controlled
2681 directions by applying force to selected amino acid pairs. We
2682 investigated the deformation response of GFP in five selected
2683 directions. We found fracture forces widely varying from 100 pN up to
2684 600 pN. We show that straining the GFP structure in one of the five
2685 directions induces partial fracture of the protein into a half-folded
2686 intermediate structure. From potential widths we estimated directional
2687 spring constants of the GFP structure and found values ranging from 1
2688 N/m up to 17 N/m. Our results show that classical continuum mechanics
2689 and simple mechanistic models fail to describe the complex mechanics of
2690 the GFP protein structure and offer insights into the mechanical design
2691 of protein materials."
2695 author = HDietz #" and "# MRief,
2696 title = "Detecting Molecular Fingerprints in Single Molecule Force
2697 Spectroscopy Using Pattern Recognition",
2702 pages = "5540--5542",
2704 doi = "10.1143/JJAP.46.5540",
2705 url = "http://jjap.ipap.jp/link?JJAP/46/5540/",
2706 keywords = "single molecule, protein mechanics, force spectroscopy, AFM,
2707 pattern recognition, GFP",
2708 abstract = "Single molecule force spectroscopy has given experimental
2709 access to the mechanical properties of protein molecules. Typically,
2710 less than 1% of the experimental recordings reflect true single
2711 molecule events due to abundant surface and multiple-molecule
2712 interactions. A key issue in single molecule force spectroscopy is thus
2713 to identify the characteristic mechanical `fingerprint' of a specific
2714 protein in noisy data sets. Here, we present an objective pattern
2715 recognition algorithm that is able to identify fingerprints in such
2717 note = "Automatic force curve selection. Seems a bit shoddy. Details
2721 @article{ berkemeier11,
2722 author = FBerkemeier #" and "# MBertz #" and "# SXiao #" and "#
2723 NPinotsis #" and "# MWilmanns #" and "# FGrater #" and "# MRief,
2724 title = "Fast-folding $\alpha$-helices as reversible strain absorbers
2725 in the muscle protein myomesin.",
2730 address = "Physik Department E22, Technische Universit{\"a}t
2731 M{\"u}nchen, James-Franck-Stra{\ss}e, 85748 Garching, Germany.",
2734 pages = "14139--14144",
2735 keywords = "Biomechanics",
2736 keywords = "Kinetics",
2737 keywords = "Microscopy, Atomic Force",
2738 keywords = "Molecular Dynamics Simulation",
2739 keywords = "Muscle Proteins",
2740 keywords = "Protein Folding",
2741 keywords = "Protein Multimerization",
2742 keywords = "Protein Stability",
2743 keywords = "Protein Structure, Secondary",
2744 keywords = "Protein Structure, Tertiary",
2745 keywords = "Protein Unfolding",
2746 abstract = "The highly oriented filamentous protein network of
2747 muscle constantly experiences significant mechanical load during
2748 muscle operation. The dimeric protein myomesin has been identified
2749 as an important M-band component supporting the mechanical
2750 integrity of the entire sarcomere. Recent structural studies have
2751 revealed a long $\alpha$-helical linker between the C-terminal
2752 immunoglobulin (Ig) domains My12 and My13 of myomesin. In this
2753 paper, we have used single-molecule force spectroscopy in
2754 combination with molecular dynamics simulations to characterize
2755 the mechanics of the myomesin dimer comprising immunoglobulin
2756 domains My12-My13. We find that at forces of approximately 30?pN
2757 the $\alpha$-helical linker reversibly elongates allowing the
2758 molecule to extend by more than the folded extension of a full
2759 domain. High-resolution measurements directly reveal the
2760 equilibrium folding/unfolding kinetics of the individual helix. We
2761 show that $\alpha$-helix unfolding mechanically protects the
2762 molecule homodimerization from dissociation at physiologically
2763 relevant forces. As fast and reversible molecular springs the
2764 myomesin $\alpha$-helical linkers are an essential component for
2765 the structural integrity of the M band.",
2767 doi = "10.1073/pnas.1105734108",
2768 URL = "http://www.ncbi.nlm.nih.gov/pubmed/21825161",
2773 author = KADill #" and "# HSChan,
2774 title = "From Levinthal to pathways to funnels.",
2782 doi = "10.1038/nsb0197-10",
2783 eprint = "http://www.nature.com/nsmb/journal/v4/n1/pdf/nsb0197-10.pdf",
2784 url = "http://www.nature.com/nsmb/journal/v4/n1/abs/nsb0197-10.html",
2785 keywords = "Kinetics;Models, Chemical;Protein Folding",
2786 abstract = "While the classical view of protein folding kinetics relies on
2787 phenomenological models, and regards folding intermediates in a
2788 structural way, the new view emphasizes the ensemble nature of protein
2789 conformations. Although folding has sometimes been regarded as a linear
2790 sequence of events, the new view sees folding as parallel microscopic
2791 multi-pathway diffusion-like processes. While the classical view
2792 invoked pathways to solve the problem of searching for the needle in
2793 the haystack, the pathway idea was then seen as conflicting with
2794 Anfinsen's experiments showing that folding is pathway-independent
2795 (Levinthal's paradox). In contrast, the new view sees no inherent
2796 paradox because it eliminates the pathway idea: folding can funnel to a
2797 single stable state by multiple routes in conformational space. The
2798 general energy landscape picture provides a conceptual framework for
2799 understanding both two-state and multi-state folding kinetics. Better
2800 tests of these ideas will come when new experiments become available
2801 for measuring not just averages of structural observables, but also
2802 correlations among their fluctuations. At that point we hope to learn
2803 much more about the real shapes of protein folding landscapes.",
2804 note = "Pretty folding funnel figures."
2807 @article { discher06,
2808 author = DDischer #" and "# NBhasin #" and "# CJohnson,
2809 title = "Covalent chemistry on distended proteins",
2814 pages = "7533--7534",
2815 doi = "10.1073/pnas.0602388103",
2816 eprint = "http://www.pnas.org/cgi/reprint/103/20/7533.pdf",
2817 url = "http://www.pnas.org/cgi/content/abstract/103/20/7533.pdf"
2821 author = OKDudko #" and "# AEFilippov #" and "# JKlafter #" and "# MUrbakh,
2822 title = "Beyond the conventional description of dynamic force spectroscopy
2830 pages = "11378--11381",
2832 doi = "10.1073/pnas.1534554100",
2833 eprint = "http://www.pnas.org/content/100/20/11378.full.pdf",
2834 url = "http://www.pnas.org/content/100/20/11378.abstract",
2835 keywords = "Spectrum Analysis;Temperature",
2836 abstract = "Dynamic force spectroscopy of single molecules is described by
2837 a model that predicts a distribution of rupture forces, the
2838 corresponding mean rupture force, and variance, which are all amenable
2839 to experimental tests. The distribution has a pronounced asymmetry,
2840 which has recently been observed experimentally. The mean rupture force
2841 follows a (lnV)2/3 dependence on the pulling velocity, V, and differs
2842 from earlier predictions. Interestingly, at low pulling velocities, a
2843 rebinding process is obtained whose signature is an intermittent
2844 behavior of the spring force, which delays the rupture. An extension to
2845 include conformational changes of the adhesion complex is proposed,
2846 which leads to the possibility of bimodal distributions of rupture
2851 author = OKDudko #" and "# GHummer #" and "# ASzabo,
2852 title = "Intrinsic rates and activation free energies from single-molecule
2853 pulling experiments",
2862 doi = "10.1103/PhysRevLett.96.108101",
2863 keywords = "Biophysics;Computer Simulation;Data Interpretation,
2864 Statistical;Kinetics;Micromanipulation;Models, Chemical;Models,
2865 Molecular;Molecular Conformation;Muscle Proteins;Nucleic Acid
2866 Conformation;Protein Binding;Protein Denaturation;Protein
2867 Folding;Protein Kinases;RNA;Stress, Mechanical;Thermodynamics;Time
2869 abstract = "We present a unified framework for extracting kinetic
2870 information from single-molecule pulling experiments at constant force
2871 or constant pulling speed. Our procedure provides estimates of not only
2872 (i) the intrinsic rate coefficient and (ii) the location of the
2873 transition state but also (iii) the free energy of activation. By
2874 analyzing simulated data, we show that the resulting rates of force-
2875 induced rupture are significantly more reliable than those obtained by
2876 the widely used approach based on Bell's formula. We consider the
2877 uniqueness of the extracted kinetic information and suggest guidelines
2878 to avoid over-interpretation of experiments."
2882 author = OKDudko #" and "# JMathe #" and "# ASzabo #" and "# AMeller #" and
2884 title = "Extracting kinetics from single-molecule force spectroscopy:
2885 Nanopore unzipping of {DNA} hairpins",
2892 pages = "4188--4195",
2894 doi = "10.1529/biophysj.106.102855",
2895 eprint = "http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1877759&blo
2897 keywords = "Computer
2898 Simulation;DNA;Elasticity;Mechanics;Micromanipulation;Microscopy,
2899 Atomic Force;Models, Chemical;Models, Molecular;Nanostructures;Nucleic
2900 Acid Conformation;Porosity;Stress, Mechanical",
2901 abstract = "Single-molecule force experiments provide powerful new tools to
2902 explore biomolecular interactions. Here, we describe a systematic
2903 procedure for extracting kinetic information from force-spectroscopy
2904 experiments, and apply it to nanopore unzipping of individual DNA
2905 hairpins. Two types of measurements are considered: unzipping at
2906 constant voltage, and unzipping at constant voltage-ramp speeds. We
2907 perform a global maximum-likelihood analysis of the experimental data
2908 at low-to-intermediate ramp speeds. To validate the theoretical models,
2909 we compare their predictions with two independent sets of data,
2910 collected at high ramp speeds and at constant voltage, by using a
2911 quantitative relation between the two types of measurements.
2912 Microscopic approaches based on Kramers theory of diffusive barrier
2913 crossing allow us to estimate not only intrinsic rates and transition
2914 state locations, as in the widely used phenomenological approach based
2915 on Bell's formula, but also free energies of activation. The problem of
2916 extracting unique and accurate kinetic parameters of a molecular
2917 transition is discussed in light of the apparent success of the
2918 microscopic theories in reproducing the experimental data."
2922 author = OKDudko #" and "# GHummer #" and "# ASzabo,
2923 title = "Theory, analysis, and interpretation of single-molecule
2924 force spectroscopy experiments.",
2929 address = "Department of Physics and Center for Theoretical
2930 Biological Physics, University of California at San Diego, La
2931 Jolla, CA 92093, USA.
2932 dudko@physics.ucsd.edu",
2935 pages = "15755--15760",
2937 keywords = "Half-Life",
2938 keywords = "Kinetics",
2939 keywords = "Microscopy, Atomic Force",
2940 keywords = "Motion",
2941 keywords = "Nucleic Acid Conformation",
2942 keywords = "Nucleic Acid Denaturation",
2943 keywords = "Protein Folding",
2944 keywords = "Thermodynamics",
2945 abstract = "Dynamic force spectroscopy probes the kinetic and
2946 thermodynamic properties of single molecules and molecular
2947 assemblies. Here, we propose a simple procedure to extract kinetic
2948 information from such experiments. The cornerstone of our method
2949 is a transformation of the rupture-force histograms obtained at
2950 different force-loading rates into the force-dependent lifetimes
2951 measurable in constant-force experiments. To interpret the
2952 force-dependent lifetimes, we derive a generalization of Bell's
2953 formula that is formally exact within the framework of Kramers
2954 theory. This result complements the analytical expression for the
2955 lifetime that we derived previously for a class of model
2956 potentials. We illustrate our procedure by analyzing the nanopore
2957 unzipping of DNA hairpins and the unfolding of a protein attached
2958 by flexible linkers to an atomic force microscope. Our procedure
2959 to transform rupture-force histograms into the force-dependent
2960 lifetimes remains valid even when the molecular extension is a
2961 poor reaction coordinate and higher-dimensional free-energy
2962 surfaces must be considered. In this case the microscopic
2963 interpretation of the lifetimes becomes more challenging because
2964 the lifetimes can reveal richer, and even nonmonotonic, dependence
2967 doi = "10.1073/pnas.0806085105",
2968 URL = "http://www.ncbi.nlm.nih.gov/pubmed/18852468",
2974 title = "Probing the relation between force--lifetime--and chemistry in
2975 single molecular bonds",
2981 doi = "10.1146/annurev.biophys.30.1.105",
2982 url = "http://arjournals.annualreviews.org/doi/abs/10.1146%2Fannurev.biophys.30.1.105",
2983 keywords = "Biophysics;Kinetics;Microscopy, Atomic Force;Models,
2984 Chemical;Protein Binding;Spectrum Analysis;Time Factors",
2985 abstract = "On laboratory time scales, the energy landscape of a weak bond
2986 along a dissociation pathway is fully explored through Brownian-thermal
2987 excitations, and energy barriers become encoded in a dissociation time
2988 that varies with applied force. Probed with ramps of force over an
2989 enormous range of rates (force/time), this kinetic profile is
2990 transformed into a dynamic spectrum of bond rupture force as a function
2991 of loading rate. On a logarithmic scale in loading rate, the force
2992 spectrum provides an easy-to-read map of the prominent energy barriers
2993 traversed along the force-driven pathway and exposes the differences in
2994 energy between barriers. In this way, the method of dynamic force
2995 spectroscopy (DFS) is being used to probe the complex relation between
2996 force-lifetime-and chemistry in single molecular bonds. Most important,
2997 DFS probes the inner world of molecular interactions to reveal barriers
2998 that are difficult or impossible to detect in assays of near
2999 equilibrium dissociation but that determine bond lifetime and strength
3000 under rapid detachment. To use an ultrasensitive force probe as a
3001 spectroscopic tool, we need to understand the physics of bond
3002 dissociation under force, the impact of experimental technique on the
3003 measurement of detachment force (bond strength), the consequences of
3004 complex interactions in macromolecular bonds, and effects of multiply-
3005 bonded attachments."
3008 @article { evans91a,
3009 author = EEvans #" and "# DBerk #" and "# ALeung,
3010 title = "Detachment of agglutinin-bonded red blood cells. {I}. Forces to
3011 rupture molecular-point attachments",
3019 keywords = "ABO Blood-Group System;Animals;Antibodies,
3020 Monoclonal;Erythrocyte Deformability;Erythrocyte
3021 Membrane;Erythrocytes;Glycophorin;Helix
3022 (Snails);Hemagglutinins;Humans;Immune Sera;Lectins;Mathematics;Models,
3024 abstract = "A simple micromechanical method has been developed to measure
3025 the rupture strength of a molecular-point attachment (focal bond)
3026 between two macroscopically smooth membrane capsules. In the procedure,
3027 one capsule is prepared with a low density coverage of adhesion
3028 molecules, formed as a stiff sphere, and held at fixed position by a
3029 micropipette. The second capsule without adhesion molecules is
3030 pressurized into a spherical shape with low suction by another pipette.
3031 This capsule is maneuvered to initiate point contact at the pole
3032 opposite the stiff capsule which leads to formation of a few (or even
3033 one) molecular attachments. Then, the deformable capsule is slowly
3034 withdrawn by displacement of the pipette. Analysis shows that the end-
3035 to-end extension of the capsule provides a direct measure of the force
3036 at the point contact and, therefore, the rupture strength when
3037 detachment occurs. The range for point forces accessible to this
3038 technique depends on the elastic moduli of the membrane, membrane
3039 tension, and the size of the capsule. For biological and synthetic
3040 vesicle membranes, the range of force lies between 10(-7)-10(-5) dyn
3041 (10(-12)-10(-10) N) which is 100-fold less than presently measurable by
3042 Atomic Force Microscopy! Here, the approach was used to study the
3043 forces required to rupture microscopic attachments between red blood
3044 cells formed by a monoclonal antibody to red cell membrane glycophorin,
3045 anti-A serum, and a lectin from the snail-helix pomatia. Failure of the
3046 attachments appeared to be a stochastic function of the magnitude and
3047 duration of the detachment force. We have correlated the statistical
3048 behavior observed for rupture with a random process model for failure
3049 of small numbers of molecular attachments. The surprising outcome of
3050 the measurements and analysis was that the forces deduced for short-
3051 time failure of 1-2 molecular attachments were nearly the same for all
3052 of the agglutinin, i.e., 1-2 x 10(-6) dyn. Hence, microfluorometric
3053 tests were carried out to determine if labeled agglutinins and/or
3054 labeled surface molecules were transferred between surfaces after
3055 separation of large areas of adhesive contact. The results showed that
3056 the attachments failed because receptors were extracted from the
3060 @article { evans91b,
3061 author = EEvans #" and "# DBerk #" and "# ALeung #" and "# NMohandas,
3062 title = "Detachment of agglutinin-bonded red blood cells. {II}. Mechanical
3063 energies to separate large contact areas",
3071 keywords = "Animals;Antibodies, Monoclonal;Cell Adhesion;Erythrocyte
3072 Membrane;Erythrocytes;Helix
3073 (Snails);Hemagglutination;Hemagglutinins;Humans;Immune
3074 Sera;Kinetics;Lectins;Mathematics",
3075 abstract = "As detailed in a companion paper (Berk, D., and E. Evans. 1991.
3076 Biophys. J. 59:861-872), a method was developed to quantitate the
3077 strength of adhesion between agglutinin-bonded membranes without
3078 ambiguity due to mechanical compliance of the cell body. The
3079 experimental method and analysis were formulated around controlled
3080 assembly and detachment of a pair of macroscopically smooth red blood
3081 cell surfaces. The approach provides precise measurement of the
3082 membrane tension applied at the perimeter of an adhesive contact and
3083 the contact angle theta c between membrane surfaces which defines the
3084 mechanical leverage factor (1-cos theta c) important in the definition
3085 of the work to separate a unit area of contact. Here, the method was
3086 applied to adhesion and detachment of red cells bound together by
3087 different monoclonal antibodies to red cell membrane glycophorin and
3088 the snail-helix pomatia-lectin. For these tests, one of the two red
3089 cells was chemically prefixed in the form of a smooth sphere then
3090 equilibrated with the agglutinin before the adhesion-detachment
3091 procedure. The other cell was not exposed to the agglutinin until it
3092 was forced into contact with the rigid cell surface by mechanical
3093 impingement. Large regions of agglutinin bonding were produced by
3094 impingement but no spontaneous spreading was observed beyond the forced
3095 contact. Measurements of suction force to detach the deformable cell
3096 yielded consistent behavior for all of the agglutinins: i.e., the
3097 strength of adhesion increased progressively with reduction in contact
3098 diameter throughout detachment. This tension-contact diameter behavior
3099 was not altered over a ten-fold range of separation rates. In special
3100 cases, contacts separated smoothly after critical tensions were
3101 reached; these were the highest values attained for tension. Based on
3102 measurements reported in another paper (Evans et al. 1991. Biophys. J.
3103 59:838-848) of the forces required to rupture molecular-point
3104 attachments, the density of cross-bridges was estimated with the
3105 assumption that the tension was proportional to the discrete rupture
3106 force x the number of attachments per unit length. These estimates
3107 showed that only a small fraction of agglutinin formed cross-bridges at
3108 initial assembly and increased progressively with separation. When
3109 critical tension levels were reached, it appeared that nearly all local
3110 agglutinin was involved as cross-bridges. Because one cell surface was
3111 chemically fixed, receptor accumulation was unlikely; thus, microscopic
3112 ``roughness'' and steric repulsion probably modulated formation of
3113 cross-bridges on initial contact.(ABSTRACT TRUNCATED AT 400 WORDS)"
3117 author = EEvans #" and "# KRitchie,
3118 title = "Dynamic strength of molecular adhesion bonds",
3124 pages = "1541--1555",
3126 eprint = "http://www.biophysj.org/cgi/reprint/72/4/1541.pdf",
3127 url = "http://www.biophysj.org/cgi/content/abstract/72/4/1541",
3128 keywords = "Avidin; Biotin; Chemistry, Physical; Computer Simulation;
3129 Mathematics; Monte Carlo Method; Protein Binding",
3130 abstract = "In biology, molecular linkages at, within, and beneath cell
3131 interfaces arise mainly from weak noncovalent interactions. These bonds
3132 will fail under any level of pulling force if held for sufficient time.
3133 Thus, when tested with ultrasensitive force probes, we expect cohesive
3134 material strength and strength of adhesion at interfaces to be time-
3135 and loading rate-dependent properties. To examine what can be learned
3136 from measurements of bond strength, we have extended Kramers' theory
3137 for reaction kinetics in liquids to bond dissociation under force and
3138 tested the predictions by smart Monte Carlo (Brownian dynamics)
3139 simulations of bond rupture. By definition, bond strength is the force
3140 that produces the most frequent failure in repeated tests of breakage,
3141 i.e., the peak in the distribution of rupture forces. As verified by
3142 the simulations, theory shows that bond strength progresses through
3143 three dynamic regimes of loading rate. First, bond strength emerges at
3144 a critical rate of loading (> or = 0) at which spontaneous dissociation
3145 is just frequent enough to keep the distribution peak at zero force. In
3146 the slow-loading regime immediately above the critical rate, strength
3147 grows as a weak power of loading rate and reflects initial coupling of
3148 force to the bonding potential. At higher rates, there is crossover to
3149 a fast regime in which strength continues to increase as the logarithm
3150 of the loading rate over many decades independent of the type of
3151 attraction. Finally, at ultrafast loading rates approaching the domain
3152 of molecular dynamics simulations, the bonding potential is quickly
3153 overwhelmed by the rapidly increasing force, so that only naked
3154 frictional drag on the structure remains to retard separation. Hence,
3155 to expose the energy landscape that governs bond strength, molecular
3156 adhesion forces must be examined over an enormous span of time scales.
3157 However, a significant gap exists between the time domain of force
3158 measurements in the laboratory and the extremely fast scale of
3159 molecular motions. Using results from a simulation of biotin-avidin
3160 bonds (Izrailev, S., S. Stepaniants, M. Balsera, Y. Oono, and K.
3161 Schulten. 1997. Molecular dynamics study of unbinding of the avidin-
3162 biotin complex. Biophys. J., this issue), we describe how Brownian
3163 dynamics can help bridge the gap between molecular dynamics and probe
3165 project = "sawtooth simulation"
3169 author = EEvans #" and "# KRitchie,
3170 title = "Strength of a weak bond connecting flexible polymer chains",
3176 pages = "2439--2447",
3178 eprint = "http://www.biophysj.org/cgi/reprint/76/5/2439.pdf",
3179 url = "http://www.biophysj.org/cgi/content/abstract/76/5/2439",
3180 keywords = "Animals; Biophysics; Biopolymers; Microscopy, Atomic Force;
3181 Models, Chemical; Muscle Proteins; Protein Folding; Protein Kinases;
3182 Stochastic Processes; Stress, Mechanical; Thermodynamics",
3183 abstract = "Bond dissociation under steadily rising force occurs most
3184 frequently at a time governed by the rate of loading (Evans and
3185 Ritchie, 1997 Biophys. J. 72:1541-1555). Multiplied by the loading
3186 rate, the breakage time specifies the force for most frequent failure
3187 (called bond strength) that obeys the same dependence on loading rate.
3188 The spectrum of bond strength versus log(loading rate) provides an
3189 image of the energy landscape traversed in the course of unbonding.
3190 However, when a weak bond is connected to very compliant elements like
3191 long polymers, the load applied to the bond does not rise steadily
3192 under constant pulling speed. Because of nonsteady loading, the most
3193 frequent breakage force can differ significantly from that of a bond
3194 loaded at constant rate through stiff linkages. Using generic models
3195 for wormlike and freely jointed chains, we have analyzed the kinetic
3196 process of failure for a bond loaded by pulling the polymer linkages at
3197 constant speed. We find that when linked by either type of polymer
3198 chain, a bond is likely to fail at lower force under steady separation
3199 than through stiff linkages. Quite unexpectedly, a discontinuous jump
3200 can occur in bond strength at slow separation speed in the case of long
3201 polymer linkages. We demonstrate that the predictions of strength
3202 versus log(loading rate) can rationalize conflicting results obtained
3203 recently for unfolding Ig domains along muscle titin with different
3205 note = "Develops Kramers improvement on Bell model for domain unfolding.
3206 Presents unfolding under variable loading rates. Often cited as the
3207 ``Bell--Evans'' model. They derive a unitless treatment, scaling force
3208 by $f_\beta$, TODO; time by $\tau_f$, TODO; elasiticity by compliance
3209 $c(f)$. The appendix has relaxation time formulas for WLC and FJC
3211 project = "sawtooth simulation"
3214 @article { fernandez04,
3215 author = JFernandez #" and "# HLi,
3216 title = "Force-clamp spectroscopy monitors the folding trajectory of a
3224 pages = "1674--1678",
3226 doi = "10.1126/science.1092497",
3227 eprint = "http://www.sciencemag.org/cgi/reprint/303/5664/1674.pdf",
3228 url = "http://www.sciencemag.org/cgi/content/abstract/303/5664/1674",
3229 keywords = "Chemistry, Physical;Microscopy, Atomic Force;Physicochemical
3230 Phenomena;Polyubiquitin;Protein Conformation;Protein
3231 Denaturation;Protein Folding;Protein Structure, Secondary;Time
3233 abstract = "We used force-clamp atomic force microscopy to measure the end-
3234 to-end length of the small protein ubiquitin during its folding
3235 reaction at the single-molecule level. Ubiquitin was first unfolded and
3236 extended at a high force, then the stretching force was quenched and
3237 protein folding was observed. The folding trajectories were continuous
3238 and marked by several distinct stages. The time taken to fold was
3239 dependent on the contour length of the unfolded protein and the
3240 stretching force applied during folding. The folding collapse was
3241 marked by large fluctuations in the end-to-end length of the protein,
3242 but these fluctuations vanished upon the final folding contraction.
3243 These direct observations of the complete folding trajectory of a
3244 protein provide a benchmark to determine the physical basis of the
3249 author = JHoward #" and "# AJHudspeth,
3250 title = {Mechanical relaxation of the hair bundle mediates
3251 adaptation in mechanoelectrical transduction by the
3252 bullfrog's saccular hair cell.},
3258 pages = {3064--3068},
3260 url = {http://www.ncbi.nlm.nih.gov/pubmed/3495007},
3261 keywords = {Acclimatization},
3262 keywords = {Animals},
3263 keywords = {Electric Conductivity},
3264 keywords = {Electric Stimulation},
3265 keywords = {Hair Cells, Auditory},
3266 keywords = {Membrane Potentials},
3267 keywords = {Microelectrodes},
3268 keywords = {Physical Stimulation},
3269 keywords = {Rana catesbeiana},
3270 keywords = {Saccule and Utricle},
3271 abstract = {Mechanoelectrical transduction by hair cells of the
3272 frog's internal ear displays adaptation: the electrical response
3273 to a maintained deflection of the hair bundle declines over a
3274 period of tens of milliseconds. We investigated the role of
3275 mechanics in adaptation by measuring changes in hair-bundle
3276 stiffness following the application of force stimuli. Following
3277 step stimulation with a glass fiber, the hair bundle of a saccular
3278 hair cell initially had a stiffness of approximately equal to
3279 $1\U{mN/m}$. The stiffness then declined to a steady-state level
3280 near $0.6\U{mN/m}$ with a time course comparable to that of
3281 adaptation in the receptor current. The hair bundle may be modeled
3282 as the parallel combination of a spring, which represents the
3283 rotational stiffness of the stereocilia, and a series spring and
3284 dashpot, which respectively, represent the elastic element
3285 responsible for channel gating and the apparatus for adaptation.},
3290 author = JHoward #" and "# AJHudspeth,
3291 title = {Compliance of the Hair Bundle Associated with Gating of
3292 Mechanoelectrical Transduction Channels in the Bullfrog's Saccular
3299 doi = {10.1016/0896-6273(88)90139-0},
3300 url = {http://www.cell.com/neuron/retrieve/pii/0896627388901390},
3301 eprint = {http://download.cell.com/neuron/pdf/PII0896627388901390.pdf},
3302 note = {Initial thermal calibration paper as cited by
3303 \citet{florin95}. This is not an AFM paper, but it uses the
3304 equipartition theorem to calculate the spring constant of hair
3305 fibers by measuring their tip displacement variance. The
3306 discussion occurs in the \emph{Manufacture and Calibration of
3307 Fibers} section on pages 197--198. Actual details are scarce, but
3308 I believe this is the original source of the ``Lorentzian'' and
3309 ``10\% accuracy'' ideas that have haunted themal calibration ever
3314 author = ELFlorin #" and "# VMoy #" and "# HEGaub,
3315 title = {Adhesion forces between individual ligand-receptor pairs},
3323 doi = {10.1126/science.8153628},
3324 url = {http://www.sciencemag.org/content/264/5157/415.abstract},
3325 eprint = {http://www.sciencemag.org/content/264/5157/415.full.pdf},
3326 abstract ={The adhesion force between the tip of an atomic force
3327 microscope cantilever derivatized with avidin and agarose beads
3328 functionalized with biotin, desthiobiotin, or iminobiotin was
3329 measured. Under conditions that allowed only a limited number of
3330 molecular pairs to interact, the force required to separate tip
3331 and bead was found to be quantized in integer multiples of
3332 $160\pm20$ piconewtons for biotin and $85\pm15$ piconewtons for
3333 iminobiotin. The measured force quanta are interpreted as the
3334 unbinding forces of individual molecular pairs.},
3337 @article { florin95,
3338 author = ELFlorin #" and "# MRief #" and "# HLehmann #" and "# MLudwig #"
3339 and "# CDornmair #" and "# VMoy #" and "# HEGaub,
3340 title = "Sensing specific molecular interactions with the atomic force
3348 doi = "10.1016/0956-5663(95)99227-C",
3349 url = "http://www.sciencedirect.com/science/article/B6TFC-
3350 3XY2HK9-G/2/6f4e9f67e9a1e14c8bbcc478e5360682",
3351 abstract = "One of the unique features of the atomic force microscope (AFM)
3352 is its capacity to measure interactions between tip and sample with
3353 high sensitivity and unparal leled spatial resolution. Since the
3354 development of methods for the functionaliza tion of the tips, the
3355 versatility of the AFM has been expanded to experiments wh ere specific
3356 molecular interactions are measured. For illustration, we present m
3357 easurements of the interaction between complementary strands of DNA. A
3358 necessary prerequisite for the quantitative analysis of the interaction
3359 force is knowledg e of the spring constant of the cantilevers. Here, we
3360 compare different techniqu es that allow for the in situ measurement of
3361 the absolute value of the spring co nstant of cantilevers.",
3362 note = {Good review of calibration to 1995, with experimental
3363 comparison between resonance-shift, reference-spring, and
3364 thermal methods. They incorrectly cite \citet{hutter93} as
3365 being published in 1994.},
3366 project = "Cantilever Calibration"
3369 @article{ burnham03,
3370 author = NABurnham #" and "# XiChen #" and "# CSHodges #" and "#
3371 GAMatei #" and "# EJThoreson #" and "# CJRoberts #" and "#
3372 MCDavies #" and "# SJBTendler,
3373 title = {Comparison of calibration methods for atomic-force
3374 microscopy cantilevers},
3381 url = {http://stacks.iop.org/0957-4484/14/i=1/a=301},
3382 abstract = {The scientific community needs a rapid and reliable way
3383 of accurately determining the stiffness of atomic-force microscopy
3384 cantilevers. We have compared the experimentally determined values
3385 of stiffness for ten cantilever probes using four different
3386 methods. For rectangular silicon cantilever beams of well defined
3387 geometry, the approaches all yield values within 17\% of the
3388 manufacturer's nominal stiffness. One of the methods is new, based
3389 on the acquisition and analysis of thermal distribution functions
3390 of the oscillator's amplitude fluctuations. We evaluate this
3391 method in comparison to the three others and recommend it for its
3392 ease of use and broad applicability.},
3393 note = {Contains both the overdamped (\fref{equation}{6}) and
3394 general (\fref{equation}{8}) power spectral densities used in
3395 thermal cantilever calibration, but punts to textbooks for the
3400 author = NRForde #" and "# DIzhaky #" and "# GRWoodcock #" and "# GJLWuite
3401 #" and "# CBustamante,
3402 title = "Using mechanical force to probe the mechanism of pausing and
3403 arrest during continuous elongation by Escherichia coli {RNA}
3411 pages = "11682--11687",
3413 doi = "10.1073/pnas.142417799",
3414 eprint = "http://www.pnas.org/cgi/reprint/99/18/11682.pdf",
3415 url = "http://www.pnas.org/content/99/18/11682",
3416 keywords = "DNA-Directed RNA Polymerases;Escherichia
3417 coli;Kinetics;Transcription, Genetic",
3418 abstract = "Escherichia coli RNA polymerase translocates along the DNA
3419 discontinuously during the elongation phase of transcription, spending
3420 proportionally more time at some template positions, known as pause and
3421 arrest sites, than at others. Current models of elongation suggest that
3422 the enzyme backtracks at these locations, but the dynamics are
3423 unresolved. Here, we study the role of lateral displacement in pausing
3424 and arrest by applying force to individually transcribing molecules. We
3425 find that an assisting mechanical force does not alter the
3426 translocation rate of the enzyme, but does reduce the efficiency of
3427 both pausing and arrest. Moreover, arrested molecules cannot be rescued
3428 by force, suggesting that arrest occurs by a bipartite mechanism: the
3429 enzyme backtracks along the DNA followed by a conformational change of
3430 the ternary complex (RNA polymerase, DNA and transcript), which cannot
3431 be reversed mechanically."
3434 @article { freitag97,
3435 author = SFreitag #" and "# ILTrong #" and "# LKlumb #" and "# PSStayton #"
3437 title = "Structural studies of the streptavidin binding loop.",
3443 pages = "1157--1166",
3445 doi = "10.1002/pro.5560060604",
3446 keywords = "Allosteric Regulation;Bacterial Proteins;Binding
3447 Sites;Biotin;Crystallography, X-Ray;Hydrogen Bonding;Ligands;Models,
3448 Molecular;Molecular Conformation;Streptavidin;Tryptophan",
3449 abstract = "The streptavidin-biotin complex provides the basis for many
3450 important biotechnological applications and is an interesting model
3451 system for studying high-affinity protein-ligand interactions. We
3452 report here crystallographic studies elucidating the conformation of
3453 the flexible binding loop of streptavidin (residues 45 to 52) in the
3454 unbound and bound forms. The crystal structures of unbound streptavidin
3455 have been determined in two monoclinic crystal forms. The binding loop
3456 generally adopts an open conformation in the unbound species. In one
3457 subunit of one crystal form, the flexible loop adopts the closed
3458 conformation and an analysis of packing interactions suggests that
3459 protein-protein contacts stabilize the closed loop conformation. In the
3460 other crystal form all loops adopt an open conformation. Co-
3461 crystallization of streptavidin and biotin resulted in two additional,
3462 different crystal forms, with ligand bound in all four binding sites of
3463 the first crystal form and biotin bound in only two subunits in a
3464 second. The major change associated with binding of biotin is the
3465 closure of the surface loop incorporating residues 45 to 52. Residues
3466 49 to 52 display a 3(10) helical conformation in unbound subunits of
3467 our structures as opposed to the disordered loops observed in other
3468 structure determinations of streptavidin. In addition, the open
3469 conformation is stabilized by a beta-sheet hydrogen bond between
3470 residues 45 and 52, which cannot occur in the closed conformation. The
3471 3(10) helix is observed in nearly all unbound subunits of both the co-
3472 crystallized and ligand-free structures. An analysis of the temperature
3473 factors of the binding loop regions suggests that the mobility of the
3474 closed loops in the complexed structures is lower than in the open
3475 loops of the ligand-free structures. The two biotin bound subunits in
3476 the tetramer found in the MONO-b1 crystal form are those that
3477 contribute Trp 120 across their respective binding pockets, suggesting
3478 a structural link between these binding sites in the tetramer. However,
3479 there are no obvious signatures of binding site communication observed
3480 upon ligand binding, such as quaternary structure changes or shifts in
3481 the region of Trp 120. These studies demonstrate that while
3482 crystallographic packing interactions can stabilize both the open and
3483 closed forms of the flexible loop, in their absence the loop is open in
3484 the unbound state and closed in the presence of biotin. If present in
3485 solution, the helical structure in the open loop conformation could
3486 moderate the entropic penalty associated with biotin binding by
3487 contributing an order-to-disorder component to the loop closure.",
3488 note = "\href{http://www.rcsb.org/pdb/explore.do?structureId=1SWE}{PDB ID:
3490 \href{http://dx.doi.org/10.2210/pdb1swe/pdb}{10.2210/pdb1swe/pdb}."
3493 @article { friddle08,
3494 author = RWFriddle #" and "# PPodsiadlo #" and "# ABArtyukhin #" and "#
3496 title = "Near-Equilibrium Chemical Force Microscopy",
3501 pages = "4986--4990",
3502 doi = "10.1021/jp7095967",
3503 eprint = "http://pubs.acs.org/doi/pdf/10.1021/jp7095967",
3504 url = "http://pubs.acs.org/doi/abs/10.1021/jp7095967"
3508 author = TFujii #" and "# YLSun #" and "# KNAn #" and "# ZPLuo,
3509 title = "Mechanical properties of single hyaluronan molecules",
3517 keywords = "Biomechanics;Cross-Linking Reagents;Elasticity;Extracellular
3518 Matrix;Humans;Hyaluronic Acid;Lasers;Microspheres;Nanotechnology",
3519 abstract = "Hyaluronan (HA) is a major component of the extracellular
3520 matrix. It plays an important role in the mechanical functions of the
3521 extracellular matrix and stabilization of cells. Currently, its
3522 mechanical properties have been investigated only at the gross level.
3523 In this study, the mechanical properties of single HA molecules were
3524 directly measured with an optical tweezer technique, yielding a
3525 persistence length of 4.5 +/- 1.2 nm. This information may help us to
3526 understand the mechanical roles in the extracellular matrix
3527 infrastructure, cell attachment, and to design tissue engineering and
3528 drug delivery systems where the mechanical functions of HA are
3532 @article { ganchev08,
3533 author = DNGanchev #" and "# NJCobb #" and "# KSurewicz #" and "#
3535 title = "Nanomechanical properties of human prion protein amyloid as probed
3536 by force spectroscopy",
3543 pages = "2909--2915",
3545 doi = "10.1529/biophysj.108.133108",
3546 abstract = "Amyloids are associated with a number of protein misfolding
3547 disorders, including prion diseases. In this study, we used single-
3548 molecule force spectroscopy to characterize the nanomechanical
3549 properties and molecular structure of amyloid fibrils formed by human
3550 prion protein PrP90-231. Force-extension curves obtained by specific
3551 attachment of a gold-covered atomic force microscope tip to engineered
3552 Cys residues could be described by the worm-like chain model for
3553 entropic elasticity of a polymer chain, with the size of the N-terminal
3554 segment that could be stretched entropically depending on the tip
3555 attachment site. The data presented here provide direct information
3556 about the forces required to extract an individual monomer from the
3557 core of the PrP90-231 amyloid, and indicate that the beta-sheet core of
3558 this amyloid starts at residue approximately 164-169. The latter
3559 finding has important implications for the ongoing debate regarding the
3560 structure of PrP amyloid."
3564 author = MGao #" and "# DCraig #" and "# OLequin #" and "# ICampbell #" and
3565 "# VVogel #" and "# KSchulten,
3566 title = "Structure and functional significance of mechanically unfolded
3567 fibronectin type {III1} intermediates",
3572 pages = "14784--14789",
3573 doi = "10.1073/pnas.2334390100",
3574 eprint = "http://www.pnas.org/cgi/reprint/100/25/14784.pdf",
3575 url = "http://www.pnas.org/cgi/content/abstract/100/25/14784",
3576 abstract = "Fibronectin (FN) forms fibrillar networks coupling cells to the
3577 extracellular matrix. The formation of FN fibrils, fibrillogenesis, is
3578 a tightly regulated process involving the exposure of cryptic binding
3579 sites in individual FN type III (FN-III) repeats presumably exposed by
3580 mechanical tension. The FN-III1 module has been previously proposed to
3581 contain such cryptic sites that promote the assembly of extracellular
3582 matrix FN fibrils. We have combined NMR and steered molecular dynamics
3583 simulations to study the structure and mechanical unfolding pathway of
3584 FN-III1. This study finds that FN-III1 consists of a {beta}-sandwich
3585 structure that unfolds to a mechanically stable intermediate about four
3586 times the length of the native folded state. Considering previous
3587 experimental findings, our studies provide a structural model by which
3588 mechanical stretching of FN-III1 may induce fibrillogenesis through
3589 this partially unfolded intermediate."
3592 @article { gavrilov01,
3593 author = LAGavrilov #" and "# NSGavrilova,
3594 title = "The reliability theory of aging and longevity",
3603 doi = "10.1006/jtbi.2001.2430",
3604 keywords = "Adult;Aged;Aging;Animals;Humans;Longevity;Middle Aged;Models,
3605 Biological;Survival Rate;Systems Theory",
3606 abstract = "Reliability theory is a general theory about systems failure.
3607 It allows researchers to predict the age-related failure kinetics for a
3608 system of given architecture (reliability structure) and given
3609 reliability of its components. Reliability theory predicts that even
3610 those systems that are entirely composed of non-aging elements (with a
3611 constant failure rate) will nevertheless deteriorate (fail more often)
3612 with age, if these systems are redundant in irreplaceable elements.
3613 Aging, therefore, is a direct consequence of systems redundancy.
3614 Reliability theory also predicts the late-life mortality deceleration
3615 with subsequent leveling-off, as well as the late-life mortality
3616 plateaus, as an inevitable consequence of redundancy exhaustion at
3617 extreme old ages. The theory explains why mortality rates increase
3618 exponentially with age (the Gompertz law) in many species, by taking
3619 into account the initial flaws (defects) in newly formed systems. It
3620 also explains why organisms ``prefer'' to die according to the Gompertz
3621 law, while technical devices usually fail according to the Weibull
3622 (power) law. Theoretical conditions are specified when organisms die
3623 according to the Weibull law: organisms should be relatively free of
3624 initial flaws and defects. The theory makes it possible to find a
3625 general failure law applicable to all adult and extreme old ages, where
3626 the Gompertz and the Weibull laws are just special cases of this more
3627 general failure law. The theory explains why relative differences in
3628 mortality rates of compared populations (within a given species) vanish
3629 with age, and mortality convergence is observed due to the exhaustion
3630 of initial differences in redundancy levels. Overall, reliability
3631 theory has an amazing predictive and explanatory power with a few, very
3632 general and realistic assumptions. Therefore, reliability theory seems
3633 to be a promising approach for developing a comprehensive theory of
3634 aging and longevity integrating mathematical methods with specific
3635 biological knowledge.",
3636 note = "An example of exponential (standard) Gomperz law."
3639 @article { gergely00,
3640 author = CGergely #" and "# JCVoegel #" and "# PSchaaf #" and "# BSenger #"
3641 and "# MMaaloum #" and "# JHorber #" and "# JHemmerle,
3642 title = "Unbinding process of adsorbed proteins under external stress
3643 studied by atomic force microscopy spectroscopy",
3648 pages = "10802--10807",
3649 doi = "10.1073/pnas.180293097",
3650 eprint = "http://www.pnas.org/cgi/reprint/97/20/10802.pdf",
3651 url = "http://www.pnas.org/cgi/content/abstract/97/20/10802"
3654 @article { gompertz25,
3656 title = "On the Nature of the Function Expressive of the Law of Human
3657 Mortality, and on a New Mode of Determining the Value of Life
3666 copyright = "Copyright \copy\ 1825 The Royal Society",
3667 url = "http://www.jstor.org/stable/107756",
3669 jstor_articletype = "primary_article",
3670 jstor_formatteddate = 1825,
3671 jstor_issuetitle = ""
3676 title = {The significance of the difference between two means when
3677 the population variances are unequal},
3684 keywords = "Population",
3686 url = "http://www.jstor.org/stable/2332010",
3692 title = {The generalization of {Student's} problems when several
3693 different population variances are involved},
3700 keywords = "Population",
3702 url = "http://www.ncbi.nlm.nih.gov/pubmed/20287819",
3703 jstor_url = "http://www.jstor.org/stable/2332510",
3707 @article { granzier97,
3708 author = HLGranzier #" and "# MSKellermayer #" and "# MHelmes #" and "#
3710 title = "Titin elasticity and mechanism of passive force development in rat
3711 cardiac myocytes probed by thin-filament extraction",
3717 pages = "2043--2053",
3719 doi = "10.1016/S0006-3495(97)78234-1",
3720 url = "http://www.cell.com/biophysj/retrieve/pii/S0006349597782341",
3721 keywords = "Amino Acid Sequence;Animals;Biomechanics;Biophysical
3722 Phenomena;Biophysics;Cell Fractionation;Elasticity;Gelsolin;Microscopy,
3723 Immunoelectron;Models, Cardiovascular;Molecular Structure;Muscle
3724 Proteins;Myocardial Contraction;Myocardium;Protein
3725 Kinases;Rats;Sarcomeres",
3726 abstract = "Titin (also known as connectin) is a giant filamentous protein
3727 whose elastic properties greatly contribute to the passive force in
3728 muscle. In the sarcomere, the elastic I-band segment of titin may
3729 interact with the thin filaments, possibly affecting the molecule's
3730 elastic behavior. Indeed, several studies have indicated that
3731 interactions between titin and actin occur in vitro and may occur in
3732 the sarcomere as well. To explore the properties of titin alone, one
3733 must first eliminate the modulating effect of the thin filaments by
3734 selectively removing them. In the present work, thin filaments were
3735 selectively removed from the cardiac myocyte by using a gelsolin
3736 fragment. Partial extraction left behind approximately 100-nm-long thin
3737 filaments protruding from the Z-line, whereas the rest of the I-band
3738 became devoid of thin filaments, exposing titin. By applying a much
3739 more extensive gelsolin treatment, we also removed the remaining short
3740 thin filaments near the Z-line. After extraction, the extensibility of
3741 titin was studied by using immunoelectron microscopy, and the passive
3742 force-sarcomere length relation was determined by using mechanical
3743 techniques. Titin's regional extensibility was not detectably affected
3744 by partial thin-filament extraction. Passive force, on the other hand,
3745 was reduced at sarcomere lengths longer than approximately 2.1 microm,
3746 with a 33 +/- 9\% reduction at 2.6 microm. After a complete extraction,
3747 the slack sarcomere length was reduced to approximately 1.7 microm. The
3748 segment of titin near the Z-line, which is otherwise inextensible,
3749 collapsed toward the Z-line in sarcomeres shorter than approximately
3750 2.0 microm, but it was extended in sarcomeres longer than approximately
3751 2.3 microm. Passive force became elevated at sarcomere lengths between
3752 approximately 1.7 and approximately 2.1 microm, but was reduced at
3753 sarcomere lengths of >2.3 microm. These changes can be accounted for by
3754 modeling titin as two wormlike chains in series, one of which increases
3755 its contour length by recruitment of the titin segment near the Z-line
3756 into the elastic pool."
3759 @article { grossman05,
3760 author = CGrossman #" and "# AStout,
3761 title = "Optical Tweezers Advanced Lab",
3765 eprint = "http://chirality.swarthmore.edu/PHYS81/OpticalTweezers.pdf",
3766 note = {Fairly complete overdamped PSD derivation in
3767 \fref{section}{4.3}. Cites \citet{tlusty98} and
3768 \citet{bechhoefer02} for further details. However, Tlusty
3769 (listed as reference 8) doesn't contain the thermal response
3770 fn.\ derivation it was cited for. Also, the single sided PSD
3771 definition credited to reference 9 (listed as Bechhoefer)
3772 looks more like Press (listed as reference 10). I imagine
3773 Grossman and Stout mixed up their references, and meant to
3774 refer to \citet{bechhoefer02} and \citet{press92} respectively
3776 project = "Cantilever Calibration"
3779 @article { halvorsen09,
3780 author = KHalvorsen #" and "# WPWong,
3781 title = "Massively parallel single-molecule manipulation using centrifugal
3785 url = "http://arxiv.org/abs/0912.5370",
3786 abstract = {Precise manipulation of single molecules has already led to
3787 remarkable insights in physics, chemistry, biology and medicine.
3788 However, widespread adoption of single-molecule techniques has been
3789 impeded by equipment cost and the laborious nature of making
3790 measurements one molecule at a time. We have solved these issues with a
3791 new approach: massively parallel single-molecule force measurements
3792 using centrifugal force. This approach is realized in a novel
3793 instrument that we call the Centrifuge Force Microscope (CFM), in which
3794 objects in an orbiting sample are subjected to a calibration-free,
3795 macroscopically uniform force-field while their micro-to-nanoscopic
3796 motions are observed. We demonstrate high-throughput single-molecule
3797 force spectroscopy with this technique by performing thousands of
3798 rupture experiments in parallel, characterizing force-dependent
3799 unbinding kinetics of an antibody-antigen pair in minutes rather than
3800 days. Additionally, we verify the force accuracy of the instrument by
3801 measuring the well-established DNA overstretching transition at 66
3802 $\pm$ 3 pN. With significant benefits in efficiency, cost, simplicity,
3803 and versatility, "single-molecule centrifugation" has the potential to
3804 revolutionize single-molecule experimentation, and open access to a
3805 wider range of researchers and experimental systems.}
3808 @article { hanggi90,
3809 author = PHanggi #" and "# PTalkner #" and "# MBorkovec,
3810 title = "Reaction-rate theory: Fifty years after {K}ramers",
3819 doi = "10.1103/RevModPhys.62.251",
3820 eprint = "http://www.physik.uni-augsburg.de/theo1/hanggi/Papers/112.pdf",
3821 url = "http://prola.aps.org/abstract/RMP/v62/i2/p251_1",
3822 note = "\emph{The} Kramers' theory review article. See pages 268--279 for
3823 the Kramers-specific introduction.",
3824 project = "sawtooth simulation"
3827 @article { hatfield99,
3828 author = JWHatfield #" and "# SRQuake,
3829 title = "Dynamic Properties of an Extended Polymer in Solution",
3835 pages = "3548--3551",
3838 doi = "10.1103/PhysRevLett.82.3548",
3839 url = "http://link.aps.org/abstract/PRL/v82/p3548",
3840 note = "Defines WLC and FJC models, citing textbooks.",
3841 project = "sawtooth simulation"
3844 @article { heymann00,
3845 author = BHeymann #" and "# HGrubmuller,
3846 title = "Dynamic force spectroscopy of molecular adhesion bonds",
3853 pages = "6126--6129",
3855 doi = "10.1103/PhysRevLett.84.6126",
3856 eprint = "http://prola.aps.org/pdf/PRL/v84/i26/p6126_1",
3857 url = "http://prola.aps.org/abstract/PRL/v84/p6126",
3858 abstract = "Recent advances in atomic force microscopy, biomembrane force
3859 probe experiments, and optical tweezers allow one to measure the
3860 response of single molecules to mechanical stress with high precision.
3861 Such experiments, due to limited spatial resolution, typically access
3862 only one single force value in a continuous force profile that
3863 characterizes the molecular response along a reaction coordinate. We
3864 develop a theory that allows one to reconstruct force profiles from
3865 force spectra obtained from measurements at varying loading rates,
3866 without requiring increased resolution. We show that spectra obtained
3867 from measurements with different spring constants contain complementary
3871 @article { hummer01,
3872 author = GHummer #" and "# ASzabo,
3873 title = "From the Cover: Free energy reconstruction from nonequilibrium
3874 single-molecule pulling experiments",
3879 pages = "3658--3661",
3880 doi = "10.1073/pnas.071034098",
3881 eprint = "http://www.pnas.org/cgi/reprint/98/7/3658.pdf",
3882 url = "http://www.pnas.org/cgi/content/abstract/98/7/3658",
3886 @article { hummer03,
3887 author = GHummer #" and "# ASzabo,
3888 title = "Kinetics from nonequilibrium single-molecule pulling experiments",
3896 eprint = "http://www.biophysj.org/cgi/reprint/85/1/5.pdf",
3897 url = "http://www.biophysj.org/cgi/content/abstract/85/1/5",
3898 keywords = "Computer Simulation; Crystallography; Energy Transfer;
3899 Kinetics; Lasers; Micromanipulation; Microscopy, Atomic Force; Models,
3900 Molecular; Molecular Conformation; Motion; Muscle Proteins;
3901 Nanotechnology; Physical Stimulation; Protein Conformation; Protein
3902 Denaturation; Protein Folding; Protein Kinases; Stress, Mechanical",
3903 abstract = "Mechanical forces exerted by laser tweezers or atomic force
3904 microscopes can be used to drive rare transitions in single molecules,
3905 such as unfolding of a protein or dissociation of a ligand. The
3906 phenomenological description of pulling experiments based on Bell's
3907 expression for the force-induced rupture rate is found to be inadequate
3908 when tested against computer simulations of a simple microscopic model
3909 of the dynamics. We introduce a new approach of comparable complexity
3910 to extract more accurate kinetic information about the molecular events
3911 from pulling experiments. Our procedure is based on the analysis of a
3912 simple stochastic model of pulling with a harmonic spring and
3913 encompasses the phenomenological approach, reducing to it in the
3914 appropriate limit. Our approach is tested against computer simulations
3915 of a multimodule titin model with anharmonic linkers and then an
3916 illustrative application is made to the forced unfolding of I27
3917 subunits of the protein titin. Our procedure to extract kinetic
3918 information from pulling experiments is simple to implement and should
3919 prove useful in the analysis of experiments on a variety of systems.",
3921 project = "sawtooth simulation"
3924 @article { hutter05,
3926 title = "Comment on tilt of atomic force microscope cantilevers: Effect on
3927 spring constant and adhesion measurements.",
3934 pages = "2630--2632",
3936 doi = "10.1021/la047670t",
3937 note = "Tilted cantilever corrections (not needed? see Ohler/VEECO note)",
3938 project = "Cantilever Calibration"
3941 @article { hutter93,
3942 author = JHutter #" and "# JBechhoefer,
3943 title = "Calibration of atomic-force microscope tips",
3948 pages = "1868--1873",
3950 doi = "10.1063/1.1143970",
3951 url = "http://link.aip.org/link/?RSI/64/1868/1",
3952 keywords = {atomic force microscopy; calibration; quality factor; probes;
3953 resonance; silicon nitrides; mica; van der waals forces},
3954 note = {Original equipartition-based calibration method (thermal
3955 calibration), after the brief mention in \citet{howard88}.
3956 This is the first paper I've found that works out the theory
3957 in detail, although they punt to page 431 of \citet{heer72}
3958 instead of listing a formula for their ``Lorentzian''. The
3959 experimental data uses high-$Q$ cantilevers in air, and their
3960 figure 2 shows clear water-layer snap-off. There is a
3961 published erratum\citep{hutter93-erratum}.},
3962 project = "Cantilever Calibration"
3965 @article{ hutter93-erratum,
3966 author = JHutter #" and "# JBechhoefer,
3967 title = "Erratum: Calibration of atomic-force microscope tips",
3975 doi = "10.1063/1.1144449",
3976 url = "http://rsi.aip.org/resource/1/rsinak/v64/i11/p3342_s1",
3977 note = {V.~Croquette pointed out that they should calibrate the
3978 response of their optical-detection electronics.},
3979 project = "Cantilever Calibration",
3984 title = {Statistical mechanics, kinetic theory, and stochastic processes},
3987 address = {New York},
3989 isbn = {0-123-36550-3},
3990 language = {English},
3991 keywords = {Statistical mechanics.; Kinetic theory of gases.; Stochastic processes.},
3995 author = CHyeon #" and "# DThirumalai,
3996 title = "Can energy landscape roughness of proteins and {RNA} be measured
3997 by using mechanical unfolding experiments?",
4004 pages = "10249--10253",
4006 doi = "10.1073/pnas.1833310100",
4007 eprint = "http://www.pnas.org/cgi/reprint/100/18/10249.pdf",
4008 url = "http://www.pnas.org/cgi/content/abstract/100/18/10249",
4009 keywords = "Protein Folding; Proteins; RNA; Temperature; Thermodynamics",
4010 abstract = "By considering temperature effects on the mechanical unfolding
4011 rates of proteins and RNA, whose energy landscape is rugged, the
4012 question posed in the title is answered in the affirmative. Adopting a
4013 theory by Zwanzig [Zwanzig, R. (1988) Proc. Natl. Acad. Sci. USA 85,
4014 2029-2030], we show that, because of roughness characterized by an
4015 energy scale epsilon, the unfolding rate at constant force is retarded.
4016 Similarly, in nonequilibrium experiments done at constant loading
4017 rates, the most probable unfolding force increases because of energy
4018 landscape roughness. The effects are dramatic at low temperatures. Our
4019 analysis suggests that, by using temperature as a variable in
4020 mechanical unfolding experiments of proteins and RNA, the ruggedness
4021 energy scale epsilon, can be directly measured.",
4022 note = "Derives the major theory behind my thesis. The Kramers rate
4023 equation is \xref{hanggi90}{equation}{4.56c} (page 275).",
4024 project = "Energy Landscape Roughness"
4027 @article { improta96,
4028 author = SImprota #" and "# ASPolitou #" and "# APastore,
4029 title = "Immunoglobulin-like modules from titin {I}-band: Extensible
4030 components of muscle elasticity.",
4039 doi = "10.1016/S0969-2126(96)00036-6",
4040 keywords = "Amino Acid Sequence;Immunoglobulins;Magnetic Resonance
4041 Spectroscopy;Models, Molecular;Molecular Sequence Data;Molecular
4042 Structure;Muscle Proteins;Protein Kinases;Protein Structure,
4043 Secondary;Protein Structure, Tertiary;Sequence Alignment",
4044 abstract = "BACKGROUND. The giant muscle protein titin forms a filament
4045 which spans half of the sarcomere and performs, along its length, quite
4046 diverse functions. The region of titin located in the sarcomere I-band
4047 is believed to play a major role in extensibility and passive
4048 elasticity of muscle. In the I-band, the titin sequence consists mostly
4049 of repetitive motifs of tandem immunoglobulin-like (Ig) modules
4050 intercalated by a potentially non-globular region. The highly
4051 repetitive titin architecture suggests that the molecular basis of its
4052 mechanical properties be approached through the characterization of the
4053 isolated components of the I-band and their interfaces. In the present
4054 paper, we report on the structure determination in solution of a
4055 representative Ig module from the I-band (I27) as solved by NMR
4056 techniques. RESULTS. The structure of I27 consists of a beta sandwich
4057 formed by two four-stranded sheets (named ABED and A'GFC). This fold
4058 belongs to the intermediate frame (I frame) of the immunoglobulin
4059 superfamily. Comparison of I27 with another titin module from the
4060 region located in the M-line (M5) shows that two loops (between the B
4061 and C and the F and G strands) are shorter in I27, conferring a less
4062 elongated appearance to this structure. Such a feature is specific to
4063 the Ig domains in the I-band and might therefore be related to the
4064 functions of the protein in this region. The structure of tandem Ig
4065 domains as modeled from I27 suggests the presence of hinge regions
4066 connecting contiguous modules. CONCLUSIONS. We suggest that titin Ig
4067 domains in the I-band function as extensible components of muscle
4068 elasticity by stretching the hinge regions.",
4069 note = "\href{http://www.rcsb.org/pdb/explore.do?structureId=1TIT}{PDB ID:
4071 \href{http://dx.doi.org/10.2210/pdb1tit/pdb}{10.2210/pdb1tit/pdb}."
4074 @article { irback05,
4075 author = AIrback #" and "# SMitternacht #" and "# SMohanty,
4076 title = "Dissecting the mechanical unfolding of ubiquitin",
4081 pages = "13427--13432",
4082 doi = "10.1073/pnas.0501581102",
4083 eprint = "http://www.pnas.org/cgi/reprint/102/38/13427.pdf",
4084 url = "http://www.pnas.org/cgi/content/abstract/102/38/13427",
4085 abstract = "The unfolding behavior of ubiquitin under the influence of a
4086 stretching force recently was investigated experimentally by single-
4087 molecule constant-force methods. Many observed unfolding traces had a
4088 simple two-state character, whereas others showed clear evidence of
4089 intermediate states. Here, we use Monte Carlo simulations to
4090 investigate the force-induced unfolding of ubiquitin at the atomic
4091 level. In agreement with experimental data, we find that the unfolding
4092 process can occur either in a single step or through intermediate
4093 states. In addition to this randomness, we find that many quantities,
4094 such as the frequency of occurrence of intermediates, show a clear
4095 systematic dependence on the strength of the applied force. Despite
4096 this diversity, one common feature can be identified in the simulated
4097 unfolding events, which is the order in which the secondary-structure
4098 elements break. This order is the same in two- and three-state events
4099 and at the different forces studied. The observed order remains to be
4100 verified experimentally but appears physically reasonable."
4103 @article{ grubmuller96,
4104 author = HGrubmuller #" and "# BHeymann #" and "# PTavan,
4105 title = {Ligand binding: molecular mechanics calculation of the
4106 streptavidin-biotin rupture force.},
4110 address = {Theoretische Biophysik, Institut f{\"u}r Medizinische
4111 Optik, Ludwig- Maximilians-Universit{\"a}t M{\"u}nchen,
4112 Germany. Helmut.Grubmueller@ Physik.uni-muenchen.de},
4118 url = {http://www.ncbi.nlm.nih.gov/pubmed/8584939},
4119 eprint = {http://pubman.mpdl.mpg.de/pubman/item/escidoc:1690312:2/component/escidoc:1690313/1690312.pdf},
4121 keywords = {Bacterial Proteins},
4122 keywords = {Biotin},
4123 keywords = {Chemistry, Physical},
4124 keywords = {Computer Simulation},
4125 keywords = {Hydrogen Bonding},
4126 keywords = {Ligands},
4127 keywords = {Microscopy, Atomic Force},
4128 keywords = {Models, Chemical},
4129 keywords = {Molecular Conformation},
4130 keywords = {Physicochemical Phenomena},
4131 keywords = {Protein Conformation},
4132 keywords = {Streptavidin},
4133 keywords = {Thermodynamics},
4134 abstract = {The force required to rupture the streptavidin-biotin
4135 complex was calculated here by computer simulations.
4136 The computed force agrees well with that obtained by
4137 recent single molecule atomic force microscope
4138 experiments. These simulations suggest a detailed
4139 multiple-pathway rupture mechanism involving five major
4140 unbinding steps. Binding forces and specificity are
4141 attributed to a hydrogen bond network between the
4142 biotin ligand and residues within the binding pocket of
4143 streptavidin. During rupture, additional water bridges
4144 substantially enhance the stability of the complex and
4145 even dominate the binding interactions. In contrast,
4146 steric restraints do not appear to contribute to the
4147 binding forces, although conformational motions were
4152 @article { izrailev97,
4153 author = SIzrailev #" and "# SStepaniants #" and "# MBalsera #" and "#
4154 YOono #" and "# KSchulten,
4155 title = "Molecular dynamics study of unbinding of the avidin-biotin
4162 pages = "1568--1581",
4164 eprint = "http://www.biophysj.org/cgi/reprint/72/4/1568.pdf",
4165 url = "http://www.biophysj.org/cgi/content/abstract/72/4/1568",
4166 keywords = "Avidin;Binding Sites;Biotin;Computer Simulation;Hydrogen
4167 Bonding;Mathematics;Microscopy, Atomic Force;Microspheres;Models,
4168 Molecular;Molecular Structure;Protein Binding;Protein
4169 Conformation;Protein Folding;Sepharose",
4170 abstract = "We report molecular dynamics simulations that induce, over
4171 periods of 40-500 ps, the unbinding of biotin from avidin by means of
4172 external harmonic forces with force constants close to those of AFM
4173 cantilevers. The applied forces are sufficiently large to reduce the
4174 overall binding energy enough to yield unbinding within the measurement
4175 time. Our study complements earlier work on biotin-streptavidin that
4176 employed a much larger harmonic force constant. The simulations reveal
4177 a variety of unbinding pathways, the role of key residues contributing
4178 to adhesion as well as the spatial range over which avidin binds
4179 biotin. In contrast to the previous studies, the calculated rupture
4180 forces exceed by far those observed. We demonstrate, in the framework
4181 of models expressed in terms of one-dimensional Langevin equations with
4182 a schematic binding potential, the associated Smoluchowski equations,
4183 and the theory of first passage times, that picosecond to nanosecond
4184 simulation of ligand unbinding requires such strong forces that the
4185 resulting protein-ligand motion proceeds far from the thermally
4186 activated regime of millisecond AFM experiments, and that simulated
4187 unbinding cannot be readily extrapolated to the experimentally observed
4191 @article { janshoff00,
4192 author = AJanshoff #" and "# MNeitzert #" and "# YOberdorfer #" and "#
4194 title = "Force Spectroscopy of Molecular Systems-Single Molecule
4195 Spectroscopy of Polymers and Biomolecules.",
4202 pages = "3212--3237",
4204 doi = "10.1002/1521-3773(20000915)39:18<3212::AID-ANIE3212>3.0.CO;2-X",
4206 url = "http://dx.doi.org/10.1002/1521-3773(20000915)39:18<3212::AID-ANIE3212>3.0.CO;2-X",
4207 abstract = "How do molecules interact with each other? What happens if a
4208 neurotransmitter binds to a ligand-operated ion channel? How do
4209 antibodies recognize their antigens? Molecular recognition events play
4210 a pivotal role in nature: in enzymatic catalysis and during the
4211 replication and transcription of the genome; it is also important for
4212 the cohesion of cellular structures and in numerous metabolic reactions
4213 that molecules interact with each other in a specific manner.
4214 Conventional methods such as calorimetry provide very precise values of
4215 binding enthalpies; these are, however, average values obtained from a
4216 large ensemble of molecules without knowledge of the dynamics of the
4217 molecular recognition event. Which forces occur when a single molecular
4218 couple meets and forms a bond? Since the development of the scanning
4219 force microscope and force spectroscopy a couple of years ago, tools
4220 have now become available for measuring the forces between interfaces
4221 with high precision-starting from colloidal forces to the interaction
4222 of single molecules. The manipulation of individual molecules using
4223 force spectroscopy is also possible. In this way, the mechanical
4224 properties on a molecular scale are measurable. The study of single
4225 molecules is not an exclusive domain of force spectroscopy; it can also
4226 be performed with a surface force apparatus, laser tweezers, or the
4227 micropipette technique. Regardless of these techniques, force
4228 spectroscopy has been proven as an extraordinary versatile tool. The
4229 intention of this review article is to present a critical evaluation of
4230 the actual development of static force spectroscopy. The article mainly
4231 focuses on experiments dealing with inter- and intramolecular forces-
4232 starting with ``simple'' electrostatic forces, then ligand-receptor
4233 systems, and finally the stretching of individual molecules."
4236 @article { jollymore09,
4237 author = AJollymore #" and "# CLethias #" and "# QPeng #" and "# YCao #"
4239 title = "Nanomechanical properties of tenascin-{X} revealed by single-
4240 molecule force spectroscopy",
4247 pages = "1277--1286",
4249 doi = "10.1016/j.jmb.2008.11.038",
4250 url = "http://dx.doi.org/10.1016/j.jmb.2008.11.038",
4251 keywords = "Animals;Biomechanics;Cattle;Fibronectins;Kinetics;Microscopy,
4252 Atomic Force;Protein Folding;Protein Structure, Tertiary;Spectrum
4254 abstract = "Tenascin-X is an extracellular matrix protein and binds a
4255 variety of molecules in extracellular matrix and on cell membrane.
4256 Tenascin-X plays important roles in regulating the structure and
4257 mechanical properties of connective tissues. Using single-molecule
4258 atomic force microscopy, we have investigated the mechanical properties
4259 of bovine tenascin-X in detail. Our results indicated that tenascin-X
4260 is an elastic protein and the fibronectin type III (FnIII) domains can
4261 unfold under a stretching force and refold to regain their mechanical
4262 stability upon the removal of the stretching force. All the 30 FnIII
4263 domains of tenascin-X show similar mechanical stability, mechanical
4264 unfolding kinetics, and contour length increment upon domain unfolding,
4265 despite their large sequence diversity. In contrast to the homogeneity
4266 in their mechanical unfolding behaviors, FnIII domains fold at
4267 different rates. Using the 10th FnIII domain of tenascin-X (TNXfn10) as
4268 a model system, we constructed a polyprotein chimera composed of
4269 alternating TNXfn10 and GB1 domains and used atomic force microscopy to
4270 confirm that the mechanical properties of TNXfn10 are consistent with
4271 those of the FnIII domains of tenascin-X. These results lay the
4272 foundation to further study the mechanical properties of individual
4273 FnIII domains and establish the relationship between point mutations
4274 and mechanical phenotypic effect on tenascin-X. Moreover, our results
4275 provided the opportunity to compare the mechanical properties and
4276 design of different forms of tenascins. The comparison between
4277 tenascin-X and tenascin-C revealed interesting common as well as
4278 distinguishing features for mechanical unfolding and folding of
4279 tenascin-C and tenascin-X and will open up new avenues to investigate
4280 the mechanical functions and architectural design of different forms of
4285 author = REJones #" and "# DPHart,
4286 title = "Force interactions between substrates and {SPM} cantilevers
4287 immersed in fluids",
4294 doi = "DOI: 10.1016/j.triboint.2004.08.016",
4295 url = "http://www.sciencedirect.com/science/article/B6V57-4DN9K7J-1/2/fef91
4296 ac022594c2c6a701376d83ecd31",
4297 keywords = "AFM;Liquid;Hydrodynamic;Lubrication",
4298 abstract = "With the availability of equipment used in Scanning Probe
4299 Microscopy (SPM), researchers have been able to probe the local fluid-
4300 substrate force interactions with resolutions of pN using a variety of
4301 SPM cantilevers. When using such methods, it is essential to
4302 differentiate between contributions to the net force on the cantilever.
4303 Specifically, the interaction between the cantilever, substrate and
4304 fluid, quantified while generating force curves, are discussed and
4305 compared with theoretical models for squeeze-film effects and drag on
4306 the SPM cantilevers. In addition we have demonstrated a simple method
4307 for utilizing the system as a micro-viscometer, independently measuring
4308 the viscosity of the lubricant for each test."
4311 @article { juckett93,
4312 author = DAJuckett #" and "# BRosenberg,
4313 title = "Comparison of the {G}ompertz and {W}eibull functions as
4314 descriptors for human mortality distributions and their intersections",
4322 doi = "10.1016/0047-6374(93)90068-3",
4323 keywords = "Adolescent;Adult;Aged;Aged, 80 and
4324 over;Aging;Biometry;Child;Child, Preschool;Data Interpretation,
4325 Statistical;Female;Humans;Infant;Infant, Newborn;Longitudinal
4326 Studies;Male;Middle Aged;Models, Biological;Models,
4327 Statistical;Mortality",
4328 abstract = "The Gompertz and Weibull functions are compared with respect to
4329 goodness-of-fit to human mortality distributions; ability to describe
4330 mortality curve intersections; and, parameter interpretation. The
4331 Gompertz function is shown to be a better descriptor for 'all-causes'
4332 of deaths and combined disease categories while the Weibull function is
4333 shown to be a better descriptor of purer, single causes-of-death. A
4334 modified form of the Weibull function maps directly to the inherent
4335 degrees of freedom of human mortality distributions while the Gompertz
4336 function does not. Intersections in the old-age tails of mortality are
4337 explored in the context of both functions and, in particular, the
4338 relationship between distribution intersections, and the Gompertz
4339 ln[R0] versus alpha regression is examined. Evidence is also presented
4340 that mortality intersections are fundamental to the survivorship form
4341 and not the rate (hazard) form. Finally, comparisons are made to the
4342 parameter estimates in recent longitudinal Gompertzian analyses and the
4343 probable errors in those analyses are discussed.",
4344 note = "Nice table of various functions associated with Gompertz and
4348 @article { kaplan58,
4349 author = ELKaplan #" and "# PMeier,
4350 title = "Nonparametric Estimation from Incomplete Observations",
4359 copyright = "Copyright \copy\ 1958 American Statistical Association",
4360 url = "http://www.jstor.org/stable/2281868",
4364 @article { kellermayer03,
4365 author = MSKellermayer #" and "# CBustamante #" and "# HLGranzier,
4366 title = "Mechanics and structure of titin oligomers explored with atomic
4374 doi = "10.1016/S0005-2728(03)00029-X",
4375 url = "http://dx.doi.org/10.1016/S0005-2728(03)00029-X",
4376 keywords = "Titin;Wormlike chain;Unfolding;Elasticity;AFM;Molecular force
4378 abstract = "Titin is a giant polypeptide that spans half of the striated
4379 muscle sarcomere and generates passive force upon stretch. To explore
4380 the elastic response and structure of single molecules and oligomers of
4381 titin, we carried out molecular force spectroscopy and atomic force
4382 microscopy (AFM) on purified full-length skeletal-muscle titin. From
4383 the force data, apparent persistence lengths as long as ~1.5 nm were
4384 obtained for the single, unfolded titin molecule. Furthermore, data
4385 suggest that titin molecules may globally associate into oligomers
4386 which mechanically behave as independent wormlike chains (WLCs).
4387 Consistent with this, AFM of surface-adsorbed titin molecules revealed
4388 the presence of oligomers. Although oligomers may form globally via
4389 head-to-head association of titin, the constituent molecules otherwise
4390 appear independent from each other along their contour. Based on the
4391 global association but local independence of titin molecules, we
4392 discuss a mechanical model of the sarcomere in which titin molecules
4393 with different contour lengths, corresponding to different isoforms,
4394 are held in a lattice. The net force response of aligned titin
4395 molecules is determined by the persistence length of the tandemly
4396 arranged, different WLC components of the individual molecules, the
4397 ratio of their overall contour lengths, and by domain unfolding events.
4398 Biased domain unfolding in mechanically selected constituent molecules
4399 may serve as a compensatory mechanism for contour- and persistence-
4400 length differences. Variation in the ratio and contour length of the
4401 component chains may provide mechanisms for the fine-tuning of the
4402 sarcomeric passive force response.",
4406 @article { kellermayer97,
4407 author = MSKellermayer #" and "# SBSmith #" and "# HLGranzier #" and "#
4409 title = "Folding-unfolding transitions in single titin molecules
4410 characterized with laser tweezers",
4417 pages = "1112--1116",
4419 keywords = "Amino Acid
4420 Sequence;Elasticity;Entropy;Immunoglobulins;Lasers;Models,
4421 Chemical;Muscle Contraction;Muscle Proteins;Muscle Relaxation;Muscle,
4422 Skeletal;Protein Denaturation;Protein Folding;Protein Kinases;Stress,
4424 abstract = "Titin, a giant filamentous polypeptide, is believed to play a
4425 fundamental role in maintaining sarcomeric structural integrity and
4426 developing what is known as passive force in muscle. Measurements of
4427 the force required to stretch a single molecule revealed that titin
4428 behaves as a highly nonlinear entropic spring. The molecule unfolds in
4429 a high-force transition beginning at 20 to 30 piconewtons and refolds
4430 in a low-force transition at approximately 2.5 piconewtons. A fraction
4431 of the molecule (5 to 40 percent) remains permanently unfolded,
4432 behaving as a wormlike chain with a persistence length (a measure of
4433 the chain's bending rigidity) of 20 angstroms. Force hysteresis arises
4434 from a difference between the unfolding and refolding kinetics of the
4435 molecule relative to the stretch and release rates in the experiments,
4436 respectively. Scaling the molecular data up to sarcomeric dimensions
4437 reproduced many features of the passive force versus extension curve of
4442 author = WKing #" and "# MSu #" and "# GYang,
4443 title = "{M}onte {C}arlo simulation of mechanical unfolding of proteins
4444 based on a simple two-state model",
4448 address = "Department of Physics, Drexel University, 3141
4449 Chestnut Street, Philadelphia, PA 19104, USA.",
4455 alternative_issn = "1879-0003",
4456 doi = "10.1016/j.ijbiomac.2009.12.001",
4457 url = "http://www.sciencedirect.com/science/article/B6T7J-
4458 4XWMND2-1/2/7ef768562b4157fc201d450553e5de5e",
4460 keywords = "Atomic force microscopy;Mechanical unfolding;Monte Carlo
4461 simulation;Worm-like chain;Single molecule methods",
4462 abstract = "Single molecule methods are becoming routine biophysical
4463 techniques for studying biological macromolecules. In mechanical
4464 unfolding of proteins, an externally applied force is used to induce
4465 the unfolding of individual protein molecules. Such experiments have
4466 revealed novel information that has significantly enhanced our
4467 understanding of the function and folding mechanisms of several types
4468 of proteins. To obtain information on the unfolding kinetics and the
4469 free energy landscape of the protein molecule from mechanical unfolding
4470 data, a Monte Carlo simulation based on a simple two-state kinetic
4471 model is often used. In this paper, we provide a detailed description
4472 of the procedure to perform such simulations and discuss the
4473 approximations and assumptions involved. We show that the appearance of
4474 the force versus extension curves from mechanical unfolding of proteins
4475 is affected by a variety of experimental parameters, such as the length
4476 of the protein polymer and the force constant of the cantilever. We
4477 also analyze the errors associated with different methods of data
4478 pooling and present a quantitative measure of how well the simulation
4479 results fit experimental data. These findings will be helpful in
4480 experimental design, artifact identification, and data analysis for
4481 single molecule studies of various proteins using the mechanical
4485 @article { kleiner07,
4486 author = AKleiner #" and "# EShakhnovich,
4487 title = "The mechanical unfolding of ubiquitin through all-atom Monte Carlo
4488 simulation with a Go-type potential",
4495 pages = "2054--2061",
4497 doi = "10.1529/biophysj.106.081257",
4498 eprint = "http://www.biophysj.org/cgi/reprint/92/6/2054",
4499 url = "http://www.biophysj.org/cgi/content/full/92/6/2054",
4500 keywords = "Computer Simulation; Models, Chemical; Models, Molecular;
4501 Models, Statistical; Monte Carlo Method; Motion; Protein Conformation;
4502 Protein Denaturation; Protein Folding; Ubiquitin",
4503 abstract = "The mechanical unfolding of proteins under a stretching force
4504 has an important role in living systems and is a logical extension of
4505 the more general protein folding problem. Recent advances in
4506 experimental methodology have allowed the stretching of single
4507 molecules, thus rendering this process ripe for computational study. We
4508 use all-atom Monte Carlo simulation with a G?-type potential to study
4509 the mechanical unfolding pathway of ubiquitin. A detailed, robust,
4510 well-defined pathway is found, confirming existing results in this vein
4511 though using a different model. Additionally, we identify the protein's
4512 fundamental stabilizing secondary structure interactions in the
4513 presence of a stretching force and show that this fundamental
4514 stabilizing role does not persist in the absence of mechanical stress.
4515 The apparent success of simulation methods in studying ubiquitin's
4516 mechanical unfolding pathway indicates their potential usefulness for
4517 future study of the stretching of other proteins and the relationship
4518 between protein structure and the response to mechanical deformation."
4521 @article { klimov00,
4522 author = DKlimov #" and "# DThirumalai,
4523 title = "Native topology determines force-induced unfolding pathways in
4531 pages = "7254--7259",
4533 doi = "10.1073/pnas.97.13.7254",
4534 eprint = "http://www.pnas.org/cgi/reprint/97/13/7254.pdf",
4535 url = "http://www.pnas.org/cgi/content/abstract/97/13/7254",
4536 keywords = "Animals; Humans; Protein Folding; Proteins; Spectrin",
4537 abstract = "Single-molecule manipulation techniques reveal that stretching
4538 unravels individually folded domains in the muscle protein titin and
4539 the extracellular matrix protein tenascin. These elastic proteins
4540 contain tandem repeats of folded domains with beta-sandwich
4541 architecture. Herein, we propose by stretching two model sequences (S1
4542 and S2) with four-stranded beta-barrel topology that unfolding forces
4543 and pathways in folded domains can be predicted by using only the
4544 structure of the native state. Thermal refolding of S1 and S2 in the
4545 absence of force proceeds in an all-or-none fashion. In contrast, phase
4546 diagrams in the force-temperature (f,T) plane and steered Langevin
4547 dynamics studies of these sequences, which differ in the native
4548 registry of the strands, show that S1 unfolds in an allor-none fashion,
4549 whereas unfolding of S2 occurs via an obligatory intermediate. Force-
4550 induced unfolding is determined by the native topology. After proving
4551 that the simulation results for S1 and S2 can be calculated by using
4552 native topology alone, we predict the order of unfolding events in Ig
4553 domain (Ig27) and two fibronectin III type domains ((9)FnIII and
4554 (10)FnIII). The calculated unfolding pathways for these proteins, the
4555 location of the transition states, and the pulling speed dependence of
4556 the unfolding forces reflect the differences in the way the strands are
4557 arranged in the native states. We also predict the mechanisms of force-
4558 induced unfolding of the coiled-coil spectrin (a three-helix bundle
4559 protein) for all 20 structures deposited in the Protein Data Bank. Our
4560 approach suggests a natural way to measure the phase diagram in the
4561 (f,C) plane, where C is the concentration of denaturants.",
4562 note = {Simulated unfolding time scales for Ig27-like S1 and S2 domains.},
4565 @article { klimov99,
4566 author = DKlimov #" and "# DThirumalai,
4567 title = "Stretching single-domain proteins: Phase diagram and kinetics of
4568 force-induced unfolding",
4575 pages = "6166--6170",
4577 keywords = "Amino Acid Sequence;Kinetics;Models, Chemical;Protein
4578 Denaturation;Protein Folding;Proteins;Thermodynamics;Time Factors",
4579 abstract = "Single-molecule force spectroscopy reveals unfolding of domains
4580 in titin on stretching. We provide a theoretical framework for these
4581 experiments by computing the phase diagrams for force-induced unfolding
4582 of single-domain proteins using lattice models. The results show that
4583 two-state folders (at zero force) unravel cooperatively, whereas
4584 stretching of non-two-state folders occurs through intermediates. The
4585 stretching rates of individual molecules show great variations
4586 reflecting the heterogeneity of force-induced unfolding pathways. The
4587 approach to the stretched state occurs in a stepwise ``quantized''
4588 manner. Unfolding dynamics and forces required to stretch proteins
4589 depend sensitively on topology. The unfolding rates increase
4590 exponentially with force f till an optimum value, which is determined
4591 by the barrier to unfolding when f = 0. A mapping of these results to
4592 proteins shows qualitative agreement with force-induced unfolding of
4593 Ig-like domains in titin. We show that single-molecule force
4594 spectroscopy can be used to map the folding free energy landscape of
4595 proteins in the absence of denaturants."
4598 @article { kosztin06,
4599 author = IKosztin #" and "# BBarz #" and "# LJanosi,
4600 title = "Calculating potentials of mean force and diffusion coefficients
4601 from nonequilibrium processes without Jarzynski's equality",
4609 doi = "10.1063/1.2166379",
4610 url = "http://link.aip.org/link/?JCPSA6/124/064106/1"
4613 @article { kramers40,
4615 title = "Brownian motion in a field of force and the diffusion model of
4616 chemical reactions",
4624 doi = "10.1016/S0031-8914(40)90098-2",
4625 url = "http://dx.doi.org/10.1016/S0031-8914(40)90098-2",
4626 abstract = "A particle which is caught in a potential hole and which,
4627 through the shuttling action of Brownian motion, can escape over a
4628 potential barrier yields a suitable model for elucidating the
4629 applicability of the transition state method for calculating the rate
4630 of chemical reactions.",
4631 note = "Seminal paper on thermally activated barrier crossings."
4634 @article { krammer99,
4635 author = AKrammer #" and "# HLu #" and "# BIsralewitz #" and "# KSchulten
4637 title = "Forced unfolding of the fibronectin type {III} module reveals a
4638 tensile molecular recognition switch",
4645 pages = "1351--1356",
4647 keywords = "Amino Acid Sequence;Binding Sites;Computer
4648 Simulation;Crystallography, X-Ray;Disulfides;Fibronectins;Hydrogen
4649 Bonding;Integrins;Models, Molecular;Oligopeptides;Protein
4650 Conformation;Protein Denaturation;Protein Folding;Protein Structure,
4651 Secondary;Protein Structure, Tertiary;Software;Tensile Strength",
4652 abstract = "The 10th type III module of fibronectin possesses a beta-
4653 sandwich structure consisting of seven beta-strands (A-G) that are
4654 arranged in two antiparallel sheets. It mediates cell adhesion to
4655 surfaces via its integrin binding motif, Arg78, Gly79, and Asp80 (RGD),
4656 which is placed at the apex of the loop connecting beta-strands F and
4657 G. Steered molecular dynamics simulations in which tension is applied
4658 to the protein's terminal ends reveal that the beta-strand G is the
4659 first to break away from the module on forced unfolding whereas the
4660 remaining fold maintains its structural integrity. The separation of
4661 strand G from the remaining fold results in a gradual shortening of the
4662 distance between the apex of the RGD-containing loop and the module
4663 surface, which potentially reduces the loop's accessibility to surface-
4664 bound integrins. The shortening is followed by a straightening of the
4665 RGD-loop from a tight beta-turn into a linear conformation, which
4666 suggests a further decrease of affinity and selectivity to integrins.
4667 The RGD-loop therefore is located strategically to undergo strong
4668 conformational changes in the early stretching stages of the module and
4669 thus constitutes a mechanosensitive control of ligand recognition."
4672 @article { kreuzer01,
4673 author = HJKreuzer #" and "# SHPayne,
4674 title = "Stretching a macromolecule in an atomic force microscope:
4675 statistical mechanical analysis",
4684 eprint = "http://www.biophysj.org/cgi/reprint/80/6/2505.pdf",
4685 url = "http://www.biophysj.org/cgi/content/abstract/80/6/2505",
4686 keywords = "Biophysics;Macromolecular Substances;Microscopy, Atomic
4687 Force;Models, Statistical;Models, Theoretical;Statistics as Topic",
4688 abstract = "We formulate the proper statistical mechanics to describe the
4689 stretching of a macromolecule under a force provided by the cantilever
4690 of an atomic force microscope. In the limit of a soft cantilever the
4691 generalized ensemble of the coupled molecule/cantilever system reduces
4692 to the Gibbs ensemble for an isolated molecule subject to a constant
4693 force in which the extension is fluctuating. For a stiff cantilever we
4694 obtain the Helmholtz ensemble for an isolated molecule held at a fixed
4695 extension with the force fluctuating. Numerical examples are given for
4696 poly (ethylene glycol) chains."
4700 author = KKroy #" and "# JGlaser,
4701 title = "The glassy wormlike chain",
4707 doi = "10.1088/1367-2630/9/11/416",
4708 eprint = "http://www.iop.org/EJ/article/1367-2630/9/11/416/njp7_11_416.pdf",
4709 url = "http://stacks.iop.org/1367-2630/9/416",
4710 abstract = "We introduce a new model for the dynamics of a wormlike chain
4711 (WLC) in an environment that gives rise to a rough free energy
4712 landscape, which we name the glassy WLC. It is obtained from the common
4713 WLC by an exponential stretching of the relaxation spectrum of its
4714 long-wavelength eigenmodes, controlled by a single parameter
4715 \\boldsymbol{\\cal E} . Predictions for pertinent observables such as
4716 the dynamic structure factor and the microrheological susceptibility
4717 exhibit the characteristics of soft glassy rheology and compare
4718 favourably with experimental data for reconstituted cytoskeletal
4719 networks and live cells. We speculate about the possible microscopic
4720 origin of the stretching, implications for the nonlinear rheology, and
4721 the potential physiological significance of our results.",
4722 note = "Has short section on WLC relaxation time in the weakly bending
4726 @article { labeit03,
4727 author = DLabeit #" and "# KWatanabe #" and "# CWitt #" and "# HFujita #"
4728 and "# YWu #" and "# SLahmers #" and "# TFunck #" and "# SLabeit #" and
4730 title = "Calcium-dependent molecular spring elements in the giant protein
4736 pages = "13716--13721",
4737 doi = "10.1073/pnas.2235652100",
4738 eprint = "http://www.pnas.org/cgi/reprint/100/23/13716.pdf",
4739 url = "http://www.pnas.org/cgi/content/abstract/100/23/13716",
4740 abstract = "Titin (also known as connectin) is a giant protein with a wide
4741 range of cellular functions, including providing muscle cells with
4742 elasticity. Its physiological extension is largely derived from the
4743 PEVK segment, rich in proline (P), glutamate (E), valine (V), and
4744 lysine (K) residues. We studied recombinant PEVK molecules containing
4745 the two conserved elements: {approx}28-residue PEVK repeats and E-rich
4746 motifs. Single molecule experiments revealed that calcium-induced
4747 conformational changes reduce the bending rigidity of the PEVK
4748 fragments, and site-directed mutagenesis identified four glutamate
4749 residues in the E-rich motif that was studied (exon 129), as critical
4750 for this process. Experiments with muscle fibers showed that titin-
4751 based tension is calcium responsive. We propose that the PEVK segment
4752 contains E-rich motifs that render titin a calcium-dependent molecular
4753 spring that adapts to the physiological state of the cell."
4757 author = SLabeit #" and "# BKolmerer,
4758 title = "Titins: Giant proteins in charge of muscle ultrastructure
4764 address = "European Molecular Biology Laboratory, Heidelberg, Germany.",
4768 keywords = "Actin Cytoskeleton",
4769 keywords = "Amino Acid Sequence",
4770 keywords = "Animals",
4771 keywords = "DNA, Complementary",
4772 keywords = "Elasticity",
4773 keywords = "Fibronectins",
4774 keywords = "Humans",
4775 keywords = "Immunoglobulins",
4776 keywords = "Molecular Sequence Data",
4777 keywords = "Muscle Contraction",
4778 keywords = "Muscle Proteins",
4779 keywords = "Muscle, Skeletal",
4780 keywords = "Myocardium",
4781 keywords = "Protein Kinases",
4782 keywords = "Rabbits",
4783 keywords = "Repetitive Sequences, Nucleic Acid",
4784 keywords = "Sarcomeres",
4785 abstract = "In addition to thick and thin filaments, vertebrate
4786 striated muscle contains a third filament system formed by the
4787 giant protein titin. Single titin molecules extend from Z discs to
4788 M lines and are longer than 1 micrometer. The titin filament
4789 contributes to muscle assembly and resting tension, but more
4790 details are not known because of the large size of the
4791 protein. The complete complementary DNA sequence of human cardiac
4792 titin was determined. The 82-kilobase complementary DNA predicts a
4793 3-megadalton protein composed of 244 copies of immunoglobulin and
4794 fibronectin type III (FN3) domains. The architecture of sequences
4795 in the A band region of titin suggests why thick filament
4796 structure is conserved among vertebrates. In the I band region,
4797 comparison of titin sequences from muscles of different passive
4798 tension identifies two elements that correlate with tissue
4799 stiffness. This suggests that titin may act as two springs in
4800 series. The differential expression of the springs provides a
4801 molecular explanation for the diversity of sarcomere length and
4802 resting tension in vertebrate striated muscles.",
4804 URL = "http://www.ncbi.nlm.nih.gov/pubmed/7569978",
4809 author = RLaw #" and "# GLiao #" and "# SHarper #" and "# GYang #" and "#
4810 DSpeicher #" and "# DDischer,
4811 title = "Pathway shifts and thermal softening in temperature-coupled forced
4812 unfolding of spectrin domains",
4813 address = "Biophysical Engineering Lab, Institute for Medicine and
4814 Engineering, and School of Engineering and Applied Science,
4815 University of Pennsylvania, Philadelphia, Pennsylvania
4822 pages = "3286--3293",
4824 keywords = "Circular Dichroism;Elasticity;Heat;Microscopy, Atomic
4825 Force;Physical Stimulation;Protein Conformation;Protein
4826 Denaturation;Protein Folding;Protein Structure,
4827 Tertiary;Spectrin;Stress, Mechanical;Temperature",
4828 abstract = "Pathways of unfolding a protein depend in principle on the
4829 perturbation-whether it is temperature, denaturant, or even forced
4830 extension. Widely-shared, helical-bundle spectrin repeats are known to
4831 melt at temperatures as low as 40-45 degrees C and are also known to
4832 unfold via multiple pathways as single molecules in atomic force
4833 microscopy. Given the varied roles of spectrin family proteins in cell
4834 deformability, we sought to determine the coupled effects of
4835 temperature on forced unfolding. Bimodal distributions of unfolding
4836 intervals are seen at all temperatures for the four-repeat beta(1-4)
4837 spectrin-an alpha-actinin homolog. The major unfolding length
4838 corresponds to unfolding of a single repeat, and a minor peak at twice
4839 the length corresponds to tandem repeats. Increasing temperature shows
4840 fewer tandem events but has no effect on unfolding intervals. As T
4841 approaches T(m), however, mean unfolding forces in atomic force
4842 microscopy also decrease; and circular dichroism studies demonstrate a
4843 nearly proportional decrease of helical content in solution. The
4844 results imply a thermal softening of a helical linker between repeats
4845 which otherwise propagates a helix-to-coil transition to adjacent
4846 repeats. In sum, structural changes with temperature correlate with
4847 both single-molecule unfolding forces and shifts in unfolding
4849 doi = "10.1016/S0006-3495(03)74747-X",
4850 URL = "http://www.ncbi.nlm.nih.gov/pubmed/14581229",
4854 @article { levinthal68,
4855 author = CLevinthal,
4856 title = "Are there pathways for protein folding?",
4863 "http://www.biochem.wisc.edu/courses/biochem704/Reading/Levinthal1968.p
4865 note = "\emph{Not} Levinthal's paradox."
4868 @inproceedings { levinthal69,
4869 editor = PDebrunner #" and "# JCMTsibris #" and "# EMunck,
4870 author = CLevinthal,
4871 title = "How to Fold Graciously.",
4872 booktitle = "Mossbauer Spectroscopy in Biological Systems",
4875 publisher = UIP:Urbana,
4876 address = "Allerton House, Monticello, IL",
4877 url = "http://www-miller.ch.cam.ac.uk/levinthal/levinthal.html"
4881 author = RLevy #" and "# MMaaloum,
4882 title = "Measuring the spring constant of atomic force microscope
4883 cantilevers: Thermal fluctuations and other methods",
4889 doi = "10.1088/0957-4484/13/1/307",
4890 url = "http://stacks.iop.org/0957-4484/13/33",
4891 abstract = "Knowledge of the interaction forces between surfaces gained
4892 using an atomic force microscope (AFM) is crucial in a variety of
4893 industrial and scientific applications and necessitates a precise
4894 knowledge of the cantilever spring constant. Many methods have been
4895 devised to experimentally determine the spring constants of AFM
4896 cantilevers. The thermal fluctuation method is elegant but requires a
4897 theoretical model of the bending modes. For a rectangular cantilever,
4898 this model is available (Butt and Jaschke). Detailed thermal
4899 fluctuation measurements of a series of AFM cantilever beams have been
4900 performed in order to test the validity and accuracy of the recent
4901 theoretical models. The spring constant of rectangular cantilevers can
4902 also be determined easily with the method of Sader and White. We found
4903 very good agreement between the two methods. In the case of the
4904 V-shaped cantilever, we have shown that the thermal fluctuation method
4905 is a valid and accurate approach to the evaluation of the spring
4906 constant. A comparison between this method and those of Sader-
4907 Neumeister and of Ducker has been established. In some cases, we found
4908 disagreement between these two methods; the effect of non-conservation
4909 of material properties over all cantilevers from a single chip is
4910 qualitatively invoked.",
4911 note = "Good review of thermal calibration to 2002, but not much on the
4912 derviation of the Lorentzian fit.",
4913 project = "Cantilever Calibration"
4917 author = HLi #" and "# AOberhauser #" and "# SFowler #" and "# JClarke #"
4919 title = "Atomic force microscopy reveals the mechanical design of a modular
4925 pages = "6527--6531",
4926 doi = "10.1073/pnas.120048697",
4927 eprint = "http://www.pnas.org/cgi/reprint/97/12/6527.pdf",
4928 url = "http://www.pnas.org/cgi/content/abstract/97/12/6527",
4930 note = "Unfolding order not from protein-surface interactions. Mechanical
4931 unfolding of a chain of interleaved domains $ABABAB\ldots$ yielded a
4932 run of $A$ unfoldings followed by a run of $B$ unfoldings."
4936 author = HLi #" and "# AOberhauser #" and "# SRedick #" and "#
4937 MCarrionVazquez #" and "# HErickson #" and "# JFernandez,
4938 title = "Multiple conformations of {PEVK} proteins detected by single-
4939 molecule techniques",
4944 pages = "10682--10686",
4945 doi = "10.1073/pnas.191189098",
4946 eprint = "http://www.pnas.org/cgi/reprint/98/19/10682.pdf",
4947 url = "http://www.pnas.org/cgi/content/abstract/98/19/10682",
4948 abstract = "An important component of muscle elasticity is the PEVK region
4949 of titin, so named because of the preponderance of these amino acids.
4950 However, the PEVK region, similar to other elastomeric proteins, is
4951 thought to form a random coil and therefore its structure cannot be
4952 determined by standard techniques. Here we combine single-molecule
4953 electron microscopy and atomic force microscopy to examine the
4954 conformations of the human cardiac titin PEVK region. In contrast to a
4955 simple random coil, we have found that cardiac PEVK shows a wide range
4956 of elastic conformations with end-to-end distances ranging from 9 to 24
4957 nm and persistence lengths from 0.4 to 2.5 nm. Individual PEVK
4958 molecules retained their distinctive elastic conformations through many
4959 stretch-relaxation cycles, consistent with the view that these PEVK
4960 conformers cannot be interconverted by force. The multiple elastic
4961 conformations of cardiac PEVK may result from varying degrees of
4962 proline isomerization. The single-molecule techniques demonstrated here
4963 may help elucidate the conformation of other proteins that lack a well-
4968 author = HLi #" and "# JFernandez,
4969 title = "Mechanical design of the first proximal Ig domain of human cardiac
4970 titin revealed by single molecule force spectroscopy",
4979 doi = "10.1016/j.jmb.2003.09.036",
4980 keywords = "Amino Acid Sequence;Disulfides;Humans;Immunoglobulins;Models,
4981 Molecular;Molecular Sequence Data;Muscle Proteins;Myocardium;Protein
4982 Denaturation;Protein Engineering;Protein Kinases;Protein Structure,
4983 Tertiary;Spectrum Analysis",
4984 abstract = "The elastic I-band part of muscle protein titin contains two
4985 tandem immunoglobulin (Ig) domain regions of distinct mechanical
4986 properties. Until recently, the only known structure was that of the
4987 I27 module of the distal region, whose mechanical properties have been
4988 reported in detail. Recently, the structure of the first proximal
4989 domain, I1, has been resolved at 2.1A. In addition to the
4990 characteristic beta-sandwich structure of all titin Ig domains, the
4991 crystal structure of I1 showed an internal disulfide bridge that was
4992 proposed to modulate its mechanical extensibility in vivo. Here, we use
4993 single molecule force spectroscopy and protein engineering to examine
4994 the mechanical architecture of this domain. In contrast to the
4995 predictions made from the X-ray crystal structure, we find that the
4996 formation of a disulfide bridge in I1 is a relatively rare event in
4997 solution, even under oxidative conditions. Furthermore, our studies of
4998 the mechanical stability of I1 modules engineered with point mutations
4999 reveal significant differences between the mechanical unfolding of the
5000 I1 and I27 modules. Our study illustrates the varying mechanical
5001 architectures of the titin Ig modules."
5005 author = LeLi #" and "# HHuang #" and "# CBadilla #" and "# JFernandez,
5006 title = "Mechanical unfolding intermediates observed by single-molecule
5007 force spectroscopy in a fibronectin type {III} module",
5016 doi = "10.1016/j.jmb.2004.11.021",
5017 keywords = "Fibronectins;Kinetics;Microscopy, Atomic Force;Models,
5018 Molecular;Mutagenesis, Site-Directed;Protein Denaturation;Protein
5019 Folding;Protein Structure, Tertiary;Recombinant Fusion Proteins",
5020 abstract = "Domain 10 of type III fibronectin (10FNIII) is known to play a
5021 pivotal role in the mechanical interactions between cell surface
5022 integrins and the extracellular matrix. Recent molecular dynamics
5023 simulations have predicted that 10FNIII, when exposed to a stretching
5024 force, unfolds along two pathways, each with a distinct, mechanically
5025 stable intermediate. Here, we use single-molecule force spectroscopy
5026 combined with protein engineering to test these predictions by probing
5027 the mechanical unfolding pathway of 10FNIII. Stretching single
5028 polyproteins containing the 10FNIII module resulted in sawtooth
5029 patterns where 10FNIII was seen unfolding in two consecutive steps. The
5030 native state unfolded at 100(+/-20) pN, elongating (10)FNIII by
5031 12(+/-2) nm and reaching a clearly marked intermediate that unfolded at
5032 50(+/-20) pN. Unfolding of the intermediate completed the elongation of
5033 the molecule by extending another 19(+/-2) nm. Site-directed
5034 mutagenesis of residues in the A and B beta-strands (E9P and L19P)
5035 resulted in sawtooth patterns with all-or-none unfolding events that
5036 elongated the molecule by 19(+/-2) nm. In contrast, mutating residues
5037 in the G beta-strand gave results that were dependent on amino acid
5038 position. The mutation I88P in the middle of the G beta-strand resulted
5039 in native like unfolding sawtooth patterns showing an intact
5040 intermediate state. The mutation Y92P, which is near the end of G beta-
5041 strand, produced sawtooth patterns with all-or-none unfolding events
5042 that lengthened the molecule by 17(+/-2) nm. These results are
5043 consistent with the view that 10FNIII can unfold in two different ways.
5044 Along one pathway, the detachment of the A and B beta-strands from the
5045 body of the folded module constitute the first unfolding event,
5046 followed by the unfolding of the remaining beta-sandwich structure.
5047 Along the second pathway, the detachment of the G beta-strands is
5048 involved in the first unfolding event. These results are in excellent
5049 agreement with the sequence of events predicted by molecular dynamics
5050 simulations of the 10FNIII module."
5054 author = MSLi #" and "# CKHu #" and "# DKlimov #" and "# DThirumalai,
5055 title = "Multiple stepwise refolding of immunoglobulin domain {I27} upon
5056 force quench depends on initial conditions",
5062 doi = "10.1073/pnas.0503758103",
5063 eprint = "http://www.pnas.org/cgi/reprint/103/1/93.pdf",
5064 url = "http://www.pnas.org/cgi/content/abstract/103/1/93",
5065 abstract = "Mechanical folding trajectories for polyproteins starting from
5066 initially stretched conformations generated by single-molecule atomic
5067 force microscopy experiments [Fernandez, J. M. & Li, H. (2004) Science
5068 303, 1674-1678] show that refolding, monitored by the end-to-end
5069 distance, occurs in distinct multiple stages. To clarify the molecular
5070 nature of folding starting from stretched conformations, we have probed
5071 the folding dynamics, upon force quench, for the single I27 domain from
5072 the muscle protein titin by using a C{alpha}-Go model. Upon temperature
5073 quench, collapse and folding of I27 are synchronous. In contrast,
5074 refolding from stretched initial structures not only increases the
5075 folding and collapse time scales but also decouples the two kinetic
5076 processes. The increase in the folding times is associated primarily
5077 with the stretched state to compact random coil transition.
5078 Surprisingly, force quench does not alter the nature of the refolding
5079 kinetics, but merely increases the height of the free-energy folding
5080 barrier. Force quench refolding times scale as f1.gif, where {Delta}xf
5081 {approx} 0.6 nm is the location of the average transition state along
5082 the reaction coordinate given by end-to-end distance. We predict that
5083 {tau}F and the folding mechanism can be dramatically altered by the
5084 initial and/or final values of force. The implications of our results
5085 for design and analysis of experiments are discussed."
5090 title = "Divergence measures based on the {S}hannon entropy",
5098 doi = "10.1109/18.61115",
5099 url = "http://ieeexplore.ieee.org/xpl/freeabs_all.jsp?isnumber=2227&arnumbe
5100 r=61115&count=35&index=9",
5101 keywords = "divergence;dissimilarity measure;discrimintation
5102 information;entropy;probability of error bounds",
5103 abstract = "A novel class of information-theoretic divergence measures
5104 based on the Shannon entropy is introduced. Unlike the well-known
5105 Kullback divergences, the new measures do not require the condition of
5106 absolute continuity to be satisfied by the probability distributions
5107 involved. More importantly, their close relationship with the
5108 variational distance and the probability of misclassification error are
5109 established in terms of bounds. These bounds are crucial in many
5110 applications of divergence measures. The measures are also well
5111 characterized by the properties of nonnegativity, finiteness,
5112 semiboundedness, and boundedness."
5116 author = WALinke #" and "# AGrutzner,
5117 title = "Pulling single molecules of titin by {AFM}--recent advances and
5118 physiological implications",
5127 doi = "10.1007/s00424-007-0389-x",
5128 abstract = "Perturbation of a protein away from its native state by
5129 mechanical stress is a physiological process immanent to many cells.
5130 The mechanical stability and conformational diversity of proteins under
5131 force therefore are important parameters in nature. Molecular-level
5132 investigations of ``mechanical proteins'' have enjoyed major
5133 breakthroughs over the last decade, a development to which atomic force
5134 microscopy (AFM) force spectroscopy has been instrumental. The giant
5135 muscle protein titin continues to be a paradigm model in this field. In
5136 this paper, we review how single-molecule mechanical measurements of
5137 titin using AFM have served to elucidate key aspects of protein
5138 unfolding-refolding and mechanisms by which biomolecular elasticity is
5139 attained. We outline recent work combining protein engineering and AFM
5140 force spectroscopy to establish the mechanical behavior of titin
5141 domains using molecular ``fingerprinting.'' Furthermore, we summarize
5142 AFM force-extension data demonstrating different mechanical stabilities
5143 of distinct molecular-spring elements in titin, compare AFM force-
5144 extension to novel force-ramp/force-clamp studies, and elaborate on
5145 exciting new results showing that AFM force clamp captures the
5146 unfolding and refolding trajectory of single mechanical proteins. Along
5147 the way, we discuss the physiological implications of the findings, not
5148 least with respect to muscle mechanics. These studies help us
5149 understand how proteins respond to forces in cells and how
5150 mechanosensing and mechanosignaling events may proceed in vivo."
5153 @article { linke98a,
5154 author = WALinke #" and "# MRStockmeier #" and "# MIvemeyer #" and "#
5155 HHosser #" and "# PMundel,
5156 title = "Characterizing titin's {I}-band {Ig} domain region as an entropic
5161 volume = "111 (Pt 11)",
5162 pages = "1567--1574",
5165 eprint = "http://jcs.biologists.org/cgi/reprint/111/11/1567",
5166 url = "http://jcs.biologists.org/cgi/content/abstract/111/11/1567",
5167 keywords = "Animals;Elasticity;Immunoglobulins;Male;Muscle Proteins;Muscle,
5168 Skeletal;Protein Kinases;Rats;Rats, Wistar;Structure-Activity
5170 abstract = "The poly-immunoglobulin domain region of titin, located within
5171 the elastic section of this giant muscle protein, determines the
5172 extensibility of relaxed myofibrils mainly at shorter physiological
5173 lengths. To elucidate this region's contribution to titin elasticity,
5174 we measured the elastic properties of the N-terminal I-band Ig region
5175 by using immunofluorescence/immunoelectron microscopy and myofibril
5176 mechanics and tried to simulate the results with a model of entropic
5177 polymer elasticity. Rat psoas myofibrils were stained with titin-
5178 specific antibodies flanking the Ig region at the N terminus and C
5179 terminus, respectively, to record the extension behaviour of that titin
5180 segment. The segment's end-to-end length increased mainly at small
5181 stretch, reaching approximately 90\% of the native contour length of
5182 the Ig region at a sarcomere length of 2.8 microm. At this extension,
5183 the average force per single titin molecule, deduced from the steady-
5184 state passive length-tension relation of myofibrils, was approximately
5185 5 or 2.5 pN, depending on whether we assumed a number of 3 or 6 titins
5186 per half thick filament. When the force-extension curve constructed for
5187 the Ig region was simulated by the wormlike chain model, best fits were
5188 obtained for a persistence length, a measure of the chain's bending
5189 rigidity, of 21 or 42 nm (for 3 or 6 titins/half thick filament), which
5190 correctly reproduced the curve for sarcomere lengths up to 3.4 microm.
5191 Systematic deviations between data and fits above that length indicated
5192 that forces of >30 pN per titin strand may induce unfolding of Ig
5193 modules. We conclude that stretches of at least 5-6 Ig domains, perhaps
5194 coinciding with known super repeat patterns of these titin modules in
5195 the I-band, may represent the unitary lengths of the wormlike chain.
5196 The poly-Ig regions might thus act as compliant entropic springs that
5197 determine the minute levels of passive tension at low extensions of a
5201 @article { linke98b,
5202 author = WALinke #" and "# MIvemeyer #" and "# PMundel #" and "#
5203 MRStockmeier #" and "# BKolmerer,
5204 title = "Nature of {PEVK}-titin elasticity in skeletal muscle",
5211 pages = "8052--8057",
5213 keywords = "Animals;Elasticity;Fluorescent Antibody
5214 Technique;Male;Microscopy, Immunoelectron;Muscle Proteins;Muscle,
5215 Skeletal;Protein Kinases;Rats;Rats, Wistar;Stress, Mechanical",
5216 abstract = "A unique sequence within the giant titin molecule, the PEVK
5217 domain, has been suggested to greatly contribute to passive force
5218 development of relaxed skeletal muscle during stretch. To explore the
5219 nature of PEVK elasticity, we used titin-specific antibodies to stain
5220 both ends of the PEVK region in rat psoas myofibrils and determined the
5221 region's force-extension relation by combining immunofluorescence and
5222 immunoelectron microscopy with isolated myofibril mechanics. We then
5223 tried to fit the results with recent models of polymer elasticity. The
5224 PEVK segment elongated substantially at sarcomere lengths above 2.4
5225 micro(m) and reached its estimated contour length at approximately 3.5
5226 micro(m). In immunofluorescently labeled sarcomeres stretched and
5227 released repeatedly above 3 micro(m), reversible PEVK lengthening could
5228 be readily visualized. At extensions near the contour length, the
5229 average force per titin molecule was calculated to be approximately 45
5230 pN. Attempts to fit the force-extension curve of the PEVK segment with
5231 a standard wormlike chain model of entropic elasticity were successful
5232 only for low to moderate extensions. In contrast, the experimental data
5233 also could be correctly fitted at high extensions with a modified
5234 wormlike chain model that incorporates enthalpic elasticity. Enthalpic
5235 contributions are likely to arise from electrostatic stiffening, as
5236 evidenced by the ionic-strength dependency of titin-based myofibril
5237 stiffness; at high stretch, hydrophobic effects also might become
5238 relevant. Thus, at physiological muscle lengths, the PEVK region does
5239 not function as a pure entropic spring. Rather, PEVK elasticity may
5240 have both entropic and enthalpic origins characterizable by a polymer
5241 persistence length and a stretch modulus."
5245 author = WLiu #" and "# VMontana #" and "# EChapman #" and "# UMohideen #"
5247 title = "Botulinum toxin type {B} micromechanosensor",
5252 pages = "13621--13625",
5253 doi = "10.1073/pnas.2233819100",
5254 eprint = "http://www.pnas.org/cgi/reprint/100/23/13621.pdf",
5255 url = "http://www.pnas.org/cgi/content/abstract/100/23/13621",
5256 abstract = "Botulinum neurotoxin (BoNT) types A, B, E, and F are toxic to
5257 humans; early and rapid detection is essential for adequate medical
5258 treatment. Presently available tests for detection of BoNTs, although
5259 sensitive, require hours to days. We report a BoNT-B sensor whose
5260 properties allow detection of BoNT-B within minutes. The technique
5261 relies on the detection of an agarose bead detachment from the tip of a
5262 micromachined cantilever resulting from BoNT-B action on its
5263 substratum, the synaptic protein synaptobrevin 2, attached to the
5264 beads. The mechanical resonance frequency of the cantilever is
5265 monitored for the detection. To suspend the bead off the cantilever we
5266 use synaptobrevin's molecular interaction with another synaptic
5267 protein, syntaxin 1A, that was deposited onto the cantilever tip.
5268 Additionally, this bead detachment technique is general and can be used
5269 in any displacement reaction, such as in receptor-ligand pairs, where
5270 the introduction of one chemical leads to the displacement of another.
5271 The technique is of broad interest and will find uses outside
5276 author = GLois #" and "# JBlawzdziewicz #" and "# CSOHern,
5277 title = "Reliable protein folding on complex energy landscapes: the free
5278 energy reaction path",
5285 pages = "2692--2701",
5287 doi = "10.1529/biophysj.108.133132",
5288 abstract = "A theoretical framework is developed to study the dynamics of
5289 protein folding. The key insight is that the search for the native
5290 protein conformation is influenced by the rate r at which external
5291 parameters, such as temperature, chemical denaturant, or pH, are
5292 adjusted to induce folding. A theory based on this insight predicts
5293 that 1), proteins with complex energy landscapes can fold reliably to
5294 their native state; 2), reliable folding can occur as an equilibrium or
5295 out-of-equilibrium process; and 3), reliable folding only occurs when
5296 the rate r is below a limiting value, which can be calculated from
5297 measurements of the free energy. We test these predictions against
5298 numerical simulations of model proteins with a single energy scale."
5302 author = HLu #" and "# AKrammer #" and "# BIsralewitz #" and "# VVogel #"
5304 title = "Computer modeling of force-induced titin domain unfolding",
5306 journal = AdvExpMedBiol,
5310 url = {http://www.ncbi.nlm.nih.gov/pubmed/10987071},
5311 keywords = "Amino Acid Sequence;Animals;Computer
5312 Simulation;Elasticity;Fibronectins;Humans;Hydrogen
5313 Bonding;Immunoglobulins;Models, Molecular;Muscle Proteins;Muscle,
5314 Skeletal;Myofibrils;Protein Conformation;Protein Denaturation;Protein
5316 abstract = "Titin, a 1 micron long protein found in striated muscle
5317 myofibrils, possesses unique elastic and extensibility properties, and
5318 is largely composed of a PEVK region and beta-sandwich immunoglobulin
5319 (Ig) and fibronectin type III (FnIII) domains. The extensibility
5320 behavior of titin has been shown in atomic force microscope and optical
5321 tweezer experiments to partially depend on the reversible unfolding of
5322 individual Ig and FnIII domains. We performed steered molecular
5323 dynamics simulations to stretch single titin Ig domains in solution
5324 with pulling speeds of 0.1-1.0 A/ps, and FnIII domains with a pulling
5325 speed of 0.5 A/ps. Resulting force-extension profiles exhibit a single
5326 dominant peak for each domain unfolding, consistent with the
5327 experimentally observed sequential, as opposed to concerted, unfolding
5328 of Ig and FnIII domains under external stretching forces. The force
5329 peaks can be attributed to an initial burst of a set of backbone
5330 hydrogen bonds connected to the domains' terminal beta-strands.
5331 Constant force stretching simulations, applying 500-1000 pN of force,
5332 were performed on Ig domains. The resulting domain extensions are
5333 halted at an initial extension of 10 A until the set of all six
5334 hydrogen bonds connecting terminal beta-strands break simultaneously.
5335 This behavior is accounted for by a barrier separating folded and
5336 unfolded states, the shape of which is consistent with AFM and chemical
5337 denaturation data.",
5338 note = "discussion in journal on pages 161--2"
5342 author = HLu #" and "# KSchulten,
5343 title = "The key event in force-induced unfolding of Titin's immunoglobulin
5352 doi = {10.1016/S0006-3495(00)76273-4},
5353 url = {http://www.cell.com/biophysj/abstract/S0006-3495%2800%2976273-4},
5354 eprint = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1300915/pdf/10866937.pdf},
5355 keywords = "Amino Acid Sequence;Computer Simulation;Double Bind
5356 Interaction;Hydrogen Bonding;Immunoglobulins;Microscopy, Atomic
5357 Force;Models, Chemical;Models, Molecular;Molecular Sequence Data;Muscle
5358 Proteins;Protein Folding;Protein Kinases;Protein Structure,
5359 Tertiary;Stress, Mechanical;Water",
5360 abstract = "Steered molecular dynamics simulation of force-induced titin
5361 immunoglobulin domain I27 unfolding led to the discovery of a
5362 significant potential energy barrier at an extension of approximately
5363 14 A on the unfolding pathway that protects the domain against
5364 stretching. Previous simulations showed that this barrier is due to the
5365 concurrent breaking of six interstrand hydrogen bonds (H-bonds) between
5366 beta-strands A' and G that is preceded by the breaking of two to three
5367 hydrogen bonds between strands A and B, the latter leading to an
5368 unfolding intermediate. The simulation results are supported by
5369 Angstrom-resolution atomic force microscopy data. Here we perform a
5370 structural and energetic analysis of the H-bonds breaking. It is
5371 confirmed that H-bonds between strands A and B break rapidly. However,
5372 the breaking of the H-bond between strands A' and G needs to be
5373 assisted by fluctuations of water molecules. In nanosecond simulations,
5374 water molecules are found to repeatedly interact with the protein
5375 backbone atoms, weakening individual interstrand H-bonds until all six
5376 A'-G H-bonds break simultaneously under the influence of external
5377 stretching forces. Only when those bonds are broken can the generic
5378 unfolding take place, which involves hydrophobic interactions of the
5379 protein core and exerts weaker resistance against stretching than the
5384 author = HLu #" and "# BIsralewitz #" and "# AKrammer #" and "# VVogel #"
5386 title = "Unfolding of titin immunoglobulin domains by steered molecular
5387 dynamics simulation",
5395 doi = "10.1016/S0006-3495(98)77556-3",
5396 eprint = "http://download.cell.com/biophysj/pdf/PIIS0006349598775563.pdf",
5397 url = "http://www.cell.com/biophysj/abstract/S0006-3495(98)77556-3",
5398 keywords = "Amino Acid Sequence;Animals;Computer Simulation;Glutamic
5399 Acid;Immunoglobulins;Lysine;Macromolecular Substances;Models,
5400 Molecular;Molecular Sequence Data;Muscle
5401 Proteins;Myocardium;Proline;Protein Denaturation;Protein
5402 Folding;Protein Kinases;Protein Structure, Secondary;Sequence
5403 Alignment;Sequence Homology, Amino Acid;Valine",
5404 abstract = "Titin, a 1-microm-long protein found in striated muscle
5405 myofibrils, possesses unique elastic and extensibility properties in
5406 its I-band region, which is largely composed of a PEVK region (70\%
5407 proline, glutamic acid, valine, and lysine residue) and seven-strand
5408 beta-sandwich immunoglobulin-like (Ig) domains. The behavior of titin
5409 as a multistage entropic spring has been shown in atomic force
5410 microscope and optical tweezer experiments to partially depend on the
5411 reversible unfolding of individual Ig domains. We performed steered
5412 molecular dynamics simulations to stretch single titin Ig domains in
5413 solution with pulling speeds of 0.5 and 1.0 A/ps. Resulting force-
5414 extension profiles exhibit a single dominant peak for each Ig domain
5415 unfolding, consistent with the experimentally observed sequential, as
5416 opposed to concerted, unfolding of Ig domains under external stretching
5417 forces. This force peak can be attributed to an initial burst of
5418 backbone hydrogen bonds, which takes place between antiparallel beta-
5419 strands A and B and between parallel beta-strands A' and G. Additional
5420 features of the simulations, including the position of the force peak
5421 and relative unfolding resistance of different Ig domains, can be
5422 related to experimental observations."
5426 author = HLu #" and "# KSchulten,
5427 title = "Steered molecular dynamics simulations of force-induced protein
5437 doi = "10.1002/(SICI)1097-0134(19990601)35:4<453::AID-PROT9>3.0.CO;2-M",
5438 eprint = "http://www3.interscience.wiley.com/cgi-bin/fulltext/65000328/PDFSTART",
5439 url = "http://www3.interscience.wiley.com/journal/65000328/abstract",
5440 keywords = "Computer Simulation;Fibronectins;Hydrogen Bonding;Microscopy,
5441 Atomic Force;Models, Molecular;Protein Denaturation",
5442 abstract = "Steered molecular dynamics (SMD), a computer simulation method
5443 for studying force-induced reactions in biopolymers, has been applied
5444 to investigate the response of protein domains to stretching apart of
5445 their terminal ends. The simulations mimic atomic force microscopy and
5446 optical tweezer experiments, but proceed on much shorter time scales.
5447 The simulations on different domains for 0.6 nanosecond each reveal two
5448 types of protein responses: the first type, arising in certain beta-
5449 sandwich domains, exhibits nanosecond unfolding only after a force
5450 above 1,500 pN is applied; the second type, arising in a wider class of
5451 protein domain structures, requires significantly weaker forces for
5452 nanosecond unfolding. In the first case, strong forces are needed to
5453 concertedly break a set of interstrand hydrogen bonds which protect the
5454 domains against unfolding through stretching; in the second case,
5455 stretching breaks backbone hydrogen bonds one by one, and does not
5456 require strong forces for this purpose. Stretching of beta-sandwich
5457 (immunoglobulin) domains has been investigated further revealing a
5458 specific relationship between response to mechanical strain and the
5459 architecture of beta-sandwich domains."
5462 @article { makarov01,
5463 author = DEMakarov #" and "# PHansma #" and "# HMetiu,
5464 title = "Kinetic Monte Carlo simulation of titin unfolding",
5470 pages = "9663--9673",
5472 doi = "10.1063/1.1369622",
5473 eprint = "http://hansmalab.physics.ucsb.edu/pdf/297%20-%20Makarov,%20D.E._J
5474 .Chem.Phys._2001.pdf",
5475 url = "http://link.aip.org/link/?JCP/114/9663/1",
5476 keywords = "proteins; hydrogen bonds; digital simulation; Monte Carlo
5477 methods; molecular biophysics; intramolecular mechanics;
5478 macromolecules; atomic force microscopy"
5482 author = JFMarko #" and "# EDSiggia,
5483 title = "Stretching {DNA}",
5489 pages = "8759--8770",
5491 eprint = "http://pubs.acs.org/cgi-
5492 bin/archive.cgi/mamobx/1995/28/i26/pdf/ma00130a008.pdf",
5494 "http://pubs3.acs.org/acs/journals/doilookup?in_doi=10.1021/ma00130a008
5497 note = "Derivation of the Worm-like Chain interpolation function."
5500 @article { marszalek02,
5501 author = PMarszalek #" and "# HLi #" and "# AOberhauser #" and "#
5503 title = "Chair-boat transitions in single polysaccharide molecules observed
5504 with force-ramp {AFM}",
5509 pages = "4278--4283",
5510 doi = "10.1073/pnas.072435699",
5511 eprint = "http://www.pnas.org/cgi/reprint/99/7/4278.pdf",
5512 url = "http://www.pnas.org/cgi/content/abstract/99/7/4278",
5513 abstract = "Under a stretching force, the sugar ring of polysaccharide
5514 molecules switches from the chair to the boat-like or inverted chair
5515 conformation. This conformational change can be observed by stretching
5516 single polysaccharide molecules with an atomic force microscope. In
5517 those early experiments, the molecules were stretched at a constant
5518 rate while the resulting force changed over wide ranges. However,
5519 because the rings undergo force-dependent transitions, an experimental
5520 arrangement where the force is the free variable introduces an
5521 undesirable level of complexity in the results. Here we demonstrate the
5522 use of force-ramp atomic force microscopy to capture the conformational
5523 changes in single polysaccharide molecules. Force-ramp atomic force
5524 microscopy readily captures the ring transitions under conditions where
5525 the entropic elasticity of the molecule is separated from its
5526 conformational transitions, enabling a quantitative analysis of the
5527 data with a simple two-state model. This analysis directly provides the
5528 physico-chemical characteristics of the ring transitions such as the
5529 width of the energy barrier, the relative energy of the conformers, and
5530 their enthalpic elasticity. Our experiments enhance the ability of
5531 single-molecule force spectroscopy to make high-resolution measurements
5532 of the conformations of single polysaccharide molecules under a
5533 stretching force, making an important addition to polysaccharide
5537 @article { marszalek99,
5538 author = PMarszalek #" and "# HLu #" and "# HLi #" and "# MCarrionVazquez
5539 #" and "# AOberhauser #" and "# KSchulten #" and "# JFernandez,
5540 title = "Mechanical unfolding intermediates in titin modules",
5549 doi = "10.1038/47083",
5550 eprint = "http://www.nature.com/nature/journal/v402/n6757/pdf/402100a0.pdf",
5551 url = "http://www.nature.com/nature/journal/v402/n6757/abs/402100a0.html",
5552 keywords = "Biomechanics;Computer Simulation;Humans;Hydrogen
5553 Bonding;Microscopy, Atomic Force;Models, Molecular;Muscle
5554 Proteins;Myocardium;Protein Folding;Protein Kinases;Recombinant
5556 abstract = "The modular protein titin, which is responsible for the passive
5557 elasticity of muscle, is subjected to stretching forces. Previous work
5558 on the experimental elongation of single titin molecules has suggested
5559 that force causes consecutive unfolding of each domain in an all-or-
5560 none fashion. To avoid problems associated with the heterogeneity of
5561 the modular, naturally occurring titin, we engineered single proteins
5562 to have multiple copies of single immunoglobulin domains of human
5563 cardiac titin. Here we report the elongation of these molecules using
5564 the atomic force microscope. We find an abrupt extension of each domain
5565 by approximately 7 A before the first unfolding event. This fast
5566 initial extension before a full unfolding event produces a reversible
5567 'unfolding intermediate' Steered molecular dynamics simulations show
5568 that the rupture of a pair of hydrogen bonds near the amino terminus of
5569 the protein domain causes an extension of about 6 A, which is in good
5570 agreement with our observations. Disruption of these hydrogen bonds by
5571 site-directed mutagenesis eliminates the unfolding intermediate. The
5572 unfolding intermediate extends titin domains by approximately 15\% of
5573 their slack length, and is therefore likely to be an important
5574 previously unrecognized component of titin elasticity."
5577 @article { mcpherson01,
5578 author = JDMcPherson #" and "# MMarra #" and "# LHillier #" and "#
5579 RHWaterston #" and "# AChinwalla #" and "# JWallis #" and "# MSekhon #"
5580 and "# KWylie #" and "# ERMardis #" and "# RKWilson #" and "# RFulton
5581 #" and "# TAKucaba #" and "# CWagner-McPherson #" and "# WBBarbazuk #"
5582 and "# SGGregory #" and "# SJHumphray #" and "# LFrench #" and "#
5583 RSEvans #" and "# GBethel #" and "# AWhittaker #" and "# JLHolden #"
5584 and "# OTMcCann #" and "# ADunham #" and "# CSoderlund #" and "#
5585 CEScott #" and "# DRBentley #" and "# GSchuler #" and "# HCChen #" and
5586 "# WJang #" and "# EDGreen #" and "# JRIdol #" and "# VVMaduro #" and
5587 "# KTMontgomery #" and "# ELee #" and "# AMiller #" and "# SEmerling #"
5588 and "# Kucherlapati #" and "# RGibbs #" and "# SScherer #" and "#
5589 JHGorrell #" and "# ESodergren #" and "# KClerc-Blankenburg #" and "#
5590 PTabor #" and "# SNaylor #" and "# DGarcia #" and "# PJdeJong #" and "#
5591 JJCatanese #" and "# NNowak #" and "# KOsoegawa #" and "# SQin #" and
5592 "# LRowen #" and "# AMadan #" and "# MDors #" and "# LHood #" and "#
5593 BTrask #" and "# CFriedman #" and "# HMassa #" and "# VGCheung #" and
5594 "# IRKirsch #" and "# TReid #" and "# RYonescu #" and "# JWeissenbach
5595 #" and "# TBruls #" and "# RHeilig #" and "# EBranscomb #" and "#
5596 AOlsen #" and "# NDoggett #" and "# JFCheng #" and "# THawkins #" and
5597 "# RMMyers #" and "# JShang #" and "# LRamirez #" and "# JSchmutz #"
5598 and "# OVelasquez #" and "# KDixon #" and "# NEStone #" and "# DRCox #"
5599 and "# DHaussler #" and "# WJKent #" and "# TFurey #" and "# SRogic #"
5600 and "# SKennedy #" and "# SJones #" and "# ARosenthal #" and "# GWen #"
5601 and "# MSchilhabel #" and "# GGloeckner #" and "# GNyakatura #" and "#
5602 RSiebert #" and "# BSchlegelberger #" and "# JKorenberg #" and "#
5603 XNChen #" and "# AFujiyama #" and "# MHattori #" and "# AToyoda #" and
5604 "# TYada #" and "# HSPark #" and "# YSakaki #" and "# NShimizu #" and
5605 "# SAsakawa #" and "# KKawasaki #" and "# TSasaki #" and "# AShintani
5606 #" and "# AShimizu #" and "# KShibuya #" and "# JKudoh #" and "#
5607 SMinoshima #" and "# JRamser #" and "# PSeranski #" and "# CHoff #" and
5608 "# APoustka #" and "# RReinhardt #" and "# HLehrach,
5609 title = "A physical map of the human genome.",
5618 doi = "10.1038/35057157",
5619 eprint = "http://www.nature.com/nature/journal/v409/n6822/pdf/409934a0.pdf",
5620 url = "http://www.nature.com/nature/journal/v409/n6822/full/409934a0.html",
5621 keywords = "Chromosomes, Artificial, Bacterial;Cloning, Molecular;Contig
5622 Mapping;DNA Fingerprinting;Gene Duplication;Genome, Human;Humans;In
5623 Situ Hybridization, Fluorescence;Repetitive Sequences, Nucleic Acid",
5624 abstract = "The human genome is by far the largest genome to be sequenced,
5625 and its size and complexity present many challenges for sequence
5626 assembly. The International Human Genome Sequencing Consortium
5627 constructed a map of the whole genome to enable the selection of clones
5628 for sequencing and for the accurate assembly of the genome sequence.
5629 Here we report the construction of the whole-genome bacterial
5630 artificial chromosome (BAC) map and its integration with previous
5631 landmark maps and information from mapping efforts focused on specific
5632 chromosomal regions. We also describe the integration of sequence data
5637 author = CCMello #" and "# DBarrick,
5638 title = "An experimentally determined protein folding energy landscape",
5645 pages = "14102--14107",
5647 doi = "10.1073/pnas.0403386101",
5648 keywords = "Animals; Ankyrin Repeat; Circular Dichroism; Drosophila
5649 Proteins; Drosophila melanogaster; Gene Deletion; Models, Chemical;
5650 Models, Molecular; Protein Denaturation; Protein Folding; Protein
5651 Structure, Tertiary; Spectrometry, Fluorescence; Thermodynamics; Urea",
5652 abstract = "Energy landscapes have been used to conceptually describe and
5653 model protein folding but have been difficult to measure
5654 experimentally, in large part because of the myriad of partly folded
5655 protein conformations that cannot be isolated and thermodynamically
5656 characterized. Here we experimentally determine a detailed energy
5657 landscape for protein folding. We generated a series of overlapping
5658 constructs containing subsets of the seven ankyrin repeats of the
5659 Drosophila Notch receptor, a protein domain whose linear arrangement of
5660 modular structural units can be fragmented without disrupting
5661 structure. To a good approximation, stabilities of each construct can
5662 be described as a sum of energy terms associated with each repeat. The
5663 magnitude of each energy term indicates that each repeat is
5664 intrinsically unstable but is strongly stabilized by interactions with
5665 its nearest neighbors. These linear energy terms define an equilibrium
5666 free energy landscape, which shows an early free energy barrier and
5667 suggests preferred low-energy routes for folding."
5670 @article { merkel99,
5671 author = RMerkel #" and "# PNassoy #" and "# ALeung #" and "# KRitchie #"
5673 title = "Energy landscapes of receptor-ligand bonds explored with dynamic
5674 force spectroscopy",
5683 doi = "10.1038/16219",
5684 url = "http://www.nature.com/nature/journal/v397/n6714/full/397050a0.html",
5685 keywords = "Biotin;Microscopy, Atomic Force;Protein Binding;Streptavidin",
5686 abstract = "Atomic force microscopy (AFM) has been used to measure the
5687 strength of bonds between biological receptor molecules and their
5688 ligands. But for weak noncovalent bonds, a dynamic spectrum of bond
5689 strengths is predicted as the loading rate is altered, with the
5690 measured strength being governed by the prominent barriers traversed in
5691 the energy landscape along the force-driven bond-dissociation pathway.
5692 In other words, the pioneering early AFM measurements represent only a
5693 single point in a continuous spectrum of bond strengths, because theory
5694 predicts that these will depend on the rate at which the load is
5695 applied. Here we report the strength spectra for the bonds between
5696 streptavidin (or avidin) and biotins-the prototype of receptor-ligand
5697 interactions used in earlier AFM studies, and which have been modelled
5698 by molecular dynamics. We have probed bond formation over six orders of
5699 magnitude in loading rate, and find that the bond survival time
5700 diminished from about 1 min to 0.001 s with increasing loading rate
5701 over this range. The bond strength, meanwhile, increased from about 5
5702 pN to 170 pN. Thus, although they are among the strongest noncovalent
5703 linkages in biology (affinity of 10(13) to 10(15) M(-1)), these bonds
5704 in fact appear strong or weak depending on how fast they are loaded. We
5705 are also able to relate the activation barriers derived from our
5706 strength spectra to the shape of the energy landscape derived from
5707 simulations of the biotin-avidin complex."
5710 @article { metropolis87,
5711 author = NMetropolis,
5712 title = "The Beginning of the {M}onte {C}arlo Method",
5718 url = "http://library.lanl.gov/cgi-bin/getfile?15-12.pdf"
5721 @article { mickler07,
5722 author = MMickler #" and "# RDima #" and "# HDietz #" and "# CHyeon #" and
5723 "# DThirumalai #" and "# MRief,
5724 title = "Revealing the bifurcation in the unfolding pathways of {GFP} by
5725 using single-molecule experiments and simulations",
5730 pages = "20268--20273",
5731 doi = "10.1073/pnas.0705458104",
5732 eprint = "http://www.pnas.org/cgi/reprint/104/51/20268.pdf",
5733 url = "http://www.pnas.org/cgi/content/abstract/104/51/20268",
5734 keywords = "AFM experiments, coarse-grained simulations, cross-link
5735 mutants, pathway bifurcation, plasticity of energy landscape",
5736 abstract = "Nanomanipulation of biomolecules by using single-molecule
5737 methods and computer simulations has made it possible to visualize the
5738 energy landscape of biomolecules and the structures that are sampled
5739 during the folding process. We use simulations and single-molecule
5740 force spectroscopy to map the complex energy landscape of GFP that is
5741 used as a marker in cell biology and biotechnology. By engineering
5742 internal disulfide bonds at selected positions in the GFP structure,
5743 mechanical unfolding routes are precisely controlled, thus allowing us
5744 to infer features of the energy landscape of the wild-type GFP. To
5745 elucidate the structures of the unfolding pathways and reveal the
5746 multiple unfolding routes, the experimental results are complemented
5747 with simulations of a self-organized polymer (SOP) model of GFP. The
5748 SOP representation of proteins, which is a coarse-grained description
5749 of biomolecules, allows us to perform forced-induced simulations at
5750 loading rates and time scales that closely match those used in atomic
5751 force microscopy experiments. By using the combined approach, we show
5752 that forced unfolding of GFP involves a bifurcation in the pathways to
5753 the stretched state. After detachment of an N-terminal {alpha}-helix,
5754 unfolding proceeds along two distinct pathways. In the dominant
5755 pathway, unfolding starts from the detachment of the primary N-terminal
5756 -strand, while in the minor pathway rupture of the last, C-terminal
5757 -strand initiates the unfolding process. The combined approach has
5758 allowed us to map the features of the complex energy landscape of GFP
5759 including a characterization of the structures, albeit at a coarse-
5760 grained level, of the three metastable intermediates.",
5761 note = {Hiccup in unfolding leg corresponds to unfolding
5762 intermediate (\fref{figure}{2}). The unfolding time scale in GFP
5763 is about $6\U{ms}$.},
5767 author = RNevo #" and "# CStroh #" and "# FKienberger #" and "# DKaftan #"
5768 and "# VBrumfeld #" and "# MElbaum #" and "# ZReich #" and "#
5770 title = "A molecular switch between alternative conformational states in
5771 the complex of {Ran} and importin beta1",
5779 doi = "10.1038/nsb940",
5780 eprint = "http://www.nature.com/nsmb/journal/v10/n7/pdf/nsb940.pdf",
5781 url = "http://www.nature.com/nsmb/journal/v10/n7/abs/nsb940.html",
5782 keywords = "Guanosine Diphosphate; Guanosine Triphosphate; Microscopy,
5783 Atomic Force; Protein Binding; Protein Conformation; beta Karyopherins;
5784 ran GTP-Binding Protein",
5785 abstract = "Several million macromolecules are exchanged each minute
5786 between the nucleus and cytoplasm by receptor-mediated transport. Most
5787 of this traffic is controlled by the small GTPase Ran, which regulates
5788 assembly and disassembly of the receptor-cargo complexes in the
5789 appropriate cellular compartment. Here we applied dynamic force
5790 spectroscopy to study the interaction of Ran with the nuclear import
5791 receptor importin beta1 (impbeta) at the single-molecule level. We
5792 found that the complex alternates between two distinct conformational
5793 states of different adhesion strength. The application of an external
5794 mechanical force shifts equilibrium toward one of these states by
5795 decreasing the height of the interstate activation energy barrier. The
5796 other state can be stabilized by a functional Ran mutant that increases
5797 this barrier. These results support a model whereby functional control
5798 of Ran-impbeta is achieved by a population shift between pre-existing
5799 alternative conformations."
5803 author = RNevo #" and "# VBrumfeld #" and "# MElbaum #" and "#
5804 PHinterdorfer #" and "# ZReich,
5805 title = "Direct discrimination between models of protein activation by
5806 single-molecule force measurements",
5812 pages = "2630--2634",
5814 doi = "10.1529/biophysj.104.041889",
5815 eprint = "http://www.biophysj.org/cgi/reprint/87/4/2630.pdf",
5816 url = "http://www.biophysj.org/cgi/content/abstract/87/4/2630",
5817 keywords = "Elasticity; Enzyme Activation; Micromanipulation; Microscopy,
5818 Atomic Force; Models, Chemical; Models, Molecular; Multiprotein
5819 Complexes; Nuclear Proteins; Physical Stimulation; Protein Binding;
5820 Stress, Mechanical; Structure-Activity Relationship; beta Karyopherins;
5821 ran GTP-Binding Protein",
5822 abstract = "The limitations imposed on the analyses of complex chemical and
5823 biological systems by ensemble averaging can be overcome by single-
5824 molecule experiments. Here, we used a single-molecule technique to
5825 discriminate between two generally accepted mechanisms of a key
5826 biological process--the activation of proteins by molecular effectors.
5827 The two mechanisms, namely induced-fit and population-shift, are
5828 normally difficult to discriminate by ensemble approaches. As a model,
5829 we focused on the interaction between the nuclear transport effector,
5830 RanBP1, and two related complexes consisting of the nuclear import
5831 receptor, importin beta, and the GDP- or GppNHp-bound forms of the
5832 small GTPase, Ran. We found that recognition by the effector proceeds
5833 through either an induced-fit or a population-shift mechanism,
5834 depending on the substrate, and that the two mechanisms can be
5835 differentiated by the data."
5839 author = RNevo #" and "# VBrumfeld #" and "# RKapon #" and "# PHinterdorfer
5841 title = "Direct measurement of protein energy landscape roughness",
5849 doi = "10.1038/sj.embor.7400403",
5850 eprint = "http://www.nature.com/embor/journal/v6/n5/pdf/7400403.pdf",
5851 url = "http://www.nature.com/embor/journal/v6/n5/abs/7400403.html",
5852 keywords = "Models, Molecular; Protein Binding; Protein Folding; Spectrum
5853 Analysis; Thermodynamics; beta Karyopherins; ran GTP-Binding Protein",
5854 abstract = "The energy landscape of proteins is thought to have an
5855 intricate, corrugated structure. Such roughness should have important
5856 consequences on the folding and binding kinetics of proteins, as well
5857 as on their equilibrium fluctuations. So far, no direct measurement of
5858 protein energy landscape roughness has been made. Here, we combined a
5859 recent theory with single-molecule dynamic force spectroscopy
5860 experiments to extract the overall energy scale of roughness epsilon
5861 for a complex consisting of the small GTPase Ran and the nuclear
5862 transport receptor importin-beta. The results gave epsilon > 5k(B)T,
5863 indicating a bumpy energy surface, which is consistent with the ability
5864 of importin-beta to accommodate multiple conformations and to interact
5865 with different, structurally distinct ligands.",
5866 note = "Applies \citet{hyeon03} to ligand-receptor binding.",
5867 project = "Energy Landscape Roughness"
5871 author = SNg #" and "# KBillings #" and "# TOhashi #" and "# MAllen #" and
5872 "# RBest #" and "# LRandles #" and "# HErickson #" and "# JClarke,
5873 title = "Designing an extracellular matrix protein with enhanced mechanical
5881 pages = "9633--9637",
5882 doi = "10.1073/pnas.0609901104",
5883 eprint = "http://www.pnas.org/cgi/reprint/104/23/9633.pdf",
5884 url = "http://www.pnas.org/cgi/content/abstract/104/23/9633",
5885 abstract = "The extracellular matrix proteins tenascin and fibronectin
5886 experience significant mechanical forces in vivo. Both contain a number
5887 of tandem repeating homologous fibronectin type III (fnIII) domains,
5888 and atomic force microscopy experiments have demonstrated that the
5889 mechanical strength of these domains can vary significantly. Previous
5890 work has shown that mutations in the core of an fnIII domain from human
5891 tenascin (TNfn3) reduce the unfolding force of that domain
5892 significantly: The composition of the core is apparently crucial to the
5893 mechanical stability of these proteins. Based on these results, we have
5894 used rational redesign to increase the mechanical stability of the 10th
5895 fnIII domain of human fibronectin, FNfn10, which is directly involved
5896 in integrin binding. The hydrophobic core of FNfn10 was replaced with
5897 that of the homologous, mechanically stronger TNfn3 domain. Despite the
5898 extensive substitution, FNoTNc retains both the three-dimensional
5899 structure and the cell adhesion activity of FNfn10. Atomic force
5900 microscopy experiments reveal that the unfolding forces of the
5901 engineered protein FNoTNc increase by {approx}20% to match those of
5902 TNfn3. Thus, we have specifically designed a protein with increased
5903 mechanical stability. Our results demonstrate that core engineering can
5904 be used to change the mechanical strength of proteins while retaining
5905 functional surface interactions."
5909 author = SNg #" and "# JClarke,
5910 title = "Experiments Suggest that Simulations May Overestimate
5911 Electrostatic Contributions to the Mechanical Stability of a
5912 Fibronectin Type {III} Domain",
5916 pages = "851–854",
5921 doi = "10.1016/j.jmb.2007.06.015",
5922 url = "http://www.sciencedirect.com/science/article/pii/S0022283607007966",
5924 keywords = "MD simulations",
5926 keywords = "forced unfolding",
5927 keywords = "extracellular matrix",
5928 abstract = "Steered molecular dynamics simulations have previously
5929 been used to investigate the mechanical properties of the
5930 extracellular matrix protein fibronectin. The simulations
5931 suggest that the mechanical stability of the tenth type III
5932 domain from fibronectin (FNfn10) is largely determined by a
5933 number of critical hydrogen bonds in the peripheral
5934 strands. Interestingly, the simulations predict that lowering
5935 the pH from 7 to ∼4.7 will increase the mechanical stability
5936 of FNfn10 significantly (by ∼33 %) due to the protonation of a
5937 few key acidic residues in the A and B strands. To test this
5938 simulation prediction, we used single-molecule atomic force
5939 microscopy (AFM) to investigate the mechanical stability of
5940 FNfn10 at neutral pH and at lower pH where these key residues
5941 have been shown to be protonated. Our AFM experimental results
5942 show no difference in the mechanical stability of FNfn10 at
5943 these different pH values. These results suggest that some
5944 simulations may overestimate the role played by electrostatic
5945 interactions in determining the mechanical stability of
5950 author = RNome #" and "# JZhao #" and "# WHoff #" and "# NScherer,
5951 title = "Axis-dependent anisotropy in protein unfolding from integrated
5952 nonequilibrium single-molecule experiments, analysis, and simulation",
5959 pages = "20799--20804",
5961 doi = "10.1073/pnas.0701281105",
5962 eprint = "http://www.pnas.org/cgi/reprint/104/52/20799.pdf",
5963 url = "http://www.pnas.org/cgi/content/abstract/104/52/20799",
5964 keywords = "Anisotropy; Bacterial Proteins; Biophysics; Computer
5965 Simulation; Cysteine; Halorhodospira halophila; Hydrogen Bonding;
5966 Kinetics; Luminescent Proteins; Microscopy, Atomic Force; Molecular
5967 Conformation; Protein Binding; Protein Conformation; Protein
5968 Denaturation; Protein Folding; Protein Structure, Secondary",
5969 abstract = "We present a comprehensive study that integrates experimental
5970 and theoretical nonequilibrium techniques to map energy landscapes
5971 along well defined pull-axis specific coordinates to elucidate
5972 mechanisms of protein unfolding. Single-molecule force-extension
5973 experiments along two different axes of photoactive yellow protein
5974 combined with nonequilibrium statistical mechanical analysis and
5975 atomistic simulation reveal energetic and mechanistic anisotropy.
5976 Steered molecular dynamics simulations and free-energy curves
5977 constructed from the experimental results reveal that unfolding along
5978 one axis exhibits a transition-state-like feature where six hydrogen
5979 bonds break simultaneously with weak interactions observed during
5980 further unfolding. The other axis exhibits a constant (unpeaked) force
5981 profile indicative of a noncooperative transition, with enthalpic
5982 (e.g., H-bond) interactions being broken throughout the unfolding
5983 process. Striking qualitative agreement was found between the force-
5984 extension curves derived from steered molecular dynamics calculations
5985 and the equilibrium free-energy curves obtained by JarzynskiHummerSzabo
5986 analysis of the nonequilibrium work data. The anisotropy persists
5987 beyond pulling distances of more than twice the initial dimensions of
5988 the folded protein, indicating a rich energy landscape to the
5989 mechanically fully unfolded state. Our findings challenge the notion
5990 that cooperative unfolding is a universal feature in protein
5996 title = "Handbook of Molecular Force Spectroscopy",
5998 isbn = "978-0-387-49987-1",
5999 publisher = SPRINGER,
6000 note = "The first book about force spectroscopy. Discusses the scaffold
6001 effect in section 8.4.1."
6004 @article { nummela07,
6005 author = JNummela #" and "# IAndricioaei,
6006 title = "{Exact Low-Force Kinetics from High-Force Single-Molecule
6012 pages = "3373--3381",
6013 doi = "10.1529/biophysj.107.111658",
6014 eprint = "http://www.biophysj.org/cgi/reprint/93/10/3373.pdf",
6015 url = "http://www.biophysj.org/cgi/content/abstract/93/10/3373",
6016 abstract = "Mechanical forces play a key role in crucial cellular processes
6017 involving force-bearing biomolecules, as well as in novel single-
6018 molecule pulling experiments. We present an exact method that enables
6019 one to extrapolate, to low (or zero) forces, entire time-correlation
6020 functions and kinetic rate constants from the conformational dynamics
6021 either simulated numerically or measured experimentally at a single,
6022 relatively higher, external force. The method has twofold relevance:
6023 1), to extrapolate the kinetics at physiological force conditions from
6024 molecular dynamics trajectories generated at higher forces that
6025 accelerate conformational transitions; and 2), to extrapolate unfolding
6026 rates from experimental force-extension single-molecule curves. The
6027 theoretical formalism, based on stochastic path integral weights of
6028 Langevin trajectories, is presented for the constant-force, constant
6029 loading rate, and constant-velocity modes of the pulling experiments.
6030 For the first relevance, applications are described for simulating the
6031 conformational isomerization of alanine dipeptide; and for the second
6032 relevance, the single-molecule pulling of RNA is considered. The
6033 ability to assign a weight to each trace in the single-molecule data
6034 also suggests a means to quantitatively compare unfolding pathways
6035 under different conditions."
6038 @article { oberhauser01,
6039 author = AOberhauser #" and "# PHansma #" and "# MCarrionVazquez #" and "#
6041 title = "Stepwise unfolding of titin under force-clamp atomic force
6048 doi = "10.1073/pnas.021321798",
6049 eprint = "http://www.pnas.org/cgi/reprint/98/2/468.pdf",
6050 url = "http://www.pnas.org/cgi/content/abstract/98/2/468",
6056 title = "Cantilever spring constant calibration using laser Doppler
6066 doi = "10.1063/1.2743272",
6067 url = "http://link.aip.org/link/?RSI/78/063701/1",
6068 keywords = "calibration; vibration measurement; measurement by laser beam;
6069 Doppler measurement; measurement uncertainty; atomic force microscopy",
6070 note = "Excellent review of thermal calibration to 2007, but nothing in the
6071 way of derivations. Compares thermal tune and Sader method with laser
6072 Doppler vibrometry.",
6073 project = "Cantilever Calibration"
6076 @article { olshansky97,
6077 author = SJOlshansky #" and "# BACarnes,
6078 title = "Ever since {G}ompertz",
6081 journal = Demography,
6086 url = "http://www.jstor.org/stable/2061656",
6087 keywords = "Aging;Biometry;History, 19th Century;History, 20th
6088 Century;Humans;Life Tables;Mortality;Sexual Maturation",
6089 abstract = "In 1825 British actuary Benjamin Gompertz made a simple but
6090 important observation that a law of geometrical progression pervades
6091 large portions of different tables of mortality for humans. The simple
6092 formula he derived describing the exponential rise in death rates
6093 between sexual maturity and old age is commonly, referred to as the
6094 Gompertz equation-a formula that remains a valuable tool in demography
6095 and in other scientific disciplines. Gompertz's observation of a
6096 mathematical regularity in the life table led him to believe in the
6097 presence of a low of mortality that explained why common age patterns
6098 of death exist. This law of mortality has captured the attention of
6099 scientists for the past 170 years because it was the first among what
6100 are now several reliable empirical tools for describing the dying-out
6101 process of many living organisms during a significant portion of their
6102 life spans. In this paper we review the literature on Gompertz's law of
6103 mortality and discuss the importance of his observations and insights
6104 in light of research on aging that has taken place since then.",
6105 note = "Hardly any actual math, but the references might be interesting.
6106 I'll look into them if I have the time. Available through several
6110 @article { onuchic96,
6111 author = JNOnuchic #" and "# NDSocci #" and "# ZLuthey-Schulten #" and "#
6113 title = "Protein folding funnels: the nature of the transition state
6121 keywords = "Animals; Cytochrome c Group; Humans; Infant; Protein Folding",
6122 abstract = "BACKGROUND: Energy landscape theory predicts that the folding
6123 funnel for a small fast-folding alpha-helical protein will have a
6124 transition state half-way to the native state. Estimates of the
6125 position of the transition state along an appropriate reaction
6126 coordinate can be obtained from linear free energy relationships
6127 observed for folding and unfolding rate constants as a function of
6128 denaturant concentration. The experimental results of Huang and Oas for
6129 lambda repressor, Fersht and collaborators for C12, and Gray and
6130 collaborators for cytochrome c indicate a free energy barrier midway
6131 between the folded and unfolded regions. This barrier arises from an
6132 entropic bottleneck for the folding process. RESULTS: In keeping with
6133 the experimental results, lattice simulations based on the folding
6134 funnel description show that the transition state is not just a single
6135 conformation, but rather an ensemble of a relatively large number of
6136 configurations that can be described by specific values of one or a few
6137 order parameters (e.g. the fraction of native contacts). Analysis of
6138 this transition state or bottleneck region from our lattice simulations
6139 and from atomistic models for small alpha-helical proteins by Boczko
6140 and Brooks indicates a broad distribution for native contact
6141 participation in the transition state ensemble centered around 50\%.
6142 Importantly, however, the lattice-simulated transition state ensemble
6143 does include some particularly hot contacts, as seen in the
6144 experiments, which have been termed by others a folding nucleus.
6145 CONCLUSIONS: Linear free energy relations provide a crude spectroscopy
6146 of the transition state, allowing us to infer the values of a reaction
6147 coordinate based on the fraction of native contacts. This bottleneck
6148 may be thought of as a collection of delocalized nuclei where different
6149 native contacts will have different degrees of participation. The
6150 agreement between the experimental results and the theoretical
6151 predictions provides strong support for the landscape analysis."
6155 author = COpitz #" and "# MKulke #" and "# MLeake #" and "# CNeagoe #" and
6156 "# HHinssen #" and "# RHajjar #" and "# WALinke,
6157 title = "Damped elastic recoil of the titin spring in myofibrils of human
6163 pages = "12688--12693",
6164 doi = "10.1073/pnas.2133733100",
6165 eprint = "http://www.pnas.org/cgi/reprint/100/22/12688.pdf",
6166 url = "http://www.pnas.org/cgi/content/abstract/100/22/12688",
6167 abstract = "The giant protein titin functions as a molecular spring in
6168 muscle and is responsible for most of the passive tension of
6169 myocardium. Because the titin spring is extended during diastolic
6170 stretch, it will recoil elastically during systole and potentially may
6171 influence the overall shortening behavior of cardiac muscle. Here,
6172 titin elastic recoil was quantified in single human heart myofibrils by
6173 using a high-speed charge-coupled device-line camera and a
6174 nanonewtonrange force sensor. Application of a slack-test protocol
6175 revealed that the passive shortening velocity (Vp) of nonactivated
6176 cardiomyofibrils depends on: (i) initial sarcomere length, (ii)
6177 release-step amplitude, and (iii) temperature. Selective digestion of
6178 titin, with low doses of trypsin, decelerated myofibrillar passive
6179 recoil and eventually stopped it. Selective extraction of actin
6180 filaments with a Ca2+-independent gelsolin fragment greatly reduced the
6181 dependency of Vp on release-step size and temperature. These results
6182 are explained by the presence of viscous forces opposing myofibrillar
6183 passive recoil that are caused mainly by weak actin-titin interactions.
6184 Thus, Vp is determined by two distinct factors: titin elastic recoil
6185 and internal viscous drag forces. The recoil could be modeled as that
6186 of a damped entropic spring consisting of independent worm-like chains.
6187 The functional importance of myofibrillar elastic recoil was addressed
6188 by comparing instantaneous Vp to unloaded shortening velocity, which
6189 was measured in demembranated, fully Ca2+-activated, human cardiac
6190 fibers. Titin-driven passive recoil was much faster than active
6191 unloaded shortening velocity in early phases of isotonic contraction.
6192 Damped myofibrillar elastic recoil could help accelerate active
6193 contraction speed of human myocardium during early systolic
6197 @article { oroudjev02,
6198 author = EOroudjev #" and "# JSoares #" and "# SArcidiacono #" and "#
6199 JThompson #" and "# SFossey #" and "# HHansma,
6200 title = "Segmented nanofibers of spider dragline silk: Atomic force
6201 microscopy and single-molecule force spectroscopy",
6206 pages = "6460--6465",
6207 doi = "10.1073/pnas.082526499",
6208 eprint = "http://www.pnas.org/cgi/reprint/99/suppl_2/6460.pdf",
6209 url = "http://www.pnas.org/cgi/content/abstract/99/suppl_2/6460",
6210 abstract = "Despite its remarkable materials properties, the structure of
6211 spider dragline silk has remained unsolved. Results from two probe
6212 microscopy techniques provide new insights into the structure of spider
6213 dragline silk. A soluble synthetic protein from dragline silk
6214 spontaneously forms nanofibers, as observed by atomic force microscopy.
6215 These nanofibers have a segmented substructure. The segment length and
6216 amino acid sequence are consistent with a slab-like shape for
6217 individual silk protein molecules. The height and width of nanofiber
6218 segments suggest a stacking pattern of slab-like molecules in each
6219 nanofiber segment. This stacking pattern produces nano-crystals in an
6220 amorphous matrix, as observed previously by NMR and x-ray diffraction
6221 of spider dragline silk. The possible importance of nanofiber formation
6222 to native silk production is discussed. Force spectra for single
6223 molecules of the silk protein demonstrate that this protein unfolds
6224 through a number of rupture events, indicating a modular substructure
6225 within single silk protein molecules. A minimal unfolding module size
6226 is estimated to be around 14 nm, which corresponds to the extended
6227 length of a single repeated module, 38 amino acids long. The structure
6228 of this spider silk protein is distinctly different from the structures
6229 of other proteins that have been analyzed by single-molecule force
6230 spectroscopy, and the force spectra show correspondingly novel
6235 author = EPaci #" and "# MKarplus,
6236 title = "Unfolding proteins by external forces and temperature: The
6237 importance of topology and energetics",
6242 pages = "6521--6526",
6243 doi = "10.1073/pnas.100124597",
6244 eprint = "http://www.pnas.org/cgi/reprint/97/12/6521.pdf",
6245 url = "http://www.pnas.org/cgi/content/abstract/97/12/6521"
6249 author = EPaci #" and "# MKarplus,
6250 title = "Forced unfolding of fibronectin type 3 modules: an analysis by
6251 biased molecular dynamics simulations",
6260 doi = "10.1006/jmbi.1999.2670",
6261 keywords = "Dimerization;Fibronectins;Humans;Hydrogen Bonding;Microscopy,
6262 Atomic Force;Protein Denaturation;Protein Folding",
6263 abstract = "Titin, an important constituent of vertebrate muscles, is a
6264 protein of the order of a micrometer in length in the folded state.
6265 Atomic force microscopy and laser tweezer experiments have been used to
6266 stretch titin molecules to more than ten times their folded lengths. To
6267 explain the observed relation between force and extension, it has been
6268 suggested that the immunoglobulin and fibronectin domains unfold one at
6269 a time in an all-or-none fashion. We use molecular dynamics simulations
6270 to study the forced unfolding of two different fibronectin type 3
6271 domains (the ninth, 9Fn3, and the tenth, 10Fn3, from human fibronectin)
6272 and of their heterodimer of known structure. An external biasing
6273 potential on the N to C distance is employed and the protein is treated
6274 in the polar hydrogen representation with an implicit solvation model.
6275 The latter provides an adiabatic solvent response, which is important
6276 for the nanosecond unfolding simulation method used here. A series of
6277 simulations is performed for each system to obtain meaningful results.
6278 The two different fibronectin domains are shown to unfold in the same
6279 way along two possible pathways. These involve the partial separation
6280 of the ``beta-sandwich'', an essential structural element, and the
6281 unfolding of the individual sheets in a stepwise fashion. The biasing
6282 potential results are confirmed by constant force unfolding
6283 simulations. For the two connected domains, there is complete unfolding
6284 of one domain (9Fn3) before major unfolding of the second domain
6285 (10Fn3). Comparison of different models for the potential energy
6286 function demonstrates that the dominant cohesive element in both
6287 proteins is due to the attractive van der Waals interactions;
6288 electrostatic interactions play a structural role but appear to make
6289 only a small contribution to the stabilization of the domains, in
6290 agreement with other studies of beta-sheet stability. The unfolding
6291 forces found in the simulations are of the order of those observed
6292 experimentally, even though the speed of the former is more than six
6293 orders of magnitude greater than that used in the latter."
6297 author = QPeng #" and "# HLi,
6298 title = "Atomic force microscopy reveals parallel mechanical unfolding
6299 pathways of T4 lysozyme: Evidence for a kinetic partitioning mechanism",
6304 pages = "1885--1890",
6305 doi = "10.1073/pnas.0706775105",
6306 eprint = "http://www.pnas.org/cgi/reprint/105/6/1885.pdf",
6307 url = "http://www.pnas.org/cgi/content/abstract/105/6/1885",
6308 abstract = "Kinetic partitioning is predicted to be a general mechanism for
6309 proteins to fold into their well defined native three-dimensional
6310 structure from unfolded states following multiple folding pathways.
6311 However, experimental evidence supporting this mechanism is still
6312 limited. By using single-molecule atomic force microscopy, here we
6313 report experimental evidence supporting the kinetic partitioning
6314 mechanism for mechanical unfolding of T4 lysozyme, a small protein
6315 composed of two subdomains. We observed that on stretching from its N
6316 and C termini, T4 lysozyme unfolds by multiple distinct unfolding
6317 pathways: the majority of T4 lysozymes unfold in an all-or-none fashion
6318 by overcoming a dominant unfolding kinetic barrier; and a small
6319 fraction of T4 lysozymes unfold in three-state fashion involving
6320 unfolding intermediate states. The three-state unfolding pathways do
6321 not follow well defined routes, instead they display variability and
6322 diversity in individual unfolding pathways. The unfolding intermediate
6323 states are local energy minima along the mechanical unfolding pathways
6324 and are likely to result from the residual structures present in the
6325 two subdomains after crossing the main unfolding barrier. These results
6326 provide direct evidence for the kinetic partitioning of the mechanical
6327 unfolding pathways of T4 lysozyme, and the complex unfolding behaviors
6328 reflect the stochastic nature of kinetic barrier rupture in mechanical
6329 unfolding processes. Our results demonstrate that single-molecule
6330 atomic force microscopy is an ideal tool to investigate the
6331 folding/unfolding dynamics of complex multimodule proteins that are
6332 otherwise difficult to study using traditional methods."
6336 author = WPress #" and "# STeukolsky #" and "# WVetterling #" and "#
6338 title = "Numerical Recipies in {C}: The Art of Scientific Computing",
6342 address = "New York",
6343 eprint = "http://www.nrbook.com/a/bookcpdf.php",
6344 note = "See Sections 12.0, 12.1, 12.3, and 13.4 for a good introduction to
6345 Fourier transforms and power spectrum estimation.",
6346 project = "Cantilever Calibration"
6349 @article { puchner08,
6350 author = EPuchner #" and "# GFranzen #" and "# MGautel #" and "# HEGaub,
6351 title = "Comparing proteins by their unfolding pattern.",
6359 doi = "10.1529/biophysj.108.129999",
6360 eprint = "http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2426622/pdf/426.pdf",
6361 url = "http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2426622/",
6362 keywords = "Algorithms;Computer Simulation;Microscopy, Atomic Force;Models,
6363 Chemical;Models, Molecular;Protein Denaturation;Protein
6365 abstract = "Single molecule force spectroscopy has evolved into an
6366 important and extremely powerful technique for investigating the
6367 folding potentials of biomolecules. Mechanical tension is applied to
6368 individual molecules, and the subsequent, often stepwise unfolding is
6369 recorded in force extension traces. However, because the energy
6370 barriers of the folding potentials are often close to the thermal
6371 energy, both the extensions and the forces at which these barriers are
6372 overcome are subject to marked fluctuations. Therefore, force extension
6373 traces are an inadequate representation despite widespread use
6374 particularly when large populations of proteins need to be compared and
6375 analyzed. We show in this article that contour length, which is
6376 independent of fluctuations and alterable experimental parameters, is a
6377 more appropriate variable than extension. By transforming force
6378 extension traces into contour length space, histograms are obtained
6379 that directly represent the energy barriers. In contrast to force
6380 extension traces, such barrier position histograms can be averaged to
6381 investigate details of the unfolding potential. The cross-superposition
6382 of barrier position histograms allows us to detect and visualize the
6383 order of unfolding events. We show with this approach that in contrast
6384 to the sequential unfolding of bacteriorhodopsin, two main steps in the
6385 unfolding of the enzyme titin kinase are independent of each other. The
6386 potential of this new method for accurate and automated analysis of
6387 force spectroscopy data and for novel automated screening techniques is
6388 shown with bacteriorhodopsin and with protein constructs containing GFP
6390 note = {Contour length space and barrier position fingerprinting.
6391 There are errors in \fref{equation}{3}, propagated from
6392 \citet{livadaru03}. I contacted Elias Puchner and pointed out the
6393 typos, and he revised his FRC fit parameters from $\gamma=22\dg$
6394 and $b=0.4\U{nm}$ to $\gamma=41\dg$ and $b=0.11\U{nm}$. The
6395 combined effect on \fref{figure}{3} of fixing the equation typos
6396 and adjusting the fit parameters was small, so their conclusions
6400 @article { raible04,
6401 author = MRaible #" and "# MEvstigneev #" and "# PReimann #" and "#
6402 FWBartels #" and "# RRos,
6403 title = "Theoretical analysis of dynamic force spectroscopy experiments on
6404 ligand-receptor complexes",
6413 doi = "10.1016/j.jbiotec.2004.04.017",
6414 keywords = "Binding Sites;Computer Simulation;DNA;DNA-Binding
6415 Proteins;Elasticity;Ligands;Macromolecular
6416 Substances;Micromanipulation;Microscopy, Atomic Force;Models,
6417 Chemical;Molecular Biology;Nucleic Acid Conformation;Physical
6418 Stimulation;Protein Binding;Protein Conformation;Stress, Mechanical",
6419 abstract = "The forced rupture of single chemical bonds in biomolecular
6420 compounds (e.g. ligand-receptor systems) as observed in dynamic force
6421 spectroscopy experiments is addressed. Under the assumption that the
6422 probability of bond rupture depends only on the instantaneously acting
6423 force, a data collapse onto a single master curve is predicted. For
6424 rupture data obtained experimentally by dynamic AFM force spectroscopy
6425 of a ligand-receptor bond between a DNA and a regulatory protein we do
6426 not find such a collapse. We conclude that the above mentioned,
6427 generally accepted assumption is not satisfied and we discuss possible
6431 @article { raible06,
6432 author = MRaible #" and "# MEvstigneev #" and "# FWBartels #" and "# REckel
6433 #" and "# MNguyen-Duong #" and "# RMerkel #" and "# RRos #" and "#
6434 DAnselmetti #" and "# PReimann,
6435 title = "Theoretical analysis of single-molecule force spectroscopy
6436 experiments: heterogeneity of chemical bonds",
6443 pages = "3851--3864",
6445 doi = "10.1529/biophysj.105.077099",
6446 eprint = "http://www.biophysj.org/cgi/reprint/90/11/3851.pdf",
6447 url = "http://www.biophysj.org/cgi/content/abstract/90/11/3851",
6448 keywords = "Biomechanics;Microscopy, Atomic Force;Models,
6449 Molecular;Statistical Distributions;Thermodynamics",
6450 abstract = "We show that the standard theoretical framework in single-
6451 molecule force spectroscopy has to be extended to consistently describe
6452 the experimental findings. The basic amendment is to take into account
6453 heterogeneity of the chemical bonds via random variations of the force-
6454 dependent dissociation rates. This results in a very good agreement
6455 between theory and rupture data from several different experiments."
6458 @article{ bartels03,
6459 author = FWBartels #" and "# BBaumgarth #" and "# DAnselmetti
6460 #" and "# RRos #" and "# ABecker,
6461 title = "Specific binding of the regulatory protein Exp{G} to
6462 promoter regions of the galactoglucan biosynthesis gene cluster of
6463 Sinorhizobium meliloti--a combined molecular biology and force
6464 spectroscopy investigation.",
6465 journal = JStructBiol,
6468 address = "Experimentelle Biophysik, Fakult{\"a}t f{\"u}r Physik,
6469 Universit{\"a}t Bielefeld, 33615 Bielefeld, Germany.",
6473 keywords = "Base Sequence",
6474 keywords = "Binding Sites",
6475 keywords = "Conserved Sequence",
6476 keywords = "Fungal Proteins",
6477 keywords = "Galactans",
6478 keywords = "Glucans",
6479 keywords = "Kinetics",
6480 keywords = "Microscopy, Atomic Force",
6481 keywords = "Multigene Family",
6482 keywords = "Polysaccharides, Bacterial",
6483 keywords = "Promoter Regions, Genetic",
6484 keywords = "Protein Binding",
6485 keywords = "Sinorhizobium meliloti",
6486 keywords = "Trans-Activators",
6487 abstract = "Specific protein-DNA interaction is fundamental for all
6488 aspects of gene transcription. We focus on a regulatory
6489 DNA-binding protein in the Gram-negative soil bacterium
6490 Sinorhizobium meliloti 2011, which is capable of fixing molecular
6491 nitrogen in a symbiotic interaction with alfalfa plants. The ExpG
6492 protein plays a central role in regulation of the biosynthesis of
6493 the exopolysaccharide galactoglucan, which promotes the
6494 establishment of symbiosis. ExpG is a transcriptional activator of
6495 exp gene expression. We investigated the molecular mechanism of
6496 binding of ExpG to three associated target sequences in the exp
6497 gene cluster with standard biochemical methods and single molecule
6498 force spectroscopy based on the atomic force microscope
6499 (AFM). Binding of ExpG to expA1, expG-expD1, and expE1 promoter
6500 fragments in a sequence specific manner was demonstrated, and a 28
6501 bp conserved region was found. AFM force spectroscopy experiments
6502 confirmed the specific binding of ExpG to the promoter regions,
6503 with unbinding forces ranging from 50 to 165 pN in a logarithmic
6504 dependence from the loading rates of 70-79000 pN/s. Two different
6505 regimes of loading rate-dependent behaviour were
6506 identified. Thermal off-rates in the range of k(off)=(1.2+/-1.0) x
6507 10(-3)s(-1) were derived from the lower loading rate regime for
6508 all promoter regions. In the upper loading rate regime, however,
6509 these fragments exhibited distinct differences which are
6510 attributed to the molecular binding mechanism.",
6512 URL = "http://www.ncbi.nlm.nih.gov/pubmed/12972351",
6517 author = MRief #" and "# HGrubmuller,
6518 title = "Force spectroscopy of single biomolecules",
6527 doi = "10.1002/1439-7641(20020315)3:3<255::AID-CPHC255>3.0.CO;2-M",
6528 url = "http://www3.interscience.wiley.com/journal/91016383/abstract",
6529 keywords = "Ligands;Microscopy, Atomic Force;Polysaccharides;Protein
6530 Denaturation;Proteins",
6531 abstract = "Many processes in the body are effected and regulated by highly
6532 specialized protein molecules: These molecules certainly deserve the
6533 name ``biochemical nanomachines''. Recent progress in single-molecule
6534 experiments and corresponding simulations with supercomputers enable us
6535 to watch these ``nanomachines'' at work, revealing a host of astounding
6536 mechanisms. Examples are the fine-tuned movements of the binding pocket
6537 of a receptor protein locking into its ligand molecule and the forced
6538 unfolding of titin, which acts as a molecular shock absorber to protect
6539 muscle cells. At present, we are not capable of designing such high
6540 precision machines, but we are beginning to understand their working
6541 principles and to simulate and predict their function.",
6542 note = "Nice, general review of force spectroscopy to 2002, but not much
6548 title = "Fundamentals of Statistical and Thermal Physics",
6550 publisher = McGraw-Hill,
6551 address = "New York",
6552 note = "Thermal noise for simple harmonic oscillators, in Chapter
6553 15, Sections 6 and 10.",
6554 project = "Cantilever Calibration"
6558 author = MRief #" and "# MGautel #" and "# FOesterhelt #" and "# JFernandez
6560 title = "Reversible Unfolding of Individual Titin Immunoglobulin Domains by
6566 pages = "1109--1112",
6567 doi = "10.1126/science.276.5315.1109",
6568 eprint = "http://www.sciencemag.org/cgi/reprint/276/5315/1109.pdf",
6569 url = "http://www.sciencemag.org/cgi/content/abstract/276/5315/1109",
6570 note = "Seminal paper for force spectroscopy on Titin. Cited by
6571 \citet{dietz04} (ref 9) as an example of how unfolding large proteins
6572 is easily interpreted (vs.\ confusing unfolding in bulk), but Titin is
6573 a rather simple example of that, because of its globular-chain
6575 project = "Energy Landscape Roughness"
6579 author = MRief #" and "# FOesterhelt #" and "# BHeymann #" and "# HEGaub,
6580 title = "Single Molecule Force Spectroscopy on Polysaccharides by Atomic
6588 pages = "1295--1297",
6590 doi = "10.1126/science.275.5304.1295",
6591 eprint = "http://www.sciencemag.org/cgi/reprint/275/5304/1295.pdf",
6592 url = "http://www.sciencemag.org/cgi/content/abstract/275/5304/1295",
6593 abstract = "Recent developments in piconewton instrumentation allow the
6594 manipulation of single molecules and measurements of intermolecular as
6595 well as intramolecular forces. Dextran filaments linked to a gold
6596 surface were probed with the atomic force microscope tip by vertical
6597 stretching. At low forces the deformation of dextran was found to be
6598 dominated by entropic forces and can be described by the Langevin
6599 function with a 6 angstrom Kuhn length. At elevated forces the strand
6600 elongation was governed by a twist of bond angles. At higher forces the
6601 dextran filaments underwent a distinct conformational change. The
6602 polymer stiffened and the segment elasticity was dominated by the
6603 bending of bond angles. The conformational change was found to be
6604 reversible and was corroborated by molecular dynamics calculations."
6608 author = MRief #" and "# JFernandez #" and "# HEGaub,
6609 title = "Elastically Coupled Two-Level Systems as a Model for Biopolymer
6616 pages = "4764--4767",
6619 doi = "10.1103/PhysRevLett.81.4764",
6620 eprint = "http://prola.aps.org/pdf/PRL/v81/i21/p4764_1",
6621 url = "http://prola.aps.org/abstract/PRL/v81/i21/p4764_1",
6622 note = "Original details on mechanical unfolding analysis via Monte Carlo
6627 author = MRief #" and "# HClausen-Schaumann #" and "# HEGaub,
6628 title = "Sequence-dependent mechanics of single {DNA} molecules",
6636 doi = "10.1038/7582",
6637 eprint = "http://www.nature.com/nsmb/journal/v6/n4/pdf/nsb0499_346.pdf",
6638 url = "http://www.nature.com/nsmb/journal/v6/n4/abs/nsb0499_346.html",
6639 keywords = "Bacteriophage lambda;Base Pairing;DNA;DNA, Single-Stranded;DNA,
6640 Viral;Gold;Mechanics;Microscopy, Atomic Force;Nucleotides;Spectrum
6641 Analysis;Thermodynamics",
6642 abstract = "Atomic force microscope-based single-molecule force
6643 spectroscopy was employed to measure sequence-dependent mechanical
6644 properties of DNA by stretching individual DNA double strands attached
6645 between a gold surface and an AFM tip. We discovered that in lambda-
6646 phage DNA the previously reported B-S transition, where 'S' represents
6647 an overstretched conformation, at 65 pN is followed by a nonequilibrium
6648 melting transition at 150 pN. During this transition the DNA is split
6649 into single strands that fully recombine upon relaxation. The sequence
6650 dependence was investigated in comparative studies with poly(dG-dC) and
6651 poly(dA-dT) DNA. Both the B-S and the melting transition occur at
6652 significantly lower forces in poly(dA-dT) compared to poly(dG-dC). We
6653 made use of the melting transition to prepare single poly(dG-dC) and
6654 poly(dA-dT) DNA strands that upon relaxation reannealed into hairpins
6655 as a result of their self-complementary sequence. The unzipping of
6656 these hairpins directly revealed the base pair-unbinding forces for G-C
6657 to be 20 +/- 3 pN and for A-T to be 9 +/- 3 pN."
6660 @article{ schmitt00,
6661 author = LSchmitt #" and "# MLudwig #" and "# HEGaub #" and "# RTampe,
6662 title = "A metal-chelating microscopy tip as a new toolbox for
6663 single-molecule experiments by atomic force microscopy.",
6667 address = "Institut f{\"u}r Physiologische Chemie,
6668 Philipps-Universit{\"a}t Marburg, 35033 Marburg,
6669 Germany. schmittl@mailer.uni-marburg.de",
6672 pages = "3275--3285",
6673 keywords = "Chelating Agents",
6674 keywords = "Edetic Acid",
6675 keywords = "Histidine",
6676 keywords = "Metals",
6677 keywords = "Microscopy, Atomic Force",
6678 keywords = "Nitrilotriacetic Acid",
6679 keywords = "Peptides",
6680 keywords = "Recombinant Fusion Proteins",
6681 abstract = "In recent years, the atomic force microscope (AFM) has
6682 contributed much to our understanding of the molecular forces
6683 involved in various high-affinity receptor-ligand
6684 systems. However, a universal anchor system for such measurements
6685 is still required. This would open up new possibilities for the
6686 study of biological recognition processes and for the
6687 establishment of high-throughput screening applications. One such
6688 candidate is the N-nitrilo-triacetic acid (NTA)/His-tag system,
6689 which is widely used in molecular biology to isolate and purify
6690 histidine-tagged fusion proteins. Here the histidine tag acts as a
6691 high-affinity recognition site for the NTA chelator. Accordingly,
6692 we have investigated the possibility of using this approach in
6693 single-molecule force measurements. Using a histidine-peptide as a
6694 model system, we have determined the binding force for various
6695 metal ions. At a loading rate of 0.5 microm/s, the determined
6696 forces varied from 22 +/- 4 to 58 +/- 5 pN. Most importantly, no
6697 interaction was detected for Ca(2+) and Mg(2+) up to
6698 concentrations of 10 mM. Furthermore, EDTA and a metal ion
6699 reloading step demonstrated the reversibility of the
6700 approach. Here the molecular interactions were turned off (EDTA)
6701 and on (metal reloading) in a switch-like fashion. Our results
6702 show that the NTA/His-tag system will expand the ``molecular
6703 toolboxes'' with which receptor-ligand systems can be investigated
6704 at the single-molecule level.",
6706 doi = "10.1016/S0006-3495(00)76863-9",
6707 URL = "http://www.ncbi.nlm.nih.gov/pubmed/10828003",
6711 @article { roters96,
6712 author = ARoters #" and "# DJohannsmann,
6713 title = "Distance-dependent noise measurements in scanning force
6719 pages = "7561-7577",
6720 doi = "10.1088/0953-8984",
6721 eprint = "http://www.iop.org/EJ/article/0953-8984/8/41/006/c64103.pdf",
6722 url = "http://stacks.iop.org/0953-8984/8/7561",
6723 abstract = "The changes in the thermal noise spectrum of a scanning-force-
6724 microscope cantilever upon approach of the tip to the sample were used
6725 to investigate the interactions between the cantilever and the sample.
6726 The investigation of thermal noise is the natural choice for dynamic
6727 measurements with little disturbance of the sample. In particular, the
6728 small amplitudes involved ensure linear dynamic response. It is
6729 possible to discriminate between viscous coupling, elastic coupling and
6730 changes in the effective mass. The technique is versatile in terms of
6731 substrates and environments. Hydrodynamic long-range interactions
6732 depending on the sample, the geometry and the ambient medium are
6733 observed. The dependence of hydrodynamic interaction on various
6734 parameters such as the viscosity and the density of the medium is
6735 described. For sufficiently soft surfaces, the method is sensitive to
6736 viscoelastic properties of the surface. For example, the viscous
6737 coupling to the surface is strongly increased when the surface is
6738 covered with a swollen `polymer brush'.",
6739 note = "They actually write down a Lagrangian formula and give a decent
6740 derivation of PSD, but don't show or work out the integrals.",
6741 project = "Cantilever Calibration"
6744 @article { ryckaert77,
6745 author = JPRyckaert #" and "# GCiccotti #" and "# HJCBerendsen,
6746 title = "Numerical integration of the cartesian equations of motion of a
6747 system with constraints: molecular dynamics of n-alkanes",
6754 doi = "10.1016/0021-9991(77)90098-5",
6755 url = "http://dx.doi.org/10.1016/0021-9991(77)90098-5",
6756 abstract = "A numerical algorithm integrating the 3N Cartesian equations of
6757 motion of a system of N points subject to holonomic constraints is
6758 formulated. The relations of constraint remain perfectly fulfilled at
6759 each step of the trajectory despite the approximate character of
6760 numerical integration. The method is applied to a molecular dynamics
6761 simulation of a liquid of 64 n-butane molecules and compared to a
6762 simulation using generalized coordinates. The method should be useful
6763 for molecular dynamics calculations on large molecules with internal
6764 degrees of freedom.",
6765 note = "Entry-level explaination of MD with rigid constraints. Explicit
6766 Verlet integrator example."
6769 @article { sarkar04,
6770 author = ASarkar #" and "# RRobertson #" and "# JFernandez,
6771 title = "Simultaneous atomic force microscope and fluorescence measurements
6772 of protein unfolding using a calibrated evanescent wave",
6777 pages = "12882--12886",
6778 doi = "10.1073/pnas.0403534101",
6779 eprint = "http://www.pnas.org/cgi/reprint/101/35/12882.pdf",
6780 url = "http://www.pnas.org/cgi/content/abstract/101/35/12882",
6781 abstract = "Fluorescence techniques for monitoring single-molecule dynamics
6782 in the vertical dimension currently do not exist. Here we use an atomic
6783 force microscope to calibrate the distance-dependent intensity decay of
6784 an evanescent wave. The measured evanescent wave transfer function was
6785 then used to convert the vertical motions of a fluorescent particle
6786 into displacement ($SD =< 1$ nm). We demonstrate the use of the
6787 calibrated evanescent wave to resolve the 20.1 {+/-} 0.5-nm step
6788 increases in the length of the small protein ubiquitin during forced
6789 unfolding. The experiments that we report here make an important
6790 contribution to fluorescence microscopy by demonstrating the
6791 unambiguous optical tracking of a single molecule with a resolution
6792 comparable to that of an atomic force microscope."
6796 author = TSato #" and "# MEsaki #" and "# JFernandez #" and "# TEndo,
6797 title = "{Comparison of the protein-unfolding pathways between
6798 mitochondrial protein import and atomic-force microscopy measurements}",
6803 pages = "17999--18004",
6804 doi = "10.1073/pnas.0504495102",
6805 eprint = "http://www.pnas.org/cgi/reprint/102/50/17999.pdf",
6806 url = "http://www.pnas.org/cgi/content/abstract/102/50/17999",
6807 abstract = "Many newly synthesized proteins have to become unfolded during
6808 translocation across biological membranes. We have analyzed the effects
6809 of various stabilization/destabilization mutations in the Ig-like
6810 module of the muscle protein titin upon its import from the N terminus
6811 or C terminus into mitochondria. The effects of mutations on the import
6812 of the titin module from the C terminus correlate well with those on
6813 forced mechanical unfolding in atomic-force microscopy (AFM)
6814 measurements. On the other hand, as long as turnover of the
6815 mitochondrial Hsp70 system is not rate-limiting for the import, import
6816 of the titin module from the N terminus is sensitive to mutations in
6817 the N-terminal region but not the ones in the C-terminal region that
6818 affect resistance to global unfolding in AFM experiments. We propose
6819 that the mitochondrial-import system can catalyze precursor-unfolding
6820 by reducing the stability of unfolding intermediates."
6823 @article { schlierf04,
6824 author = MSchlierf #" and "# HLi #" and "# JFernandez,
6825 title = "The unfolding kinetics of ubiquitin captured with single-molecule
6826 force-clamp techniques",
6833 pages = "7299--7304",
6835 doi = "10.1073/pnas.0400033101",
6836 eprint = "http://www.pnas.org/cgi/reprint/101/19/7299.pdf",
6837 url = "http://www.pnas.org/cgi/content/abstract/101/19/7299",
6838 keywords = "Kinetics;Microscopy, Atomic Force;Probability;Ubiquitin",
6839 abstract = "We use single-molecule force spectroscopy to study the kinetics
6840 of unfolding of the small protein ubiquitin. Upon a step increase in
6841 the stretching force, a ubiquitin polyprotein extends in discrete steps
6842 of 20.3 +/- 0.9 nm marking each unfolding event. An average of the time
6843 course of these unfolding events was well described by a single
6844 exponential, which is a necessary condition for a memoryless Markovian
6845 process. Similar ensemble averages done at different forces showed that
6846 the unfolding rate was exponentially dependent on the stretching force.
6847 Stretching a ubiquitin polyprotein with a force that increased at a
6848 constant rate (force-ramp) directly measured the distribution of
6849 unfolding forces. This distribution was accurately reproduced by the
6850 simple kinetics of an all-or-none unfolding process. Our force-clamp
6851 experiments directly demonstrate that an ensemble average of ubiquitin
6852 unfolding events is well described by a two-state Markovian process
6853 that obeys the Arrhenius equation. However, at the single-molecule
6854 level, deviant behavior that is not well represented in the ensemble
6855 average is readily observed. Our experiments make an important addition
6856 to protein spectroscopy by demonstrating an unambiguous method of
6857 analysis of the kinetics of protein unfolding by a stretching force."
6860 @article { schlierf06,
6861 author = MSchlierf #" and "# MRief,
6862 title = "Single-molecule unfolding force distributions reveal a funnel-
6863 shaped energy landscape",
6872 doi = "10.1529/biophysj.105.077982",
6873 url = "http://www.biophysj.org/cgi/content/abstract/90/4/L33",
6874 keywords = "Models, Molecular; Protein Folding; Proteins; Thermodynamics",
6875 abstract = "The protein folding process is described as diffusion on a
6876 high-dimensional energy landscape. Experimental data showing details of
6877 the underlying energy surface are essential to understanding folding.
6878 So far in single-molecule mechanical unfolding experiments a simplified
6879 model assuming a force-independent transition state has been used to
6880 extract such information. Here we show that this so-called Bell model,
6881 although fitting well to force velocity data, fails to reproduce full
6882 unfolding force distributions. We show that by applying Kramers'
6883 diffusion model, we were able to reconstruct a detailed funnel-like
6884 curvature of the underlying energy landscape and establish full
6885 agreement with the data. We demonstrate that obtaining spatially
6886 resolved details of the unfolding energy landscape from mechanical
6887 single-molecule protein unfolding experiments requires models that go
6888 beyond the Bell model.",
6889 note = {The inspiration behind my sawtooth simulation. Bell model
6890 fit to $f_{unfold}(v)$, but Kramers model fit to unfolding
6891 distribution for a given $v$. \fref{equation}{3} in the
6892 supplement is \xref{evans99}{equation}{2}, but it is just
6893 $[\text{dying percent}] \cdot [\text{surviving population}]
6895 $\nu \equiv k$ is the force/time-dependent off rate. The Kramers'
6896 rate equation (on page L34, the second equation in the paper) is
6897 \xref{hanggi90}{equation}{4.56b} (page 275) and
6898 \xref{socci96}{equation}{2} but \citet{schlierf06} gets the minus
6899 sign wrong in the exponent. $U_F(x=0)\gg 0$ and
6900 $U_F(x_\text{max})\ll 0$ (\cf~\xref{schlierf06}{figure}{1}).
6901 Schlierf's integral (as written) contains
6902 $\exp{-U_F(x_\text{max})}\cdot\exp{U_F(0)}$, which is huge, when
6903 it should contain $\exp{U_F(x_\text{max})}\cdot\exp{-U_F(0)}$,
6904 which is tiny. For more details and a picture of the peak that
6905 forms the bulk of the integrand, see
6906 \cref{eq:kramers,fig:kramers:integrand}. I pointed out this
6907 problem to Michael Schlierf, but he was unconvinced.},
6910 @article { schwaiger04,
6911 author = ISchwaiger #" and "# AKardinal #" and "# MSchleicher #" and "#
6912 AANoegel #" and "# MRief,
6913 title = "A mechanical unfolding intermediate in an actin-crosslinking
6923 doi = "10.1038/nsmb705",
6924 eprint = "http://www.nature.com/nsmb/journal/v11/n1/pdf/nsmb705.pdf",
6925 url = "http://www.nature.com/nsmb/journal/v11/n1/full/nsmb705.html",
6926 keywords = "Actins; Animals; Contractile Proteins; Cross-Linking Reagents;
6927 Dictyostelium; Dimerization; Microfilament Proteins; Microscopy, Atomic
6928 Force; Mutagenesis, Site-Directed; Protein Denaturation; Protein
6929 Folding; Protein Structure, Tertiary; Protozoan Proteins",
6930 abstract = "Many F-actin crosslinking proteins consist of two actin-binding
6931 domains separated by a rod domain that can vary considerably in length
6932 and structure. In this study, we used single-molecule force
6933 spectroscopy to investigate the mechanics of the immunoglobulin (Ig)
6934 rod domains of filamin from Dictyostelium discoideum (ddFLN). We find
6935 that one of the six Ig domains unfolds at lower forces than do those of
6936 all other domains and exhibits a stable unfolding intermediate on its
6937 mechanical unfolding pathway. Amino acid inserts into various loops of
6938 this domain lead to contour length changes in the single-molecule
6939 unfolding pattern. These changes allowed us to map the stable core of
6940 approximately 60 amino acids that constitutes the unfolding
6941 intermediate. Fast refolding in combination with low unfolding forces
6942 suggest a potential in vivo role for this domain as a mechanically
6943 extensible element within the ddFLN rod.",
6944 note = "ddFLN unfolding with WLC params for sacrificial domains. Gives
6945 persistence length $p = 0.5\mbox{ nm}$ in ``high force regime'', $p =
6946 0.9\mbox{ nm}$ in ``low force regime'', with a transition at $F =
6948 project = "sawtooth simulation"
6951 @article { schwaiger05,
6952 author = ISchwaiger #" and "# MSchleicher #" and "# AANoegel #" and "#
6954 title = "The folding pathway of a fast-folding immunoglobulin domain
6955 revealed by single-molecule mechanical experiments",
6963 doi = "10.1038/sj.embor.7400317",
6964 eprint = "http://www.nature.com/embor/journal/v6/n1/pdf/7400317.pdf",
6965 url = "http://www.nature.com/embor/journal/v6/n1/index.html",
6966 keywords = "Animals; Contractile Proteins; Dictyostelium; Immunoglobulins;
6967 Kinetics; Microfilament Proteins; Models, Molecular; Protein Folding;
6968 Protein Structure, Tertiary",
6969 abstract = "The F-actin crosslinker filamin from Dictyostelium discoideum
6970 (ddFLN) has a rod domain consisting of six structurally similar
6971 immunoglobulin domains. When subjected to a stretching force, domain 4
6972 unfolds at a lower force than all the other domains in the chain.
6973 Moreover, this domain shows a stable intermediate along its mechanical
6974 unfolding pathway. We have developed a mechanical single-molecule
6975 analogue to a double-jump stopped-flow experiment to investigate the
6976 folding kinetics and pathway of this domain. We show that an obligatory
6977 and productive intermediate also occurs on the folding pathway of the
6978 domain. Identical mechanical properties suggest that the unfolding and
6979 refolding intermediates are closely related. The folding process can be
6980 divided into two consecutive steps: in the first step 60 C-terminal
6981 amino acids form an intermediate at the rate of 55 s(-1); and in the
6982 second step the remaining 40 amino acids are packed on this core at the
6983 rate of 179 s(-1). This division increases the overall folding rate of
6984 this domain by a factor of ten compared with all other homologous
6985 domains of ddFLN that lack the folding intermediate."
6988 @article { sharma07,
6989 author = DSharma #" and "# OPerisic #" and "# QPeng #" and "# YCao #" and
6990 "# CLam #" and "# HLu #" and "# HLi,
6991 title = "Single-molecule force spectroscopy reveals a mechanically stable
6992 protein fold and the rational tuning of its mechanical stability",
6997 pages = "9278--9283",
6998 doi = "10.1073/pnas.0700351104",
6999 eprint = "http://www.pnas.org/cgi/reprint/104/22/9278.pdf",
7000 url = "http://www.pnas.org/cgi/content/abstract/104/22/9278",
7001 abstract = "It is recognized that shear topology of two directly connected
7002 force-bearing terminal [beta]-strands is a common feature among the
7003 vast majority of mechanically stable proteins known so far. However,
7004 these proteins belong to only two distinct protein folds, Ig-like
7005 [beta] sandwich fold and [beta]-grasp fold, significantly hindering
7006 delineating molecular determinants of mechanical stability and rational
7007 tuning of mechanical properties. Here we combine single-molecule atomic
7008 force microscopy and steered molecular dynamics simulation to reveal
7009 that the de novo designed Top7 fold [Kuhlman B, Dantas G, Ireton GC,
7010 Varani G, Stoddard BL, Baker D (2003) Science 302:13641368] represents
7011 a mechanically stable protein fold that is distinct from Ig-like [beta]
7012 sandwich and [beta]-grasp folds. Although the two force-bearing [beta]
7013 strands of Top7 are not directly connected, Top7 displays significant
7014 mechanical stability, demonstrating that the direct connectivity of
7015 force-bearing [beta] strands in shear topology is not mandatory for
7016 mechanical stability. This finding broadens our understanding of the
7017 design of mechanically stable proteins and expands the protein fold
7018 space where mechanically stable proteins can be screened. Moreover, our
7019 results revealed a substructure-sliding mechanism for the mechanical
7020 unfolding of Top7 and the existence of two possible unfolding pathways
7021 with different height of energy barrier. Such insights enabled us to
7022 rationally tune the mechanical stability of Top7 by redesigning its
7023 mechanical unfolding pathway. Our study demonstrates that computational
7024 biology methods (including de novo design) offer great potential for
7025 designing proteins of defined topology to achieve significant and
7026 tunable mechanical properties in a rational and systematic fashion."
7030 author = YJSheng #" and "# SJiang #" and "# HKTsao,
7031 title = "Forced Kramers escape in single-molecule pulling experiments",
7041 doi = "10.1063/1.2046632",
7042 url = "http://link.aip.org/link/?JCP/123/091102/1",
7043 keywords = "molecular biophysics; bonds (chemical); proteins",
7044 note = "Gives appropriate Einstein-S... relation for diffusion to damping",
7045 project = "sawtooth simulation"
7048 @article { shillcock98,
7049 author = JShillcock #" and "# USeifert,
7050 title = "Escape from a metastable well under a time-ramped force",
7056 pages = "7301--7304",
7059 doi = "10.1103/PhysRevE.57.7301",
7060 eprint = "http://prola.aps.org/pdf/PRE/v57/i6/p7301_1",
7061 url = "http://link.aps.org/abstract/PRE/v57/p7301",
7062 project = "sawtooth simulation"
7066 author = GESims #" and "# SRJun #" and "# GAWu #" and "# SHKim,
7067 title = "Alignment-free genome comparison with feature frequency profiles
7068 ({FFP}) and optimal resolutions",
7075 pages = "2677--2682",
7077 doi = "10.1073/pnas.0813249106",
7078 eprint = "http://www.pnas.org/cgi/reprint/106/31/12826",
7079 url = "http://www.pnas.org/content/106/8/2677",
7080 keywords = "Genome;Introns;Phylogeny",
7081 abstract = "For comparison of whole-genome (genic + nongenic) sequences,
7082 multiple sequence alignment of a few selected genes is not appropriate.
7083 One approach is to use an alignment-free method in which feature (or
7084 l-mer) frequency profiles (FFP) of whole genomes are used for
7085 comparison-a variation of a text or book comparison method, using word
7086 frequency profiles. In this approach it is critical to identify the
7087 optimal resolution range of l-mers for the given set of genomes
7088 compared. The optimum FFP method is applicable for comparing whole
7089 genomes or large genomic regions even when there are no common genes
7090 with high homology. We outline the method in 3 stages: (i) We first
7091 show how the optimal resolution range can be determined with English
7092 books which have been transformed into long character strings by
7093 removing all punctuation and spaces. (ii) Next, we test the robustness
7094 of the optimized FFP method at the nucleotide level, using a mutation
7095 model with a wide range of base substitutions and rearrangements. (iii)
7096 Finally, to illustrate the utility of the method, phylogenies are
7097 reconstructed from concatenated mammalian intronic genomes; the FFP
7098 derived intronic genome topologies for each l within the optimal range
7099 are all very similar. The topology agrees with the established
7100 mammalian phylogeny revealing that intron regions contain a similar
7101 level of phylogenic signal as do coding regions."
7105 author = SBSmith #" and "# LFinzi #" and "# CBustamante,
7106 title = "Direct mechanical measurements of the elasticity of single {DNA}
7107 molecules by using magnetic beads",
7114 pages = "1122--1126",
7116 doi = "10.1126/science.1439819",
7117 eprint = "http://www.sciencemag.org/cgi/reprint/258/5085/1122.pdf",
7118 url = "http://www.sciencemag.org/cgi/content/abstract/258/5085/1122",
7119 keywords = "Chemistry,
7120 Physical;Cisplatin;DNA;Elasticity;Ethidium;Glass;Indoles;Intercalating
7121 Agents;Magnetics;Mathematics;Microspheres",
7122 abstract = "Single DNA molecules were chemically attached by one end to a
7123 glass surface and by their other end to a magnetic bead. Equilibrium
7124 positions of the beads were observed in an optical microscope while the
7125 beads were acted on by known magnetic and hydrodynamic forces.
7126 Extension versus force curves were obtained for individual DNA
7127 molecules at three different salt concentrations with forces between
7128 10(-14) and 10(-11) newtons. Deviations from the force curves predicted
7129 by the freely jointed chain model suggest that DNA has significant
7130 local curvature in solution. Ethidium bromide and
7131 4',6-diamidino-2-phenylindole had little effect on the elastic response
7132 of the molecules, but their extent of intercalation was directly
7133 measured. Conversely, the effect of bend-inducing cis-
7134 diamminedichloroplatinum (II) was large and supports the hypothesis of
7135 natural curvature in DNA."
7139 author = SBSmith #" and "# YCui #" and "# CBustamante,
7140 title = "Overstretching {B}-{DNA}: the elastic response of individual
7141 double-stranded and single-stranded {DNA} molecules",
7150 keywords = "Base Composition;Chemistry, Physical;DNA;DNA, Single-
7151 Stranded;Elasticity;Nucleic Acid Conformation;Osmolar
7152 Concentration;Thermodynamics",
7153 abstract = "Single molecules of double-stranded DNA (dsDNA) were stretched
7154 with force-measuring laser tweezers. Under a longitudinal stress of
7155 approximately 65 piconewtons (pN), dsDNA molecules in aqueous buffer
7156 undergo a highly cooperative transition into a stable form with 5.8
7157 angstroms rise per base pair, that is, 70\% longer than B form dsDNA.
7158 When the stress was relaxed below 65 pN, the molecules rapidly and
7159 reversibly contracted to their normal contour lengths. This transition
7160 was affected by changes in the ionic strength of the medium and the
7161 water activity or by cross-linking of the two strands of dsDNA.
7162 Individual molecules of single-stranded DNA were also stretched giving
7163 a persistence length of 7.5 angstroms and a stretch modulus of 800 pN.
7164 The overstretched form may play a significant role in the energetics of
7169 author = NDSocci #" and "# JNOnuchic #" and "# PGWolynes,
7170 title = "Diffusive dynamics of the reaction coordinate for protein folding
7177 pages = "5860--5868",
7179 doi = "10.1063/1.471317",
7180 eprint = "http://arxiv.org/pdf/cond-mat/9601091",
7181 url = "http://link.aip.org/link/?JCP/104/5860/1",
7182 keywords = "PROTEINS; FOLDS; DIFFUSION; MONTE CARLO METHOD; SIMULATION;
7184 abstract = "The quantitative description of model protein folding kinetics
7185 using a diffusive collective reaction coordinate is examined. Direct
7186 folding kinetics, diffusional coefficients and free energy profiles are
7187 determined from Monte Carlo simulations of a 27-mer, 3 letter code
7188 lattice model, which corresponds roughly to a small helical protein.
7189 Analytic folding calculations, using simple diffusive rate theory,
7190 agree extremely well with the full simulation results. Folding in this
7191 system is best seen as a diffusive, funnel-like process.",
7192 note = "A nice introduction to some quantitative ramifications of the
7193 funnel energy landscape. There's also a bit of Kramers' theory and
7194 graph theory thrown in for good measure."
7198 author = NDSocci #" and "# JNOnuchic #" and "# PGWolynes,
7199 title = "Stretching lattice models of protein folding",
7206 pages = "2031--2035",
7208 keywords = "Amino Acid Sequence;Drug Stability;Kinetics;Models,
7209 Theoretical;Molecular Sequence Data;Peptides;Protein
7210 Denaturation;Protein Folding",
7211 abstract = "A new class of experiments that probe folding of individual
7212 protein domains uses mechanical stretching to cause the transition. We
7213 show how stretching forces can be incorporated in lattice models of
7214 folding. For fast folding proteins, the analysis suggests a complex
7215 relation between the force dependence and the reaction coordinate for
7219 @article { staple08,
7220 author = DBStaple #" and "# SHPayne #" and "# ALCReddin #" and "# HJKreuzer,
7221 title = "Model for stretching and unfolding the giant multidomain muscle
7222 protein using single-molecule force spectroscopy.",
7231 doi = "10.1103/PhysRevLett.101.248301",
7232 url = "http://dx.doi.org/10.1103/PhysRevLett.101.248301",
7233 keywords = "Kinetics;Microscopy, Atomic Force;Models, Chemical;Muscle
7234 Proteins;Protein Conformation;Protein Folding;Protein Kinases;Protein
7235 Structure, Tertiary;Thermodynamics",
7236 abstract = "Single-molecule manipulation has allowed the forced unfolding
7237 of multidomain proteins. Here we outline a theory that not only
7238 explains these experiments but also points out a number of difficulties
7239 in their interpretation and makes suggestions for further experiments.
7240 For titin we reproduce force-extension curves, the dependence of break
7241 force on pulling speed, and break-force distributions and also validate
7242 two common experimental views: Unfolding titin Ig domains can be
7243 explained as stepwise increases in contour length, and increasing force
7244 peaks in native Ig sequences represent a hierarchy of bond strengths.
7245 Our theory is valid for essentially any molecule that can be unfolded
7246 in atomic force microscopy; as a further example, we present force-
7247 extension curves for the unfolding of RNA hairpins."
7251 author = RStark #" and "# TDrobek #" and "# WHeckl,
7252 title = "Thermomechanical noise of a free v-shaped cantilever for atomic-
7261 doi = "http://dx.doi.org/10.1016/S0304-3991(00)00077-2",
7262 abstract = "We have calculated the thermal noise of a v-shaped AFM
7263 cantilever (Microlever, Type E, Thermomicroscopes) by means of a finite
7264 element analysis. The modal shapes of the first 10 eigenmodes are
7265 displayed as well as the numerical constants, which are needed for the
7266 calibration using the thermal noise method. In the first eigenmode,
7267 values for the thermomechanical noise of the z-displacement at 22
7268 degrees C temperature of square root of u2(1) = A/square root of
7269 c(cant) and the photodiode signal (normal-force) of S2(1) = A/square
7270 root of c(cant) were obtained. The results also indicate a systematic
7271 deviation ofthe spectral density of the thermomechanical noise of
7272 v-shaped cantilevers as compared to rectangular beam-shaped
7274 note = "Higher mode adjustments for v-shaped cantilevers from simulation.",
7275 project = "Cantilever Calibration"
7278 @article { strick96,
7279 author = TRStrick #" and "# JFAllemand #" and "# DBensimon #" and "#
7280 ABensimon #" and "# VCroquette,
7281 title = "The elasticity of a single supercoiled {DNA} molecule",
7288 pages = "1835--1837",
7290 keywords = "Bacteriophage lambda;DNA, Superhelical;DNA,
7291 Viral;Elasticity;Magnetics;Nucleic Acid Conformation;Temperature",
7292 abstract = "Single linear DNA molecules were bound at multiple sites at one
7293 extremity to a treated glass cover slip and at the other to a magnetic
7294 bead. The DNA was therefore torsionally constrained. A magnetic field
7295 was used to rotate the beads and thus to coil and pull the DNA. The
7296 stretching force was determined by analysis of the Brownian
7297 fluctuations of the bead. Here the elastic behavior of individual
7298 lambda DNA molecules over- and underwound by up to 500 turns was
7299 studied. A sharp transition was discovered from a low to a high
7300 extension state at a force of approximately 0.45 piconewtons for
7301 underwound molecules and at a force of approximately 3 piconewtons for
7302 overwound ones. These transitions, probably reflecting the formation of
7303 alternative structures in stretched coiled DNA molecules, might be
7304 relevant for DNA transcription and replication."
7307 @article { strunz99,
7308 author = TStrunz #" and "# KOroszlan #" and "# RSchafer #" and "#
7310 title = "Dynamic force spectroscopy of single {DNA} molecules",
7315 pages = "11277--11282",
7316 doi = "10.1073/pnas.96.20.11277",
7317 eprint = "http://www.pnas.org/cgi/reprint/96/20/11277.pdf",
7318 url = "http://www.pnas.org/cgi/content/abstract/96/20/11277"
7322 author = ASzabo #" and "# KSchulten #" and "# ZSchulten,
7323 title = "First passage time approach to diffusion controlled reactions",
7329 pages = "4350--4357",
7331 doi = "10.1063/1.439715",
7332 url = "http://link.aip.org/link/?JCP/72/4350/1",
7333 keywords = "DIFFUSION; CHEMICAL REACTIONS; CHEMICAL REACTION KINETICS;
7334 PROBABILITY; DIFFERENTIAL EQUATIONS"
7337 @article { talaga00,
7338 author = DTalaga #" and "# WLau #" and "# HRoder #" and "# JTang #" and "#
7339 YJia #" and "# WDeGrado #" and "# RHochstrasser,
7340 title = "Dynamics and folding of single two-stranded coiled-coil peptides
7341 studied by fluorescent energy transfer confocal microscopy",
7346 pages = "13021--13026",
7347 doi = "10.1073/pnas.97.24.13021",
7348 eprint = "http://www.pnas.org/cgi/reprint/97/24/13021.pdf",
7349 url = "http://www.pnas.org/cgi/content/abstract/97/24/13021"
7352 @article { thirumalai05,
7353 author = DThirumalai #" and "# CHyeon,
7354 title = "{RNA} and Protein Folding: Common Themes and Variations",
7355 affiliation = "Biophysics Program, and Department of Chemistry and
7356 Biochemistry, Institute for Physical Science and Technology, University
7357 of Maryland, College Park, Maryland 20742",
7362 pages = "4957--4970",
7365 "http://pubs3.acs.org/acs/journals/doilookup?in_doi=10.1021/bi047314+",
7366 abstract = "Visualizing the navigation of an ensemble of unfolded molecules
7367 through the bumpy energy landscape in search of the native state gives
7368 a pictorial view of biomolecular folding. This picture, when combined
7369 with concepts in polymer theory, provides a unified theory of RNA and
7370 protein folding. Just as for proteins, the major folding free energy
7371 barrier for RNA scales sublinearly with the number of nucleotides,
7372 which allows us to extract the elusive prefactor for RNA folding.
7373 Several folding scenarios can be anticipated by considering variations
7374 in the energy landscape that depend on sequence, native topology, and
7375 external conditions. RNA and protein folding mechanism can be described
7376 by the kinetic partitioning mechanism (KPM) according to which a
7377 fraction () of molecules reaches the native state directly, whereas the
7378 remaining fraction gets kinetically trapped in metastable
7379 conformations. For two-state folders 1. Molecular chaperones are
7380 recruited to assist protein folding whenever is small. We show that the
7381 iterative annealing mechanism, introduced to describe chaperonin-
7382 mediated folding, can be generalized to understand protein-assisted RNA
7383 folding. The major differences between the folding of proteins and RNA
7384 arise in the early stages of folding. For RNA, folding can only begin
7385 after the polyelectrolyte problem is solved, whereas protein collapse
7386 requires burial of hydrophobic residues. Cross-fertilization of ideas
7387 between the two fields should lead to an understanding of how RNA and
7388 proteins solve their folding problems.",
7389 note = "unfolding-refolding"
7393 author = SThornton #" and "# JMarion,
7394 title = "Classical Dynamics of Particles and Systems",
7397 isbn = "0-534-40896-6",
7398 publisher = BrooksCole,
7399 address = "Belmont, CA"
7402 @article { tlusty98,
7403 author = TTlusty #" and "# AMeller #" and "# RBar-Ziv,
7404 title = "Optical Gradient Forces of Strongly Localized Fields",
7410 pages = "1738--1741",
7413 doi = "10.1103/PhysRevLett.81.1738",
7414 eprint = "http://prola.aps.org/pdf/PRL/v81/i8/p1738_1",
7416 \url{http://nanoscience.bu.edu/papers/p1738_1_Meller.pdf}.
7417 Cited by \citet{grossman05} for derivation of thermal response
7418 functions. However, I only see a referenced thermal energy when
7419 they list the likelyhood of a small partical (radius $<R_c$)
7420 escaping due to thermal energy, where $R_c$ is roughly $R_c \sim
7421 (k_B T / \alpha I_0)^{1/3}$, $\alpha$ is a dielectric scaling
7422 term, and $I_0$ is the maximum beam energy density. I imagine
7423 Grossman and Stout mixed up this reference.",
7424 project = "Cantilever Calibration"
7427 @article { tshiprut08,
7428 author = ZTshiprut #" and "# JKlafter #" and "# MUrbakh,
7429 title = "Single-molecule pulling experiments: when the stiffness of the
7430 pulling device matters",
7439 doi = "10.1529/biophysj.108.141580",
7440 eprint = "http://www.biophysj.org/cgi/reprint/95/6/L42.pdf",
7441 abstract = "Using Langevin modeling, we investigate the role of the
7442 experimental setup on the unbinding forces measured in single-molecule
7443 pulling experiments. We demonstrate that the stiffness of the pulling
7444 device, K(eff), may influence the unbinding forces through its effect
7445 on the barrier heights for both unbinding and rebinding processes.
7446 Under realistic conditions the effect of K(eff) on the rebinding
7447 barrier is shown to play the most important role. This results in a
7448 significant increase of the mean unbinding force with the stiffness for
7449 a given loading rate. Thus, in contrast to the phenomenological Bell
7450 model, we find that the loading rate (the multiplicative value K(eff)V,
7451 V being the pulling velocity) is not the only control parameter that
7452 determines the mean unbinding force. If interested in intrinsic
7453 properties of a molecular system, we recommend probing the system in
7454 the parameter range corresponding to a weak spring and relatively high
7455 loading rates where rebinding is negligible.",
7456 note = "Cites \citet{dudko03} for Kramers' description of irreversible
7457 rupture, and claims it is required to explain the deviations in
7458 $\avg{F}$ at the same loading rate. Proposes Moese equation as an
7459 example potential. Cites \citet{walton08} for experimental evidence of
7460 $\avg{F}$ increasing with linker stiffness."
7463 @article { uniprot10,
7464 author = UniProtConsort,
7466 title = "The Universal Protein Resource (UniProt) in 2010.",
7472 number = "Database issue",
7473 pages = "D142--D148",
7475 doi = "10.1093/nar/gkp846",
7476 url = "http://nar.oxfordjournals.org/cgi/content/abstract/38/suppl_1/D142",
7477 keywords = "Algorithms;Animals;Computational Biology;Databases, Nucleic
7478 Acid;Databases, Protein;Europe;Genome, Fungal;Genome,
7479 Viral;Humans;Information Storage and Retrieval;Internet;Protein
7480 Isoforms;Proteome;Proteomics;Software",
7481 abstract = "The primary mission of UniProt is to support biological
7482 research by maintaining a stable, comprehensive, fully classified,
7483 richly and accurately annotated protein sequence knowledgebase, with
7484 extensive cross-references and querying interfaces freely accessible to
7485 the scientific community. UniProt is produced by the UniProt Consortium
7486 which consists of groups from the European Bioinformatics Institute
7487 (EBI), the Swiss Institute of Bioinformatics (SIB) and the Protein
7488 Information Resource (PIR). UniProt is comprised of four major
7489 components, each optimized for different uses: the UniProt Archive, the
7490 UniProt Knowledgebase, the UniProt Reference Clusters and the UniProt
7491 Metagenomic and Environmental Sequence Database. UniProt is updated and
7492 distributed every 3 weeks and can be accessed online for searches or
7493 download at http://www.uniprot.org."
7496 @misc { uniprot:STRAV,
7497 key = "uniprot:STRAV",
7498 url = "http://www.uniprot.org/uniprot/P22629"
7501 @book { vanKampen07,
7502 author = NGvanKampen,
7503 title = "Stochastic Processes in Physics and Chemistry",
7507 address = "Amsterdam",
7509 project = "sawtooth simulation"
7512 @article { venter01,
7513 author = JCVenter #" and "# MDAdams #" and "# EWMyers #" and "# PWLi #" and
7514 "# RJMural #" and "# GGSutton #" and "# HOSmith #" and "# MYandell #"
7515 and "# CAEvans #" and "# RAHolt #" and "# JDGocayne #" and "#
7516 PAmanatides #" and "# RMBallew #" and "# DHHuson #" and "# JRWortman #"
7517 and "# QZhang #" and "# CDKodira #" and "# XHZheng #" and "# LChen #"
7518 and "# MSkupski #" and "# GSubramanian #" and "# PDThomas #" and "#
7519 JZhang #" and "# GLGaborMiklos #" and "# CNelson #" and "# SBroder #"
7520 and "# AGClark #" and "# JNadeau #" and "# VAMcKusick #" and "# NZinder
7521 #" and "# AJLevine #" and "# RJRoberts #" and "# MSimon #" and "#
7522 CSlayman #" and "# MHunkapiller #" and "# RBolanos #" and "# ADelcher
7523 #" and "# IDew #" and "# DFasulo #" and "# MFlanigan #" and "# LFlorea
7524 #" and "# AHalpern #" and "# SHannenhalli #" and "# SKravitz #" and "#
7525 SLevy #" and "# CMobarry #" and "# KReinert #" and "# KRemington #" and
7526 "# JAbu-Threideh #" and "# EBeasley #" and "# KBiddick #" and "#
7527 VBonazzi #" and "# RBrandon #" and "# MCargill #" and "#
7528 IChandramouliswaran #" and "# RCharlab #" and "# KChaturvedi #" and "#
7529 ZDeng #" and "# VDiFrancesco #" and "# PDunn #" and "# KEilbeck #" and
7530 "# CEvangelista #" and "# AEGabrielian #" and "# WGan #" and "# WGe #"
7531 and "# FGong #" and "# ZGu #" and "# PGuan #" and "# TJHeiman #" and "#
7532 MEHiggins #" and "# RRJi #" and "# ZKe #" and "# KAKetchum #" and "#
7533 ZLai #" and "# YLei #" and "# ZLi #" and "# JLi #" and "# YLiang #" and
7534 "# XLin #" and "# FLu #" and "# GVMerkulov #" and "# NMilshina #" and
7535 "# HMMoore #" and "# AKNaik #" and "# VANarayan #" and "# BNeelam #"
7536 and "# DNusskern #" and "# DBRusch #" and "# SSalzberg #" and "# WShao
7537 #" and "# BShue #" and "# JSun #" and "# ZWang #" and "# AWang #" and
7538 "# XWang #" and "# JWang #" and "# MWei #" and "# RWides #" and "#
7539 CXiao #" and "# CYan #" and "# AYao #" and "# JYe #" and "# MZhan #"
7540 and "# WZhang #" and "# HZhang #" and "# QZhao #" and "# LZheng #" and
7541 "# FZhong #" and "# WZhong #" and "# SZhu #" and "# SZhao #" and "#
7542 DGilbert #" and "# SBaumhueter #" and "# GSpier #" and "# CCarter #"
7543 and "# ACravchik #" and "# TWoodage #" and "# FAli #" and "# HAn #" and
7544 "# AAwe #" and "# DBaldwin #" and "# HBaden #" and "# MBarnstead #" and
7545 "# IBarrow #" and "# KBeeson #" and "# DBusam #" and "# ACarver #" and
7546 "# ACenter #" and "# MLCheng #" and "# LCurry #" and "# SDanaher #" and
7547 "# LDavenport #" and "# RDesilets #" and "# SDietz #" and "# KDodson #"
7548 and "# LDoup #" and "# SFerriera #" and "# NGarg #" and "# AGluecksmann
7549 #" and "# BHart #" and "# JHaynes #" and "# CHaynes #" and "# CHeiner
7550 #" and "# SHladun #" and "# DHostin #" and "# JHouck #" and "# THowland
7551 #" and "# CIbegwam #" and "# JJohnson #" and "# FKalush #" and "#
7552 LKline #" and "# SKoduru #" and "# ALove #" and "# FMann #" and "# DMay
7553 #" and "# SMcCawley #" and "# TMcIntosh #" and "# IMcMullen #" and "#
7554 MMoy #" and "# LMoy #" and "# BMurphy #" and "# KNelson #" and "#
7555 CPfannkoch #" and "# EPratts #" and "# VPuri #" and "# HQureshi #" and
7556 "# MReardon #" and "# RRodriguez #" and "# YHRogers #" and "# DRomblad
7557 #" and "# BRuhfel #" and "# RScott #" and "# CSitter #" and "#
7558 MSmallwood #" and "# EStewart #" and "# RStrong #" and "# ESuh #" and
7559 "# RThomas #" and "# NNTint #" and "# STse #" and "# CVech #" and "#
7560 GWang #" and "# JWetter #" and "# SWilliams #" and "# MWilliams #" and
7561 "# SWindsor #" and "# EWinn-Deen #" and "# KWolfe #" and "# JZaveri #"
7562 and "# KZaveri #" and "# JFAbril #" and "# RGuigo #" and "# MJCampbell
7563 #" and "# KVSjolander #" and "# BKarlak #" and "# AKejariwal #" and "#
7564 HMi #" and "# BLazareva #" and "# THatton #" and "# ANarechania #" and
7565 "# KDiemer #" and "# AMuruganujan #" and "# NGuo #" and "# SSato #" and
7566 "# VBafna #" and "# SIstrail #" and "# RLippert #" and "# RSchwartz #"
7567 and "# BWalenz #" and "# SYooseph #" and "# DAllen #" and "# ABasu #"
7568 and "# JBaxendale #" and "# LBlick #" and "# MCaminha #" and "#
7569 JCarnes-Stine #" and "# PCaulk #" and "# YHChiang #" and "# MCoyne #"
7570 and "# CDahlke #" and "# AMays #" and "# MDombroski #" and "# MDonnelly
7571 #" and "# DEly #" and "# SEsparham #" and "# CFosler #" and "# HGire #"
7572 and "# SGlanowski #" and "# KGlasser #" and "# AGlodek #" and "#
7573 MGorokhov #" and "# KGraham #" and "# BGropman #" and "# MHarris #" and
7574 "# JHeil #" and "# SHenderson #" and "# JHoover #" and "# DJennings #"
7575 and "# CJordan #" and "# JJordan #" and "# JKasha #" and "# LKagan #"
7576 and "# CKraft #" and "# ALevitsky #" and "# MLewis #" and "# XLiu #"
7577 and "# JLopez #" and "# DMa #" and "# WMajoros #" and "# JMcDaniel #"
7578 and "# SMurphy #" and "# MNewman #" and "# TNguyen #" and "# NNguyen #"
7579 and "# MNodell #" and "# SPan #" and "# JPeck #" and "# MPeterson #"
7580 and "# WRowe #" and "# RSanders #" and "# JScott #" and "# MSimpson #"
7581 and "# TSmith #" and "# ASprague #" and "# TStockwell #" and "# RTurner
7582 #" and "# EVenter #" and "# MWang #" and "# MWen #" and "# DWu #" and
7583 "# MWu #" and "# AXia #" and "# AZandieh #" and "# XZhu,
7584 title = "The sequence of the human genome.",
7591 pages = "1304--1351",
7593 doi = "10.1126/science.1058040",
7594 eprint = "http://www.sciencemag.org/cgi/content/pdf/291/5507/1304",
7595 url = "http://www.sciencemag.org/cgi/content/short/291/5507/1304",
7596 keywords = "Algorithms;Animals;Chromosome Banding;Chromosome
7597 Mapping;Chromosomes, Artificial, Bacterial;Computational
7598 Biology;Consensus Sequence;CpG Islands;DNA, Intergenic;Databases,
7599 Factual;Evolution, Molecular;Exons;Female;Gene
7600 Duplication;Genes;Genetic Variation;Genome, Human;Human Genome
7601 Project;Humans;Introns;Male;Phenotype;Physical Chromosome
7602 Mapping;Polymorphism, Single Nucleotide;Proteins;Pseudogenes;Repetitive
7603 Sequences, Nucleic Acid;Retroelements;Sequence Analysis, DNA;Species
7605 abstract = "A 2.91-billion base pair (bp) consensus sequence of the
7606 euchromatic portion of the human genome was generated by the whole-
7607 genome shotgun sequencing method. The 14.8-billion bp DNA sequence was
7608 generated over 9 months from 27,271,853 high-quality sequence reads
7609 (5.11-fold coverage of the genome) from both ends of plasmid clones
7610 made from the DNA of five individuals. Two assembly strategies-a whole-
7611 genome assembly and a regional chromosome assembly-were used, each
7612 combining sequence data from Celera and the publicly funded genome
7613 effort. The public data were shredded into 550-bp segments to create a
7614 2.9-fold coverage of those genome regions that had been sequenced,
7615 without including biases inherent in the cloning and assembly procedure
7616 used by the publicly funded group. This brought the effective coverage
7617 in the assemblies to eightfold, reducing the number and size of gaps in
7618 the final assembly over what would be obtained with 5.11-fold coverage.
7619 The two assembly strategies yielded very similar results that largely
7620 agree with independent mapping data. The assemblies effectively cover
7621 the euchromatic regions of the human chromosomes. More than 90\% of the
7622 genome is in scaffold assemblies of 100,000 bp or more, and 25\% of the
7623 genome is in scaffolds of 10 million bp or larger. Analysis of the
7624 genome sequence revealed 26,588 protein-encoding transcripts for which
7625 there was strong corroborating evidence and an additional approximately
7626 12,000 computationally derived genes with mouse matches or other weak
7627 supporting evidence. Although gene-dense clusters are obvious, almost
7628 half the genes are dispersed in low G+C sequence separated by large
7629 tracts of apparently noncoding sequence. Only 1.1\% of the genome is
7630 spanned by exons, whereas 24\% is in introns, with 75\% of the genome
7631 being intergenic DNA. Duplications of segmental blocks, ranging in size
7632 up to chromosomal lengths, are abundant throughout the genome and
7633 reveal a complex evolutionary history. Comparative genomic analysis
7634 indicates vertebrate expansions of genes associated with neuronal
7635 function, with tissue-specific developmental regulation, and with the
7636 hemostasis and immune systems. DNA sequence comparisons between the
7637 consensus sequence and publicly funded genome data provided locations
7638 of 2.1 million single-nucleotide polymorphisms (SNPs). A random pair of
7639 human haploid genomes differed at a rate of 1 bp per 1250 on average,
7640 but there was marked heterogeneity in the level of polymorphism across
7641 the genome. Less than 1\% of all SNPs resulted in variation in
7642 proteins, but the task of determining which SNPs have functional
7643 consequences remains an open challenge."
7646 @article { verdier70,
7648 title = "Relaxation Behavior of the Freely Jointed Chain",
7654 pages = "5512--5517",
7656 doi = "10.1063/1.1672818",
7657 url = "http://link.aip.org/link/?JCP/52/5512/1"
7660 @article { walther07,
7661 author = KWalther #" and "# FGrater #" and "# LDougan #" and "# CBadilla #"
7662 and "# BBerne #" and "# JFernandez,
7663 title = "Signatures of hydrophobic collapse in extended proteins captured
7664 with force spectroscopy",
7669 pages = "7916--7921",
7670 doi = "10.1073/pnas.0702179104",
7671 eprint = "http://www.pnas.org/cgi/reprint/104/19/7916.pdf",
7672 url = "http://www.pnas.org/cgi/content/abstract/104/19/7916",
7673 abstract = "We unfold and extend single proteins at a high force and then
7674 linearly relax the force to probe their collapse mechanisms. We observe
7675 a large variability in the extent of their recoil. Although chain
7676 entropy makes a small contribution, we show that the observed
7677 variability results from hydrophobic interactions with randomly varying
7678 magnitude from protein to protein. This collapse mechanism is common to
7679 highly extended proteins, including nonfolding elastomeric proteins
7680 like PEVK from titin. Our observations explain the puzzling differences
7681 between the folding behavior of highly extended proteins, from those
7682 folding after chemical or thermal denaturation. Probing the collapse of
7683 highly extended proteins with force spectroscopy allows separation of
7684 the different driving forces in protein folding."
7687 @article { walton08,
7688 author = EBWalton #" and "# SLee #" and "# KJVanVliet,
7689 title = "Extending {B}ell's model: How force transducer stiffness alters
7690 measured unbinding forces and kinetics of molecular complexes",
7697 pages = "2621--2630",
7699 doi = "10.1529/biophysj.107.114454",
7700 keywords = "Biotin;Computer
7701 Simulation;Elasticity;Kinetics;Mechanotransduction, Cellular;Models,
7702 Chemical;Models, Molecular;Molecular Motor
7703 Proteins;Motion;Streptavidin;Stress, Mechanical;Transducers",
7704 abstract = "Forced unbinding of complementary macromolecules such as
7705 ligand-receptor complexes can reveal energetic and kinetic details
7706 governing physiological processes ranging from cellular adhesion to
7707 drug metabolism. Although molecular-level experiments have enabled
7708 sampling of individual ligand-receptor complex dissociation events,
7709 disparities in measured unbinding force F(R) among these methods lead
7710 to marked variation in inferred binding energetics and kinetics at
7711 equilibrium. These discrepancies are documented for even the ubiquitous
7712 ligand-receptor pair, biotin-streptavidin. We investigated these
7713 disparities and examined atomic-level unbinding trajectories via
7714 steered molecular dynamics simulations, as well as via molecular force
7715 spectroscopy experiments on biotin-streptavidin. In addition to the
7716 well-known loading rate dependence of F(R) predicted by Bell's model,
7717 we find that experimentally accessible parameters such as the effective
7718 stiffness of the force transducer k can significantly perturb the
7719 energy landscape and the apparent unbinding force of the complex for
7720 sufficiently stiff force transducers. Additionally, at least 20\%
7721 variation in unbinding force can be attributed to minute differences in
7722 initial atomic positions among energetically and structurally
7723 comparable complexes. For force transducers typical of molecular force
7724 spectroscopy experiments and atomistic simulations, this energy barrier
7725 perturbation results in extrapolated energetic and kinetic parameters
7726 of the complex that depend strongly on k. We present a model that
7727 explicitly includes the effect of k on apparent unbinding force of the
7728 ligand-receptor complex, and demonstrate that this correction enables
7729 prediction of unbinding distances and dissociation rates that are
7730 decoupled from the stiffness of actual or simulated molecular linkers.",
7731 note = "Some detailed estimates at U(x)."
7734 @article { walton86,
7736 title = "The Abbe theory of imaging: an alternative derivation of the
7743 url = "http://stacks.iop.org/0143-0807/7/62"
7746 @article { watanabe05,
7747 author = HWatanabe #" and "# TInoue,
7748 title = "Conformational dynamics of Rouse chains during creep/recovery
7749 processes: a review",
7754 pages = "R607--R636",
7755 doi = "10.1088/0953-8984/17/19/R01",
7756 eprint = "http://www.iop.org/EJ/article/0953-8984/17/19/R01/cm5_19_R01.pdf",
7757 url = "http://stacks.iop.org/0953-8984/17/R607",
7758 abstract = "The Rouse model is a well-established model for non-entangled
7759 polymer chains and also serves as a fundamental model for entangled
7760 chains. The dynamic behaviour of this model under strain-controlled
7761 conditions has been fully analysed in the literature. However, despite
7762 the importance of the Rouse model, no analysis has been made so far of
7763 the orientational anisotropy of the Rouse eigenmodes during the stress-
7764 controlled, creep and recovery processes. For completeness of the
7765 analysis of the model, the Rouse equation of motion is solved to
7766 calculate this anisotropy for monodisperse chains and their binary
7767 blends during the creep/recovery processes. The calculation is simple
7768 and straightforward, but the result is intriguing in the sense that
7769 each Rouse eigenmode during these processes has a distribution in the
7770 retardation times. This behaviour, reflecting the interplay/correlation
7771 among the Rouse eigenmodes of different orders (and for different
7772 chains in the blends) under the constant stress condition, is quite
7773 different from the behaviour under rate-controlled flow (where each
7774 eigenmode exhibits retardation/relaxation associated with a single
7775 characteristic time). Furthermore, the calculation indicates that the
7776 Rouse chains exhibit affine deformation on sudden imposition/removal of
7777 the stress and the magnitude of this deformation is inversely
7778 proportional to the number of bond vectors per chain. In relation to
7779 these results, a difference between the creep and relaxation properties
7780 is also discussed for chains obeying multiple relaxation mechanisms
7781 (Rouse and reptation mechanisms).",
7782 note = "Middly-detailed Rouse model review."
7786 author = AWiita #" and "# SAinavarapu #" and "# HHuang #" and "# JFernandez,
7787 title = "From the Cover: Force-dependent chemical kinetics of disulfide
7788 bond reduction observed with single-molecule techniques",
7793 pages = "7222--7227",
7794 doi = "10.1073/pnas.0511035103",
7795 eprint = "http://www.pnas.org/cgi/reprint/103/19/7222.pdf",
7796 url = "http://www.pnas.org/cgi/content/abstract/103/19/7222",
7797 abstract = "The mechanism by which mechanical force regulates the kinetics
7798 of a chemical reaction is unknown. Here, we use single-molecule force-
7799 clamp spectroscopy and protein engineering to study the effect of force
7800 on the kinetics of thiol/disulfide exchange. Reduction of disulfide
7801 bonds through the thiol/disulfide exchange chemical reaction is crucial
7802 in regulating protein function and is known to occur in mechanically
7803 stressed proteins. We apply a constant stretching force to single
7804 engineered disulfide bonds and measure their rate of reduction by DTT.
7805 Although the reduction rate is linearly dependent on the concentration
7806 of DTT, it is exponentially dependent on the applied force, increasing
7807 10-fold over a 300-pN range. This result predicts that the disulfide
7808 bond lengthens by 0.34 A at the transition state of the thiol/disulfide
7809 exchange reaction. Our work at the single bond level directly
7810 demonstrates that thiol/disulfide exchange in proteins is a force-
7811 dependent chemical reaction. Our findings suggest that mechanical force
7812 plays a role in disulfide reduction in vivo, a property that has never
7813 been explored by traditional biochemistry. Furthermore, our work also
7814 indicates that the kinetics of any chemical reaction that results in
7815 bond lengthening will be force-dependent."
7818 @article { wilcox05,
7819 author = AWilcox #" and "# JChoy #" and "# CBustamante #" and "#
7821 title = "Effect of protein structure on mitochondrial import",
7826 pages = "15435--15440",
7827 doi = "10.1073/pnas.0507324102",
7828 eprint = "http://www.pnas.org/cgi/reprint/102/43/15435.pdf",
7829 url = "http://www.pnas.org/cgi/content/abstract/102/43/15435",
7830 abstract = "Most proteins that are to be imported into the mitochondrial
7831 matrix are synthesized as precursors, each composed of an N-terminal
7832 targeting sequence followed by a mature domain. Precursors are
7833 recognized through their targeting sequences by receptors at the
7834 mitochondrial surface and are then threaded through import channels
7835 into the matrix. Both the targeting sequence and the mature domain
7836 contribute to the efficiency with which proteins are imported into
7837 mitochondria. Precursors must be in an unfolded conformation during
7838 translocation. Mitochondria can unfold some proteins by changing their
7839 unfolding pathways. The effectiveness of this unfolding mechanism
7840 depends on the local structure of the mature domain adjacent to the
7841 targeting sequence. This local structure determines the extent to which
7842 the unfolding pathway can be changed and, therefore, the unfolding rate
7843 increased. Atomic force microscopy studies find that the local
7844 structures of proteins near their N and C termini also influence their
7845 resistance to mechanical unfolding. Thus, protein unfolding during
7846 import resembles mechanical unfolding, and the specificity of import is
7847 determined by the resistance of the mature domain to unfolding as well
7848 as by the properties of the targeting sequence."
7851 @article { wolfsberg01,
7852 author = TGWolfsberg #" and "# JMcEntyre #" and "# GDSchuler,
7853 title = "Guide to the draft human genome.",
7862 doi = "10.1038/35057000",
7863 eprint = "http://www.nature.com/nature/journal/v409/n6822/pdf/409824a0.pdf",
7864 url = "http://www.nature.com/nature/journal/v409/n6822/full/409824a0.html",
7865 keywords = "Amino Acid Sequence;Chromosome Mapping;Computational
7866 Biology;Genes;Genetic Variation;Genome, Human;Human Genome
7867 Project;Humans;Internet;Molecular Sequence Data;Sequence Analysis, DNA",
7868 abstract = "There are a number of ways to investigate the structure,
7869 function and evolution of the human genome. These include examining the
7870 morphology of normal and abnormal chromosomes, constructing maps of
7871 genomic landmarks, following the genetic transmission of phenotypes and
7872 DNA sequence variations, and characterizing thousands of individual
7873 genes. To this list we can now add the elucidation of the genomic DNA
7874 sequence, albeit at 'working draft' accuracy. The current challenge is
7875 to weave together these disparate types of data to produce the
7876 information infrastructure needed to support the next generation of
7877 biomedical research. Here we provide an overview of the different
7878 sources of information about the human genome and how modern
7879 information technology, in particular the internet, allows us to link
7884 author = JWWu #" and "# WLHung #" and "# CHTsai,
7885 title = "Estimation of parameters of the {G}ompertz distribution using the
7886 least squares method",
7895 doi = "10.1016/j.amc.2003.08.086",
7896 url = "http://dx.doi.org/10.1016/j.amc.2003.08.086",
7897 keywords = "Gompertz distribution; Least squares estimate; Maximum
7898 likelihood estimate; First failure-censored; Series system",
7899 abstract = "The Gompertz distribution has been used to describe human
7900 mortality and establish actuarial tables. Recently, this distribution
7901 has been again studied by some authors. The maximum likelihood
7902 estimates for the parameters of the Gompertz distribution has been
7903 discussed by Garg et al. [J. R. Statist. Soc. C 19 (1970) 152]. The
7904 purpose of this paper is to propose unweighted and weighted least
7905 squares estimates for parameters of the Gompertz distribution under the
7906 complete data and the first failure-censored data (series systems; see
7907 [J. Statist. Comput. Simulat. 52 (1995) 337]). A simulation study is
7908 carried out to compare the proposed estimators and the maximum
7909 likelihood estimators. Results of the simulation studies show that the
7910 performance of the weighted least squares estimators is acceptable."
7914 author = GYang #" and "# CCecconi #" and "# WBaase #" and "# IVetter #" and
7915 "# WBreyer #" and "# JHaack #" and "# BMatthews #" and "# FDahlquist #"
7917 title = "Solid-state synthesis and mechanical unfolding of polymers of {T4}
7924 doi = "10.1073/pnas.97.1.139",
7925 eprint = "http://www.pnas.org/cgi/reprint/97/1/139.pdf",
7926 url = "http://www.pnas.org/cgi/content/abstract/97/1/139"
7930 author = YYang #" and "# FCLin #" and "# GYang,
7931 title = "Temperature control device for single molecule measurements using
7932 the atomic force microscope",
7942 doi = "10.1063/1.2204580",
7943 url = "http://link.aip.org/link/?RSI/77/063701/1",
7944 keywords = "temperature control; atomic force microscopy; thermocouples;
7946 note = "Introduces our temperature control system",
7947 project = "Energy Landscape Roughness"
7951 author = WYu #" and "# JLamb #" and "# FHan #" and "# JBirchler,
7952 title = "Telomere-mediated chromosomal truncation in maize",
7957 pages = "17331--17336",
7958 doi = "10.1073/pnas.0605750103",
7959 eprint = "http://www.pnas.org/cgi/reprint/103/46/17331.pdf",
7960 url = "http://www.pnas.org/cgi/content/abstract/103/46/17331",
7961 abstract = "Direct repeats of Arabidopsis telomeric sequence were
7962 constructed to test telomere-mediated chromosomal truncation in maize.
7963 Two constructs with 2.6 kb of telomeric sequence were used to transform
7964 maize immature embryos by Agrobacterium-mediated transformation. One
7965 hundred seventy-six transgenic lines were recovered in which 231
7966 transgene loci were revealed by a FISH analysis. To analyze chromosomal
7967 truncations that result in transgenes located near chromosomal termini,
7968 Southern hybridization analyses were performed. A pattern of smear in
7969 truncated lines was seen as compared with discrete bands for internal
7970 integrations, because telomeres in different cells are elongated
7971 differently by telomerase. When multiple restriction enzymes were used
7972 to map the transgene positions, the size of the smears shifted in
7973 accordance with the locations of restriction sites on the construct.
7974 This result demonstrated that the transgene was present at the end of
7975 the chromosome immediately before the integrated telomere sequence.
7976 Direct evidence for chromosomal truncation came from the results of
7977 FISH karyotyping, which revealed broken chromosomes with transgene
7978 signals at the ends. These results demonstrate that telomere-mediated
7979 chromosomal truncation operates in plant species. This technology will
7980 be useful for chromosomal engineering in maize as well as other plant
7985 author = JZhao #" and "# HLee #" and "# RNome #" and "# SMajid #" and "#
7986 NScherer #" and "# WHoff,
7987 title = "Single-molecule detection of structural changes during
7988 {P}er-{A}rnt-{S}im ({PAS}) domain activation",
7993 pages = "11561--11566",
7994 doi = "10.1073/pnas.0601567103",
7995 eprint = "http://www.pnas.org/cgi/reprint/103/31/11561.pdf",
7996 url = "http://www.pnas.org/cgi/content/abstract/103/31/11561",
7997 abstract = "The Per-Arnt-Sim (PAS) domain is a ubiquitous protein module
7998 with a common three-dimensional fold involved in a wide range of
7999 regulatory and sensory functions in all domains of life. The activation
8000 of these functions is thought to involve partial unfolding of N- or
8001 C-terminal helices attached to the PAS domain. Here we use atomic force
8002 microscopy to probe receptor activation in single molecules of
8003 photoactive yellow protein (PYP), a prototype of the PAS domain family.
8004 Mechanical unfolding of Cys-linked PYP multimers in the presence and
8005 absence of illumination reveals that, in contrast to previous studies,
8006 the PAS domain itself is extended by {approx}3 nm (at the 10-pN
8007 detection limit of the measurement) and destabilized by {approx}30% in
8008 the light-activated state of PYP. Comparative measurements and steered
8009 molecular dynamics simulations of two double-Cys PYP mutants that probe
8010 different regions of the PAS domain quantify the anisotropy in
8011 stability and changes in local structure, thereby demonstrating the
8012 partial unfolding of their PAS domain upon activation. These results
8013 establish a generally applicable single-molecule approach for mapping
8014 functional conformational changes to selected regions of a protein. In
8015 addition, the results have profound implications for the molecular
8016 mechanism of PAS domain activation and indicate that stimulus-induced
8017 partial protein unfolding can be used as a signaling mechanism."
8020 @article { zhuang06,
8021 author = WZhuang #" and "# DAbramavicius #" and "# SMukamel,
8022 title = "Two-dimensional vibrational optical probes for peptide fast
8023 folding investigation",
8028 pages = "18934--18938",
8029 doi = "10.1073/pnas.0606912103",
8030 eprint = "http://www.pnas.org/cgi/reprint/103/50/18934.pdf",
8031 url = "http://www.pnas.org/cgi/content/abstract/103/50/18934",
8032 abstract = "A simulation study shows that early protein folding events may
8033 be investigated by using a recently developed family of nonlinear
8034 infrared techniques that combine the high temporal and spatial
8035 resolution of multidimensional spectroscopy with the chirality-specific
8036 sensitivity of amide vibrations to structure. We demonstrate how the
8037 structural sensitivity of cross-peaks in two-dimensional correlation
8038 plots of chiral signals of an {alpha} helix and a [beta] hairpin may be
8039 used to clearly resolve structural and dynamical details undetectable
8040 by one-dimensional techniques (e.g. circular dichroism) and identify
8041 structures indistinguishable by NMR."
8044 @article { zinober02,
8045 author = RCZinober #" and "# DJBrockwell #" and "# GSBeddard #" and "#
8046 AWBlake #" and "# PDOlmsted #" and "# SERadford #" and "# DASmith,
8047 title = "Mechanically unfolding proteins: the effect of unfolding history
8048 and the supramolecular scaffold",
8054 pages = "2759--2765",
8056 doi = "10.1110/ps.0224602",
8057 eprint = "http://www.proteinscience.org/cgi/reprint/11/12/2759.pdf",
8058 url = "http://www.proteinscience.org/cgi/content/abstract/11/12/2759",
8059 keywords = "Computer Simulation; Models, Molecular; Monte Carlo Method;
8060 Protein Folding; Protein Structure, Tertiary; Proteins",
8061 abstract = "The mechanical resistance of a folded domain in a polyprotein
8062 of five mutant I27 domains (C47S, C63S I27)(5)is shown to depend on the
8063 unfolding history of the protein. This observation can be understood on
8064 the basis of competition between two effects, that of the changing
8065 number of domains attempting to unfold, and the progressive increase in
8066 the compliance of the polyprotein as domains unfold. We present Monte
8067 Carlo simulations that show the effect and experimental data that
8068 verify these observations. The results are confirmed using an
8069 analytical model based on transition state theory. The model and
8070 simulations also predict that the mechanical resistance of a domain
8071 depends on the stiffness of the surrounding scaffold that holds the
8072 domain in vivo, and on the length of the unfolded domain. Together,
8073 these additional factors that influence the mechanical resistance of
8074 proteins have important consequences for our understanding of natural
8075 proteins that have evolved to withstand force.",
8076 note = "Introduces unfolding-order \emph{scaffold effect} on average
8078 project = "sawtooth simulation"
8081 @article { zwanzig92,
8082 author = RZwanzig #" and "# ASzabo #" and "# BBagchi,
8083 title = "Levinthal's paradox.",
8093 "http://www.ncbi.nlm.nih.gov/pmc/articles/PMC48166/pdf/pnas01075-0036.p
8095 url = "http://www.ncbi.nlm.nih.gov/pmc/articles/PMC48166/",
8096 keywords = "Mathematics;Models, Theoretical;Protein Conformation;Proteins",
8097 abstract = "Levinthal's paradox is that finding the native folded state of
8098 a protein by a random search among all possible configurations can take
8099 an enormously long time. Yet proteins can fold in seconds or less.
8100 Mathematical analysis of a simple model shows that a small and
8101 physically reasonable energy bias against locally unfavorable
8102 configurations, of the order of a few kT, can reduce Levinthal's time
8103 to a biologically significant size."
8107 author = XHong #" and "# XChu #" and "# PZou #" and "# YLiu
8109 title = "Magnetic-field-assisted rapid ultrasensitive
8110 immunoassays using Fe3{O4}/Zn{O}/Au nanorices as Raman
8116 address = "Centre for Advanced Optoelectronic Functional
8117 Materials Research, Key Laboratory for UV
8118 Light-Emitting Materials and Technology of Ministry of
8119 Education, Northeast Normal University, Changchun
8124 keywords = "Biosensing Techniques",
8125 keywords = "Electromagnetic Fields",
8126 keywords = "Equipment Design",
8127 keywords = "Equipment Failure Analysis",
8128 keywords = "Immunoassay",
8129 keywords = "Magnetite Nanoparticles",
8130 keywords = "Spectrum Analysis, Raman",
8131 keywords = "Zinc Oxide",
8132 abstract = "Rapid and ultrasensitive immunoassays were developed
8133 by using biofunctional Fe3O4/ZnO/Au nanorices as Raman
8134 probes. Taking advantage of the superparamagnetic
8135 property of the nanorices, the labeled proteins can
8136 rapidly be separated and purified with a commercial
8137 permanent magnet. The unsusceptible multiphonon
8138 resonant Raman scattering of the nanorices provided a
8139 characteristic spectroscopic fingerprint function,
8140 which allowed an accurate detection of the analyte.
8141 High specificity and selectivity of the assay were
8142 demonstrated. It was found that the diffusion barriers
8143 and the boundary layer effects had a great influence on
8144 the detection limit. Manipulation of the nanorice
8145 probes using an external magnetic field can enhance the
8146 assay sensitivity by several orders of magnitude, and
8147 reduce the detection time from 1 h to 3 min. This
8148 magnetic-field-assisted rapid and ultrasensitive
8149 immunoassay based on the resonant Raman scatting of
8150 semiconductor shows significant value for potential
8151 applications in biomedicine, food safety, and
8152 environmental defence.",
8154 doi = "10.1016/j.bios.2010.06.066",
8155 URL = "http://www.ncbi.nlm.nih.gov/pubmed/20667438",
8160 author = LZhao #" and "# ABulhassan #" and "# GYang #" and "#
8162 title = "Real-time detection of the morphological change in
8163 cellulose by a nanomechanical sensor.",
8168 address = "Department of Physics, Drexel University,
8169 Philadelphia, Pennsylvania, USA.",
8173 keywords = "Cellulose",
8174 keywords = "Computer Systems",
8175 keywords = "Equipment Design",
8176 keywords = "Equipment Failure Analysis",
8177 keywords = "Micro-Electrical-Mechanical Systems",
8178 keywords = "Molecular Conformation",
8179 keywords = "Nanotechnology",
8180 keywords = "Transducers",
8181 abstract = "Up to now, experimental limitations have prevented
8182 researchers from achieving the molecular-level
8183 understanding for the initial steps of the enzymatic
8184 hydrolysis of cellulose, where cellulase breaks down
8185 the crystal structure on the surface region of
8186 cellulose and exposes cellulose chains for the
8187 subsequent hydrolysis by cellulase. Because one of
8188 these non-hydrolytic enzymatic steps could be the
8189 rate-limiting step for the entire enzymatic hydrolysis
8190 of crystalline cellulose by cellulase, being able to
8191 analyze and understand these steps is instrumental in
8192 uncovering novel leads for improving the efficiency of
8193 cellulase. In this communication, we report an
8194 innovative application of the microcantilever technique
8195 for a real-time assessment of the morphological change
8196 of cellulose induced by a treatment of sodium chloride.
8197 This sensitive nanomechanical approach to define
8198 changes in surface structure of cellulose has the
8199 potential to permit a real-time assessment of the
8200 effect of the non-hydrolytic activities of cellulase on
8201 cellulose and thereby to provide a comprehensive
8202 understanding of the initial steps of the enzymatic
8203 hydrolysis of cellulose.",
8205 doi = "10.1002/bit.22754",
8206 URL = "http://www.ncbi.nlm.nih.gov/pubmed/20653025",
8211 author = RLiu #" and "# MRoman #" and "# GYang,
8212 title = "Correction of the viscous drag induced errors in
8213 macromolecular manipulation experiments using atomic
8218 address = "Department of Physics, Drexel University,
8219 Philadelphia, Pennsylvania 19104, USA.",
8223 keywords = "Algorithms",
8224 keywords = "Artifacts",
8225 keywords = "Macromolecular Substances",
8226 keywords = "Mechanical Processes",
8227 keywords = "Microscopy, Atomic Force",
8228 keywords = "Models, Theoretical",
8229 keywords = "Motion",
8230 keywords = "Protein Folding",
8231 keywords = "Signal Processing, Computer-Assisted",
8232 keywords = "Viscosity",
8233 abstract = "We describe a method to correct the errors induced by
8234 viscous drag on the cantilever in macromolecular
8235 manipulation experiments using the atomic force
8236 microscope. The cantilever experiences a viscous drag
8237 force in these experiments because of its motion
8238 relative to the surrounding liquid. This viscous force
8239 superimposes onto the force generated by the
8240 macromolecule under study, causing ambiguity in the
8241 experimental data. To remove this artifact, we analyzed
8242 the motions of the cantilever and the liquid in
8243 macromolecular manipulation experiments, and developed
8244 a novel model to treat the viscous drag on the
8245 cantilever as the superposition of the viscous force on
8246 a static cantilever in a moving liquid and that on a
8247 bending cantilever in a static liquid. The viscous
8248 force was measured under both conditions and the
8249 results were used to correct the viscous drag induced
8250 errors from the experimental data. The method will be
8251 useful for many other cantilever based techniques,
8252 especially when high viscosity and high cantilever
8253 speed are involved.",
8255 doi = "10.1063/1.3436646",
8256 URL = "http://www.ncbi.nlm.nih.gov/pubmed/20590242",
8260 @phdthesis { roman12,
8262 title = "Macromolecular crowding effects in the mechanical unfolding
8263 forces of proteins",
8267 url = "http://hdl.handle.net/1860/3854",
8268 eprint = "http://idea.library.drexel.edu/bitstream/1860/3854/1/Roman_Marisa.pdf",
8269 keywords = "Physics",
8270 keywords = "Biophysics",
8271 keywords = "Protein folding",
8272 abstract = "Macromolecules can occupy a large fraction of the volume
8273 of a cell and this crowded environment influences the behavior and
8274 properties of the proteins, such as mechanical unfolding forces,
8275 thermal stability and rates of folding and diffusion. Although
8276 much is already known about molecular crowding, it is not well
8277 understood how it affects a protein’s resistance to mechanical
8278 stress in a crowded environment and how the size of the crowders
8279 affect those changes. An atomic force microscope-based single
8280 molecule method was used to measure the effects of the crowding on
8281 the mechanical stability of a model protein, in this case I-27. As
8282 proteins tend to aggregate, single molecule methods provided a way
8283 to prevent aggregation because of the very low concentration of
8284 proteins in the solution under study. Dextran was used as the
8285 crowding agent with three different molecular weights 6kDa, 10 kDa
8286 and 40 kDa, with concentrations varying from zero to 300 grams per
8287 liter in a pH neutral buffer solution at room temperature. Results
8288 showed that the forces required to unfold biomolecules were
8289 increased when a high concentration of crowder molecules were
8290 added to the buffer solution and that the maximum force required
8291 to unfold a domain was when the crowder size was 10 kDa, which is
8292 comparable to the protein size. Unfolding rates obtained from
8293 Monte Carlo simulations showed that they were also affected in the
8294 presence of crowders. As a consequence, the energy barrier was
8295 also affected. These effects were most notable when the size of
8296 the crowder was 10 kDa, comparable to the size of the protein. On
8297 the other hand, distances to the transition state did not seem to
8298 change when crowders were added to the solution. The effect of
8299 Dextran on the energy barrier was modeled by using established
8300 theories such as Ogston’s and scaled particle theory, neither of
8301 which was completely convincing at describing the results. It can
8302 be hypothesized that the composition of Dextran plays a role in
8303 the deviation of the predicted behavior with respect to the
8304 experimental data.",
8308 @article { measey09,
8309 author = TMeasey #" and "# KBSmith #" and "# SDecatur #" and "#
8310 LZhao #" and "# GYang #" and "# RSchweitzerStenner,
8311 title = "Self-aggregation of a polyalanine octamer promoted by
8312 its {C}-terminal tyrosine and probed by a strongly
8313 enhanced vibrational circular dichroism signal.",
8318 address = "Department of Chemistry, Drexel University, 3141
8319 Chestnut Street, Philadelphia, Pennsylvania 19104,
8323 pages = "18218--18219",
8324 keywords = "Amyloid",
8325 keywords = "Circular Dichroism",
8326 keywords = "Dimerization",
8327 keywords = "Oligopeptides",
8328 keywords = "Peptides",
8329 keywords = "Protein Conformation",
8330 keywords = "Tyrosine",
8331 abstract = "The eight-residue alanine oligopeptide
8332 Ac-A(4)KA(2)Y-NH(2) (AKY8) was found to form
8333 amyloid-like fibrils upon incubation at room
8334 temperature in acidified aqueous solution at peptide
8335 concentrations >10 mM. The fibril solution exhibits an
8336 enhanced vibrational circular dichroism (VCD) couplet
8337 in the amide I' band region that is nearly 2 orders of
8338 magnitude larger than typical polypeptide/protein
8339 signals in this region. The UV-CD spectrum of the
8340 fibril solution shows CD in the region associated with
8341 the tyrosine side chain absorption. A similar peptide,
8342 Ac-A(4)KA(2)-NH(2) (AK7), which lacks a terminal
8343 tyrosine residue, does not aggregate. These results
8344 suggest a pivotal role for the C-terminal tyrosine
8345 residue in stabilizing the aggregation state of this
8346 peptide. It is speculated that interactions between the
8347 lysine and tyrosine side chains of consecutive strands
8348 in an antiparallel arrangement (e.g., cation-pi
8349 interactions) are responsible for the stabilization of
8350 the resulting fibrils. These results offer
8351 considerations and insight regarding the de novo design
8352 of self-assembling oligopeptides for biomedical and
8353 biotechnological applications and highlight the
8354 usefulness of VCD as a tool for probing amyloid fibril
8357 doi = "10.1021/ja908324m",
8358 URL = "http://www.ncbi.nlm.nih.gov/pubmed/19958029",
8363 author = GShan #" and "# SWang #" and "# XFei #" and "# YLiu
8365 title = "Heterostructured Zn{O}/Au nanoparticles-based resonant
8366 Raman scattering for protein detection.",
8371 address = "Center for Advanced Optoelectronic Functional
8372 Materials Research, Northeast Normal University,
8373 Changchun 130024, P. R. China.",
8376 pages = "1468--1472",
8377 keywords = "Animals",
8379 keywords = "Humans",
8380 keywords = "Immunoglobulin G",
8381 keywords = "Metal Nanoparticles",
8382 keywords = "Microscopy, Electron, Transmission",
8383 keywords = "Spectrum Analysis, Raman",
8384 keywords = "Zinc Oxide",
8385 abstract = "A new method of protein detection was explored on the
8386 resonant Raman scattering signal of ZnO nanoparticles.
8387 A probe for the target protein was constructed by
8388 binding the ZnO/Au nanoparticles to secondary protein
8389 by eletrostatic interaction. The detection of proteins
8390 was achieved by an antibody-based sandwich assay. A
8391 first antibody, which could be specifically recognized
8392 by target protein, was attached to a solid silicon
8393 surface. The ZnO/Au protein probe could specifically
8394 recognize and bind to the complex of the target protein
8395 and first antibody. This method on the resonant Raman
8396 scattering signal of ZnO nanoparticles showed good
8397 selectivity and sensitivity for the target protein.",
8399 doi = "10.1021/jp8046032",
8400 URL = "http://www.ncbi.nlm.nih.gov/pubmed/19138135",
8405 author = JMYuan #" and "# CLChyan #" and "# HXZhou #" and "#
8406 TYChung #" and "# HPeng #" and "# GPing #" and "#
8408 title = "The effects of macromolecular crowding on the
8409 mechanical stability of protein molecules.",
8414 address = "Department of Physics, Drexel University,
8415 Philadelphia, Pennsylvania 19104, USA.",
8418 pages = "2156--2166",
8419 keywords = "Circular Dichroism",
8420 keywords = "Dextrans",
8421 keywords = "Kinetics",
8422 keywords = "Microscopy, Atomic Force",
8423 keywords = "Microscopy, Scanning Probe",
8424 keywords = "Protein Folding",
8425 keywords = "Protein Stability",
8426 keywords = "Protein Structure, Secondary",
8427 keywords = "Thermodynamics",
8428 keywords = "Ubiquitin",
8429 abstract = "Macromolecular crowding, a common phenomenon in the
8430 cellular environments, can significantly affect the
8431 thermodynamic and kinetic properties of proteins. A
8432 single-molecule method based on atomic force microscopy
8433 (AFM) was used to investigate the effects of
8434 macromolecular crowding on the forces required to
8435 unfold individual protein molecules. It was found that
8436 the mechanical stability of ubiquitin molecules was
8437 enhanced by macromolecular crowding from added dextran
8438 molecules. The average unfolding force increased from
8439 210 pN in the absence of dextran to 234 pN in the
8440 presence of 300 g/L dextran at a pulling speed of 0.25
8441 microm/sec. A theoretical model, accounting for the
8442 effects of macromolecular crowding on the native and
8443 transition states of the protein molecule by applying
8444 the scaled-particle theory, was used to quantitatively
8445 explain the crowding-induced increase in the unfolding
8446 force. The experimental results and interpretation
8447 presented could have wide implications for the many
8448 proteins that experience mechanical stresses and
8449 perform mechanical functions in the crowded environment
8452 doi = "10.1110/ps.037325.108",
8453 URL = "http://www.ncbi.nlm.nih.gov/pubmed/18780817",
8458 author = YLiu #" and "# MZhong #" and "# GShan #" and "# YLi
8459 #" and "# BHuang #" and "# GYang,
8460 title = "Biocompatible Zn{O}/Au nanocomposites for
8461 ultrasensitive {DNA} detection using resonance Raman
8467 address = "Centre for Advanced Optoelectronic Functional
8468 Materials Research, Institute of Genetics and Cytology,
8469 Northeast Normal University, Changchun, People's
8470 Republic of China. ycliu@nenu.edu.cn",
8473 pages = "6484--6489",
8474 keywords = "Base Sequence",
8477 keywords = "Microscopy, Electron, Transmission",
8478 keywords = "Nanocomposites",
8479 keywords = "Sensitivity and Specificity",
8480 keywords = "Spectrum Analysis, Raman",
8481 keywords = "Zinc Oxide",
8482 abstract = "A novel method for identifying DNA microarrays based
8483 on ZnO/Au nanocomposites functionalized with
8484 thiol-oligonucleotide as probes is descried here. DNA
8485 labeled with ZnO/Au nanocomposites has a strong Raman
8486 signal even without silver acting as a surface-enhanced
8487 Raman scattering promoter. X-ray photoelectron spectra
8488 confirmed the formation of a three-component sandwich
8489 assay, i.e., constituted DNA and ZnO/Au nanocomposites.
8490 The resonance multiple-phonon Raman signal of the
8491 ZnO/Au nanocomposites as a spectroscopic fingerprint is
8492 used to detect a target sequence of oligonucleotide.
8493 This method exhibits extraordinary sensitivity and the
8494 detection limit is at least 1 fM.",
8496 doi = "10.1021/jp710399d",
8497 URL = "http://www.ncbi.nlm.nih.gov/pubmed/18444675",
8502 author = YGuo #" and "# AMylonakis #" and "# ZZhang #" and "#
8503 GYang #" and "# PLelkes #" and "# SChe #" and "#
8505 title = "Templated synthesis of electroactive periodic
8506 mesoporous organosilica bridged with oligoaniline.",
8509 address = "Department of Chemistry, Drexel University,
8510 Philadelphia, Pennsylvania 19104, USA.",
8513 pages = "2909--2917",
8514 keywords = "Aniline Compounds",
8515 keywords = "Cetrimonium Compounds",
8516 keywords = "Electrochemistry",
8517 keywords = "Hydrolysis",
8518 keywords = "Microscopy, Electron, Transmission",
8519 keywords = "Molecular Structure",
8520 keywords = "Organosilicon Compounds",
8521 keywords = "Particle Size",
8522 keywords = "Porosity",
8523 keywords = "Spectroscopy, Fourier Transform Infrared",
8524 keywords = "Surface Properties",
8525 keywords = "Thermogravimetry",
8526 keywords = "X-Ray Diffraction",
8527 abstract = "The synthesis and characterization of novel
8528 electroactive periodic mesoporous organosilica (PMO)
8529 are reported. The silsesquioxane precursor,
8530 N,N'-bis(4'-(3-triethoxysilylpropylureido)phenyl)-1,4-quinonene-diimine
8531 (TSUPQD), was prepared from the emeraldine base of
8532 amino-capped aniline trimer (EBAT) using a one-step
8533 coupling reaction and was used as an organic silicon
8534 source in the co-condensation with tetraethyl
8535 orthosilicate (TEOS) in proper ratios. By means of a
8536 hydrothermal sol-gel approach with the cationic
8537 surfactant cetyltrimethyl-ammonium bromide (CTAB) as
8538 the structure-directing template and acetone as the
8539 co-solvent for the dissolution of TSUPQD, a series of
8540 novel MCM-41 type siliceous materials (TSU-PMOs) were
8541 successfully prepared under mild alkaline conditions.
8542 The resultant mesoporous organosilica were
8543 characterized by Fourier transform infrared (FT-IR)
8544 spectroscopy, thermogravimetry, X-ray diffraction,
8545 nitrogen sorption, and transmission electron microscopy
8546 (TEM) and showed that this series of TSU-PMOs exhibited
8547 hexagonally patterned mesostructures with pore
8548 diameters of 2.1-2.8 nm. Although the structural
8549 regularity and pore parameters gradually deteriorated
8550 with increasing loading of organic bridges, the
8551 electrochemical behavior of TSU-PMOs monitored by
8552 cyclic voltammetry demonstrated greater
8553 electroactivities for samples with higher concentration
8554 of the incorporated TSU units.",
8556 doi = "10.1002/chem.200701605",
8557 URL = "http://www.ncbi.nlm.nih.gov/pubmed/18224650",
8562 author = LiLi #" and "# BLi #" and "# GYang #" and "# CYLi,
8563 title = "Polymer decoration on carbon nanotubes via physical
8569 address = "A. J. Drexel Nanotechnology Institute and Department
8570 of Materials Science and Engineering, Drexel
8571 University, Philadelphia, Pennsylvania 19104, USA.",
8574 pages = "8522--8525",
8575 keywords = "Microscopy, Atomic Force",
8576 keywords = "Microscopy, Electron, Transmission",
8577 keywords = "Nanotubes, Carbon",
8578 keywords = "Polymers",
8579 keywords = "Surface Properties",
8580 keywords = "Volatilization",
8581 abstract = "The polymer decoration technique has been widely used
8582 to study the chain folding behavior of polymer single
8583 crystals. In this article, we demonstrate that this
8584 method can be successfully adopted to pattern a variety
8585 of polymers on carbon nanotubes (CNTs). The resulting
8586 structure is a two-dimensional nanohybrid shish kebab
8587 (2D NHSK), wherein the CNT forms the shish and the
8588 polymer crystals form the kebabs. 2D NHSKs consisting
8589 of CNTs and polymers such as polyethylene, nylon 66,
8590 polyvinylidene fluoride and poly(L-lysine) have been
8591 achieved. Transmission electron microscopy and atomic
8592 force microscopy were used to study the nanoscale
8593 morphology of these hybrid materials. Relatively
8594 periodic decoration of polymers on both single-walled
8595 and multi-walled CNTs was observed. It is envisaged
8596 that this unique method offers a facile means to
8597 achieve patterned CNTs for nanodevice applications.",
8599 doi = "10.1021/la700480z",
8600 URL = "http://www.ncbi.nlm.nih.gov/pubmed/17602575",
8605 author = MSu #" and "# YYang #" and "# GYang,
8606 title = "Quantitative measurement of hydroxyl radical induced
8607 {DNA} double-strand breaks and the effect of
8608 {N}-acetyl-{L}-cysteine.",
8613 address = "Department of Physics, Drexel University,
8614 Philadelphia, PA 19104, USA.",
8617 pages = "4136--4142",
8618 keywords = "Acetylcysteine",
8619 keywords = "Animals",
8620 keywords = "DNA Damage",
8621 keywords = "Humans",
8622 keywords = "Hydroxyl Radical",
8623 keywords = "Microscopy, Atomic Force",
8624 keywords = "Nucleic Acid Conformation",
8625 keywords = "Plasmids",
8626 abstract = "Reactive oxygen species, such as hydroxyl or
8627 superoxide radicals, can be generated by exogenous
8628 agents as well as from normal cellular metabolism.
8629 Those radicals are known to induce various lesions in
8630 DNA, including strand breaks and base modifications.
8631 These lesions have been implicated in a variety of
8632 diseases such as cancer, arteriosclerosis, arthritis,
8633 neurodegenerative disorders and others. To assess these
8634 oxidative DNA damages and to evaluate the effects of
8635 the antioxidant N-acetyl-L-cysteine (NAC), atomic force
8636 microscopy (AFM) was used to image DNA molecules
8637 exposed to hydroxyl radicals generated via Fenton
8638 chemistry. AFM images showed that the circular DNA
8639 molecules became linear after incubation with hydroxyl
8640 radicals, indicating the development of double-strand
8641 breaks. The occurrence of the double-strand breaks was
8642 found to depend on the concentration of the hydroxyl
8643 radicals and the duration of the reaction. Under the
8644 conditions of the experiments, NAC was found to
8645 exacerbate the free radical-induced DNA damage.",
8647 doi = "10.1016/j.febslet.2006.06.060",
8648 URL = "http://www.ncbi.nlm.nih.gov/pubmed/16828758",
8653 author = LiLi #" and "# YYang #" and "# GYang #" and "# XuChen
8654 #" and "# BHsiao #" and "# BChu #" and "#
8655 JSpanier #" and "# CYLi,
8656 title = "Patterning polyethylene oligomers on carbon nanotubes
8657 using physical vapor deposition.",
8661 address = "A. J. Drexel Nanotechnology Institute and Department
8662 of Materials Science and Engineering, Drexel
8663 University, Philadelphia, Pennsylvania 19104, USA.",
8666 pages = "1007--1012",
8667 keywords = "Microscopy, Atomic Force",
8668 keywords = "Nanotechnology",
8669 keywords = "Nanotubes, Carbon",
8670 keywords = "Polyethylenes",
8671 keywords = "Volatilization",
8672 abstract = "Periodic patterning on one-dimensional (1D) carbon
8673 nanotubes (CNTs) is of great interest from both
8674 scientific and technological points of view. In this
8675 letter, we report using a facile physical vapor
8676 deposition method to achieve periodic polyethylene (PE)
8677 oligomer patterning on individual CNTs. Upon heating
8678 under vacuum, PE degraded into oligomers and
8679 crystallized into rod-shaped single crystals. These PE
8680 rods periodically decorate on CNTs with their long axes
8681 perpendicular to the CNT axes. The formation mechanism
8682 was attributed to ``soft epitaxy'' growth of PE
8683 oligomer crystals on CNTs. Both SWNTs and MWNTs were
8684 decorated successfully with PE rods. The intermediate
8685 state of this hybrid structure, MWNTs absorbed with a
8686 thin layer of PE, was captured successfully by
8687 depositing PE vapor on MWNTs detached from the solid
8688 substrate, and was observed using high-resolution
8689 transmission electron microscopy. Furthermore, this
8690 hybrid structure formation depends critically on CNT
8691 surface chemistry: alkane-modification of the MWNT
8692 surface prohibited the PE single-crystal growth on the
8693 CNTs. We anticipate that this work could open a gateway
8694 for creating complex CNT-based nanoarchitectures for
8695 nanodevice applications.",
8697 doi = "10.1021/nl060276q",
8698 URL = "http://www.ncbi.nlm.nih.gov/pubmed/16683841",
8703 author = MKuhn #" and "# HJanovjak #" and "# MHubain #" and "# DJMuller,
8704 title = {Automated alignment and pattern recognition of
8705 single-molecule force spectroscopy data.},
8708 address = {Division of Computer Science, California Institute of
8709 Technology, Pasadena, California 91125, USA.},
8715 doi = {10.1111/j.1365-2818.2005.01478.x},
8716 URL = {http://www.ncbi.nlm.nih.gov/pubmed/15857374},
8718 keywords = {Algorithms},
8719 keywords = {Bacteriorhodopsins},
8720 keywords = {Data Interpretation, Statistical},
8721 keywords = {Escherichia coli Proteins},
8722 keywords = {Microscopy, Atomic Force},
8723 keywords = {Protein Folding},
8724 keywords = {Sodium-Hydrogen Antiporter},
8725 keywords = {Software},
8726 abstract = {Recently, direct measurements of forces stabilizing
8727 single proteins or individual receptor-ligand bonds became
8728 possible with ultra-sensitive force probe methods like the atomic
8729 force microscope (AFM). In force spectroscopy experiments using
8730 AFM, a single molecule or receptor-ligand pair is tethered between
8731 the tip of a micromachined cantilever and a supporting
8732 surface. While the molecule is stretched, forces are measured by
8733 the deflection of the cantilever and plotted against extension,
8734 yielding a force spectrum characteristic for each biomolecular
8735 system. In order to obtain statistically relevant results, several
8736 hundred to thousand single-molecule experiments have to be
8737 performed, each resulting in a unique force spectrum. We developed
8738 software and algorithms to analyse large numbers of force
8739 spectra. Our algorithms include the fitting polymer extension
8740 models to force peaks as well as the automatic alignment of
8741 spectra. The aligned spectra allowed recognition of patterns of
8742 peaks across different spectra. We demonstrate the capabilities of
8743 our software by analysing force spectra that were recorded by
8744 unfolding single transmembrane proteins such as bacteriorhodopsin
8745 and NhaA. Different unfolding pathways were detected by
8746 classifying peak patterns. Deviant spectra, e.g. those with no
8747 attachment or erratic peaks, can be easily identified. The
8748 software is based on the programming language C++, the GNU
8749 Scientific Library (GSL), the software WaveMetrics IGOR Pro and
8750 available open-source at http://bioinformatics.org/fskit/.},
8751 note = {Development stalled in 2005 after Michael graduated.},
8754 @article{ janovjak05,
8755 author = HJanovjak #" and "# JStruckmeier #" and "# DJMuller,
8756 title = {Hydrodynamic effects in fast {AFM} single-molecule
8757 force measurements.},
8761 address = {BioTechnological Center, University of Technology
8762 Dresden, 01307 Dresden, Germany.},
8768 doi = {10.1007/s00249-004-0430-3},
8769 url = {http://www.ncbi.nlm.nih.gov/pubmed/15257425},
8771 keywords = {Algorithms},
8772 keywords = {Computer Simulation},
8773 keywords = {Elasticity},
8774 keywords = {Microfluidics},
8775 keywords = {Microscopy, Atomic Force},
8776 keywords = {Models, Chemical},
8777 keywords = {Models, Molecular},
8778 keywords = {Physical Stimulation},
8779 keywords = {Protein Binding},
8780 keywords = {Proteins},
8781 keywords = {Stress, Mechanical},
8782 keywords = {Viscosity},
8783 abstract = {Atomic force microscopy (AFM) allows the critical forces
8784 that unfold single proteins and rupture individual receptor-ligand
8785 bonds to be measured. To derive the shape of the energy landscape,
8786 the dynamic strength of the system is probed at different force
8787 loading rates. This is usually achieved by varying the pulling
8788 speed between a few nm/s and a few $\mu$m/s, although for a more
8789 complete investigation of the kinetic properties higher speeds are
8790 desirable. Above 10 $\mu$m/s, the hydrodynamic drag force acting
8791 on the AFM cantilever reaches the same order of magnitude as the
8792 molecular forces. This has limited the maximum pulling speed in
8793 AFM single-molecule force spectroscopy experiments. Here, we
8794 present an approach for considering these hydrodynamic effects,
8795 thereby allowing a correct evaluation of AFM force measurements
8796 recorded over an extended range of pulling speeds (and thus
8797 loading rates). To support and illustrate our theoretical
8798 considerations, we experimentally evaluated the mechanical
8799 unfolding of a multi-domain protein recorded at $30\U{$mu$m/s}$
8804 author = MSandal #" and "# FBenedetti #" and "# MBrucale #" and "#
8805 AGomezCasado #" and "# BSamori,
8806 title = "Hooke: An open software platform for force spectroscopy.",
8811 address = "Department of Biochemistry, University of Bologna,
8812 Bologna, Italy. massimo.sandal@unibo.it",
8815 pages = "1428--1430",
8816 keywords = "Algorithms",
8817 keywords = "Computational Biology",
8818 keywords = "Internet",
8819 keywords = "Microscopy, Atomic Force",
8820 keywords = "Proteome",
8821 keywords = "Proteomics",
8822 keywords = "Software",
8823 abstract = "SUMMARY: Hooke is an open source, extensible software
8824 intended for analysis of atomic force microscope (AFM)-based
8825 single molecule force spectroscopy (SMFS) data. We propose it as a
8826 platform on which published and new algorithms for SMFS analysis
8827 can be integrated in a standard, open fashion, as a general
8828 solution to the current lack of a standard software for SMFS data
8829 analysis. Specific features and support for file formats are coded
8830 as independent plugins. Any user can code new plugins, extending
8831 the software capabilities. Basic automated dataset filtering and
8832 semi-automatic analysis facilities are included. AVAILABILITY:
8833 Software and documentation are available at
8834 (http://code.google.com/p/hooke). Hooke is a free software under
8835 the GNU Lesser General Public License.",
8837 doi = "10.1093/bioinformatics/btp180",
8838 URL = "http://www.ncbi.nlm.nih.gov/pubmed/19336443",
8842 @article{ materassi09,
8843 author = DMaterassi #" and "# PBaschieri #" and "# BTiribilli #" and "#
8844 GZuccheri #" and "# BSamori,
8845 title = {An open source/real-time atomic force microscope
8846 architecture to perform customizable force spectroscopy
8850 address = {Department of Electrical and Computer Engineering,
8851 University of Minnesota, 200 Union St. SE, Minneapolis,
8852 Minnesota 55455, USA. mater013@umn.edu},
8858 doi = "10.1063/1.3194046",
8859 url = "http://www.ncbi.nlm.nih.gov/pubmed/19725671",
8861 keywords = {Algorithms},
8862 keywords = {Animals},
8863 keywords = {Calibration},
8865 keywords = {Microscopy, Atomic Force},
8866 keywords = {Muscle Proteins},
8867 keywords = {Myocardium},
8868 keywords = {Optics and Photonics},
8869 keywords = {Ownership},
8870 keywords = {Protein Kinases},
8871 keywords = {Software},
8872 keywords = {Spectrum Analysis},
8873 keywords = {Time Factors},
8874 abstract = {We describe the realization of an atomic force
8875 microscope architecture designed to perform customizable
8876 experiments in a flexible and automatic way. Novel technological
8877 contributions are given by the software implementation platform
8878 (RTAI-LINUX), which is free and open source, and from a functional
8879 point of view, by the implementation of hard real-time control
8880 algorithms. Some other technical solutions such as a new way to
8881 estimate the optical lever constant are described as well. The
8882 adoption of this architecture provides many degrees of freedom in
8883 the device behavior and, furthermore, allows one to obtain a
8884 flexible experimental instrument at a relatively low cost. In
8885 particular, we show how such a system has been employed to obtain
8886 measures in sophisticated single-molecule force spectroscopy
8887 experiments\citep{fernandez04}. Experimental results on proteins
8888 already studied using the same methodologies are provided in order
8889 to show the reliability of the measure system.},
8890 note = {Although this paper claims to present an open source
8891 experiment control framework (on Linux!), it doesn't actually link
8892 to any source code. This is puzzling and frusterating.},
8895 @article{ aioanei11,
8896 author = DAioanei #" and "# MBrucale #" and "# BSamori,
8897 title = {Open source platform for the execution and analysis of
8898 mechanical refolding experiments.},
8902 address = {Department of Biochemistry G.~Moruzzi,
8903 University of Bologna, Via Irnerio 48, 40126 Bologna, Italy.
8904 aioaneid@gmail.com},
8910 doi = {10.1093/bioinformatics/btq663},
8911 url = {http://www.ncbi.nlm.nih.gov/pubmed/21123222},
8913 keywords = {Computational Biology},
8914 keywords = {Kinetics},
8915 keywords = {Protein Denaturation},
8916 keywords = {Protein Refolding},
8917 keywords = {Software},
8918 abstract = {Single-molecule force spectroscopy has facilitated the
8919 experimental investigation of biomolecular force-coupled kinetics,
8920 from which the kinetics at zero force can be extrapolated via
8921 explicit theoretical models. The atomic force microscope (AFM) in
8922 particular is routinely used to study protein unfolding kinetics,
8923 but only rarely protein folding kinetics. The discrepancy arises
8924 because mechanical protein refolding studies are more technically
8926 note = {\href{http://code.google.com/p/refolding/}{Refolding} is a
8927 suite for performing and analyzing double-pulse refolding
8928 experiments. The experiment-driver is mostly written in Java with
8929 the analysis code in Python. The driver is curious; it uses the
8930 NanoScope scripting interface to drive the experiment through the
8931 NanoScope software by impersonating a mouse-wielding user (like
8932 Selenium does for web browsers). See the
8933 \imint{sh}|RobotNanoDriver.java| code for details. There is also
8934 support for automatic velocity clamp analysis.},
8937 @article{ benedetti11,
8938 author = FBenedetti #" and "# CMicheletti #" and "# GBussi #" and "#
8939 SKSekatskii #" and "# GDietler,
8940 title = {Nonkinetic modeling of the mechanical unfolding of
8941 multimodular proteins: theory and experiments.},
8945 address = {Laboratory of Physics of Living Matter,
8946 Ecole Polytechnique F{\'e}d{\'e}rale de Lausanne,
8947 Lausanne, Switzerland.},
8951 pages = {1504--1512},
8953 doi = {10.1016/j.bpj.2011.07.047},
8954 url = {http://www.ncbi.nlm.nih.gov/pubmed/21943432},
8956 keywords = {Kinetics},
8957 keywords = {Microscopy, Atomic Force},
8958 keywords = {Models, Molecular},
8959 keywords = {Monte Carlo Method},
8960 keywords = {Protein Unfolding},
8961 keywords = {Stochastic Processes},
8962 abstract = {We introduce and discuss a novel approach called
8963 back-calculation for analyzing force spectroscopy experiments on
8964 multimodular proteins. The relationship between the histograms of
8965 the unfolding forces for different peaks, corresponding to a
8966 different number of not-yet-unfolded protein modules, is exploited
8967 in such a manner that the sole distribution of the forces for one
8968 unfolding peak can be used to predict the unfolding forces for
8969 other peaks. The scheme is based on a bootstrap prediction method
8970 and does not rely on any specific kinetic model for multimodular
8971 unfolding. It is tested and validated in both
8972 theoretical/computational contexts (based on stochastic
8973 simulations) and atomic force microscopy experiments on (GB1)(8)
8974 multimodular protein constructs. The prediction accuracy is so
8975 high that the predicted average unfolding forces corresponding to
8976 each peak for the GB1 construct are within only 5 pN of the
8977 averaged directly-measured values. Experimental data are also used
8978 to illustrate how the limitations of standard kinetic models can
8979 be aptly circumvented by the proposed approach.},
8982 @phdthesis{ benedetti12,
8983 author = FBenedetti,
8984 title = {Statistical Study of the Unfolding of Multimodular Proteins
8985 and their Energy Landscape by Atomic Force Microscopy},
8987 address = {Lausanne},
8988 affiliation = {EPFL},
8991 doi = {10.5075/epfl-thesis-5440},
8992 url = {http://infoscience.epfl.ch/record/181215},
8993 eprint = {http://infoscience.epfl.ch/record/181215/files/EPFL_TH5440.pdf},
8994 keywords = {atomic force microscope (AFM); single molecule force
8995 spectrosopy; velocity clamp AFM; Monte carlo simulations; force
8996 modulation spectroscopy; energy barrier model; non kinetic methods
8997 for force spectroscopy},
8998 abstract = {The aim of the present thesis is to investigate several
8999 aspects of: the proteins mechanics, interprotein interactions and
9000 to study also new techniques, theoretical and technical, to obtain
9001 and analyze the force spectroscopy experiments. The first section
9002 is dedicated to the statistical properties of the unfolding forces
9003 in a chain of homomeric multimodular proteins. The basic idea of
9004 this kind of statistic is to divide the peaks observed in a force
9005 extension curve in separate groups and then analyze these groups
9006 considering their position in the force curves. In fact in a
9007 multimodular homomeric protein the unfolding force is related to
9008 the number of not yet unfolded modules (we call it "N"). Such
9009 effect yields to a linear dependence of the most probable
9010 unfolding force of a peak on ln(N). We demonstrate how such
9011 dependence can be used to extract the kinetic parameters and how,
9012 ignoring it, could lead to significant errors. Following this
9013 topic we continue with non kinetic methods that, using the
9014 resampling from the rupture forces of any peak, could reconstruct
9015 the rupture forces for all the other peaks in a chain. Then a
9016 discussion about the Monte Carlo simulation for protein pulling is
9017 present. In fact a theoretical framework for such methodology has
9018 to be introduced to understand the various simulations done. In
9019 this chapter we also introduce a methodology to study the ligand
9020 receptor interactions when we directly functionalize the AFM tip
9021 and the substrate. In fact, in many of our experiments, we see a
9022 "cloud of points" in the force vs loading rate graph. We have
9023 modeled a system composed by "N" parallel springs, and studying
9024 the distribution of forces obtained in the force vs loading rate
9025 graph we have establish a procedure to restore the kinetic
9026 parameters used. Such procedure has then been used to discuss real
9027 experiments similar to biotin-avidin interaction. In the following
9028 chapter we discuss a first order approximation of the Bell-Evans
9029 model where a more explicit form of the potential is
9030 considered. In particular the dependence of the curvature of the
9031 potential on the applied force at the minimum and at the
9032 metastable state is considered. In the well known Bell-Evans model
9033 the prefactors of the transition rate are fixed at any force,
9034 however this is not what happen in nature, where the prefactors
9035 (that are the second local derivative of the interacting energy
9036 with respect to the reaction coordinate in its minimum and
9037 maximum) depend on the force applied. The results obtained with
9038 the force spectroscopy of the Laminin-binding-protein are
9039 discussed, in particular this protein showed a phase transition
9040 when the pH was changed. The behavior of this protein changes,
9041 from a normal WLC behavior to a plateau behavior. The analysis of
9042 the force spectroscopy curves shows a distribution of length where
9043 the maximum of the first prominent peak correspond to the full
9044 length of the protein. However, length that could be associated
9045 with dimers and trymers are also present in this
9046 distribution. Later a new approach to study the lock and key
9047 mechanism, using "handles" with a specific force extension
9048 pattern, is introduced. In particular handles of (I27)3 and
9049 (I27–SNase)3 were biochemically attached to: strept-actin
9050 molecules, biotin molecules, RNase and Angiogenin. The main idea
9051 is to have a system composed by "handle-(molecule A)-(molecule
9052 B)-handle" where the handles are covalently attached to the
9053 respective molecules and the two molecules "A and B" are attached
9054 by secondary bonds. This approach allows a better recognition of
9055 the protein-protein interaction enabling us to filter out spurious
9056 events. Doing a statistic on the rupture forces and comparing this
9057 with the statistic of the detachments of the system of the bare
9058 handles, we are able to extract the information of the interaction
9059 between the molecule A and B. The two last chapters are of more
9060 preliminary character that the previous part of the thesis. A
9061 section is dedicated to the estimation of effective mass and
9062 viscous drag of the cantilevers studied by autocorrelation and
9063 noise power spectrum. Usually the noise power spectrum method is
9064 the most used, however the autocorrelation should give
9065 approximately the same information. The parameters obtained are
9066 important in high frequency modulation techniques. In fact, they
9067 are needed to interpret the results. The results of these two
9068 methods show a good agreement in the estimation of the mass and
9069 the viscous drag of the various cantilever used. Afterwards a
9070 chapter is dedicated to the discussion of the force spectroscopy
9071 experiments using a low frequency modulation of the cantilever
9072 base. Such experiments allow us to record the phase and the
9073 amplitude shift of the modulation signal used. Using the amplitude
9074 channel we managed to restore the static force signal with a lower
9075 level of noise. Moreover these signals give us direct information
9076 about the dynamic stiffness and the lose of energy in the system,
9077 information that, using the standard technique would be difficult
9078 (or even impossible) to obtain.},
9082 author = TKempe #" and "# SBHKent #" and "# FChow #" and "# SMPeterson
9083 #" and "# WSundquist #" and "# JLItalien #" and "# DHarbrecht
9084 #" and "# DPlunkett #" and "# WDeLorbe,
9085 title = "Multiple-copy genes: Production and modification of
9086 monomeric peptides from large multimeric fusion proteins.",
9092 keywords = "Cloning, Molecular",
9093 keywords = "Cyanogen Bromide",
9094 keywords = "DNA, Recombinant",
9095 keywords = "Escherichia coli",
9096 keywords = "Gene Expression Regulation",
9097 keywords = "Genetic Vectors",
9098 keywords = "Humans",
9099 keywords = "Molecular Weight",
9100 keywords = "Peptide Fragments",
9101 keywords = "Plasmids",
9102 keywords = "Substance P",
9103 keywords = "beta-Galactosidase",
9104 abstract = "A vector system has been designed for obtaining high
9105 yields of polypeptides synthesized in Escherichia coli. Multiple
9106 copies of a synthetic gene encoding the neuropeptide substance P
9107 (SP) (Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2) have been
9108 linked and fused to the lacZ gene. Each copy of the SP gene was
9109 flanked by codons for methionine to create sites for cleavage by
9110 cyanogen bromide (CNBr). The isolated multimeric SP fusion
9111 protein was converted to monomers of SP analog, each containing a
9112 carboxyl-terminal homoserine lactone (Hse-lactone) residue
9113 (Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Hse-lactone), upon
9114 treatment with CNBr in formic acid. The Hse-lactone moiety was
9115 subjected to chemical modifications to produce an SP Hse
9116 amide. This method permits synthesis of peptide amide analogs and
9117 other peptide derivatives by combining recombinant DNA techniques
9118 and chemical methods.",
9120 URL = "http://www.ncbi.nlm.nih.gov/pubmed/2419204",
9125 author = MHonda #" and "# YBaba #" and "# NHiaro #" and "# TSekiguchi,
9126 title = "Metal-molecular interface of sulfur-containing amino acid
9127 and thiophene on gold surface",
9132 url = "http://dx.doi.org/10.1088/1742-6596/100/5/052071",
9134 abstract = "Chemical-bonding states of metal-molecular interface
9135 have been investigated for L-cysteine and thiophene on gold by
9136 x-ray photoelectron spectroscopy (XPS) and near edge x-ray
9137 adsorption fine structure (NEXAFS). A remarkable difference in
9138 Au-S bonding states was found between L-cysteine and
9139 thiophene. For mono-layered L-cysteine on gold, the binding energy
9140 of S 1s in XPS and the resonance energy at the S K-edge in NEXAFS
9141 are higher by 8–9 eV than those for multi-layered film (molecular
9142 L-cysteine). In contrast, the S K-edge resonance energy for
9143 mono-layered thiophene on gold was 2475.0 eV, which is the same as
9144 that for molecular L-cysteine. In S 1s XPS for mono-layered
9145 thiophene, two peaks were observed. The higher binging-energy and
9146 more intense peak at 2473.4 eV are identified as gold sulfide. The
9147 binding energy of smaller peak, whose intensity is less than 1/3
9148 of the higher binding energy peak, is 2472.2 eV, which is the same
9149 as that for molecular thiophene. These observations indicate that
9150 Au-S interface behavior shows characteristic chemical bond only
9151 for the Au-S interface of L-cysteine monolayer on gold
9157 title = "Formation and Structure of Self-Assembled Monolayers.",
9162 address = "Department of Chemical Engineering, Chemistry and
9163 Materials Science, and the Herman F. Mark Polymer Research
9164 Institute, Polytechnic University, Six MetroTech Center, Brooklyn,
9168 pages = "1533--1554",
9170 URL = "http://www.ncbi.nlm.nih.gov/pubmed/11848802",
9175 author = GHager #" and "# ABrolo,
9176 title = "Adsorption/desorption behaviour of cysteine and cystine in
9177 neutral and basic media: electrochemical evidence for differing
9178 thiol and disulfide adsorption to a {Au(111)} single crystal
9181 volume = "550--551",
9186 doi = "10.1016/S0022-0728(03)00052-4",
9187 url = "http://www.sciencedirect.com/science/article/pii/S0022072803000524",
9189 keywords = "Disulfide",
9190 keywords = "Thiol adsorption",
9191 keywords = "Self-assembled monolayers",
9192 keywords = "Au(111) single crystal electrode",
9193 keywords = "Cysteine",
9194 keywords = "Cystine",
9195 abstract = "The adsorption/desorption behaviour of the
9196 thiol/disulfide redox couple, cysteine/cystine, was monitored at a
9197 Au(111) single crystal electrode. The monolayers were formed
9198 electrochemically from 0.1 M KClO4 and 0.1 M NaOH solutions
9199 containing either the thiol or the disulfide. Distinct features in
9200 the adsorption potential were noted. An adsorption peak was
9201 observed in the cyclic voltammograms (CVs) from Au(111) in 0.1 M
9202 KClO4 solutions containing cystine at $-0.57$ V vs. saturated
9203 calomel electrode. Under the same conditions, the CVs from
9204 solutions containing cysteine showed an adsorption peak at $-0.43$
9205 V (0.14 V more positive than the corresponding peak from disulfide
9206 solutions). This showed that the thiol and disulfide species have
9207 different adsorption properties. Similar behaviour was observed in
9208 0.1 M NaOH. Cyclic voltammetric and chronocoulometric data were
9209 employed to determine the surface coverage of the different
9210 monolayers. Cysteine solutions prepared in 0.1 M KClO4 provided
9211 coverages of $3.0\times10^{-10}$ and $2.5\times10^{-10}$
9212 mol~cm$^{-2}$ for the L and the D--L species, respectively as
9213 evaluated from the desorption peaks. Desorption of cystine in the
9214 same medium yielded coverages of $1.2\times10^{-10}$ mol~cm$^{-2}$
9215 for both L and D--L solutions (or $2.4\times10^{-10}$
9216 mol~cm$^{-2}$ in cysteine equivalents). Surface coverages obtained
9217 from Au(111) in 0.1 M NaOH corresponded to $3.9\times10^{10}$
9218 mol~cm$^{-2}$ for L-cysteine, and $1.2\times10^{-10}$
9219 mol~cm$^{-2}$ (or $2.4\times10^{-10}$ mol~cm$^{-2}$ cysteine
9220 equivalents) for L and D--L cystine.",
9225 title = "The Nanomechanics of Polycystin-1: A Kidney Mechanosensor",
9229 url = "http://etd.utmb.edu/theses/available/etd-07072010-132038/",
9231 keywords = "Polycystin-1",
9232 keywords = "Missense mutations",
9233 keywords = "Atomic Force Microscopy",
9234 keywords = "Osmolyte",
9235 keywords = "Mechanosensor",
9236 abstract = "Mutations in polycystin-1 (PC1) can cause Autosomal
9237 Dominant Polycystic Kidney Disease (ADPKD), which is a leading
9238 cause of renal failure. The available evidence suggests that PC1
9239 acts as a mechanosensor, receiving signals from the primary cilia,
9240 neighboring cells, and extracellular matrix. PC1 is a large
9241 membrane protein that has a long N-terminal extracellular region
9242 (about 3000 aa) with a multimodular structure including sixteen
9243 Ig-like PKD domains, which are targeted by many naturally
9244 occurring missense mutations. Nothing is known about the effects
9245 of these mutations on the biophysical properties of PKD
9246 domains. In addition, PC1 is expressed along the renal tubule,
9247 where it is exposed to a wide range of concentration of urea. Urea
9248 is known to destabilize proteins. Other osmolytes found in the
9249 kidney such as sorbitol, betaine and TMAO are known to counteract
9250 urea's negative effects on proteins. Nothing is known about how
9251 the mechanical properties of PC1 are affected by these
9252 osmolytes. Here I use nano-mechanical techniques to study the
9253 effects of missense mutations and effects of denaturants and
9254 various osmolytes on the mechanical properties of PKD
9255 domains. Several missense mutations were found to alter the
9256 mechanical stability of PKD domains resulting in distinct
9257 mechanical phenotypes. Based on these findings, I hypothesize that
9258 missense mutations may cause ADPKD by altering the stability of
9259 the PC1 ectodomain, thereby perturbing its ability to sense
9260 mechanical signals. I also found that urea has a significant
9261 impact on both the mechanical stability and refolding rate of PKD
9262 domains. It not only lowers their mechanical stability, but also
9263 slows down their refolding rate. Moreover, several osmolytes were
9264 found to effectively counteract the effects of urea. Our data
9265 provide the evidence that naturally occurring osmolytes can help
9266 to maintain Polycystin-1 mechanical stability and folding
9267 kinetics. This study has the potential to provide new therapeutic
9268 approaches (e.g. through the use of osmolytes or chemical
9269 chaperones) for rescuing destabilized and misfolded PKD domains.",
9273 @article{ sundberg03,
9274 author = MSundberg #" and "# JRosengren #" and "# RBunk
9275 #" and "# JLindahl #" and "# INicholls #" and "# STagerud
9276 #" and "# POmling #" and "# LMontelius #" and "# AMansson,
9277 title = "Silanized surfaces for in vitro studies of actomyosin
9278 function and nanotechnology applications.",
9283 address = "Department of Chemistry and Biomedical Sciences,
9284 University of Kalmar, SE-391 82 Kalmar, Sweden.",
9288 keywords = "Actomyosin",
9289 keywords = "Adsorption",
9290 keywords = "Animals",
9291 keywords = "Collodion",
9292 keywords = "Kinetics",
9293 keywords = "Methods",
9294 keywords = "Movement",
9295 keywords = "Nanotechnology",
9296 keywords = "Rabbits",
9297 keywords = "Silicon",
9298 keywords = "Surface Properties",
9299 keywords = "Trimethylsilyl Compounds",
9300 abstract = "We have previously shown that selective heavy meromyosin
9301 (HMM) adsorption to predefined regions of nanostructured polymer
9302 resist surfaces may be used to produce a nanostructured in vitro
9303 motility assay. However, actomyosin function was of lower quality
9304 than on conventional nitrocellulose films. We have therefore
9305 studied actomyosin function on differently derivatized glass
9306 surfaces with the aim to find a substitute for the polymer
9307 resists. We have found that surfaces derivatized with
9308 trimethylchlorosilane (TMCS) were superior to all other surfaces
9309 tested, including nitrocellulose. High-quality actin filament
9310 motility was observed up to 6 days after incubation with HMM and
9311 the fraction of motile actin filaments and the velocity of smooth
9312 sliding were generally higher on TMCS than on nitrocellulose. The
9313 actomyosin function on TMCS-derivatized glass and nitrocellulose
9314 is considered in relation to roughness and hydrophobicity of these
9315 surfaces. The results suggest that TMCS is an ideal substitute for
9316 polymer resists in the nanostructured in vitro motility
9317 assay. Furthermore, TMCS derivatized glass also seems to offer
9318 several advantages over nitrocellulose for HMM adsorption in the
9319 ordinary in /vitro motility assay.",
9321 URL = "http://www.ncbi.nlm.nih.gov/pubmed/14622967",
9322 doi = "10.1016/j.ab.2003.07.022",
9327 author = HItoh #" and "# ATakahashi #" and "# KAdachi #" and "#
9328 HNoji #" and "# RYasuda #" and "# MYoshida #" and "#
9330 title = "Mechanically driven {ATP} synthesis by {F1}-{ATP}ase.",
9335 address = "Tsukuba Research Laboratory, Hamamatsu Photonics KK,
9336 Joko, Hamamatsu 431-3103, Japan.
9337 hiritoh@hpk.trc-net.co.jp",
9341 keywords = "Adenosine Diphosphate",
9342 keywords = "Adenosine Triphosphate",
9343 keywords = "Bacillus",
9344 keywords = "Catalysis",
9346 keywords = "Magnetics",
9347 keywords = "Microchemistry",
9348 keywords = "Microspheres",
9349 keywords = "Molecular Motor Proteins",
9350 keywords = "Proton-Translocating ATPases",
9351 keywords = "Rotation",
9352 keywords = "Torque",
9353 abstract = "ATP, the main biological energy currency, is synthesized
9354 from ADP and inorganic phosphate by ATP synthase in an
9355 energy-requiring reaction. The F1 portion of ATP synthase, also
9356 known as F1-ATPase, functions as a rotary molecular motor: in
9357 vitro its gamma-subunit rotates against the surrounding
9358 alpha3beta3 subunits, hydrolysing ATP in three separate catalytic
9359 sites on the beta-subunits. It is widely believed that reverse
9360 rotation of the gamma-subunit, driven by proton flow through the
9361 associated F(o) portion of ATP synthase, leads to ATP synthesis in
9362 biological systems. Here we present direct evidence for the
9363 chemical synthesis of ATP driven by mechanical energy. We attached
9364 a magnetic bead to the gamma-subunit of isolated F1 on a glass
9365 surface, and rotated the bead using electrical magnets. Rotation
9366 in the appropriate direction resulted in the appearance of ATP in
9367 the medium as detected by the luciferase-luciferin reaction. This
9368 shows that a vectorial force (torque) working at one particular
9369 point on a protein machine can influence a chemical reaction
9370 occurring in physically remote catalytic sites, driving the
9371 reaction far from equilibrium.",
9373 doi = "10.1038/nature02212",
9374 URL = "http://www.ncbi.nlm.nih.gov/pubmed/14749837",
9379 author = NSakaki #" and "# RShimoKon #" and "# KAdachi
9380 #" and "# HItoh #" and "# SFuruike #" and "# EMuneyuki
9381 #" and "# MYoshida #" and "# KKinosita,
9382 title = "One rotary mechanism for {F1}-{ATP}ase over {ATP}
9383 concentrations from millimolar down to nanomolar.",
9388 address = "Department of Functional Molecular Science, The Graduate
9389 University for Advanced Studies, Nishigonaka 38, Myodaiji, Okazaki
9393 pages = "2047--2056",
9394 keywords = "Adenosine Triphosphate",
9395 keywords = "Hydrolysis",
9396 keywords = "Kinetics",
9397 keywords = "Microchemistry",
9398 keywords = "Molecular Motor Proteins",
9399 keywords = "Nanostructures",
9400 keywords = "Protein Binding",
9401 keywords = "Protein Conformation",
9402 keywords = "Proton-Translocating ATPases",
9403 keywords = "Rotation",
9404 keywords = "Torque",
9405 abstract = "F(1)-ATPase is a rotary molecular motor in which the
9406 central gamma-subunit rotates inside a cylinder made of
9407 alpha(3)beta(3)-subunits. The rotation is driven by ATP hydrolysis
9408 in three catalytic sites on the beta-subunits. How many of the
9409 three catalytic sites are filled with a nucleotide during the
9410 course of rotation is an important yet unsettled question. Here we
9411 inquire whether F(1) rotates at extremely low ATP concentrations
9412 where the site occupancy is expected to be low. We observed under
9413 an optical microscope rotation of individual F(1) molecules that
9414 carried a bead duplex on the gamma-subunit. Time-averaged rotation
9415 rate was proportional to the ATP concentration down to 200 pM,
9416 giving an apparent rate constant for ATP binding of 2 x 10(7)
9417 M(-1)s(-1). A similar rate constant characterized bulk ATP
9418 hydrolysis in solution, which obeyed a simple Michaelis-Menten
9419 scheme between 6 mM and 60 nM ATP. F(1) produced the same torque
9420 of approximately 40 pN.nm at 2 mM, 60 nM, and 2 nM ATP. These
9421 results point to one rotary mechanism governing the entire range
9422 of nanomolar to millimolar ATP, although a switchover between two
9423 mechanisms cannot be dismissed. Below 1 nM ATP, we observed less
9424 regular rotations, indicative of the appearance of another
9427 doi = "10.1529/biophysj.104.054668",
9428 URL = "http://www.ncbi.nlm.nih.gov/pubmed/15626703",
9432 @article{ schmidt02,
9433 author = JSchmidt #" and "# XJiang #" and "# CMontemagno,
9434 title = "Force Tolerances of Hybrid Nanodevices",
9438 pages = "1229--1233",
9440 doi = "10.1021/nl025773v",
9441 URL = "http://pubs.acs.org/doi/abs/10.1021/nl025773v",
9442 eprint = "http://pubs.acs.org/doi/pdf/10.1021/nl025773v",
9443 abstract = "We have created hybrid devices consisting of nanoscale
9444 fabricated inorganic components integrated with and powered by a
9445 genetically engineered motor protein. We wish to increase the
9446 assembly yield and lifetime of these devices through
9447 identification, measurement, and improvement of weak internal
9448 bonds. Using dynamic force spectroscopy, we have measured the bond
9449 rupture force of (histidine)\textsubscript{6} on a number of
9450 different surfaces as a function of loading rate. The bond sizes,
9451 lifetimes, and energy barrier heights were derived from these
9452 measurements. We compare the (His)\textsubscript{6}--nickel bonds
9453 to other bonds composing the hybrid device and describe
9454 preliminary measurements of the force tolerances of the protein
9455 itself. Pathways for improvement of device longevity and
9456 robustness are discussed.",
9460 author = YSLo #" and "# YJZhu #" and "# TBeebe,
9461 title = "Loading-Rate Dependence of Individual Ligand−Receptor
9462 Bond-Rupture Forces Studied by Atomic Force Microscopy",
9466 pages = "3741--3748",
9468 doi = "10.1021/la001569g",
9469 URL = "http://pubs.acs.org/doi/abs/10.1021/la001569g",
9470 eprint = "http://pubs.acs.org/doi/pdf/10.1021/la001569g",
9471 abstract = "It is known that bond strength is a dynamic property
9472 that is dependent upon the force loading rate applied during the
9473 rupturing of a bond. For biotin--avidin and biotin--streptavidin
9474 systems, dynamic force spectra, which are plots of bond strength
9475 vs loge(loading rate), have been acquired in a recent biomembrane
9476 force probe (BFP) study at force loading rates in the range
9477 0.05--60 000 pN/s. In the present study, the dynamic force spectrum
9478 of the biotin--streptavidin bond strength in solution was extended
9479 from loading rates of ∼104 to ∼107 pN/s with the atomic force
9480 microscope (AFM). A Poisson statistical analysis method was
9481 applied to extract the magnitude of individual bond-rupture forces
9482 and nonspecific interactions from the AFM force--distance curve
9483 measurements. The bond strengths were found to scale linearly with
9484 the logarithm of the loading rate. The nonspecific interactions
9485 also exhibited a linear dependence on the logarithm of loading
9486 rate, although not increasing as rapidly as the specific
9487 interactions. The dynamic force spectra acquired here with the AFM
9488 combined well with BFP measurements by Merkel et al. The combined
9489 spectrum exhibited two linear regimes, consistent with the view
9490 that multiple energy barriers are present along the unbinding
9491 coordinate of the biotin--streptavidin complex. This study
9492 demonstrated that unbinding forces measured by different
9493 techniques are in agreement and can be used together to obtain a
9494 dynamic force spectrum covering 9 orders of magnitude in loading
9496 note = "These guys seem to be pretty thorough, give this one another read.",
9500 author = ABaljon #" and "# MRobbins,
9501 title = "Energy Dissipation During Rupture of Adhesive Bonds",
9508 doi = "10.1126/science.271.5248.482",
9509 URL = "http://www.sciencemag.org/content/271/5248/482.abstract",
9510 eprint = "http://www.sciencemag.org/content/271/5248/482.full.pdf",
9511 abstract = "Molecular dynamics simulations were used to study
9512 energy-dissipation mechanisms during the rupture of a thin
9513 adhesive bond formed by short chain molecules. The degree of
9514 dissipation and its velocity dependence varied with the state of
9515 the film. When the adhesive was in a liquid phase, dissipation was
9516 caused by viscous loss. In glassy films, dissipation occurred
9517 during a sequence of rapid structural rearrangements. Roughly
9518 equal amounts of energy were dissipated in each of three types of
9519 rapid motion: cavitation, plastic yield, and bridge rupture. These
9520 mechanisms have similarities to nucleation, plastic flow, and
9521 crazing in commercial polymeric adhesives.",
9524 @article{ fisher99a,
9525 author = TEFisher #" and "# PMarszalek #" and "# AOberhauser
9526 #" and "# MCarrionVazquez #" and "# JFernandez,
9527 title = "The micro-mechanics of single molecules studied with
9528 atomic force microscopy.",
9533 address = "Department of Physiology and Biophysics, Mayo Foundation,
9534 1-117 Medical Sciences Building, Rochester, MN 55905, USA.",
9535 volume = "520 Pt 1",
9537 keywords = "Animals",
9538 keywords = "Extracellular Matrix",
9539 keywords = "Extracellular Matrix Proteins",
9540 keywords = "Humans",
9541 keywords = "Microscopy, Atomic Force",
9542 keywords = "Polysaccharides",
9543 abstract = "The atomic force microscope (AFM) in its force-measuring
9544 mode is capable of effecting displacements on an angstrom scale
9545 (10 A = 1 nm) and measuring forces of a few piconewtons. Recent
9546 experiments have applied AFM techniques to study the mechanical
9547 properties of single biological polymers. These properties
9548 contribute to the function of many proteins exposed to mechanical
9549 strain, including components of the extracellular matrix
9550 (ECM). The force-bearing proteins of the ECM typically contain
9551 multiple tandem repeats of independently folded domains, a common
9552 feature of proteins with structural and mechanical
9553 roles. Polysaccharide moieties of adhesion glycoproteins such as
9554 the selectins are also subject to strain. Force-induced extension
9555 of both types of molecules with the AFM results in conformational
9556 changes that could contribute to their mechanical function. The
9557 force-extension curve for amylose exhibits a transition in
9558 elasticity caused by the conversion of its glucopyranose rings
9559 from the chair to the boat conformation. Extension of multi-domain
9560 proteins causes sequential unraveling of domains, resulting in a
9561 force-extension curve displaying a saw tooth pattern of peaks. The
9562 engineering of multimeric proteins consisting of repeats of
9563 identical domains has allowed detailed analysis of the mechanical
9564 properties of single protein domains. Repetitive extension and
9565 relaxation has enabled direct measurement of rates of domain
9566 unfolding and refolding. The combination of site-directed
9567 mutagenesis with AFM can be used to elucidate the amino acid
9568 sequences that determine mechanical stability. The AFM thus offers
9569 a novel way to explore the mechanical functions of proteins and
9570 will be a useful tool for studying the micro-mechanics of
9573 URL = "http://www.ncbi.nlm.nih.gov/pubmed/10517795",
9577 @article{ fisher99b,
9578 author = TEFisher #" and "# AOberhauser #" and "# MCarrionVazquez
9579 #" and "# PMarszalek #" and "# JFernandez,
9580 title = "The study of protein mechanics with the atomic force microscope.",
9581 journal = "Trends in biochemical sciences",
9584 address = "Dept of Physiology and Biophysics, Mayo Foundation, 1-117
9585 Medical Sciences Building, Rochester, MN 55905, USA.",
9589 keywords = "Entropy",
9590 keywords = "Kinetics",
9591 keywords = "Microscopy, Atomic Force",
9592 keywords = "Protein Binding",
9593 keywords = "Protein Folding",
9594 keywords = "Proteins",
9595 abstract = "The unfolding and folding of single protein molecules
9596 can be studied with an atomic force microscope (AFM). Many
9597 proteins with mechanical functions contain multiple, individually
9598 folded domains with similar structures. Protein engineering
9599 techniques have enabled the construction and expression of
9600 recombinant proteins that contain multiple copies of identical
9601 domains. Thus, the AFM in combination with protein engineering
9602 has enabled the kinetic analysis of the force-induced unfolding
9603 and refolding of individual domains as well as the study of the
9604 determinants of mechanical stability.",
9606 URL = "http://www.ncbi.nlm.nih.gov/pubmed/10500301",
9610 @article{ zlatanova00,
9611 author = JZlatanova #" and "# SLindsay #" and "# SLeuba,
9612 title = "Single molecule force spectroscopy in biology using the
9613 atomic force microscope.",
9616 address = "Biochip Technology Center, Argonne National Laboratory,
9617 9700 South Cass Avenue, Bldg. 202-A253, Argonne, IL 60439,
9618 USA. jzlatano@duke.poly.edu",
9622 keywords = "Biophysics",
9623 keywords = "Cell Adhesion",
9625 keywords = "Elasticity",
9626 keywords = "Microscopy, Atomic Force",
9627 keywords = "Polysaccharides",
9628 keywords = "Proteins",
9629 keywords = "Signal Processing, Computer-Assisted",
9630 keywords = "Viscosity",
9631 abstract = "The importance of forces in biology has been recognized
9632 for quite a while but only in the past decade have we acquired
9633 instrumentation and methodology to directly measure interactive
9634 forces at the level of single biological macromolecules and/or
9635 their complexes. This review focuses on force measurements
9636 performed with the atomic force microscope. A general introduction
9637 to the principle of action is followed by review of the types of
9638 interactions being studied, describing the main results and
9639 discussing the biological implications.",
9641 URL = "http://www.ncbi.nlm.nih.gov/pubmed/11106806",
9643 note = "Lots of great force-clamp cartoons explaining different
9644 approach/retract features.",
9648 author = MViani #" and "# TESchafer #" and "# AChand #" and "# MRief
9649 #" and "# HEGaub #" and "# HHansma,
9650 title = "Small cantilevers for force spectroscopy of single molecules",
9655 pages = "2258--2262",
9656 abstract = "We have used a simple process to fabricate small
9657 rectangular cantilevers out of silicon nitride. They have lengths
9658 of 9--50 $\mu$m, widths of 3--5 $\mu$m, and thicknesses of 86 and
9659 102 nm. We have added metallic reflector pads to some of the
9660 cantilever ends to maximize reflectivity while minimizing
9661 sensitivity to temperature changes. We have characterized small
9662 cantilevers through their thermal spectra and show that they can
9663 measure smaller forces than larger cantilevers with the same
9664 spring constant because they have lower coefficients of viscous
9665 damping. Finally, we show that small cantilevers can be used for
9666 experiments requiring large measurement bandwidths, and have used
9667 them to unfold single titin molecules over an order of magnitude
9668 faster than previously reported with conventional cantilevers.",
9670 issn_online = "1089-7550",
9671 doi = "10.1063/1.371039",
9672 URL = "http://jap.aip.org/resource/1/japiau/v86/i4/p2258_s1",
9676 @article{ capitanio02,
9677 author = MCapitanio #" and "# GRomano #" and "# RBallerini #" and "#
9678 MGiuntini #" and "# FPavone #" and "# DDunlap #" and "# LFinzi,
9679 title = "Calibration of optical tweezers with differential
9680 interference contrast signals",
9685 pages = "1687--1696",
9686 abstract = "A comparison of different calibration methods for
9687 optical tweezers with the differential interference contrast (DIC)
9688 technique was performed to establish the uses and the advantages
9689 of each method. A detailed experimental and theoretical analysis
9690 of each method was performed with emphasis on the anisotropy
9691 involved in the DIC technique and the noise components in the
9692 detection. Finally, a time of flight method that permits the
9693 reconstruction of the optical potential well was demonstrated.",
9695 issn_online = "1089-7623",
9696 doi = "10.1063/1.1460929",
9697 URL = "http://rsi.aip.org/resource/1/rsinak/v73/i4/p1687_s1",
9702 author = GBinnig #" and "# CQuate #" and "# CGerber,
9703 title = "Atomic force microscope",
9711 abstract = "The scanning tunneling microscope is proposed as a
9712 method to measure forces as small as $10^{-18}$ N. As one
9713 application for this concept, we introduce a new type of
9714 microscope capable of investigating surfaces of insulators on an
9715 atomic scale. The atomic force microscope is a combination of the
9716 principles of the scanning tunneling microscope and the stylus
9717 profilometer. It incorporates a probe that does not damage the
9718 surface. Our preliminary results in air demonstrate a lateral
9719 resolution of 30 \AA and a vertical resolution less than 1 \AA.",
9721 doi = "10.1103/PhysRevLett.56.930",
9722 URL = "http://www.ncbi.nlm.nih.gov/pubmed/10033323",
9723 eprint = {http://prl.aps.org/pdf/PRL/v56/i9/p930_1},
9725 note = "Original AFM paper.",
9729 author = BDrake #" and "# CBPrater #" and "# ALWeisenhorn #" and "#
9730 SAGould #" and "# TRAlbrecht #" and "# CQuate #" and "#
9731 DSCannell #" and "# HHansma #" and "# PHansma,
9732 title = {Imaging crystals, polymers, and processes in water with the
9733 atomic force microscope},
9740 pages = {1586--1589},
9741 doi = {10.1126/science.2928794},
9742 url = {http://www.sciencemag.org/content/243/4898/1586.abstract},
9743 eprint = {http://www.sciencemag.org/content/243/4898/1586.full.pdf},
9744 abstract ={The atomic force microscope (AFM) can be used to image
9745 the surface of both conductors and nonconductors even if they are
9746 covered with water or aqueous solutions. An AFM was used that
9747 combines microfabricated cantilevers with a previously described
9748 optical lever system to monitor deflection. Images of mica
9749 demonstrate that atomic resolution is possible on rigid materials,
9750 thus opening the possibility of atomic-scale corrosion experiments
9751 on nonconductors. Images of polyalanine, an amino acid polymer,
9752 show the potential of the AFM for revealing the structure of
9753 molecules important in biology and medicine. Finally, a series of
9754 ten images of the polymerization of fibrin, the basic component of
9755 blood clots, illustrate the potential of the AFM for revealing
9756 subtle details of biological processes as they occur in real
9760 @article{ radmacher92,
9761 author = MRadmacher #" and "# RWTillmann #" and "# MFritz #" and "# HEGaub,
9762 title = {From molecules to cells: imaging soft samples with the
9763 atomic force microscope},
9770 pages = {1900--1905},
9771 doi = {10.1126/science.1411505},
9772 url = {http://www.sciencemag.org/content/257/5078/1900.abstract},
9773 eprint = {http://www.sciencemag.org/content/257/5078/1900.full.pdf},
9774 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.},
9777 @article{ williams86,
9778 author = CCWilliams #" and "# HKWickramasinghe,
9779 title = "Scanning thermal profiler",
9786 pages = "1587--1589",
9787 abstract = "A new high-resolution profilometer has been demonstrated
9788 based upon a noncontacting near-field thermal probe. The thermal
9789 probe consists of a thermocouple sensor with dimensions
9790 approaching 100 nm. Profiling is achieved by scanning the heated
9791 sensor above but close to the surface of a solid. The conduction
9792 of heat between tip and sample via the air provides a means for
9793 maintaining the sample spacing constant during the lateral
9794 scan. The large difference in thermal properties between air and
9795 solids makes the profiling technique essentially independent of
9796 the material properties of the solid. Noncontact profiling of
9797 resist and metal films has shown a lateral resolution of 100 nm
9798 and a depth solution of 3 nm. The basic theory of the new probe is
9799 described and the results presented.",
9801 issn_online = "1077-3118",
9802 doi = "10.1063/1.97288",
9803 URL = "http://apl.aip.org/resource/1/applab/v49/i23/p1587_s1",
9808 author = GMeyer #" and "# NMAmer,
9809 title = "Novel optical approach to atomic force microscopy",
9816 pages = "1045--1047",
9817 abstract = "A sensitive and simple optical method for detecting the
9818 cantilever deflection in atomic force microscopy is described. The
9819 method was incorporated in an atomic force microscope, and imaging
9820 and force measurements, in ultrahigh vacuum, were successfully
9823 issn_online = "1077-3118",
9824 doi = "10.1063/1.100061",
9825 URL = "http://apl.aip.org/resource/1/applab/v53/i12/p1045_s1",
9831 title = {Notes on Structured Programming},
9834 url = {http://www.cs.utexas.edu/users/EWD/ewd02xx/EWD249.PDF},
9835 publisher = THEMath,
9836 note = {T.H. Report 70-WSK-03},
9841 title = {On the Composition of Well-Structured Programs},
9850 doi = {10.1145/356635.356639},
9851 url = {http://doi.acm.org/10.1145/356635.356639},
9853 address = {New York, NY, USA},
9856 @article{ shneiderman79,
9857 author = BShneiderman #" and "# RMayer,
9858 title = {Syntactic/semantic interactions in programmer behavior: A
9859 model and experimental results},
9866 doi = {10.1007/BF00977789},
9867 url = {http://dx.doi.org/10.1007/BF00977789},
9869 keywords = {Programming; programming languages; cognitive models;
9870 program composition; program comprehension; debugging;
9871 modification; learning; education; information processing},
9872 language = {English},
9877 title = {Why Functional Programming Matters},
9883 doi = {10.1093/comjnl/32.2.98},
9884 URL = {http://comjnl.oxfordjournals.org/content/32/2/98.abstract},
9885 eprint = {http://comjnl.oxfordjournals.org/content/32/2/98.full.pdf+html},
9886 abstract ={As software becomes more and more complex, it is more and
9887 more important to structure it well. Well-structured software is
9888 easy to write, easy to debug, and provides a collection of modules
9889 that can be re-used to reduce future programming
9890 costs. Conventional languages place conceptual limits on the way
9891 problems can be modularised. Functional languages push those
9892 limits back. In this paper we show that two features of functional
9893 languages in particular, higher-order functions and lazy
9894 evaluation, can contribute greatly to modularity. As examples, we
9895 manipulate lists and trees, program several numerical algorithms,
9896 and implement the alpha-beta heuristics (an Artificial
9897 Intelligence algorithm used in game-playing programs). Since
9898 modularity is the key to successful programming, functional
9899 languages are vitally important to the real world.},
9902 @article{ hilburn93,
9904 title = {A top-down approach to teaching an introductory computer science course},
9905 journal = ACM:SIGCSE,
9913 doi = {10.1145/169073.169349},
9914 url = {http://doi.acm.org/10.1145/169073.169349},
9917 address = {New York, NY, USA},
9922 title = {The mythical man-month},
9923 edition = {20$^\text{th}$ anniversary},
9925 isbn = {0-201-83595-9},
9927 address = {Boston, MA, USA},
9928 url = {http://dl.acm.org/citation.cfm?id=207583},
9929 note = {First published in 1975},
9932 @inproceedings{ claerbout92,
9933 author = JClaerbout #" and "# MKarrenbach,
9934 title = {Electronic documents give reproducible research a new meaning},
9935 booktitle = {SEG Technical Program Expanded Abstracts 1992},
9939 doi = {10.1190/1.1822162},
9942 url = {http://library.seg.org/doi/abs/10.1190/1.1822162},
9943 eprint = {http://sepwww.stanford.edu/doku.php?id=sep:research:reproducible:seg92},
9946 @incollection{ buckheit95,
9947 author = JBuckheit #" and "# DDonoho,
9948 title = {WaveLab and Reproducible Research},
9949 booktitle = {Wavelets and Statistics},
9950 series = {Lecture Notes in Statistics},
9951 editor = AAntoniadis #" and "# GOppenheim,
9955 isbn = {978-0-387-94564-4},
9956 doi = {10.1007/978-1-4612-2544-7_5},
9957 url = {http://dx.doi.org/10.1007/978-1-4612-2544-7_5},
9958 eprint = {http://www-stat.stanford.edu/~wavelab/Wavelab_850/wavelab.pdf},
9959 publisher = SPRINGER,
9960 language = {English},
9964 author = MSchwab #" and "# MKarrenbach #" and "# JClaerbout,
9965 title = {Making scientific computations reproducible},
9968 month = {November--December},
9972 doi = {10.1109/5992.881708},
9974 keywords = {document handling;file organisation;natural sciences
9975 computing;research and development
9976 management;ReDoc;authors;computational results;reproducible
9977 scientific computations;research paper;software filing
9978 system;standardized rules;Computer
9979 interfaces;Documentation;Electronic
9980 publishing;Laboratories;Organizing;Reproducibility of
9981 results;Software maintenance;Software systems;Software
9982 testing;Technological innovation},
9983 abstract = {To verify a research paper's computational results,
9984 readers typically have to recreate them from scratch. ReDoc is a
9985 simple software filing system for authors that lets readers easily
9986 reproduce computational results using standardized rules and
9990 @article{ wilson06a,
9992 title = {Where's the Real Bottleneck in Scientific Computing?},
9995 month = {January--February},
9998 @article{ wilson06b,
10000 title = {Software Carpentry: Getting Scientists to Write Better
10001 Code by Making Them More Productive},
10004 month = {November--December},
10007 @article{ vandewalle09,
10008 author = PVandewalle #" and "# JKovacevic #" and "# MVetterli ,
10009 title = {Reproducible Research in Signal Processing - What, why, and how},
10010 journal = IEEE:SPM,
10016 doi = {10.1109/MSP.2009.932122},
10017 issn = {1053-5888},
10018 url = {http://rr.epfl.ch/17/},
10019 eprint = {http://rr.epfl.ch/17/1/VandewalleKV09.pdf},
10020 keywords={research and development;signal processing;high-quality
10021 reviewing process;large data set;reproducible research;signal
10022 processing;win-win situation;Advertising;Digital signal
10023 processing;Education;Programming;Reproducibility of
10024 results;Scholarships;Signal processing;Signal processing
10025 algorithms;Testing;Wikipedia},
10026 abstract = {Have you ever tried to reproduce the results presented
10027 in a research paper? For many of our current publications, this
10028 would unfortunately be a challenging task. For a computational
10029 algorithm, details such as the exact data set, initialization or
10030 termination procedures, and precise parameter values are often
10031 omitted in the publication for various reasons, such as a lack of
10032 space, a lack of self-discipline, or an apparent lack of interest
10033 to the readers, to name a few. This makes it difficult, if not
10034 impossible, for someone else to obtain the same results. In our
10035 experience, it is often even worse as even we are not always able
10036 to reproduce our own experiments, making it difficult to answer
10037 questions from colleagues about details. Following are some
10038 examples of e-mails we have received: ``I just read your paper
10039 X. It is very completely described, however I am confused by
10040 Y. Could you provide the implementation code to me for reference
10041 if possible?'' ``Hi! I am also working on a project related to
10042 X. I have implemented your algorithm but cannot get the same
10043 results as described in your paper. Which values should I use for
10044 parameters Y and Z?''},
10047 @article{ aruliah12,
10048 author = DAruliah #" and "# CTBrown #" and "# MPCHong #" and "#
10049 MDavis #" and "# RTGuy #" and "# SHaddock #" and "# KHuff #" and "#
10050 IMitchell #" and "# MPlumbley #" and "# BWaugh #" and "#
10051 EPWhite #" and "# GWilson #" and "# PWilson,
10052 title = {Best Practices for Scientific Computing},
10054 volume = {abs/1210.0530},
10059 url = {http://arxiv.org/abs/1210.0530},
10060 eprint = {http://arxiv.org/pdf/1210.0530v3},
10061 note = {v3: Thu, 29 Nov 2012 19:28:27 GMT},
10064 @article{ ziegler42,
10065 author = JZiegler #" and "# NNichols,
10066 title = {Optimum Settings for Automatic Controllers},
10071 pages = {759--765},
10072 url = {http://www.driedger.ca/Z-N/Z-N.html},
10073 eprint = {http://www.driedger.ca/Z-N/Z-n.pdf},
10077 author = GHCohen #" and "# GACoon,
10078 title = {Theoretical considerations of retarded control},
10082 pages = {827--834},
10086 author = FSWang #" and "# WSJuang #" and "# CTChan,
10087 title = {Optimal tuning of {PID} controllers for single and
10088 cascade control loops},
10094 publisher = GordonBreach,
10095 issn = {0098-6445},
10096 doi = {10.1080/00986449508936294},
10097 url = {http://www.tandfonline.com/doi/abs/10.1080/00986449508936294},
10098 keywords = {process control; cascade control; controller tuning},
10099 abstract = {Design of one parameter tuning of three-mode PID
10100 controller was developed in this present study. The integral time
10101 and the derivative time of the controller were expressed in terms
10102 of the time constant and dead time of the process. Only the
10103 proportional gain was observed to be dependent on the implemented
10104 tunable parameter in which the stable region could be
10105 predetermined by the Routh test. Extension of the concept towards
10106 designing cascade PID controllers was straightforward such that
10107 only two parameters for the inner and outer PID controllers
10108 required to be tuned, respectively. The optimal tuning correlative
10109 formulas of the proportional gain for single and cascade control
10110 systems were obtained by the least square regression method.},
10113 @article{ astrom93,
10114 author = KAstrom #" and "# THagglund #" and "# CCHang #" and "# WKHo,
10115 title = {Automatic tuning and adaptation for {PID} controllers---a survey},
10120 pages = {699--714},
10121 issn = "0967-0661",
10122 doi = "10.1016/0967-0661(93)91394-C",
10123 url = "http://www.sciencedirect.com/science/article/pii/096706619391394C",
10124 keywords = {Adaptive control},
10125 keywords = {automatic tuning},
10126 keywords = {gain scheduling},
10127 keywords = {{PID} control},
10128 abstract = {Adaptive techniques such as gain scheduling, automatic
10129 tuning and continuous adaptation have been used in industrial
10130 single-loop controllers for about ten years. This paper gives a
10131 survey of the different adaptive techniques, the underlying
10132 process models and control designs. An overview of industrial
10133 products is also presented, which includes a fairly detailed
10134 investigation of four different adaptive single-loop
10140 title = {Notes on the use of propagation of error formulas},
10146 pages = {263--273},
10148 issn = {0022-4316},
10149 url = {http://nistdigitalarchives.contentdm.oclc.org/cdm/compoundobject/collection/p13011coll6/id/78003/rec/5},
10150 eprint = {http://nistdigitalarchives.contentdm.oclc.org/utils/getfile/collection/p13011coll6/id/78003/filename/print/page/download},
10151 keywords = {Approximation; error; formula; imprecision; law of
10152 error; products; propagation of error; random; ratio; systematic;
10154 abstract = {The ``law of propagation of error'' is a tool that
10155 physical scientists have conveniently and frequently used in their
10156 work for many years, yet an adequate reference is difficult to
10157 find. In this paper an expository review of this topic is
10158 presented, particularly in the light of current practices and
10159 interpretations. Examples on the accuracy of the approximations
10160 are given. The reporting of the uncertainties of final results is
10164 @article{ livadaru03,
10165 author = LLivadaru #" and "# RRNetz #" and "# HJKreuzer,
10166 title = {Stretching Response of Discrete Semiflexible Polymers},
10170 journal = Macromol,
10173 pages = {3732--3744},
10174 doi = {10.1021/ma020751g},
10175 URL = {http://pubs.acs.org/doi/abs/10.1021/ma020751g},
10176 eprint = {http://pubs.acs.org/doi/pdf/10.1021/ma020751g},
10177 abstract = {We demonstrate that semiflexible polymer chains
10178 (characterized by a persistence length $l$) made up of discrete
10179 segments or bonds of length $b$ show at large stretching forces a
10180 crossover from the standard wormlike chain (WLC) behavior to a
10181 discrete-chain (DC) behavior. In the DC regime, the stretching
10182 response is independent of the persistence length and shows a
10183 different force dependence than in the WLC regime. We perform
10184 extensive transfer-matrix calculations for the force-response of a
10185 freely rotating chain (FRC) model as a function of varying bond
10186 angle $\gamma$ (and thus varying persistence length) and chain
10187 length. The FRC model is a first step toward the understanding of
10188 the stretching behavior of synthetic polymers, denatured proteins,
10189 and single-stranded DNA under large tensile forces. We also
10190 present scaling results for the force response of the elastically
10191 jointed chain (EJC) model, that is, a chain made up of freely
10192 jointed bonds that are connected by joints with some bending
10193 stiffness; this is the discretized version of the continuum WLC
10194 model. The EJC model might be applicable to stiff biopolymers such
10195 as double-stranded DNA or Actin. Both models show a similar
10196 crossover from the WLC to the DC behavior, which occurs at a force
10197 $f/k_BT\sim l/b^2$ and is thus (for polymers with a moderately
10198 large persistence length) in the piconewton range probed in many
10199 AFM experiments. We also give a heuristic simple function for the
10200 force--distance relation of a FRC, valid in the global force
10201 range, which can be used to fit experimental data. Our findings
10202 might help to resolve the discrepancies encountered when trying to
10203 fit experimental data for the stretching response of polymers in a
10204 broad force range with a single effective persistence length.},
10205 note = {There are two typos in \fref{equation}{46}.
10206 \citet{livadaru03} have
10208 \frac{R_z}{L} = \begin{cases}
10209 \frac{fa}{3k_BT} & \frac{fb}{k_BT} < \frac{b}{l} \\
10210 1 - \p({\frac{fl}{4k_BT}})^{-0.5}
10211 & \frac{b}{l} < \frac{fb}{k_BT} < \frac{l}{b} \\
10212 1 - \p({\frac{fb}{ck_BT}})^{-1} & \frac{1}{b} < \frac{fb}{k_BT} \;,
10215 but the correct formula is
10217 \frac{R_z}{L} = \begin{cases}
10218 \frac{fa}{3k_BT} & \frac{fb}{k_BT} < \frac{b}{l} \\
10219 1 - \p({\frac{4fl}{k_BT}})^{-0.5}
10220 & \frac{b}{l} < \frac{fb}{k_BT} < \frac{l}{b} \\
10221 1 - \p({\frac{cfb}{k_BT}})^{-1} & \frac{1}{b} < \frac{fb}{k_BT} \;,
10224 with both the $4$ and the $c$ moved into their respective
10225 numerators. I pointed these errors out to Roland Netz in 2012,
10226 along with the fact that even with the corrected formula there is
10227 a discontinuity between the low- and moderate-force regimes. Netz
10228 confirmed the errors, and pointed out that the discontinuity is
10229 because \fref{equation}{46} only accounts for the scaling (without
10230 prefactors). Unfortunately, there does not seem to be a published
10231 erratum pointing out the error and at least \citet{puchner08} have
10232 quoted the incorrect form.},
10236 author = PCarl #" and "# PDalhaimer,
10237 title = {{PUNIAS}: Protein Unfolding and Nano-indentation Analysis
10242 note = {4 Int. Workshop, Scanning Probe Microscopy in Life Sciences},
10243 address = {Berlin},
10244 url = {http://punias.voila.net/},
10248 author = PCarl #" and "# HSchillers,
10249 title = {Elasticity measurement of living cells with an atomic force
10250 microscope: data acquisition and processing.},
10254 address = {Institute of Physiology II, University of M{\"u}nster,
10255 Robert-Koch-Str. 27b, 48149, M{\"u}nster, Germany.},
10259 pages = {551--559},
10260 issn = {0031-6768},
10261 doi = {10.1007/s00424-008-0524-3},
10262 url = {http://www.ncbi.nlm.nih.gov/pubmed/18481081},
10264 keywords = {Animals},
10265 keywords = {Biomechanics},
10266 keywords = {CHO Cells},
10267 keywords = {Cricetinae},
10268 keywords = {Cricetulus},
10269 keywords = {Cystic Fibrosis Transmembrane Conductance Regulator},
10270 keywords = {Elastic Modulus},
10271 keywords = {Equipment Design},
10272 keywords = {Microscopy, Atomic Force},
10273 keywords = {Models, Biological},
10274 keywords = {Reproducibility of Results},
10275 keywords = {Signal Processing, Computer-Assisted},
10276 keywords = {Transfection},
10277 abstract = {Elasticity of living cells is a parameter of increasing
10278 importance in cellular physiology, and the atomic force microscope
10279 is a suitable instrument to quantitatively measure it. The
10280 principle of an elasticity measurement is to physically indent a
10281 cell with a probe, to measure the applied force, and to process
10282 this force-indentation data using an appropriate model. It is
10283 crucial to know what extent the geometry of the indenting probe
10284 influences the result. Therefore, we indented living Chinese
10285 hamster ovary cells at 37 degrees C with sharp tips and colloidal
10286 probes (spherical particle tips) of different sizes and
10287 materials. We furthermore developed an implementation of the Hertz
10288 model, which simplifies the data processing. Our results show (a)
10289 that the size of the colloidal probe does not influence the result
10290 over a wide range (radii $0.5$-$26\U{$\mu$m}$) and (b) indenting
10291 cells with sharp tips results in higher Young's moduli
10292 (approximately $1,300\U{Pa}$) than using colloidal probes
10293 (approximately $400\U{Pa}$).},
10294 note = {Mentions \citetalias{punias} as if it was in-house software,
10295 which makes sense because Philippe Carl seems to be a major author.},
10298 @article{ struckmeier08,
10299 author = JStruckmeier #" and "# RWahl #" and "# MLeuschner #" and "#
10300 JNunes #" and "# HJanovjak #" and "# UGeisler #" and "#
10301 GHofmann #" and "# TJahnke #" and "# DJMuller,
10302 title = {Fully automated single-molecule force spectroscopy for
10303 screening applications},
10307 address = {Cellular Machines, Biotechnology Center,
10308 Technische Universit{\"a}t Dresden, Tatzberg 47, D-01307
10314 issn = {0957-4484},
10315 doi = {10.1088/0957-4484/19/38/384020},
10316 url = {http://www.ncbi.nlm.nih.gov/pubmed/21832579},
10318 abstract = {With the introduction of single-molecule force
10319 spectroscopy (SMFS) it has become possible to directly access the
10320 interactions of various molecular systems. A bottleneck in
10321 conventional SMFS is collecting the large amount of data required
10322 for statistically meaningful analysis. Currently, atomic force
10323 microscopy (AFM)-based SMFS requires the user to tediously `fish'
10324 for single molecules. In addition, most experimental and
10325 environmental conditions must be manually adjusted. Here, we
10326 developed a fully automated single-molecule force
10327 spectroscope. The instrument is able to perform SMFS while
10328 monitoring and regulating experimental conditions such as buffer
10329 composition and temperature. Cantilever alignment and calibration
10330 can also be automatically performed during experiments. This,
10331 combined with in-line data analysis, enables the instrument, once
10332 set up, to perform complete SMFS experiments autonomously.},
10333 note = {An advertisement for JPK's \citetalias{force-robot}.},
10336 @article{ andreopoulos11,
10337 author = BAndreopoulos #" and "# DLabudde,
10338 title = {Efficient unfolding pattern recognition in single molecule
10339 force spectroscopy data},
10343 address = {Department of Bioinformatics, Biotechnological Center,
10344 University of Technology Dresden, Dresden, Germany.
10345 williama@biotec.tu-dresden.de},
10350 issn = {1748-7188},
10351 doi = {10.1186/1748-7188-6-16},
10352 url = {http://www.ncbi.nlm.nih.gov/pubmed/21645400},
10354 abstract = {Single-molecule force spectroscopy (SMFS) is a technique
10355 that measures the force necessary to unfold a protein. SMFS
10356 experiments generate Force-Distance (F-D) curves. A statistical
10357 analysis of a set of F-D curves reveals different unfolding
10358 pathways. Information on protein structure, conformation,
10359 functional states, and inter- and intra-molecular interactions can
10364 editor = HWTurnbull,
10366 title = {The correspondence of Isaac Newton},
10371 url = {http://books.google.com/books?id=pr8WAQAAMAAJ},
10372 note = {The ``Giants'' quote is on page 416, in a letter to Robert
10373 Hooke dated February 5, 1676.},
10376 @book{ whitehead11,
10377 author = ANWhitehead,
10378 title = {An introduction to mathematics},
10382 address = {London},
10383 url = {http://archive.org/details/introductiontoma00whitiala},
10384 note = {The ``civilization'' quote is on page 61.},
10388 author = NJMlot #" and "# CATovey #" and "# DLHu,
10389 title = {Fire ants self-assemble into waterproof rafts to survive floods},
10393 address = {Schools of Mechanical Engineering, Industrial and
10394 Systems Engineering, and Biology,
10395 Georgia Institute of Technology, Atlanta, GA 30318, USA.},
10399 pages = {7669--7673},
10400 issn = {1091-6490},
10401 doi = {10.1073/pnas.1016658108},
10402 url = {http://www.ncbi.nlm.nih.gov/pubmed/21518911},
10404 keywords = {Animals},
10406 keywords = {Behavior, Animal},
10407 keywords = {Biophysical Phenomena},
10408 keywords = {Floods},
10409 keywords = {Hydrophobic and Hydrophilic Interactions},
10410 keywords = {Microscopy, Electron, Scanning},
10411 keywords = {Models, Biological},
10412 keywords = {Social Behavior},
10413 keywords = {Surface Properties},
10414 keywords = {Time-Lapse Imaging},
10415 keywords = {Video Recording},
10416 keywords = {Water},
10417 abstract = {Why does a single fire ant \species{Solenopsis invicta}
10418 struggle in water, whereas a group can float effortlessly for
10419 days? We use time-lapse photography to investigate how fire ants
10420 \species{S.~invicta} link their bodies together to build
10421 waterproof rafts. Although water repellency in nature has been
10422 previously viewed as a static material property of plant leaves
10423 and insect cuticles, we here demonstrate a self-assembled
10424 hydrophobic surface. We find that ants can considerably enhance
10425 their water repellency by linking their bodies together, a process
10426 analogous to the weaving of a waterproof fabric. We present a
10427 model for the rate of raft construction based on observations of
10428 ant trajectories atop the raft. Central to the construction
10429 process is the trapping of ants at the raft edge by their
10430 neighbors, suggesting that some ``cooperative'' behaviors may rely
10432 note = {Higher resolution pictures are available at
10433 \url{http://antlab.gatech.edu/antlab/The_Ant_Raft.html}.},
10436 @article{ chauhan97,
10437 author = VPChauhan #" and "# IRay #" and "# AChauhan #" and "#
10438 JWegiel #" and "# HMWisniewski,
10439 title = {Metal cations defibrillize the amyloid beta-protein fibrils.},
10442 address = {New York State Institute for Basic Research in
10443 Developmental Disabilities, Staten Island 10314-6399,
10448 pages = {805--809},
10449 issn = {0364-3190},
10450 url = {http://www.ncbi.nlm.nih.gov/pubmed/9232632},
10451 doi = {10.1023/A:1022079709085},
10453 keywords = {Alzheimer Disease},
10454 keywords = {Amyloid beta-Peptides},
10455 keywords = {Drug Evaluation, Preclinical},
10456 keywords = {Humans},
10457 keywords = {Metals},
10458 keywords = {Peptide Fragments},
10459 keywords = {Solubility},
10460 abstract = {Amyloid beta-protein (A beta) is the major constituent
10461 of amyloid fibrils composing beta-amyloid plaques and
10462 cerebrovascular amyloid in Alzheimer's disease (AD). We studied
10463 the effect of metal cations on preformed fibrils of synthetic A
10464 beta by Thioflavin T (ThT) fluorescence spectroscopy and
10465 electronmicroscopy (EM) in negative staining. The amount of cross
10466 beta-pleated sheet structure of A beta 1-40 fibrils was found to
10467 decrease by metal cations in a concentration-dependent manner as
10468 measured by ThT fluorescence spectroscopy. The order of
10469 defibrillization of A beta 1-40 fibrils by metal cations was: Ca2+
10470 and Zn2+ (IC50 = 100 microM) > Mg3+ (IC50 = 300 microM) > Al3+
10471 (IC50 = 1.1 mM). EM analysis in negative staining showed that A
10472 beta 1-40 fibrils in the absence of cations were organized in a
10473 fine network with a little or no amorphous material. The addition
10474 of Ca2+, Mg2+, and Zn2+ to preformed A beta 1-40 fibrils
10475 defibrillized the fibrils or converted them into short rods or to
10476 amorphous material. Al3+ was less effective, and reduced the
10477 fibril network by about 80\% of that in the absence of any metal
10478 cation. Studies with A beta 1-42 showed that this peptide forms
10479 more dense network of fibrils as compared to A beta 1-40. Both ThT
10480 fluorescence spectroscopy and EM showed that similar to A beta
10481 1-40, A beta 1-42 fibrils are also defibrillized in the presence
10482 of millimolar concentrations of Ca2+. These studies suggest that
10483 metal cations can defibrillize the fibrils of synthetic A beta.},
10484 note = {From page 806, ``The exact mechanism by which these metal
10485 ions affect the fibrillization of A$\beta$ is not known.''},
10488 @article{ friedman05,
10489 author = RFriedman #" and "# ENachliel #" and "# MGutman,
10490 title = {Molecular dynamics of a protein surface: ion-residues
10495 address = {Laser Laboratory for Fast Reactions in Biology,
10496 Department of Biochemistry, The George S. Wise Faculty
10497 for Life Sciences, Tel Aviv University, Israel.},
10501 pages = {768--781},
10502 issn = {0006-3495},
10503 doi = {10.1529/biophysj.105.058917},
10504 url = {http://www.ncbi.nlm.nih.gov/pubmed/15894639},
10506 keywords = {Amino Acids},
10507 keywords = {Binding Sites},
10508 keywords = {Chlorine},
10509 keywords = {Computer Simulation},
10511 keywords = {Models, Chemical},
10512 keywords = {Models, Molecular},
10513 keywords = {Motion},
10514 keywords = {Protein Binding},
10515 keywords = {Protein Conformation},
10516 keywords = {Ribosomal Protein S6},
10517 keywords = {Sodium},
10518 keywords = {Solutions},
10519 keywords = {Static Electricity},
10520 keywords = {Surface Properties},
10521 keywords = {Water},
10522 abstract = {Time-resolved measurements indicated that protons could
10523 propagate on the surface of a protein or a membrane by a special
10524 mechanism that enhanced the shuttle of the proton toward a
10525 specific site. It was proposed that a suitable location of
10526 residues on the surface contributes to the proton shuttling
10527 function. In this study, this notion was further investigated by
10528 the use of molecular dynamics simulations, where Na(+) and Cl(-)
10529 are the ions under study, thus avoiding the necessity for quantum
10530 mechanical calculations. Molecular dynamics simulations were
10531 carried out using as a model a few Na(+) and Cl(-) ions enclosed
10532 in a fully hydrated simulation box with a small globular protein
10533 (the S6 of the bacterial ribosome). Three independent 10-ns-long
10534 simulations indicated that the ions and the protein's surface were
10535 in equilibrium, with rapid passage of the ions between the
10536 protein's surface and the bulk. However, it was noted that close
10537 to some domains the ions extended their duration near the surface,
10538 thus suggesting that the local electrostatic potential hindered
10539 their diffusion to the bulk. During the time frame in which the
10540 ions were detained next to the surface, they could rapidly shuttle
10541 between various attractor sites located under the electrostatic
10542 umbrella. Statistical analysis of the molecular dynamics and
10543 electrostatic potential/entropy consideration indicated that the
10544 detainment state is an energetic compromise between attractive
10545 forces and entropy of dilution. The similarity between the motion
10546 of free ions next to a protein and the proton transfer on the
10547 protein's surface are discussed.},
10550 @article{ friedman11,
10551 author = RFriedman,
10552 title = {Ions and the protein surface revisited: extensive molecular
10553 dynamics simulations and analysis of protein structures in
10554 alkali-chloride solutions.},
10558 address = {School of Natural Sciences, Linn{\ae}us University,
10559 391 82 Kalmar, Sweden. ran.friedman@lnu.se},
10563 pages = {9213--9223},
10564 issn = {1520-5207},
10565 doi = {10.1021/jp112155m},
10566 URL = {http://www.ncbi.nlm.nih.gov/pubmed/21688775},
10568 keywords = {Alkalies},
10569 keywords = {Amyloid},
10570 keywords = {Chlorides},
10571 keywords = {Databases, Protein},
10572 keywords = {Fungal Proteins},
10573 keywords = {HIV Protease},
10574 keywords = {Humans},
10575 keywords = {Molecular Dynamics Simulation},
10576 keywords = {Protein Multimerization},
10577 keywords = {Protein Structure, Secondary},
10578 keywords = {Proteins},
10579 keywords = {Ribosomal Protein S6},
10580 keywords = {Solutions},
10581 keywords = {Solvents},
10582 keywords = {Surface Properties},
10583 abstract = {Proteins interact with ions in various ways. The surface
10584 of proteins has an innate capability to bind ions, and it is also
10585 influenced by the screening of the electrostatic potential owing
10586 to the presence of salts in the bulk solution. Alkali metal ions
10587 and chlorides interact with the protein surface, but such
10588 interactions are relatively weak and often transient. In this
10589 paper, computer simulations and analysis of protein structures are
10590 used to characterize the interactions between ions and the protein
10591 surface. The results show that the ion-binding properties of
10592 protein residues are highly variable. For example, alkali metal
10593 ions are more often associated with aspartate residues than with
10594 glutamates, whereas chlorides are most likely to be located near
10595 arginines. When comparing NaCl and KCl solutions, it was found
10596 that certain surface residues attract the anion more strongly in
10597 NaCl. This study demonstrates that protein-salt interactions
10598 should be accounted for in the planning and execution of
10599 experiments and simulations involving proteins, particularly if
10600 subtle structural details are sought after.},
10604 author = YZhang #" and "# PSCremer,
10605 title = {Interactions between macromolecules and ions: The
10606 {H}ofmeister series.},
10610 address = {Department of Chemistry, Texas A\&M University,
10611 College Station, TX 77843, USA.},
10615 pages = {658--663},
10616 issn = {1367-5931},
10617 doi = {10.1016/j.cbpa.2006.09.020},
10618 url = {http://www.ncbi.nlm.nih.gov/pubmed/17035073},
10620 keywords = {Acrylamides},
10621 keywords = {Biopolymers},
10622 keywords = {Solubility},
10623 keywords = {Thermodynamics},
10624 keywords = {Water},
10625 abstract = {The Hofmeister series, first noted in 1888, ranks the
10626 relative influence of ions on the physical behavior of a wide
10627 variety of aqueous processes ranging from colloidal assembly to
10628 protein folding. Originally, it was thought that an ion's
10629 influence on macromolecular properties was caused at least in part
10630 by `making' or `breaking' bulk water structure. Recent
10631 time-resolved and thermodynamic studies of water molecules in salt
10632 solutions, however, demonstrate that bulk water structure is not
10633 central to the Hofmeister effect. Instead, models are being
10634 developed that depend upon direct ion-macromolecule interactions
10635 as well as interactions with water molecules in the first
10636 hydration shell of the macromolecule.},
10637 note = {A quick pass through Hofmeister history, but no discussion
10638 of cations (``A complete picture will inevitably involve an
10639 integrated understanding of the role of cations (including
10640 guanidinium ions) and osmolytes (such as urea and tri-methylamine
10641 N-oxide) as well. There has been some progress in these fields,
10642 although such subjects are generally beyond the scope of this
10643 short review.'').},
10646 @article{ isaacs06,
10647 author = AMIsaacs #" and "# DBSenn #" and "# MYuan #" and "#
10648 JPShine #" and "# BAYankner,
10649 title = {Acceleration of amyloid beta-peptide aggregation by
10650 physiological concentrations of calcium.},
10654 address = {Department of Neurology and Division of Neuroscience,
10655 The Children's Hospital, Harvard Medical School,
10656 Boston, Massachusetts 02115, USA.},
10660 pages = {27916--27923},
10661 issn = {0021-9258},
10662 doi = {10.1074/jbc.M602061200},
10663 url = {http://www.ncbi.nlm.nih.gov/pubmed/16870617},
10665 keywords = {Alzheimer Disease},
10666 keywords = {Amyloid},
10667 keywords = {Amyloid beta-Peptides},
10668 keywords = {Animals},
10669 keywords = {Calcium},
10670 keywords = {Cells, Cultured},
10671 keywords = {Copper},
10672 keywords = {Neurons},
10675 abstract = {Alzheimer disease is characterized by the accumulation
10676 of aggregated amyloid beta-peptide (Abeta) in the brain. The
10677 physiological mechanisms and factors that predispose to Abeta
10678 aggregation and deposition are not well understood. In this
10679 report, we show that calcium can predispose to Abeta aggregation
10680 and fibril formation. Calcium increased the aggregation of early
10681 forming protofibrillar structures and markedly increased
10682 conversion of protofibrils to mature amyloid fibrils. This
10683 occurred at levels 20-fold below the calcium concentration in the
10684 extracellular space of the brain, the site at which amyloid plaque
10685 deposition occurs. In the absence of calcium, protofibrils can
10686 remain stable in vitro for several days. Using this approach, we
10687 directly compared the neurotoxicity of protofibrils and mature
10688 amyloid fibrils and demonstrate that both species are inherently
10689 toxic to neurons in culture. Thus, calcium may be an important
10690 predisposing factor for Abeta aggregation and toxicity. The high
10691 extracellular concentration of calcium in the brain, together with
10692 impaired intraneuronal calcium regulation in the aging brain and
10693 Alzheimer disease, may play an important role in the onset of
10694 amyloid-related pathology.},
10695 note = {Physiological levels of \NaCl\ are $\sim 150\U{mM}$. \Ca\
10696 is $\sim 2\U{mM}$.},
10700 author = AItkin #" and "# VDupres #" and "# YFDufrene #" and "#
10701 BBechinger #" and "# JMRuysschaert #" and "# VRaussens,
10702 title = {Calcium ions promote formation of amyloid $\beta$-peptide
10703 (1-40) oligomers causally implicated in neuronal toxicity of
10704 {A}lzheimer's disease.},
10708 address = {Laboratory of Structure and Function of Biological
10709 Membranes, Center for Structural Biology and
10710 Bioinformatics, Universit{\'e} Libre de Bruxelles,
10711 Brussels, Belgium.},
10712 journal = PLOS:ONE,
10716 keywords = {Alzheimer Disease},
10717 keywords = {Amyloid beta-Peptides},
10718 keywords = {Blotting, Western},
10719 keywords = {Calcium},
10720 keywords = {Fluorescence},
10721 keywords = {Humans},
10723 keywords = {Models, Biological},
10724 keywords = {Mutant Proteins},
10725 keywords = {Neurons},
10726 keywords = {Protein Structure, Quaternary},
10727 keywords = {Protein Structure, Secondary},
10728 keywords = {Spectroscopy, Fourier Transform Infrared},
10729 keywords = {Thiazoles},
10730 ISSN = {1932-6203},
10731 doi = {10.1371/journal.pone.0018250},
10732 URL = {http://www.ncbi.nlm.nih.gov/pubmed/21464905},
10734 abstract = {Amyloid $\beta$-peptide (A$\beta$) is directly linked to
10735 Alzheimer's disease (AD). In its monomeric form, A$\beta$
10736 aggregates to produce fibrils and a range of oligomers, the latter
10737 being the most neurotoxic. Dysregulation of Ca(2+) homeostasis in
10738 aging brains and in neurodegenerative disorders plays a crucial
10739 role in numerous processes and contributes to cell dysfunction and
10740 death. Here we postulated that calcium may enable or accelerate
10741 the aggregation of A$\beta$. We compared the aggregation pattern
10742 of A$\beta$(1-40) and that of A$\beta$(1-40)E22G, an amyloid
10743 peptide carrying the Arctic mutation that causes early onset of
10744 the disease. We found that in the presence of Ca(2+),
10745 A$\beta$(1-40) preferentially formed oligomers similar to those
10746 formed by A$\beta$(1-40)E22G with or without added Ca(2+), whereas
10747 in the absence of added Ca(2+) the A$\beta$(1-40) aggregated to
10748 form fibrils. Morphological similarities of the oligomers were
10749 confirmed by contact mode atomic force microscopy imaging. The
10750 distribution of oligomeric and fibrillar species in different
10751 samples was detected by gel electrophoresis and Western blot
10752 analysis, the results of which were further supported by
10753 thioflavin T fluorescence experiments. In the samples without
10754 Ca(2+), Fourier transform infrared spectroscopy revealed
10755 conversion of oligomers from an anti-parallel $\beta$-sheet to the
10756 parallel $\beta$-sheet conformation characteristic of
10757 fibrils. Overall, these results led us to conclude that calcium
10758 ions stimulate the formation of oligomers of A$\beta$(1-40), that
10759 have been implicated in the pathogenesis of AD.},
10760 note = {$2\U{mM}$ of \Ca\ is the \emph{extracellular} concentration.
10761 Cytosol concetrations are in the $\mu$M range.},
10765 author = JZidar #" and "# FMerzel,
10766 title = {Probing amyloid-beta fibril stability by increasing ionic
10771 address = {National Institute of Chemistry, Hajdrihova 19,
10772 SI-1000 Ljubljana, Slovenia.},
10776 pages = {2075--2081},
10777 issn = {1520-5207},
10778 doi = {10.1021/jp109025b},
10779 URL = {http://www.ncbi.nlm.nih.gov/pubmed/21329333},
10781 keywords = {Amyloid beta-Peptides},
10782 keywords = {Entropy},
10783 keywords = {Hydrogen Bonding},
10784 keywords = {Molecular Dynamics Simulation},
10785 keywords = {Osmolar Concentration},
10786 keywords = {Protein Multimerization},
10787 keywords = {Protein Stability},
10788 keywords = {Protein Structure, Secondary},
10789 keywords = {Solvents},
10790 keywords = {Vibration},
10791 abstract = {Previous experimental studies have demonstrated changing
10792 the ionic strength of the solvent to have a great impact on the
10793 mechanism of aggregation of amyloid-beta (A$\beta$) protein
10794 leading to distinct fibril morphology at high and low ionic
10795 strength. Here, we use molecular dynamics simulations to elucidate
10796 the ionic strength-dependent effects on the structure and dynamics
10797 of the model A$\beta$ fibril. The change in ionic strength was
10798 brought forth by varying the NaCl concentration in the environment
10799 surrounding the A$\beta$ fibril. Comparison of the calculated
10800 vibrational spectra of A$\beta$ derived from 40 ns all-atom
10801 molecular dynamics simulations at different ionic strength reveals
10802 the fibril structure to be stiffer with increasing ionic
10803 strength. This finding is further corroborated by the calculation
10804 of the stretching force constants. Decomposition of binding and
10805 dynamical properties into contributions from different structural
10806 segments indicates the elongation of the fibril at low ionic
10807 strength is most likely promoted by hydrogen bonding between
10808 N-terminal parts of the fibril, whereas aggregation at higher
10809 ionic strength is suggested to be driven by the hydrophobic
10811 note = {Only study \NaCl\ over the range to $308\U{mM}$, but show a
10812 general decreased hydrogen bonding as concentration increases.},
10816 author = LMiao #" and "# HQin #" and "# PKoehl #" and "# JSong,
10817 title = {Selective and specific ion binding on proteins at
10818 physiologically-relevant concentrations.},
10822 address = {Department of Biological Sciences, Faculty of Science,
10823 National University of Singapore, Singapore.},
10827 pages = {3126--3132},
10828 issn = {1873-3468},
10829 doi = {10.1016/j.febslet.2011.08.048},
10830 url = {http://www.ncbi.nlm.nih.gov/pubmed/21907714},
10832 keywords = {Amino Acid Sequence},
10833 keywords = {Ephrin-B2},
10835 keywords = {Models, Molecular},
10836 keywords = {Molecular Sequence Data},
10837 keywords = {Nuclear Magnetic Resonance, Biomolecular},
10838 keywords = {Protein Binding},
10839 keywords = {Protein Folding},
10840 keywords = {Protein Structure, Tertiary},
10841 keywords = {Salts},
10842 keywords = {Solutions},
10843 keywords = {Thermodynamics},
10844 keywords = {Water},
10845 abstract = {Insoluble proteins dissolved in unsalted water appear to
10846 have no well-folded tertiary structures. This raises a fundamental
10847 question as to whether being unstructured is due to the absence of
10848 salt ions. To address this issue, we solubilized the insoluble
10849 ephrin-B2 cytoplasmic domain in unsalted water and first confirmed
10850 using NMR spectroscopy that it is only partially folded. Using NMR
10851 HSQC titrations with 14 different salts, we further demonstrate
10852 that the addition of salt triggers no significant folding of the
10853 protein within physiologically relevant ion concentrations. We
10854 reveal however that their 8 anions bind to the ephrin-B2 protein
10855 with high affinity and specificity at biologically-relevant
10856 concentrations. Interestingly, the binding is found to be both
10857 salt- and residue-specific.},
10858 note = {They suggest that for low concentrations ($<100\U{mM}$),
10859 protein-ion interactions are mostly electrostatic. The Hofmeister
10860 effects only kick in at higher consentrations.},
10864 author = HJDyson #" and "# PEWright,
10865 title = {Intrinsically unstructured proteins and their functions.},
10869 address = {Department of Molecular Biology and Skaggs Institute
10870 for Chemical Biology, The Scripps Research Institute,
10871 10550 North Torrey Pines Road, La Jolla, California
10872 92037, USA. dyson@scripps.edu},
10875 pages = {197--208},
10876 issn = {1471-0072},
10877 doi = {10.1038/nrm1589},
10878 url = {http://www.ncbi.nlm.nih.gov/pubmed/15738986},
10880 keywords = {CREB-Binding Protein},
10881 keywords = {Humans},
10882 keywords = {Nuclear Proteins},
10883 keywords = {Nucleic Acids},
10884 keywords = {Protein Binding},
10885 keywords = {Protein Processing, Post-Translational},
10886 keywords = {Protein Structure, Tertiary},
10887 keywords = {Proteins},
10888 keywords = {Trans-Activators},
10889 keywords = {Tumor Suppressor Protein p53},
10890 abstract = {Many gene sequences in eukaryotic genomes encode entire
10891 proteins or large segments of proteins that lack a well-structured
10892 three-dimensional fold. Disordered regions can be highly conserved
10893 between species in both composition and sequence and, contrary to
10894 the traditional view that protein function equates with a stable
10895 three-dimensional structure, disordered regions are often
10896 functional, in ways that we are only beginning to discover. Many
10897 disordered segments fold on binding to their biological targets
10898 (coupled folding and binding), whereas others constitute flexible
10899 linkers that have a role in the assembly of macromolecular
10903 @article{ cleland64,
10904 author = WWCleland,
10905 title = {Dithiothreitol, a New Protective Reagent for SH Groups},
10911 pages = {480--482},
10912 keywords = {Alcohols},
10913 keywords = {Chromatography},
10914 keywords = {Coenzyme A},
10915 keywords = {Oxidation-Reduction},
10916 keywords = {Research},
10917 keywords = {Sulfhydryl Compounds},
10918 keywords = {Sulfides},
10919 keywords = {Ultraviolet Rays},
10920 issn = {0006-2960},
10921 doi = {10.1021/bi00892a002},
10922 url = {http://www.ncbi.nlm.nih.gov/pubmed/14192894},
10923 eprint = {http://pubs.acs.org/doi/pdf/10.1021/bi00892a002},