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"
2148 author = YCao #" and "# MBalamurali #" and "# DSharma #" and "# HLi,
2149 title = "A functional single-molecule binding assay via force spectroscopy",
2154 pages = "15677--15681",
2155 doi = "10.1073/pnas.0705367104",
2156 eprint = "http://www.pnas.org/cgi/reprint/104/40/15677.pdf",
2157 url = "http://www.pnas.org/cgi/content/abstract/104/40/15677",
2158 abstract = "Protein-ligand interactions, including protein-protein
2159 interactions, are ubiquitously essential in biological processes and
2160 also have important applications in biotechnology. A wide range of
2161 methodologies have been developed for quantitative analysis of protein-
2162 ligand interactions. However, most of them do not report direct
2163 functional/structural consequence of ligand binding. Instead they only
2164 detect the change of physical properties, such as fluorescence and
2165 refractive index, because of the colocalization of protein and ligand,
2166 and are susceptible to false positives. Thus, important information
2167 about the functional state of proteinligand complexes cannot be
2168 obtained directly. Here we report a functional single-molecule binding
2169 assay that uses force spectroscopy to directly probe the functional
2170 consequence of ligand binding and report the functional state of
2171 protein-ligand complexes. As a proof of principle, we used protein G
2172 and the Fc fragment of IgG as a model system in this study. Binding of
2173 Fc to protein G does not induce major structural changes in protein G
2174 but results in significant enhancement of its mechanical stability.
2175 Using mechanical stability of protein G as an intrinsic functional
2176 reporter, we directly distinguished and quantified Fc-bound and Fc-free
2177 forms of protein G on a single-molecule basis and accurately determined
2178 their dissociation constant. This single-molecule functional binding
2179 assay is label-free, nearly background-free, and can detect functional
2180 heterogeneity, if any, among proteinligand interactions. This
2181 methodology opens up avenues for studying protein-ligand interactions
2182 in a functional context, and we anticipate that it will find broad
2183 application in diverse protein-ligand systems."
2187 author = PCarl #" and "# CKwok #" and "# GManderson #" and "# DSpeicher #"
2189 title = "Forced unfolding modulated by disulfide bonds in the Ig domains of
2190 a cell adhesion molecule",
2195 pages = "1565--1570",
2196 doi = "10.1073/pnas.031409698",
2197 eprint = "http://www.pnas.org/cgi/reprint/98/4/1565.pdf",
2198 url = "http://www.pnas.org/cgi/content/abstract/98/4/1565",
2202 @article { carrion-vazquez00,
2203 author = MCarrionVazquez #" and "# AOberhauser #" and "# TEFisher #" and "#
2204 PMarszalek #" and "# HLi #" and "# JFernandez,
2205 title = "Mechanical design of proteins studied by single-molecule force
2206 spectroscopy and protein engineering",
2212 doi = "10.1016/S0079-6107(00)00017-1",
2214 eprint = "http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1302160&blo
2216 url = "http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1302160",
2217 keywords = "Elasticity;Hydrogen Bonding;Microscopy, Atomic Force;Protein
2218 Denaturation;Protein Engineering;Protein Folding;Recombinant
2219 Proteins;Signal Processing, Computer-Assisted",
2220 abstract = "Mechanical unfolding and refolding may regulate the molecular
2221 elasticity of modular proteins with mechanical functions. The
2222 development of the atomic force microscopy (AFM) has recently enabled
2223 the dynamic measurement of these processes at the single-molecule
2224 level. Protein engineering techniques allow the construction of
2225 homomeric polyproteins for the precise analysis of the mechanical
2226 unfolding of single domains. alpha-Helical domains are mechanically
2227 compliant, whereas beta-sandwich domains, particularly those that
2228 resist unfolding with backbone hydrogen bonds between strands
2229 perpendicular to the applied force, are more stable and appear
2230 frequently in proteins subject to mechanical forces. The mechanical
2231 stability of a domain seems to be determined by its hydrogen bonding
2232 pattern and is correlated with its kinetic stability rather than its
2233 thermodynamic stability. Force spectroscopy using AFM promises to
2234 elucidate the dynamic mechanical properties of a wide variety of
2235 proteins at the single molecule level and provide an important
2236 complement to other structural and dynamic techniques (e.g., X-ray
2237 crystallography, NMR spectroscopy, patch-clamp).",
2238 note = {Surface contact \fref{figure}{2} is a modified version of
2239 \xref{baljon96}{figure}{1}. They are both good pictures for
2240 explaining that the tip's radius of curvature ($\sim 20\U{nm}$) is
2241 larger than the I27 domains\citet{improta96} ($\sim 2\U{nm}$).},
2244 @article { carrion-vazquez03,
2245 author = MCarrionVazquez #" and "# HLi #" and "# HLu #" and "# PMarszalek
2246 #" and "# AOberhauser #" and "# JFernandez,
2247 title = "The mechanical stability of ubiquitin is linkage dependent",
2256 doi = "10.1038/nsb965",
2257 eprint = "http://www.nature.com/nsmb/journal/v10/n9/pdf/nsb965.pdf",
2258 url = "http://www.nature.com/nsmb/journal/v10/n9/abs/nsb965.html",
2259 keywords = "Humans;Hydrogen Bonding;Kinetics;Lysine;Microscopy, Atomic
2260 Force;Models, Molecular;Polyubiquitin;Protein Binding;Protein
2261 Folding;Protein Structure, Tertiary;Ubiquitin",
2262 abstract = "Ubiquitin chains are formed through the action of a set of
2263 enzymes that covalently link ubiquitin either through peptide bonds or
2264 through isopeptide bonds between their C terminus and any of four
2265 lysine residues. These naturally occurring polyproteins allow one to
2266 study the mechanical stability of a protein, when force is applied
2267 through different linkages. Here we used single-molecule force
2268 spectroscopy techniques to examine the mechanical stability of
2269 N-C-linked and Lys48-C-linked ubiquitin chains. We combined these
2270 experiments with steered molecular dynamics (SMD) simulations and found
2271 that the mechanical stability and unfolding pathway of ubiquitin
2272 strongly depend on the linkage through which the mechanical force is
2273 applied to the protein. Hence, a protein that is otherwise very stable
2274 may be easily unfolded by a relatively weak mechanical force applied
2275 through the right linkage. This may be a widespread mechanism in
2276 biological systems."
2279 @article { carrion-vazquez99a,
2280 author = MCarrionVazquez #" and "# PMarszalek #" and "# AOberhauser #" and
2282 title = "Atomic force microscopy captures length phenotypes in single
2288 pages = "11288--11292",
2289 doi = "10.1073/pnas.96.20.11288",
2290 eprint = "http://www.pnas.org/cgi/reprint/96/20/11288.pdf",
2291 url = "http://www.pnas.org/cgi/content/abstract/96/20/11288",
2295 @article { carrion-vazquez99b,
2296 author = MCarrionVazquez #" and "# AOberhauser #" and "# SFowler #" and "#
2297 PMarszalek #" and "# SBroedel #" and "# JClarke #" and "# JFernandez,
2298 title = "Mechanical and chemical unfolding of a single protein: A
2304 pages = "3694--3699",
2305 doi = "10.1073/pnas.96.7.3694",
2306 eprint = "http://www.pnas.org/cgi/reprint/96/7/3694.pdf",
2307 url = "http://www.pnas.org/cgi/content/abstract/96/7/3694"
2311 author = CLChyan #" and "# FCLin #" and "# HPeng #" and "# JMYuan #" and "#
2312 CHChang #" and "# SHLin #" and "# GYang,
2313 title = "Reversible mechanical unfolding of single ubiquitin molecules",
2317 address = "Department of Chemistry, National Dong Hwa University,
2322 pages = "3995--4006",
2324 doi = "10.1529/biophysj.104.042754",
2325 eprint = "http://download.cell.com/biophysj/pdf/PIIS0006349504738643.pdf",
2326 url = "http://www.cell.com/biophysj/abstract/S0006-3495(04)73864-3",
2328 keywords = "Computer
2329 Simulation;Elasticity;Mechanics;Micromanipulation;Microscopy, Atomic
2330 Force;Models, Chemical;Models, Molecular;Protein Conformation;Protein
2331 Denaturation;Protein Folding;Stress, Mechanical;Structure-Activity
2332 Relationship;Ubiquitin",
2333 abstract = "Single-molecule manipulation techniques have enabled the
2334 characterization of the unfolding and refolding process of individual
2335 protein molecules, using mechanical forces to initiate the unfolding
2336 transition. Experimental and computational results following this
2337 approach have shed new light on the mechanisms of the mechanical
2338 functions of proteins involved in several cellular processes, as well
2339 as revealed new information on the protein folding/unfolding free-
2340 energy landscapes. To investigate how protein molecules of different
2341 folds respond to a stretching force, and to elucidate the effects of
2342 solution conditions on the mechanical stability of a protein, we
2343 synthesized polymers of the protein ubiquitin and characterized the
2344 force-induced unfolding and refolding of individual ubiquitin molecules
2345 using an atomic-force-microscope-based single-molecule manipulation
2346 technique. The ubiquitin molecule was highly resistant to a stretching
2347 force, and the mechanical unfolding process was reversible. A model
2348 calculation based on the hydrogen-bonding pattern in the native
2349 structure was performed to explain the origin of this high mechanical
2350 stability. Furthermore, pH effects were studied and it was found that
2351 the forces required to unfold the protein remained constant within a pH
2352 range around the neutral value, and forces decreased as the solution pH
2353 was lowered to more acidic values.",
2354 note = "includes pH effects",
2357 @article { ciccotti86,
2358 author = GCiccotti #" and "# JPRyckaert,
2359 title = "Molecular dynamics simulation of rigid molecules",
2366 doi = "10.1016/0167-7977(86)90022-5",
2367 url = "http://dx.doi.org/10.1016/0167-7977(86)90022-5",
2368 note = "I haven't read this, but it looks like a nice review of MD with
2372 @article { claverie01,
2373 author = JMClaverie,
2374 title = "Gene number. What if there are only 30,000 human genes?",
2381 pages = "1255--1257",
2383 url = "http://www.sciencemag.org/cgi/content/full/291/5507/1255",
2384 keywords = "Animals;Computational Biology;Drug Industry;Expressed Sequence
2385 Tags;Gene Expression;Gene Expression Regulation;Genes;Genetic
2386 Techniques;Genome, Human;Genomics;Human Genome Project;Humans;Models,
2387 Genetic;Polymorphism, Single Nucleotide;Proteins;RNA, Messenger"
2390 @misc { codata-boltzmann,
2391 key = "codata-boltzmann",
2392 crossref = "codata06",
2393 url = "http://physics.nist.gov/cgi-bin/cuu/Value?k"
2396 @article { codata06,
2397 author = PJMohr #" and "# BNTaylor #" and "# DBNewell,
2399 title = "{CODATA} recommended values of the fundamental physical constants:
2409 doi = "10.1103/RevModPhys.80.633"
2412 @article { collins03,
2413 author = FSCollins #" and "# MMorgan #" and "# APatrinos,
2414 title = "The Human Genome Project: Lessons from large-scale biology.",
2423 doi = "10.1126/science.1084564",
2424 eprint = "http://www.sciencemag.org/cgi/reprint/300/5617/286.pdf",
2425 url = "http://www.sciencemag.org/cgi/content/summary/300/5617/277",
2426 keywords = "Access to Information;Computational Biology;Databases, Nucleic
2427 Acid;Genome, Human;Genomics;Government Agencies;History, 20th
2428 Century;Human Genome Project;Humans;International Cooperation;National
2429 Institutes of Health (U.S.);Private Sector;Public Policy;Public
2430 Sector;Publishing;Quality Control;Sequence Analysis, DNA;United States",
2431 note = "See also: \href{http://www.ornl.gov/sci/techresources/Human_Genome/
2432 project/journals/journals.shtml}{Landmark HPG Papers}"
2435 @article { cornish07,
2436 author = PVCornish #" and "# THa,
2437 title = "A survey of single-molecule techniques in chemical biology",
2441 journal = ACS:ChemBiol,
2446 doi = "10.1021/cb600342a",
2447 keywords = "Animals;Data Collection;Humans;Microscopy, Atomic
2448 Force;Microscopy, Fluorescence;Molecular Biology",
2449 abstract = "Single-molecule methods have revolutionized scientific research
2450 by rendering the investigation of once-inaccessible biological
2451 processes amenable to scientific inquiry. Several of the more
2452 established techniques will be emphasized in this Review, including
2453 single-molecule fluorescence microscopy, optical tweezers, and atomic
2454 force microscopy, which have been applied to many diverse biological
2455 processes. Serving as a taste of all the exciting research currently
2456 underway, recent examples will be discussed of translocation of RNA
2457 polymerase, myosin VI walking, protein folding, and enzyme activity. We
2458 will end by providing an assessment of what the future holds, including
2459 techniques that are currently in development."
2464 title = "Statistical Data Analysis",
2467 address = "New York",
2468 note = "Noise deconvolution in Chapter 11",
2469 project = "Cantilever Calibration"
2473 author = DCraig #" and "# AKrammer #" and "# KSchulten #" and "# VVogel,
2474 title = "Comparison of the early stages of forced unfolding for fibronectin
2475 type {III} modules",
2480 pages = "5590--5595",
2481 doi = "10.1073/pnas.101582198",
2482 eprint = "http://www.pnas.org/cgi/reprint/98/10/5590.pdf",
2483 url = "http://www.pnas.org/cgi/content/abstract/98/10/5590",
2487 @article { delpech01,
2488 author = BDelpech #" and "# MNCourel #" and "# CMaingonnat #" and "#
2489 CChauzy #" and "# RSesboue #" and "# GPratesi,
2490 title = "Hyaluronan digestion and synthesis in an experimental model of
2493 month = "September/October",
2494 journal = HistochemJ,
2499 keywords = "Animals;Culture Media;Humans;Hyaluronic
2500 Acid;Hyaluronoglucosaminidase;Mice;Mice, Nude;Neoplasm
2501 Metastasis;Neoplasm Transplantation;Neoplasms, Experimental;Tumor
2503 abstract = "To approach the question of hyaluronan catabolism in tumours,
2504 we have selected the cancer cell line H460M, a highly metastatic cell
2505 line in the nude mouse. H460M cells release hyaluronidase in culture
2506 media at a high rate of 57 pU/cell/h, without producing hyaluronan.
2507 Hyaluronidase was measured in the H460M cell culture medium at the
2508 optimum pH 3.8, and was not found above pH 4.5, with the enzyme-linked
2509 sorbent assay technique and zymography. Tritiated hyaluronan was
2510 digested at pH 3.8 by cells or cell membranes as shown by gel
2511 permeation chromatography, but no activity was recorded at pH 7 with
2512 this technique. Hyaluronan was digested in culture medium by tumour
2513 slices, prepared from tumours developed in nude mice grafted with H460M
2514 cells, showing that hyaluronan could be digested in complex tissue at
2515 physiological pH. Culture of tumour slices with tritiated acetate
2516 resulted in the accumulation within 2 days of radioactive
2517 macromolecules in the culture medium. The radioactive macromolecular
2518 material was mostly digested by Streptomyces hyaluronidase, showing
2519 that hyaluronan was its main component and that hyaluronan synthesis
2520 occurred together with its digestion. These results demonstrate that
2521 the membrane-associated hyaluronidase of H460M cells can act in vivo,
2522 and that hyaluronan, which is synthesised by the tumour stroma, can be
2523 made soluble and reduced to a smaller size by tumour cells before being
2524 internalised and further digested."
2527 @article { diCola05,
2528 author = EDCola #" and "# TAWaigh #" and "# JTrinick #" and "#
2529 LTskhovrebova #" and "# AHoumeida #" and "# WPyckhout-Hintzen #" and "#
2532 title = "Persistence length of titin from rabbit skeletal muscles measured
2533 with scattering and microrheology techniques",
2540 pages = "4095--4106",
2542 doi = "10.1529/biophysj.104.054908",
2543 eprint = "http://download.cell.com/biophysj/pdf/PIIS0006349505734603.pdf",
2544 url = "http://www.cell.com/biophysj/retrieve/pii/S0006349505734603",
2545 keywords = "Animals;Biophysics;Elasticity;Light;Muscle Proteins;Muscle,
2546 Skeletal;Neutrons;Protein Conformation;Protein
2547 Kinases;Rabbits;Rheology;Scattering, Radiation;Temperature",
2548 abstract = "The persistence length of titin from rabbit skeletal muscles
2549 was measured using a combination of static and dynamic light
2550 scattering, and neutron small angle scattering. Values of persistence
2551 length in the range 9-16 nm were found for titin-II, which corresponds
2552 to mainly physiologically inelastic A-band part of the protein, and for
2553 a proteolytic fragment with 100-nm contour length from the
2554 physiologically elastic I-band part. The ratio of the hydrodynamic
2555 radius to the static radius of gyration indicates that the proteins
2556 obey Gaussian statistics typical of a flexible polymer in a -solvent.
2557 Furthermore, measurements of the flexibility as a function of
2558 temperature demonstrate that titin-II and the I-band titin fragment
2559 experience a similar denaturation process; unfolding begins at 318 K
2560 and proceeds in two stages: an initial gradual 50\% change in
2561 persistence length is followed by a sharp unwinding transition at 338
2562 K. Complementary microrheology (video particle tracking) measurements
2563 indicate that the viscoelasticity in dilute solution behaves according
2564 to the Flory/Fox model, providing a value of the radius of gyration for
2565 titin-II (63 +/- 1 nm) in agreement with static light scattering and
2566 small angle neutron scattering results."
2570 author = HDietz #" and "# MRief,
2571 title = "Exploring the energy landscape of {GFP} by single-molecule
2572 mechanical experiments",
2577 pages = "16192--16197",
2578 doi = "10.1073/pnas.0404549101",
2579 eprint = "http://www.pnas.org/cgi/reprint/101/46/16192.pdf",
2580 url = "http://www.pnas.org/cgi/content/abstract/101/46/16192",
2581 abstract = "We use single-molecule force spectroscopy to drive
2582 single GFP molecules from the native state through their
2583 complex energy landscape into the completely unfolded
2584 state. Unlike many smaller proteins, mechanical GFP unfolding
2585 proceeds by means of two subsequent intermediate states. The
2586 transition from the native state to the first intermediate
2587 state occurs near thermal equilibrium at $\approx35\U{pN}$ and
2588 is characterized by detachment of a seven-residue N-terminal
2589 $\alpha$-helix from the beta barrel. We measure the
2590 equilibrium free energy cost associated with this transition
2591 as 22 kBT. Detachment of this small $\alpha$-helix completely
2592 destabilizes GFP thermodynamically even though the
2593 $\beta$-barrel is still intact and can bear load. Mechanical
2594 stability of the protein on the millisecond timescale,
2595 however, is determined by the activation barrier of unfolding
2596 the $\beta$-barrel out of this thermodynamically unstable
2597 intermediate state. High bandwidth, time-resolved measurements
2598 of the cantilever relaxation phase upon unfolding of the
2599 $\beta$-barrel revealed a second metastable mechanical
2600 intermediate with one complete $\beta$-strand detached from
2601 the barrel. Quantitative analysis of force distributions and
2602 lifetimes lead to a detailed picture of the complex mechanical
2603 unfolding pathway through a rough energy landscape.",
2604 note = "Towards use of Green Flourescent Protein (GFP) as an
2605 embedded force probe. Nice energy-landscape-to-one-dimension
2606 compression graphic.",
2607 project = "Energy landscape roughness"
2610 @article { dietz06a,
2611 author = HDietz #" and "# MRief,
2612 title = "Protein structure by mechanical triangulation",
2619 pages = "1244--1247",
2620 doi = "10.1073/pnas.0509217103",
2621 eprint = "http://www.pnas.org/cgi/reprint/103/5/1244.pdf",
2622 url = "http://www.pnas.org/cgi/content/abstract/103/5/1244",
2623 abstract = "Knowledge of protein structure is essential to understand
2624 protein function. High-resolution protein structure has so far been the
2625 domain of ensemble methods. Here, we develop a simple single-molecule
2626 technique to measure spatial position of selected residues within a
2627 folded and functional protein structure in solution. Construction and
2628 mechanical unfolding of cysteine-engineered polyproteins with
2629 controlled linkage topology allows measuring intramolecular distance
2630 with angstrom precision. We demonstrate the potential of this technique
2631 by determining the position of three residues in the structure of green
2632 fluorescent protein (GFP). Our results perfectly agree with the GFP
2633 crystal structure. Mechanical triangulation can find many applications
2634 where current bulk structural methods fail."
2637 @article { dietz06b,
2638 author = HDietz #" and "# FBerkemeier #" and "# MBertz #" and "# MRief,
2639 title = "Anisotropic deformation response of single protein molecules",
2646 pages = "12724--12728",
2647 doi = "10.1073/pnas.0602995103",
2648 eprint = "http://www.pnas.org/cgi/reprint/103/34/12724.pdf",
2649 url = "http://www.pnas.org/cgi/content/abstract/103/34/12724",
2650 abstract = "Single-molecule methods have given experimental access to the
2651 mechanical properties of single protein molecules. So far, access has
2652 been limited to mostly one spatial direction of force application.
2653 Here, we report single-molecule experiments that explore the mechanical
2654 properties of a folded protein structure in precisely controlled
2655 directions by applying force to selected amino acid pairs. We
2656 investigated the deformation response of GFP in five selected
2657 directions. We found fracture forces widely varying from 100 pN up to
2658 600 pN. We show that straining the GFP structure in one of the five
2659 directions induces partial fracture of the protein into a half-folded
2660 intermediate structure. From potential widths we estimated directional
2661 spring constants of the GFP structure and found values ranging from 1
2662 N/m up to 17 N/m. Our results show that classical continuum mechanics
2663 and simple mechanistic models fail to describe the complex mechanics of
2664 the GFP protein structure and offer insights into the mechanical design
2665 of protein materials."
2669 author = HDietz #" and "# MRief,
2670 title = "Detecting Molecular Fingerprints in Single Molecule Force
2671 Spectroscopy Using Pattern Recognition",
2676 pages = "5540--5542",
2678 doi = "10.1143/JJAP.46.5540",
2679 url = "http://jjap.ipap.jp/link?JJAP/46/5540/",
2680 keywords = "single molecule, protein mechanics, force spectroscopy, AFM,
2681 pattern recognition, GFP",
2682 abstract = "Single molecule force spectroscopy has given experimental
2683 access to the mechanical properties of protein molecules. Typically,
2684 less than 1% of the experimental recordings reflect true single
2685 molecule events due to abundant surface and multiple-molecule
2686 interactions. A key issue in single molecule force spectroscopy is thus
2687 to identify the characteristic mechanical `fingerprint' of a specific
2688 protein in noisy data sets. Here, we present an objective pattern
2689 recognition algorithm that is able to identify fingerprints in such
2691 note = "Automatic force curve selection. Seems a bit shoddy. Details
2695 @article{ berkemeier11,
2696 author = FBerkemeier #" and "# MBertz #" and "# SXiao #" and "#
2697 NPinotsis #" and "# MWilmanns #" and "# FGrater #" and "# MRief,
2698 title = "Fast-folding $\alpha$-helices as reversible strain absorbers
2699 in the muscle protein myomesin.",
2704 address = "Physik Department E22, Technische Universit{\"a}t
2705 M{\"u}nchen, James-Franck-Stra{\ss}e, 85748 Garching, Germany.",
2708 pages = "14139--14144",
2709 keywords = "Biomechanics",
2710 keywords = "Kinetics",
2711 keywords = "Microscopy, Atomic Force",
2712 keywords = "Molecular Dynamics Simulation",
2713 keywords = "Muscle Proteins",
2714 keywords = "Protein Folding",
2715 keywords = "Protein Multimerization",
2716 keywords = "Protein Stability",
2717 keywords = "Protein Structure, Secondary",
2718 keywords = "Protein Structure, Tertiary",
2719 keywords = "Protein Unfolding",
2720 abstract = "The highly oriented filamentous protein network of
2721 muscle constantly experiences significant mechanical load during
2722 muscle operation. The dimeric protein myomesin has been identified
2723 as an important M-band component supporting the mechanical
2724 integrity of the entire sarcomere. Recent structural studies have
2725 revealed a long $\alpha$-helical linker between the C-terminal
2726 immunoglobulin (Ig) domains My12 and My13 of myomesin. In this
2727 paper, we have used single-molecule force spectroscopy in
2728 combination with molecular dynamics simulations to characterize
2729 the mechanics of the myomesin dimer comprising immunoglobulin
2730 domains My12-My13. We find that at forces of approximately 30?pN
2731 the $\alpha$-helical linker reversibly elongates allowing the
2732 molecule to extend by more than the folded extension of a full
2733 domain. High-resolution measurements directly reveal the
2734 equilibrium folding/unfolding kinetics of the individual helix. We
2735 show that $\alpha$-helix unfolding mechanically protects the
2736 molecule homodimerization from dissociation at physiologically
2737 relevant forces. As fast and reversible molecular springs the
2738 myomesin $\alpha$-helical linkers are an essential component for
2739 the structural integrity of the M band.",
2741 doi = "10.1073/pnas.1105734108",
2742 URL = "http://www.ncbi.nlm.nih.gov/pubmed/21825161",
2747 author = KADill #" and "# HSChan,
2748 title = "From Levinthal to pathways to funnels.",
2756 doi = "10.1038/nsb0197-10",
2757 eprint = "http://www.nature.com/nsmb/journal/v4/n1/pdf/nsb0197-10.pdf",
2758 url = "http://www.nature.com/nsmb/journal/v4/n1/abs/nsb0197-10.html",
2759 keywords = "Kinetics;Models, Chemical;Protein Folding",
2760 abstract = "While the classical view of protein folding kinetics relies on
2761 phenomenological models, and regards folding intermediates in a
2762 structural way, the new view emphasizes the ensemble nature of protein
2763 conformations. Although folding has sometimes been regarded as a linear
2764 sequence of events, the new view sees folding as parallel microscopic
2765 multi-pathway diffusion-like processes. While the classical view
2766 invoked pathways to solve the problem of searching for the needle in
2767 the haystack, the pathway idea was then seen as conflicting with
2768 Anfinsen's experiments showing that folding is pathway-independent
2769 (Levinthal's paradox). In contrast, the new view sees no inherent
2770 paradox because it eliminates the pathway idea: folding can funnel to a
2771 single stable state by multiple routes in conformational space. The
2772 general energy landscape picture provides a conceptual framework for
2773 understanding both two-state and multi-state folding kinetics. Better
2774 tests of these ideas will come when new experiments become available
2775 for measuring not just averages of structural observables, but also
2776 correlations among their fluctuations. At that point we hope to learn
2777 much more about the real shapes of protein folding landscapes.",
2778 note = "Pretty folding funnel figures."
2781 @article { discher06,
2782 author = DDischer #" and "# NBhasin #" and "# CJohnson,
2783 title = "Covalent chemistry on distended proteins",
2788 pages = "7533--7534",
2789 doi = "10.1073/pnas.0602388103",
2790 eprint = "http://www.pnas.org/cgi/reprint/103/20/7533.pdf",
2791 url = "http://www.pnas.org/cgi/content/abstract/103/20/7533.pdf"
2795 author = OKDudko #" and "# AEFilippov #" and "# JKlafter #" and "# MUrbakh,
2796 title = "Beyond the conventional description of dynamic force spectroscopy
2804 pages = "11378--11381",
2806 doi = "10.1073/pnas.1534554100",
2807 eprint = "http://www.pnas.org/content/100/20/11378.full.pdf",
2808 url = "http://www.pnas.org/content/100/20/11378.abstract",
2809 keywords = "Spectrum Analysis;Temperature",
2810 abstract = "Dynamic force spectroscopy of single molecules is described by
2811 a model that predicts a distribution of rupture forces, the
2812 corresponding mean rupture force, and variance, which are all amenable
2813 to experimental tests. The distribution has a pronounced asymmetry,
2814 which has recently been observed experimentally. The mean rupture force
2815 follows a (lnV)2/3 dependence on the pulling velocity, V, and differs
2816 from earlier predictions. Interestingly, at low pulling velocities, a
2817 rebinding process is obtained whose signature is an intermittent
2818 behavior of the spring force, which delays the rupture. An extension to
2819 include conformational changes of the adhesion complex is proposed,
2820 which leads to the possibility of bimodal distributions of rupture
2825 author = OKDudko #" and "# GHummer #" and "# ASzabo,
2826 title = "Intrinsic rates and activation free energies from single-molecule
2827 pulling experiments",
2836 doi = "10.1103/PhysRevLett.96.108101",
2837 keywords = "Biophysics;Computer Simulation;Data Interpretation,
2838 Statistical;Kinetics;Micromanipulation;Models, Chemical;Models,
2839 Molecular;Molecular Conformation;Muscle Proteins;Nucleic Acid
2840 Conformation;Protein Binding;Protein Denaturation;Protein
2841 Folding;Protein Kinases;RNA;Stress, Mechanical;Thermodynamics;Time
2843 abstract = "We present a unified framework for extracting kinetic
2844 information from single-molecule pulling experiments at constant force
2845 or constant pulling speed. Our procedure provides estimates of not only
2846 (i) the intrinsic rate coefficient and (ii) the location of the
2847 transition state but also (iii) the free energy of activation. By
2848 analyzing simulated data, we show that the resulting rates of force-
2849 induced rupture are significantly more reliable than those obtained by
2850 the widely used approach based on Bell's formula. We consider the
2851 uniqueness of the extracted kinetic information and suggest guidelines
2852 to avoid over-interpretation of experiments."
2856 author = OKDudko #" and "# JMathe #" and "# ASzabo #" and "# AMeller #" and
2858 title = "Extracting kinetics from single-molecule force spectroscopy:
2859 Nanopore unzipping of {DNA} hairpins",
2866 pages = "4188--4195",
2868 doi = "10.1529/biophysj.106.102855",
2869 eprint = "http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1877759&blo
2871 keywords = "Computer
2872 Simulation;DNA;Elasticity;Mechanics;Micromanipulation;Microscopy,
2873 Atomic Force;Models, Chemical;Models, Molecular;Nanostructures;Nucleic
2874 Acid Conformation;Porosity;Stress, Mechanical",
2875 abstract = "Single-molecule force experiments provide powerful new tools to
2876 explore biomolecular interactions. Here, we describe a systematic
2877 procedure for extracting kinetic information from force-spectroscopy
2878 experiments, and apply it to nanopore unzipping of individual DNA
2879 hairpins. Two types of measurements are considered: unzipping at
2880 constant voltage, and unzipping at constant voltage-ramp speeds. We
2881 perform a global maximum-likelihood analysis of the experimental data
2882 at low-to-intermediate ramp speeds. To validate the theoretical models,
2883 we compare their predictions with two independent sets of data,
2884 collected at high ramp speeds and at constant voltage, by using a
2885 quantitative relation between the two types of measurements.
2886 Microscopic approaches based on Kramers theory of diffusive barrier
2887 crossing allow us to estimate not only intrinsic rates and transition
2888 state locations, as in the widely used phenomenological approach based
2889 on Bell's formula, but also free energies of activation. The problem of
2890 extracting unique and accurate kinetic parameters of a molecular
2891 transition is discussed in light of the apparent success of the
2892 microscopic theories in reproducing the experimental data."
2896 author = OKDudko #" and "# GHummer #" and "# ASzabo,
2897 title = "Theory, analysis, and interpretation of single-molecule
2898 force spectroscopy experiments.",
2903 address = "Department of Physics and Center for Theoretical
2904 Biological Physics, University of California at San Diego, La
2905 Jolla, CA 92093, USA.
2906 dudko@physics.ucsd.edu",
2909 pages = "15755--15760",
2911 keywords = "Half-Life",
2912 keywords = "Kinetics",
2913 keywords = "Microscopy, Atomic Force",
2914 keywords = "Motion",
2915 keywords = "Nucleic Acid Conformation",
2916 keywords = "Nucleic Acid Denaturation",
2917 keywords = "Protein Folding",
2918 keywords = "Thermodynamics",
2919 abstract = "Dynamic force spectroscopy probes the kinetic and
2920 thermodynamic properties of single molecules and molecular
2921 assemblies. Here, we propose a simple procedure to extract kinetic
2922 information from such experiments. The cornerstone of our method
2923 is a transformation of the rupture-force histograms obtained at
2924 different force-loading rates into the force-dependent lifetimes
2925 measurable in constant-force experiments. To interpret the
2926 force-dependent lifetimes, we derive a generalization of Bell's
2927 formula that is formally exact within the framework of Kramers
2928 theory. This result complements the analytical expression for the
2929 lifetime that we derived previously for a class of model
2930 potentials. We illustrate our procedure by analyzing the nanopore
2931 unzipping of DNA hairpins and the unfolding of a protein attached
2932 by flexible linkers to an atomic force microscope. Our procedure
2933 to transform rupture-force histograms into the force-dependent
2934 lifetimes remains valid even when the molecular extension is a
2935 poor reaction coordinate and higher-dimensional free-energy
2936 surfaces must be considered. In this case the microscopic
2937 interpretation of the lifetimes becomes more challenging because
2938 the lifetimes can reveal richer, and even nonmonotonic, dependence
2941 doi = "10.1073/pnas.0806085105",
2942 URL = "http://www.ncbi.nlm.nih.gov/pubmed/18852468",
2948 title = "Probing the relation between force--lifetime--and chemistry in
2949 single molecular bonds",
2955 doi = "10.1146/annurev.biophys.30.1.105",
2956 url = "http://arjournals.annualreviews.org/doi/abs/10.1146%2Fannurev.biophys.30.1.105",
2957 keywords = "Biophysics;Kinetics;Microscopy, Atomic Force;Models,
2958 Chemical;Protein Binding;Spectrum Analysis;Time Factors",
2959 abstract = "On laboratory time scales, the energy landscape of a weak bond
2960 along a dissociation pathway is fully explored through Brownian-thermal
2961 excitations, and energy barriers become encoded in a dissociation time
2962 that varies with applied force. Probed with ramps of force over an
2963 enormous range of rates (force/time), this kinetic profile is
2964 transformed into a dynamic spectrum of bond rupture force as a function
2965 of loading rate. On a logarithmic scale in loading rate, the force
2966 spectrum provides an easy-to-read map of the prominent energy barriers
2967 traversed along the force-driven pathway and exposes the differences in
2968 energy between barriers. In this way, the method of dynamic force
2969 spectroscopy (DFS) is being used to probe the complex relation between
2970 force-lifetime-and chemistry in single molecular bonds. Most important,
2971 DFS probes the inner world of molecular interactions to reveal barriers
2972 that are difficult or impossible to detect in assays of near
2973 equilibrium dissociation but that determine bond lifetime and strength
2974 under rapid detachment. To use an ultrasensitive force probe as a
2975 spectroscopic tool, we need to understand the physics of bond
2976 dissociation under force, the impact of experimental technique on the
2977 measurement of detachment force (bond strength), the consequences of
2978 complex interactions in macromolecular bonds, and effects of multiply-
2979 bonded attachments."
2982 @article { evans91a,
2983 author = EEvans #" and "# DBerk #" and "# ALeung,
2984 title = "Detachment of agglutinin-bonded red blood cells. {I}. Forces to
2985 rupture molecular-point attachments",
2993 keywords = "ABO Blood-Group System;Animals;Antibodies,
2994 Monoclonal;Erythrocyte Deformability;Erythrocyte
2995 Membrane;Erythrocytes;Glycophorin;Helix
2996 (Snails);Hemagglutinins;Humans;Immune Sera;Lectins;Mathematics;Models,
2998 abstract = "A simple micromechanical method has been developed to measure
2999 the rupture strength of a molecular-point attachment (focal bond)
3000 between two macroscopically smooth membrane capsules. In the procedure,
3001 one capsule is prepared with a low density coverage of adhesion
3002 molecules, formed as a stiff sphere, and held at fixed position by a
3003 micropipette. The second capsule without adhesion molecules is
3004 pressurized into a spherical shape with low suction by another pipette.
3005 This capsule is maneuvered to initiate point contact at the pole
3006 opposite the stiff capsule which leads to formation of a few (or even
3007 one) molecular attachments. Then, the deformable capsule is slowly
3008 withdrawn by displacement of the pipette. Analysis shows that the end-
3009 to-end extension of the capsule provides a direct measure of the force
3010 at the point contact and, therefore, the rupture strength when
3011 detachment occurs. The range for point forces accessible to this
3012 technique depends on the elastic moduli of the membrane, membrane
3013 tension, and the size of the capsule. For biological and synthetic
3014 vesicle membranes, the range of force lies between 10(-7)-10(-5) dyn
3015 (10(-12)-10(-10) N) which is 100-fold less than presently measurable by
3016 Atomic Force Microscopy! Here, the approach was used to study the
3017 forces required to rupture microscopic attachments between red blood
3018 cells formed by a monoclonal antibody to red cell membrane glycophorin,
3019 anti-A serum, and a lectin from the snail-helix pomatia. Failure of the
3020 attachments appeared to be a stochastic function of the magnitude and
3021 duration of the detachment force. We have correlated the statistical
3022 behavior observed for rupture with a random process model for failure
3023 of small numbers of molecular attachments. The surprising outcome of
3024 the measurements and analysis was that the forces deduced for short-
3025 time failure of 1-2 molecular attachments were nearly the same for all
3026 of the agglutinin, i.e., 1-2 x 10(-6) dyn. Hence, microfluorometric
3027 tests were carried out to determine if labeled agglutinins and/or
3028 labeled surface molecules were transferred between surfaces after
3029 separation of large areas of adhesive contact. The results showed that
3030 the attachments failed because receptors were extracted from the
3034 @article { evans91b,
3035 author = EEvans #" and "# DBerk #" and "# ALeung #" and "# NMohandas,
3036 title = "Detachment of agglutinin-bonded red blood cells. {II}. Mechanical
3037 energies to separate large contact areas",
3045 keywords = "Animals;Antibodies, Monoclonal;Cell Adhesion;Erythrocyte
3046 Membrane;Erythrocytes;Helix
3047 (Snails);Hemagglutination;Hemagglutinins;Humans;Immune
3048 Sera;Kinetics;Lectins;Mathematics",
3049 abstract = "As detailed in a companion paper (Berk, D., and E. Evans. 1991.
3050 Biophys. J. 59:861-872), a method was developed to quantitate the
3051 strength of adhesion between agglutinin-bonded membranes without
3052 ambiguity due to mechanical compliance of the cell body. The
3053 experimental method and analysis were formulated around controlled
3054 assembly and detachment of a pair of macroscopically smooth red blood
3055 cell surfaces. The approach provides precise measurement of the
3056 membrane tension applied at the perimeter of an adhesive contact and
3057 the contact angle theta c between membrane surfaces which defines the
3058 mechanical leverage factor (1-cos theta c) important in the definition
3059 of the work to separate a unit area of contact. Here, the method was
3060 applied to adhesion and detachment of red cells bound together by
3061 different monoclonal antibodies to red cell membrane glycophorin and
3062 the snail-helix pomatia-lectin. For these tests, one of the two red
3063 cells was chemically prefixed in the form of a smooth sphere then
3064 equilibrated with the agglutinin before the adhesion-detachment
3065 procedure. The other cell was not exposed to the agglutinin until it
3066 was forced into contact with the rigid cell surface by mechanical
3067 impingement. Large regions of agglutinin bonding were produced by
3068 impingement but no spontaneous spreading was observed beyond the forced
3069 contact. Measurements of suction force to detach the deformable cell
3070 yielded consistent behavior for all of the agglutinins: i.e., the
3071 strength of adhesion increased progressively with reduction in contact
3072 diameter throughout detachment. This tension-contact diameter behavior
3073 was not altered over a ten-fold range of separation rates. In special
3074 cases, contacts separated smoothly after critical tensions were
3075 reached; these were the highest values attained for tension. Based on
3076 measurements reported in another paper (Evans et al. 1991. Biophys. J.
3077 59:838-848) of the forces required to rupture molecular-point
3078 attachments, the density of cross-bridges was estimated with the
3079 assumption that the tension was proportional to the discrete rupture
3080 force x the number of attachments per unit length. These estimates
3081 showed that only a small fraction of agglutinin formed cross-bridges at
3082 initial assembly and increased progressively with separation. When
3083 critical tension levels were reached, it appeared that nearly all local
3084 agglutinin was involved as cross-bridges. Because one cell surface was
3085 chemically fixed, receptor accumulation was unlikely; thus, microscopic
3086 ``roughness'' and steric repulsion probably modulated formation of
3087 cross-bridges on initial contact.(ABSTRACT TRUNCATED AT 400 WORDS)"
3091 author = EEvans #" and "# KRitchie,
3092 title = "Dynamic strength of molecular adhesion bonds",
3098 pages = "1541--1555",
3100 eprint = "http://www.biophysj.org/cgi/reprint/72/4/1541.pdf",
3101 url = "http://www.biophysj.org/cgi/content/abstract/72/4/1541",
3102 keywords = "Avidin; Biotin; Chemistry, Physical; Computer Simulation;
3103 Mathematics; Monte Carlo Method; Protein Binding",
3104 abstract = "In biology, molecular linkages at, within, and beneath cell
3105 interfaces arise mainly from weak noncovalent interactions. These bonds
3106 will fail under any level of pulling force if held for sufficient time.
3107 Thus, when tested with ultrasensitive force probes, we expect cohesive
3108 material strength and strength of adhesion at interfaces to be time-
3109 and loading rate-dependent properties. To examine what can be learned
3110 from measurements of bond strength, we have extended Kramers' theory
3111 for reaction kinetics in liquids to bond dissociation under force and
3112 tested the predictions by smart Monte Carlo (Brownian dynamics)
3113 simulations of bond rupture. By definition, bond strength is the force
3114 that produces the most frequent failure in repeated tests of breakage,
3115 i.e., the peak in the distribution of rupture forces. As verified by
3116 the simulations, theory shows that bond strength progresses through
3117 three dynamic regimes of loading rate. First, bond strength emerges at
3118 a critical rate of loading (> or = 0) at which spontaneous dissociation
3119 is just frequent enough to keep the distribution peak at zero force. In
3120 the slow-loading regime immediately above the critical rate, strength
3121 grows as a weak power of loading rate and reflects initial coupling of
3122 force to the bonding potential. At higher rates, there is crossover to
3123 a fast regime in which strength continues to increase as the logarithm
3124 of the loading rate over many decades independent of the type of
3125 attraction. Finally, at ultrafast loading rates approaching the domain
3126 of molecular dynamics simulations, the bonding potential is quickly
3127 overwhelmed by the rapidly increasing force, so that only naked
3128 frictional drag on the structure remains to retard separation. Hence,
3129 to expose the energy landscape that governs bond strength, molecular
3130 adhesion forces must be examined over an enormous span of time scales.
3131 However, a significant gap exists between the time domain of force
3132 measurements in the laboratory and the extremely fast scale of
3133 molecular motions. Using results from a simulation of biotin-avidin
3134 bonds (Izrailev, S., S. Stepaniants, M. Balsera, Y. Oono, and K.
3135 Schulten. 1997. Molecular dynamics study of unbinding of the avidin-
3136 biotin complex. Biophys. J., this issue), we describe how Brownian
3137 dynamics can help bridge the gap between molecular dynamics and probe
3139 project = "sawtooth simulation"
3143 author = EEvans #" and "# KRitchie,
3144 title = "Strength of a weak bond connecting flexible polymer chains",
3150 pages = "2439--2447",
3152 eprint = "http://www.biophysj.org/cgi/reprint/76/5/2439.pdf",
3153 url = "http://www.biophysj.org/cgi/content/abstract/76/5/2439",
3154 keywords = "Animals; Biophysics; Biopolymers; Microscopy, Atomic Force;
3155 Models, Chemical; Muscle Proteins; Protein Folding; Protein Kinases;
3156 Stochastic Processes; Stress, Mechanical; Thermodynamics",
3157 abstract = "Bond dissociation under steadily rising force occurs most
3158 frequently at a time governed by the rate of loading (Evans and
3159 Ritchie, 1997 Biophys. J. 72:1541-1555). Multiplied by the loading
3160 rate, the breakage time specifies the force for most frequent failure
3161 (called bond strength) that obeys the same dependence on loading rate.
3162 The spectrum of bond strength versus log(loading rate) provides an
3163 image of the energy landscape traversed in the course of unbonding.
3164 However, when a weak bond is connected to very compliant elements like
3165 long polymers, the load applied to the bond does not rise steadily
3166 under constant pulling speed. Because of nonsteady loading, the most
3167 frequent breakage force can differ significantly from that of a bond
3168 loaded at constant rate through stiff linkages. Using generic models
3169 for wormlike and freely jointed chains, we have analyzed the kinetic
3170 process of failure for a bond loaded by pulling the polymer linkages at
3171 constant speed. We find that when linked by either type of polymer
3172 chain, a bond is likely to fail at lower force under steady separation
3173 than through stiff linkages. Quite unexpectedly, a discontinuous jump
3174 can occur in bond strength at slow separation speed in the case of long
3175 polymer linkages. We demonstrate that the predictions of strength
3176 versus log(loading rate) can rationalize conflicting results obtained
3177 recently for unfolding Ig domains along muscle titin with different
3179 note = "Develops Kramers improvement on Bell model for domain unfolding.
3180 Presents unfolding under variable loading rates. Often cited as the
3181 ``Bell--Evans'' model. They derive a unitless treatment, scaling force
3182 by $f_\beta$, TODO; time by $\tau_f$, TODO; elasiticity by compliance
3183 $c(f)$. The appendix has relaxation time formulas for WLC and FJC
3185 project = "sawtooth simulation"
3188 @article { fernandez04,
3189 author = JFernandez #" and "# HLi,
3190 title = "Force-clamp spectroscopy monitors the folding trajectory of a
3198 pages = "1674--1678",
3200 doi = "10.1126/science.1092497",
3201 eprint = "http://www.sciencemag.org/cgi/reprint/303/5664/1674.pdf",
3202 url = "http://www.sciencemag.org/cgi/content/abstract/303/5664/1674",
3203 keywords = "Chemistry, Physical;Microscopy, Atomic Force;Physicochemical
3204 Phenomena;Polyubiquitin;Protein Conformation;Protein
3205 Denaturation;Protein Folding;Protein Structure, Secondary;Time
3207 abstract = "We used force-clamp atomic force microscopy to measure the end-
3208 to-end length of the small protein ubiquitin during its folding
3209 reaction at the single-molecule level. Ubiquitin was first unfolded and
3210 extended at a high force, then the stretching force was quenched and
3211 protein folding was observed. The folding trajectories were continuous
3212 and marked by several distinct stages. The time taken to fold was
3213 dependent on the contour length of the unfolded protein and the
3214 stretching force applied during folding. The folding collapse was
3215 marked by large fluctuations in the end-to-end length of the protein,
3216 but these fluctuations vanished upon the final folding contraction.
3217 These direct observations of the complete folding trajectory of a
3218 protein provide a benchmark to determine the physical basis of the
3223 author = JHoward #" and "# AJHudspeth,
3224 title = {Mechanical relaxation of the hair bundle mediates
3225 adaptation in mechanoelectrical transduction by the
3226 bullfrog's saccular hair cell.},
3232 pages = {3064--3068},
3234 url = {http://www.ncbi.nlm.nih.gov/pubmed/3495007},
3235 keywords = {Acclimatization},
3236 keywords = {Animals},
3237 keywords = {Electric Conductivity},
3238 keywords = {Electric Stimulation},
3239 keywords = {Hair Cells, Auditory},
3240 keywords = {Membrane Potentials},
3241 keywords = {Microelectrodes},
3242 keywords = {Physical Stimulation},
3243 keywords = {Rana catesbeiana},
3244 keywords = {Saccule and Utricle},
3245 abstract = {Mechanoelectrical transduction by hair cells of the
3246 frog's internal ear displays adaptation: the electrical response
3247 to a maintained deflection of the hair bundle declines over a
3248 period of tens of milliseconds. We investigated the role of
3249 mechanics in adaptation by measuring changes in hair-bundle
3250 stiffness following the application of force stimuli. Following
3251 step stimulation with a glass fiber, the hair bundle of a saccular
3252 hair cell initially had a stiffness of approximately equal to
3253 $1\U{mN/m}$. The stiffness then declined to a steady-state level
3254 near $0.6\U{mN/m}$ with a time course comparable to that of
3255 adaptation in the receptor current. The hair bundle may be modeled
3256 as the parallel combination of a spring, which represents the
3257 rotational stiffness of the stereocilia, and a series spring and
3258 dashpot, which respectively, represent the elastic element
3259 responsible for channel gating and the apparatus for adaptation.},
3264 author = JHoward #" and "# AJHudspeth,
3265 title = {Compliance of the Hair Bundle Associated with Gating of
3266 Mechanoelectrical Transduction Channels in the Bullfrog's Saccular
3273 doi = {10.1016/0896-6273(88)90139-0},
3274 url = {http://www.cell.com/neuron/retrieve/pii/0896627388901390},
3275 eprint = {http://download.cell.com/neuron/pdf/PII0896627388901390.pdf},
3276 note = {Initial thermal calibration paper as cited by
3277 \citet{florin95}. This is not an AFM paper, but it uses the
3278 equipartition theorem to calculate the spring constant of hair
3279 fibers by measuring their tip displacement variance. The
3280 discussion occurs in the \emph{Manufacture and Calibration of
3281 Fibers} section on pages 197--198. Actual details are scarce, but
3282 I believe this is the original source of the ``Lorentzian'' and
3283 ``10\% accuracy'' ideas that have haunted themal calibration ever
3288 author = ELFlorin #" and "# VMoy #" and "# HEGaub,
3289 title = {Adhesion forces between individual ligand-receptor pairs},
3297 doi = {10.1126/science.8153628},
3298 url = {http://www.sciencemag.org/content/264/5157/415.abstract},
3299 eprint = {http://www.sciencemag.org/content/264/5157/415.full.pdf},
3300 abstract ={The adhesion force between the tip of an atomic force
3301 microscope cantilever derivatized with avidin and agarose beads
3302 functionalized with biotin, desthiobiotin, or iminobiotin was
3303 measured. Under conditions that allowed only a limited number of
3304 molecular pairs to interact, the force required to separate tip
3305 and bead was found to be quantized in integer multiples of
3306 $160\pm20$ piconewtons for biotin and $85\pm15$ piconewtons for
3307 iminobiotin. The measured force quanta are interpreted as the
3308 unbinding forces of individual molecular pairs.},
3311 @article { florin95,
3312 author = ELFlorin #" and "# MRief #" and "# HLehmann #" and "# MLudwig #"
3313 and "# CDornmair #" and "# VMoy #" and "# HEGaub,
3314 title = "Sensing specific molecular interactions with the atomic force
3322 doi = "10.1016/0956-5663(95)99227-C",
3323 url = "http://www.sciencedirect.com/science/article/B6TFC-
3324 3XY2HK9-G/2/6f4e9f67e9a1e14c8bbcc478e5360682",
3325 abstract = "One of the unique features of the atomic force microscope (AFM)
3326 is its capacity to measure interactions between tip and sample with
3327 high sensitivity and unparal leled spatial resolution. Since the
3328 development of methods for the functionaliza tion of the tips, the
3329 versatility of the AFM has been expanded to experiments wh ere specific
3330 molecular interactions are measured. For illustration, we present m
3331 easurements of the interaction between complementary strands of DNA. A
3332 necessary prerequisite for the quantitative analysis of the interaction
3333 force is knowledg e of the spring constant of the cantilevers. Here, we
3334 compare different techniqu es that allow for the in situ measurement of
3335 the absolute value of the spring co nstant of cantilevers.",
3336 note = {Good review of calibration to 1995, with experimental
3337 comparison between resonance-shift, reference-spring, and
3338 thermal methods. They incorrectly cite \citet{hutter93} as
3339 being published in 1994.},
3340 project = "Cantilever Calibration"
3343 @article{ burnham03,
3344 author = NABurnham #" and "# XiChen #" and "# CSHodges #" and "#
3345 GAMatei #" and "# EJThoreson #" and "# CJRoberts #" and "#
3346 MCDavies #" and "# SJBTendler,
3347 title = {Comparison of calibration methods for atomic-force
3348 microscopy cantilevers},
3355 url = {http://stacks.iop.org/0957-4484/14/i=1/a=301},
3356 abstract = {The scientific community needs a rapid and reliable way
3357 of accurately determining the stiffness of atomic-force microscopy
3358 cantilevers. We have compared the experimentally determined values
3359 of stiffness for ten cantilever probes using four different
3360 methods. For rectangular silicon cantilever beams of well defined
3361 geometry, the approaches all yield values within 17\% of the
3362 manufacturer's nominal stiffness. One of the methods is new, based
3363 on the acquisition and analysis of thermal distribution functions
3364 of the oscillator's amplitude fluctuations. We evaluate this
3365 method in comparison to the three others and recommend it for its
3366 ease of use and broad applicability.},
3367 note = {Contains both the overdamped (\fref{equation}{6}) and
3368 general (\fref{equation}{8}) power spectral densities used in
3369 thermal cantilever calibration, but punts to textbooks for the
3374 author = NRForde #" and "# DIzhaky #" and "# GRWoodcock #" and "# GJLWuite
3375 #" and "# CBustamante,
3376 title = "Using mechanical force to probe the mechanism of pausing and
3377 arrest during continuous elongation by Escherichia coli {RNA}
3385 pages = "11682--11687",
3387 doi = "10.1073/pnas.142417799",
3388 eprint = "http://www.pnas.org/cgi/reprint/99/18/11682.pdf",
3389 url = "http://www.pnas.org/content/99/18/11682",
3390 keywords = "DNA-Directed RNA Polymerases;Escherichia
3391 coli;Kinetics;Transcription, Genetic",
3392 abstract = "Escherichia coli RNA polymerase translocates along the DNA
3393 discontinuously during the elongation phase of transcription, spending
3394 proportionally more time at some template positions, known as pause and
3395 arrest sites, than at others. Current models of elongation suggest that
3396 the enzyme backtracks at these locations, but the dynamics are
3397 unresolved. Here, we study the role of lateral displacement in pausing
3398 and arrest by applying force to individually transcribing molecules. We
3399 find that an assisting mechanical force does not alter the
3400 translocation rate of the enzyme, but does reduce the efficiency of
3401 both pausing and arrest. Moreover, arrested molecules cannot be rescued
3402 by force, suggesting that arrest occurs by a bipartite mechanism: the
3403 enzyme backtracks along the DNA followed by a conformational change of
3404 the ternary complex (RNA polymerase, DNA and transcript), which cannot
3405 be reversed mechanically."
3408 @article { freitag97,
3409 author = SFreitag #" and "# ILTrong #" and "# LKlumb #" and "# PSStayton #"
3411 title = "Structural studies of the streptavidin binding loop.",
3417 pages = "1157--1166",
3419 doi = "10.1002/pro.5560060604",
3420 keywords = "Allosteric Regulation;Bacterial Proteins;Binding
3421 Sites;Biotin;Crystallography, X-Ray;Hydrogen Bonding;Ligands;Models,
3422 Molecular;Molecular Conformation;Streptavidin;Tryptophan",
3423 abstract = "The streptavidin-biotin complex provides the basis for many
3424 important biotechnological applications and is an interesting model
3425 system for studying high-affinity protein-ligand interactions. We
3426 report here crystallographic studies elucidating the conformation of
3427 the flexible binding loop of streptavidin (residues 45 to 52) in the
3428 unbound and bound forms. The crystal structures of unbound streptavidin
3429 have been determined in two monoclinic crystal forms. The binding loop
3430 generally adopts an open conformation in the unbound species. In one
3431 subunit of one crystal form, the flexible loop adopts the closed
3432 conformation and an analysis of packing interactions suggests that
3433 protein-protein contacts stabilize the closed loop conformation. In the
3434 other crystal form all loops adopt an open conformation. Co-
3435 crystallization of streptavidin and biotin resulted in two additional,
3436 different crystal forms, with ligand bound in all four binding sites of
3437 the first crystal form and biotin bound in only two subunits in a
3438 second. The major change associated with binding of biotin is the
3439 closure of the surface loop incorporating residues 45 to 52. Residues
3440 49 to 52 display a 3(10) helical conformation in unbound subunits of
3441 our structures as opposed to the disordered loops observed in other
3442 structure determinations of streptavidin. In addition, the open
3443 conformation is stabilized by a beta-sheet hydrogen bond between
3444 residues 45 and 52, which cannot occur in the closed conformation. The
3445 3(10) helix is observed in nearly all unbound subunits of both the co-
3446 crystallized and ligand-free structures. An analysis of the temperature
3447 factors of the binding loop regions suggests that the mobility of the
3448 closed loops in the complexed structures is lower than in the open
3449 loops of the ligand-free structures. The two biotin bound subunits in
3450 the tetramer found in the MONO-b1 crystal form are those that
3451 contribute Trp 120 across their respective binding pockets, suggesting
3452 a structural link between these binding sites in the tetramer. However,
3453 there are no obvious signatures of binding site communication observed
3454 upon ligand binding, such as quaternary structure changes or shifts in
3455 the region of Trp 120. These studies demonstrate that while
3456 crystallographic packing interactions can stabilize both the open and
3457 closed forms of the flexible loop, in their absence the loop is open in
3458 the unbound state and closed in the presence of biotin. If present in
3459 solution, the helical structure in the open loop conformation could
3460 moderate the entropic penalty associated with biotin binding by
3461 contributing an order-to-disorder component to the loop closure.",
3462 note = "\href{http://www.rcsb.org/pdb/explore.do?structureId=1SWE}{PDB ID:
3464 \href{http://dx.doi.org/10.2210/pdb1swe/pdb}{10.2210/pdb1swe/pdb}."
3467 @article { friddle08,
3468 author = RWFriddle #" and "# PPodsiadlo #" and "# ABArtyukhin #" and "#
3470 title = "Near-Equilibrium Chemical Force Microscopy",
3475 pages = "4986--4990",
3476 doi = "10.1021/jp7095967",
3477 eprint = "http://pubs.acs.org/doi/pdf/10.1021/jp7095967",
3478 url = "http://pubs.acs.org/doi/abs/10.1021/jp7095967"
3482 author = TFujii #" and "# YLSun #" and "# KNAn #" and "# ZPLuo,
3483 title = "Mechanical properties of single hyaluronan molecules",
3491 keywords = "Biomechanics;Cross-Linking Reagents;Elasticity;Extracellular
3492 Matrix;Humans;Hyaluronic Acid;Lasers;Microspheres;Nanotechnology",
3493 abstract = "Hyaluronan (HA) is a major component of the extracellular
3494 matrix. It plays an important role in the mechanical functions of the
3495 extracellular matrix and stabilization of cells. Currently, its
3496 mechanical properties have been investigated only at the gross level.
3497 In this study, the mechanical properties of single HA molecules were
3498 directly measured with an optical tweezer technique, yielding a
3499 persistence length of 4.5 +/- 1.2 nm. This information may help us to
3500 understand the mechanical roles in the extracellular matrix
3501 infrastructure, cell attachment, and to design tissue engineering and
3502 drug delivery systems where the mechanical functions of HA are
3506 @article { ganchev08,
3507 author = DNGanchev #" and "# NJCobb #" and "# KSurewicz #" and "#
3509 title = "Nanomechanical properties of human prion protein amyloid as probed
3510 by force spectroscopy",
3517 pages = "2909--2915",
3519 doi = "10.1529/biophysj.108.133108",
3520 abstract = "Amyloids are associated with a number of protein misfolding
3521 disorders, including prion diseases. In this study, we used single-
3522 molecule force spectroscopy to characterize the nanomechanical
3523 properties and molecular structure of amyloid fibrils formed by human
3524 prion protein PrP90-231. Force-extension curves obtained by specific
3525 attachment of a gold-covered atomic force microscope tip to engineered
3526 Cys residues could be described by the worm-like chain model for
3527 entropic elasticity of a polymer chain, with the size of the N-terminal
3528 segment that could be stretched entropically depending on the tip
3529 attachment site. The data presented here provide direct information
3530 about the forces required to extract an individual monomer from the
3531 core of the PrP90-231 amyloid, and indicate that the beta-sheet core of
3532 this amyloid starts at residue approximately 164-169. The latter
3533 finding has important implications for the ongoing debate regarding the
3534 structure of PrP amyloid."
3538 author = MGao #" and "# DCraig #" and "# OLequin #" and "# ICampbell #" and
3539 "# VVogel #" and "# KSchulten,
3540 title = "Structure and functional significance of mechanically unfolded
3541 fibronectin type {III1} intermediates",
3546 pages = "14784--14789",
3547 doi = "10.1073/pnas.2334390100",
3548 eprint = "http://www.pnas.org/cgi/reprint/100/25/14784.pdf",
3549 url = "http://www.pnas.org/cgi/content/abstract/100/25/14784",
3550 abstract = "Fibronectin (FN) forms fibrillar networks coupling cells to the
3551 extracellular matrix. The formation of FN fibrils, fibrillogenesis, is
3552 a tightly regulated process involving the exposure of cryptic binding
3553 sites in individual FN type III (FN-III) repeats presumably exposed by
3554 mechanical tension. The FN-III1 module has been previously proposed to
3555 contain such cryptic sites that promote the assembly of extracellular
3556 matrix FN fibrils. We have combined NMR and steered molecular dynamics
3557 simulations to study the structure and mechanical unfolding pathway of
3558 FN-III1. This study finds that FN-III1 consists of a {beta}-sandwich
3559 structure that unfolds to a mechanically stable intermediate about four
3560 times the length of the native folded state. Considering previous
3561 experimental findings, our studies provide a structural model by which
3562 mechanical stretching of FN-III1 may induce fibrillogenesis through
3563 this partially unfolded intermediate."
3566 @article { gavrilov01,
3567 author = LAGavrilov #" and "# NSGavrilova,
3568 title = "The reliability theory of aging and longevity",
3577 doi = "10.1006/jtbi.2001.2430",
3578 keywords = "Adult;Aged;Aging;Animals;Humans;Longevity;Middle Aged;Models,
3579 Biological;Survival Rate;Systems Theory",
3580 abstract = "Reliability theory is a general theory about systems failure.
3581 It allows researchers to predict the age-related failure kinetics for a
3582 system of given architecture (reliability structure) and given
3583 reliability of its components. Reliability theory predicts that even
3584 those systems that are entirely composed of non-aging elements (with a
3585 constant failure rate) will nevertheless deteriorate (fail more often)
3586 with age, if these systems are redundant in irreplaceable elements.
3587 Aging, therefore, is a direct consequence of systems redundancy.
3588 Reliability theory also predicts the late-life mortality deceleration
3589 with subsequent leveling-off, as well as the late-life mortality
3590 plateaus, as an inevitable consequence of redundancy exhaustion at
3591 extreme old ages. The theory explains why mortality rates increase
3592 exponentially with age (the Gompertz law) in many species, by taking
3593 into account the initial flaws (defects) in newly formed systems. It
3594 also explains why organisms ``prefer'' to die according to the Gompertz
3595 law, while technical devices usually fail according to the Weibull
3596 (power) law. Theoretical conditions are specified when organisms die
3597 according to the Weibull law: organisms should be relatively free of
3598 initial flaws and defects. The theory makes it possible to find a
3599 general failure law applicable to all adult and extreme old ages, where
3600 the Gompertz and the Weibull laws are just special cases of this more
3601 general failure law. The theory explains why relative differences in
3602 mortality rates of compared populations (within a given species) vanish
3603 with age, and mortality convergence is observed due to the exhaustion
3604 of initial differences in redundancy levels. Overall, reliability
3605 theory has an amazing predictive and explanatory power with a few, very
3606 general and realistic assumptions. Therefore, reliability theory seems
3607 to be a promising approach for developing a comprehensive theory of
3608 aging and longevity integrating mathematical methods with specific
3609 biological knowledge.",
3610 note = "An example of exponential (standard) Gomperz law."
3613 @article { gergely00,
3614 author = CGergely #" and "# JCVoegel #" and "# PSchaaf #" and "# BSenger #"
3615 and "# MMaaloum #" and "# JHorber #" and "# JHemmerle,
3616 title = "Unbinding process of adsorbed proteins under external stress
3617 studied by atomic force microscopy spectroscopy",
3622 pages = "10802--10807",
3623 doi = "10.1073/pnas.180293097",
3624 eprint = "http://www.pnas.org/cgi/reprint/97/20/10802.pdf",
3625 url = "http://www.pnas.org/cgi/content/abstract/97/20/10802"
3628 @article { gompertz25,
3630 title = "On the Nature of the Function Expressive of the Law of Human
3631 Mortality, and on a New Mode of Determining the Value of Life
3640 copyright = "Copyright \copy\ 1825 The Royal Society",
3641 url = "http://www.jstor.org/stable/107756",
3643 jstor_articletype = "primary_article",
3644 jstor_formatteddate = 1825,
3645 jstor_issuetitle = ""
3650 title = {The significance of the difference between two means when
3651 the population variances are unequal},
3658 keywords = "Population",
3660 url = "http://www.jstor.org/stable/2332010",
3666 title = {The generalization of {Student's} problems when several
3667 different population variances are involved},
3674 keywords = "Population",
3676 url = "http://www.ncbi.nlm.nih.gov/pubmed/20287819",
3677 jstor_url = "http://www.jstor.org/stable/2332510",
3681 @article { granzier97,
3682 author = HLGranzier #" and "# MSKellermayer #" and "# MHelmes #" and "#
3684 title = "Titin elasticity and mechanism of passive force development in rat
3685 cardiac myocytes probed by thin-filament extraction",
3691 pages = "2043--2053",
3693 doi = "10.1016/S0006-3495(97)78234-1",
3694 url = "http://www.cell.com/biophysj/retrieve/pii/S0006349597782341",
3695 keywords = "Amino Acid Sequence;Animals;Biomechanics;Biophysical
3696 Phenomena;Biophysics;Cell Fractionation;Elasticity;Gelsolin;Microscopy,
3697 Immunoelectron;Models, Cardiovascular;Molecular Structure;Muscle
3698 Proteins;Myocardial Contraction;Myocardium;Protein
3699 Kinases;Rats;Sarcomeres",
3700 abstract = "Titin (also known as connectin) is a giant filamentous protein
3701 whose elastic properties greatly contribute to the passive force in
3702 muscle. In the sarcomere, the elastic I-band segment of titin may
3703 interact with the thin filaments, possibly affecting the molecule's
3704 elastic behavior. Indeed, several studies have indicated that
3705 interactions between titin and actin occur in vitro and may occur in
3706 the sarcomere as well. To explore the properties of titin alone, one
3707 must first eliminate the modulating effect of the thin filaments by
3708 selectively removing them. In the present work, thin filaments were
3709 selectively removed from the cardiac myocyte by using a gelsolin
3710 fragment. Partial extraction left behind approximately 100-nm-long thin
3711 filaments protruding from the Z-line, whereas the rest of the I-band
3712 became devoid of thin filaments, exposing titin. By applying a much
3713 more extensive gelsolin treatment, we also removed the remaining short
3714 thin filaments near the Z-line. After extraction, the extensibility of
3715 titin was studied by using immunoelectron microscopy, and the passive
3716 force-sarcomere length relation was determined by using mechanical
3717 techniques. Titin's regional extensibility was not detectably affected
3718 by partial thin-filament extraction. Passive force, on the other hand,
3719 was reduced at sarcomere lengths longer than approximately 2.1 microm,
3720 with a 33 +/- 9\% reduction at 2.6 microm. After a complete extraction,
3721 the slack sarcomere length was reduced to approximately 1.7 microm. The
3722 segment of titin near the Z-line, which is otherwise inextensible,
3723 collapsed toward the Z-line in sarcomeres shorter than approximately
3724 2.0 microm, but it was extended in sarcomeres longer than approximately
3725 2.3 microm. Passive force became elevated at sarcomere lengths between
3726 approximately 1.7 and approximately 2.1 microm, but was reduced at
3727 sarcomere lengths of >2.3 microm. These changes can be accounted for by
3728 modeling titin as two wormlike chains in series, one of which increases
3729 its contour length by recruitment of the titin segment near the Z-line
3730 into the elastic pool."
3733 @article { grossman05,
3734 author = CGrossman #" and "# AStout,
3735 title = "Optical Tweezers Advanced Lab",
3739 eprint = "http://chirality.swarthmore.edu/PHYS81/OpticalTweezers.pdf",
3740 note = {Fairly complete overdamped PSD derivation in
3741 \fref{section}{4.3}. Cites \citet{tlusty98} and
3742 \citet{bechhoefer02} for further details. However, Tlusty
3743 (listed as reference 8) doesn't contain the thermal response
3744 fn.\ derivation it was cited for. Also, the single sided PSD
3745 definition credited to reference 9 (listed as Bechhoefer)
3746 looks more like Press (listed as reference 10). I imagine
3747 Grossman and Stout mixed up their references, and meant to
3748 refer to \citet{bechhoefer02} and \citet{press92} respectively
3750 project = "Cantilever Calibration"
3753 @article { halvorsen09,
3754 author = KHalvorsen #" and "# WPWong,
3755 title = "Massively parallel single-molecule manipulation using centrifugal
3759 url = "http://arxiv.org/abs/0912.5370",
3760 abstract = {Precise manipulation of single molecules has already led to
3761 remarkable insights in physics, chemistry, biology and medicine.
3762 However, widespread adoption of single-molecule techniques has been
3763 impeded by equipment cost and the laborious nature of making
3764 measurements one molecule at a time. We have solved these issues with a
3765 new approach: massively parallel single-molecule force measurements
3766 using centrifugal force. This approach is realized in a novel
3767 instrument that we call the Centrifuge Force Microscope (CFM), in which
3768 objects in an orbiting sample are subjected to a calibration-free,
3769 macroscopically uniform force-field while their micro-to-nanoscopic
3770 motions are observed. We demonstrate high-throughput single-molecule
3771 force spectroscopy with this technique by performing thousands of
3772 rupture experiments in parallel, characterizing force-dependent
3773 unbinding kinetics of an antibody-antigen pair in minutes rather than
3774 days. Additionally, we verify the force accuracy of the instrument by
3775 measuring the well-established DNA overstretching transition at 66
3776 $\pm$ 3 pN. With significant benefits in efficiency, cost, simplicity,
3777 and versatility, "single-molecule centrifugation" has the potential to
3778 revolutionize single-molecule experimentation, and open access to a
3779 wider range of researchers and experimental systems.}
3782 @article { hanggi90,
3783 author = PHanggi #" and "# PTalkner #" and "# MBorkovec,
3784 title = "Reaction-rate theory: Fifty years after {K}ramers",
3793 doi = "10.1103/RevModPhys.62.251",
3794 eprint = "http://www.physik.uni-augsburg.de/theo1/hanggi/Papers/112.pdf",
3795 url = "http://prola.aps.org/abstract/RMP/v62/i2/p251_1",
3796 note = "\emph{The} Kramers' theory review article. See pages 268--279 for
3797 the Kramers-specific introduction.",
3798 project = "sawtooth simulation"
3801 @article { hatfield99,
3802 author = JWHatfield #" and "# SRQuake,
3803 title = "Dynamic Properties of an Extended Polymer in Solution",
3809 pages = "3548--3551",
3812 doi = "10.1103/PhysRevLett.82.3548",
3813 url = "http://link.aps.org/abstract/PRL/v82/p3548",
3814 note = "Defines WLC and FJC models, citing textbooks.",
3815 project = "sawtooth simulation"
3818 @article { heymann00,
3819 author = BHeymann #" and "# HGrubmuller,
3820 title = "Dynamic force spectroscopy of molecular adhesion bonds",
3827 pages = "6126--6129",
3829 doi = "10.1103/PhysRevLett.84.6126",
3830 eprint = "http://prola.aps.org/pdf/PRL/v84/i26/p6126_1",
3831 url = "http://prola.aps.org/abstract/PRL/v84/p6126",
3832 abstract = "Recent advances in atomic force microscopy, biomembrane force
3833 probe experiments, and optical tweezers allow one to measure the
3834 response of single molecules to mechanical stress with high precision.
3835 Such experiments, due to limited spatial resolution, typically access
3836 only one single force value in a continuous force profile that
3837 characterizes the molecular response along a reaction coordinate. We
3838 develop a theory that allows one to reconstruct force profiles from
3839 force spectra obtained from measurements at varying loading rates,
3840 without requiring increased resolution. We show that spectra obtained
3841 from measurements with different spring constants contain complementary
3845 @article { hummer01,
3846 author = GHummer #" and "# ASzabo,
3847 title = "From the Cover: Free energy reconstruction from nonequilibrium
3848 single-molecule pulling experiments",
3853 pages = "3658--3661",
3854 doi = "10.1073/pnas.071034098",
3855 eprint = "http://www.pnas.org/cgi/reprint/98/7/3658.pdf",
3856 url = "http://www.pnas.org/cgi/content/abstract/98/7/3658",
3860 @article { hummer03,
3861 author = GHummer #" and "# ASzabo,
3862 title = "Kinetics from nonequilibrium single-molecule pulling experiments",
3870 eprint = "http://www.biophysj.org/cgi/reprint/85/1/5.pdf",
3871 url = "http://www.biophysj.org/cgi/content/abstract/85/1/5",
3872 keywords = "Computer Simulation; Crystallography; Energy Transfer;
3873 Kinetics; Lasers; Micromanipulation; Microscopy, Atomic Force; Models,
3874 Molecular; Molecular Conformation; Motion; Muscle Proteins;
3875 Nanotechnology; Physical Stimulation; Protein Conformation; Protein
3876 Denaturation; Protein Folding; Protein Kinases; Stress, Mechanical",
3877 abstract = "Mechanical forces exerted by laser tweezers or atomic force
3878 microscopes can be used to drive rare transitions in single molecules,
3879 such as unfolding of a protein or dissociation of a ligand. The
3880 phenomenological description of pulling experiments based on Bell's
3881 expression for the force-induced rupture rate is found to be inadequate
3882 when tested against computer simulations of a simple microscopic model
3883 of the dynamics. We introduce a new approach of comparable complexity
3884 to extract more accurate kinetic information about the molecular events
3885 from pulling experiments. Our procedure is based on the analysis of a
3886 simple stochastic model of pulling with a harmonic spring and
3887 encompasses the phenomenological approach, reducing to it in the
3888 appropriate limit. Our approach is tested against computer simulations
3889 of a multimodule titin model with anharmonic linkers and then an
3890 illustrative application is made to the forced unfolding of I27
3891 subunits of the protein titin. Our procedure to extract kinetic
3892 information from pulling experiments is simple to implement and should
3893 prove useful in the analysis of experiments on a variety of systems.",
3895 project = "sawtooth simulation"
3898 @article { hutter05,
3900 title = "Comment on tilt of atomic force microscope cantilevers: Effect on
3901 spring constant and adhesion measurements.",
3908 pages = "2630--2632",
3910 doi = "10.1021/la047670t",
3911 note = "Tilted cantilever corrections (not needed? see Ohler/VEECO note)",
3912 project = "Cantilever Calibration"
3915 @article { hutter93,
3916 author = JHutter #" and "# JBechhoefer,
3917 title = "Calibration of atomic-force microscope tips",
3922 pages = "1868--1873",
3924 doi = "10.1063/1.1143970",
3925 url = "http://link.aip.org/link/?RSI/64/1868/1",
3926 keywords = {atomic force microscopy; calibration; quality factor; probes;
3927 resonance; silicon nitrides; mica; van der waals forces},
3928 note = {Original equipartition-based calibration method (thermal
3929 calibration), after the brief mention in \citet{howard88}.
3930 This is the first paper I've found that works out the theory
3931 in detail, although they punt to page 431 of \citet{heer72}
3932 instead of listing a formula for their ``Lorentzian''. The
3933 experimental data uses high-$Q$ cantilevers in air, and their
3934 figure 2 shows clear water-layer snap-off. There is a
3935 published erratum\citep{hutter93-erratum}.},
3936 project = "Cantilever Calibration"
3939 @article{ hutter93-erratum,
3940 author = JHutter #" and "# JBechhoefer,
3941 title = "Erratum: Calibration of atomic-force microscope tips",
3949 doi = "10.1063/1.1144449",
3950 url = "http://rsi.aip.org/resource/1/rsinak/v64/i11/p3342_s1",
3951 note = {V.~Croquette pointed out that they should calibrate the
3952 response of their optical-detection electronics.},
3953 project = "Cantilever Calibration",
3958 title = {Statistical mechanics, kinetic theory, and stochastic processes},
3961 address = {New York},
3963 isbn = {0-123-36550-3},
3964 language = {English},
3965 keywords = {Statistical mechanics.; Kinetic theory of gases.; Stochastic processes.},
3969 author = CHyeon #" and "# DThirumalai,
3970 title = "Can energy landscape roughness of proteins and {RNA} be measured
3971 by using mechanical unfolding experiments?",
3978 pages = "10249--10253",
3980 doi = "10.1073/pnas.1833310100",
3981 eprint = "http://www.pnas.org/cgi/reprint/100/18/10249.pdf",
3982 url = "http://www.pnas.org/cgi/content/abstract/100/18/10249",
3983 keywords = "Protein Folding; Proteins; RNA; Temperature; Thermodynamics",
3984 abstract = "By considering temperature effects on the mechanical unfolding
3985 rates of proteins and RNA, whose energy landscape is rugged, the
3986 question posed in the title is answered in the affirmative. Adopting a
3987 theory by Zwanzig [Zwanzig, R. (1988) Proc. Natl. Acad. Sci. USA 85,
3988 2029-2030], we show that, because of roughness characterized by an
3989 energy scale epsilon, the unfolding rate at constant force is retarded.
3990 Similarly, in nonequilibrium experiments done at constant loading
3991 rates, the most probable unfolding force increases because of energy
3992 landscape roughness. The effects are dramatic at low temperatures. Our
3993 analysis suggests that, by using temperature as a variable in
3994 mechanical unfolding experiments of proteins and RNA, the ruggedness
3995 energy scale epsilon, can be directly measured.",
3996 note = "Derives the major theory behind my thesis. The Kramers rate
3997 equation is \xref{hanggi90}{equation}{4.56c} (page 275).",
3998 project = "Energy Landscape Roughness"
4001 @article { improta96,
4002 author = SImprota #" and "# ASPolitou #" and "# APastore,
4003 title = "Immunoglobulin-like modules from titin {I}-band: Extensible
4004 components of muscle elasticity.",
4013 doi = "10.1016/S0969-2126(96)00036-6",
4014 keywords = "Amino Acid Sequence;Immunoglobulins;Magnetic Resonance
4015 Spectroscopy;Models, Molecular;Molecular Sequence Data;Molecular
4016 Structure;Muscle Proteins;Protein Kinases;Protein Structure,
4017 Secondary;Protein Structure, Tertiary;Sequence Alignment",
4018 abstract = "BACKGROUND. The giant muscle protein titin forms a filament
4019 which spans half of the sarcomere and performs, along its length, quite
4020 diverse functions. The region of titin located in the sarcomere I-band
4021 is believed to play a major role in extensibility and passive
4022 elasticity of muscle. In the I-band, the titin sequence consists mostly
4023 of repetitive motifs of tandem immunoglobulin-like (Ig) modules
4024 intercalated by a potentially non-globular region. The highly
4025 repetitive titin architecture suggests that the molecular basis of its
4026 mechanical properties be approached through the characterization of the
4027 isolated components of the I-band and their interfaces. In the present
4028 paper, we report on the structure determination in solution of a
4029 representative Ig module from the I-band (I27) as solved by NMR
4030 techniques. RESULTS. The structure of I27 consists of a beta sandwich
4031 formed by two four-stranded sheets (named ABED and A'GFC). This fold
4032 belongs to the intermediate frame (I frame) of the immunoglobulin
4033 superfamily. Comparison of I27 with another titin module from the
4034 region located in the M-line (M5) shows that two loops (between the B
4035 and C and the F and G strands) are shorter in I27, conferring a less
4036 elongated appearance to this structure. Such a feature is specific to
4037 the Ig domains in the I-band and might therefore be related to the
4038 functions of the protein in this region. The structure of tandem Ig
4039 domains as modeled from I27 suggests the presence of hinge regions
4040 connecting contiguous modules. CONCLUSIONS. We suggest that titin Ig
4041 domains in the I-band function as extensible components of muscle
4042 elasticity by stretching the hinge regions.",
4043 note = "\href{http://www.rcsb.org/pdb/explore.do?structureId=1TIT}{PDB ID:
4045 \href{http://dx.doi.org/10.2210/pdb1tit/pdb}{10.2210/pdb1tit/pdb}."
4048 @article { irback05,
4049 author = AIrback #" and "# SMitternacht #" and "# SMohanty,
4050 title = "Dissecting the mechanical unfolding of ubiquitin",
4055 pages = "13427--13432",
4056 doi = "10.1073/pnas.0501581102",
4057 eprint = "http://www.pnas.org/cgi/reprint/102/38/13427.pdf",
4058 url = "http://www.pnas.org/cgi/content/abstract/102/38/13427",
4059 abstract = "The unfolding behavior of ubiquitin under the influence of a
4060 stretching force recently was investigated experimentally by single-
4061 molecule constant-force methods. Many observed unfolding traces had a
4062 simple two-state character, whereas others showed clear evidence of
4063 intermediate states. Here, we use Monte Carlo simulations to
4064 investigate the force-induced unfolding of ubiquitin at the atomic
4065 level. In agreement with experimental data, we find that the unfolding
4066 process can occur either in a single step or through intermediate
4067 states. In addition to this randomness, we find that many quantities,
4068 such as the frequency of occurrence of intermediates, show a clear
4069 systematic dependence on the strength of the applied force. Despite
4070 this diversity, one common feature can be identified in the simulated
4071 unfolding events, which is the order in which the secondary-structure
4072 elements break. This order is the same in two- and three-state events
4073 and at the different forces studied. The observed order remains to be
4074 verified experimentally but appears physically reasonable."
4077 @article{ grubmuller96,
4078 author = HGrubmuller #" and "# BHeymann #" and "# PTavan,
4079 title = {Ligand binding: molecular mechanics calculation of the
4080 streptavidin-biotin rupture force.},
4084 address = {Theoretische Biophysik, Institut f{\"u}r Medizinische
4085 Optik, Ludwig- Maximilians-Universit{\"a}t M{\"u}nchen,
4086 Germany. Helmut.Grubmueller@ Physik.uni-muenchen.de},
4092 url = {http://www.ncbi.nlm.nih.gov/pubmed/8584939},
4093 eprint = {http://pubman.mpdl.mpg.de/pubman/item/escidoc:1690312:2/component/escidoc:1690313/1690312.pdf},
4095 keywords = {Bacterial Proteins},
4096 keywords = {Biotin},
4097 keywords = {Chemistry, Physical},
4098 keywords = {Computer Simulation},
4099 keywords = {Hydrogen Bonding},
4100 keywords = {Ligands},
4101 keywords = {Microscopy, Atomic Force},
4102 keywords = {Models, Chemical},
4103 keywords = {Molecular Conformation},
4104 keywords = {Physicochemical Phenomena},
4105 keywords = {Protein Conformation},
4106 keywords = {Streptavidin},
4107 keywords = {Thermodynamics},
4108 abstract = {The force required to rupture the streptavidin-biotin
4109 complex was calculated here by computer simulations.
4110 The computed force agrees well with that obtained by
4111 recent single molecule atomic force microscope
4112 experiments. These simulations suggest a detailed
4113 multiple-pathway rupture mechanism involving five major
4114 unbinding steps. Binding forces and specificity are
4115 attributed to a hydrogen bond network between the
4116 biotin ligand and residues within the binding pocket of
4117 streptavidin. During rupture, additional water bridges
4118 substantially enhance the stability of the complex and
4119 even dominate the binding interactions. In contrast,
4120 steric restraints do not appear to contribute to the
4121 binding forces, although conformational motions were
4126 @article { izrailev97,
4127 author = SIzrailev #" and "# SStepaniants #" and "# MBalsera #" and "#
4128 YOono #" and "# KSchulten,
4129 title = "Molecular dynamics study of unbinding of the avidin-biotin
4136 pages = "1568--1581",
4138 eprint = "http://www.biophysj.org/cgi/reprint/72/4/1568.pdf",
4139 url = "http://www.biophysj.org/cgi/content/abstract/72/4/1568",
4140 keywords = "Avidin;Binding Sites;Biotin;Computer Simulation;Hydrogen
4141 Bonding;Mathematics;Microscopy, Atomic Force;Microspheres;Models,
4142 Molecular;Molecular Structure;Protein Binding;Protein
4143 Conformation;Protein Folding;Sepharose",
4144 abstract = "We report molecular dynamics simulations that induce, over
4145 periods of 40-500 ps, the unbinding of biotin from avidin by means of
4146 external harmonic forces with force constants close to those of AFM
4147 cantilevers. The applied forces are sufficiently large to reduce the
4148 overall binding energy enough to yield unbinding within the measurement
4149 time. Our study complements earlier work on biotin-streptavidin that
4150 employed a much larger harmonic force constant. The simulations reveal
4151 a variety of unbinding pathways, the role of key residues contributing
4152 to adhesion as well as the spatial range over which avidin binds
4153 biotin. In contrast to the previous studies, the calculated rupture
4154 forces exceed by far those observed. We demonstrate, in the framework
4155 of models expressed in terms of one-dimensional Langevin equations with
4156 a schematic binding potential, the associated Smoluchowski equations,
4157 and the theory of first passage times, that picosecond to nanosecond
4158 simulation of ligand unbinding requires such strong forces that the
4159 resulting protein-ligand motion proceeds far from the thermally
4160 activated regime of millisecond AFM experiments, and that simulated
4161 unbinding cannot be readily extrapolated to the experimentally observed
4165 @article { janshoff00,
4166 author = AJanshoff #" and "# MNeitzert #" and "# YOberdorfer #" and "#
4168 title = "Force Spectroscopy of Molecular Systems-Single Molecule
4169 Spectroscopy of Polymers and Biomolecules.",
4176 pages = "3212--3237",
4178 doi = "10.1002/1521-3773(20000915)39:18<3212::AID-ANIE3212>3.0.CO;2-X",
4180 url = "http://dx.doi.org/10.1002/1521-3773(20000915)39:18<3212::AID-ANIE3212>3.0.CO;2-X",
4181 abstract = "How do molecules interact with each other? What happens if a
4182 neurotransmitter binds to a ligand-operated ion channel? How do
4183 antibodies recognize their antigens? Molecular recognition events play
4184 a pivotal role in nature: in enzymatic catalysis and during the
4185 replication and transcription of the genome; it is also important for
4186 the cohesion of cellular structures and in numerous metabolic reactions
4187 that molecules interact with each other in a specific manner.
4188 Conventional methods such as calorimetry provide very precise values of
4189 binding enthalpies; these are, however, average values obtained from a
4190 large ensemble of molecules without knowledge of the dynamics of the
4191 molecular recognition event. Which forces occur when a single molecular
4192 couple meets and forms a bond? Since the development of the scanning
4193 force microscope and force spectroscopy a couple of years ago, tools
4194 have now become available for measuring the forces between interfaces
4195 with high precision-starting from colloidal forces to the interaction
4196 of single molecules. The manipulation of individual molecules using
4197 force spectroscopy is also possible. In this way, the mechanical
4198 properties on a molecular scale are measurable. The study of single
4199 molecules is not an exclusive domain of force spectroscopy; it can also
4200 be performed with a surface force apparatus, laser tweezers, or the
4201 micropipette technique. Regardless of these techniques, force
4202 spectroscopy has been proven as an extraordinary versatile tool. The
4203 intention of this review article is to present a critical evaluation of
4204 the actual development of static force spectroscopy. The article mainly
4205 focuses on experiments dealing with inter- and intramolecular forces-
4206 starting with ``simple'' electrostatic forces, then ligand-receptor
4207 systems, and finally the stretching of individual molecules."
4210 @article { jollymore09,
4211 author = AJollymore #" and "# CLethias #" and "# QPeng #" and "# YCao #"
4213 title = "Nanomechanical properties of tenascin-{X} revealed by single-
4214 molecule force spectroscopy",
4221 pages = "1277--1286",
4223 doi = "10.1016/j.jmb.2008.11.038",
4224 url = "http://dx.doi.org/10.1016/j.jmb.2008.11.038",
4225 keywords = "Animals;Biomechanics;Cattle;Fibronectins;Kinetics;Microscopy,
4226 Atomic Force;Protein Folding;Protein Structure, Tertiary;Spectrum
4228 abstract = "Tenascin-X is an extracellular matrix protein and binds a
4229 variety of molecules in extracellular matrix and on cell membrane.
4230 Tenascin-X plays important roles in regulating the structure and
4231 mechanical properties of connective tissues. Using single-molecule
4232 atomic force microscopy, we have investigated the mechanical properties
4233 of bovine tenascin-X in detail. Our results indicated that tenascin-X
4234 is an elastic protein and the fibronectin type III (FnIII) domains can
4235 unfold under a stretching force and refold to regain their mechanical
4236 stability upon the removal of the stretching force. All the 30 FnIII
4237 domains of tenascin-X show similar mechanical stability, mechanical
4238 unfolding kinetics, and contour length increment upon domain unfolding,
4239 despite their large sequence diversity. In contrast to the homogeneity
4240 in their mechanical unfolding behaviors, FnIII domains fold at
4241 different rates. Using the 10th FnIII domain of tenascin-X (TNXfn10) as
4242 a model system, we constructed a polyprotein chimera composed of
4243 alternating TNXfn10 and GB1 domains and used atomic force microscopy to
4244 confirm that the mechanical properties of TNXfn10 are consistent with
4245 those of the FnIII domains of tenascin-X. These results lay the
4246 foundation to further study the mechanical properties of individual
4247 FnIII domains and establish the relationship between point mutations
4248 and mechanical phenotypic effect on tenascin-X. Moreover, our results
4249 provided the opportunity to compare the mechanical properties and
4250 design of different forms of tenascins. The comparison between
4251 tenascin-X and tenascin-C revealed interesting common as well as
4252 distinguishing features for mechanical unfolding and folding of
4253 tenascin-C and tenascin-X and will open up new avenues to investigate
4254 the mechanical functions and architectural design of different forms of
4259 author = REJones #" and "# DPHart,
4260 title = "Force interactions between substrates and {SPM} cantilevers
4261 immersed in fluids",
4268 doi = "DOI: 10.1016/j.triboint.2004.08.016",
4269 url = "http://www.sciencedirect.com/science/article/B6V57-4DN9K7J-1/2/fef91
4270 ac022594c2c6a701376d83ecd31",
4271 keywords = "AFM;Liquid;Hydrodynamic;Lubrication",
4272 abstract = "With the availability of equipment used in Scanning Probe
4273 Microscopy (SPM), researchers have been able to probe the local fluid-
4274 substrate force interactions with resolutions of pN using a variety of
4275 SPM cantilevers. When using such methods, it is essential to
4276 differentiate between contributions to the net force on the cantilever.
4277 Specifically, the interaction between the cantilever, substrate and
4278 fluid, quantified while generating force curves, are discussed and
4279 compared with theoretical models for squeeze-film effects and drag on
4280 the SPM cantilevers. In addition we have demonstrated a simple method
4281 for utilizing the system as a micro-viscometer, independently measuring
4282 the viscosity of the lubricant for each test."
4285 @article { juckett93,
4286 author = DAJuckett #" and "# BRosenberg,
4287 title = "Comparison of the {G}ompertz and {W}eibull functions as
4288 descriptors for human mortality distributions and their intersections",
4296 doi = "10.1016/0047-6374(93)90068-3",
4297 keywords = "Adolescent;Adult;Aged;Aged, 80 and
4298 over;Aging;Biometry;Child;Child, Preschool;Data Interpretation,
4299 Statistical;Female;Humans;Infant;Infant, Newborn;Longitudinal
4300 Studies;Male;Middle Aged;Models, Biological;Models,
4301 Statistical;Mortality",
4302 abstract = "The Gompertz and Weibull functions are compared with respect to
4303 goodness-of-fit to human mortality distributions; ability to describe
4304 mortality curve intersections; and, parameter interpretation. The
4305 Gompertz function is shown to be a better descriptor for 'all-causes'
4306 of deaths and combined disease categories while the Weibull function is
4307 shown to be a better descriptor of purer, single causes-of-death. A
4308 modified form of the Weibull function maps directly to the inherent
4309 degrees of freedom of human mortality distributions while the Gompertz
4310 function does not. Intersections in the old-age tails of mortality are
4311 explored in the context of both functions and, in particular, the
4312 relationship between distribution intersections, and the Gompertz
4313 ln[R0] versus alpha regression is examined. Evidence is also presented
4314 that mortality intersections are fundamental to the survivorship form
4315 and not the rate (hazard) form. Finally, comparisons are made to the
4316 parameter estimates in recent longitudinal Gompertzian analyses and the
4317 probable errors in those analyses are discussed.",
4318 note = "Nice table of various functions associated with Gompertz and
4322 @article { kaplan58,
4323 author = ELKaplan #" and "# PMeier,
4324 title = "Nonparametric Estimation from Incomplete Observations",
4333 copyright = "Copyright \copy\ 1958 American Statistical Association",
4334 url = "http://www.jstor.org/stable/2281868",
4338 @article { kellermayer03,
4339 author = MSKellermayer #" and "# CBustamante #" and "# HLGranzier,
4340 title = "Mechanics and structure of titin oligomers explored with atomic
4348 doi = "10.1016/S0005-2728(03)00029-X",
4349 url = "http://dx.doi.org/10.1016/S0005-2728(03)00029-X",
4350 keywords = "Titin;Wormlike chain;Unfolding;Elasticity;AFM;Molecular force
4352 abstract = "Titin is a giant polypeptide that spans half of the striated
4353 muscle sarcomere and generates passive force upon stretch. To explore
4354 the elastic response and structure of single molecules and oligomers of
4355 titin, we carried out molecular force spectroscopy and atomic force
4356 microscopy (AFM) on purified full-length skeletal-muscle titin. From
4357 the force data, apparent persistence lengths as long as ~1.5 nm were
4358 obtained for the single, unfolded titin molecule. Furthermore, data
4359 suggest that titin molecules may globally associate into oligomers
4360 which mechanically behave as independent wormlike chains (WLCs).
4361 Consistent with this, AFM of surface-adsorbed titin molecules revealed
4362 the presence of oligomers. Although oligomers may form globally via
4363 head-to-head association of titin, the constituent molecules otherwise
4364 appear independent from each other along their contour. Based on the
4365 global association but local independence of titin molecules, we
4366 discuss a mechanical model of the sarcomere in which titin molecules
4367 with different contour lengths, corresponding to different isoforms,
4368 are held in a lattice. The net force response of aligned titin
4369 molecules is determined by the persistence length of the tandemly
4370 arranged, different WLC components of the individual molecules, the
4371 ratio of their overall contour lengths, and by domain unfolding events.
4372 Biased domain unfolding in mechanically selected constituent molecules
4373 may serve as a compensatory mechanism for contour- and persistence-
4374 length differences. Variation in the ratio and contour length of the
4375 component chains may provide mechanisms for the fine-tuning of the
4376 sarcomeric passive force response.",
4380 @article { kellermayer97,
4381 author = MSKellermayer #" and "# SBSmith #" and "# HLGranzier #" and "#
4383 title = "Folding-unfolding transitions in single titin molecules
4384 characterized with laser tweezers",
4391 pages = "1112--1116",
4393 keywords = "Amino Acid
4394 Sequence;Elasticity;Entropy;Immunoglobulins;Lasers;Models,
4395 Chemical;Muscle Contraction;Muscle Proteins;Muscle Relaxation;Muscle,
4396 Skeletal;Protein Denaturation;Protein Folding;Protein Kinases;Stress,
4398 abstract = "Titin, a giant filamentous polypeptide, is believed to play a
4399 fundamental role in maintaining sarcomeric structural integrity and
4400 developing what is known as passive force in muscle. Measurements of
4401 the force required to stretch a single molecule revealed that titin
4402 behaves as a highly nonlinear entropic spring. The molecule unfolds in
4403 a high-force transition beginning at 20 to 30 piconewtons and refolds
4404 in a low-force transition at approximately 2.5 piconewtons. A fraction
4405 of the molecule (5 to 40 percent) remains permanently unfolded,
4406 behaving as a wormlike chain with a persistence length (a measure of
4407 the chain's bending rigidity) of 20 angstroms. Force hysteresis arises
4408 from a difference between the unfolding and refolding kinetics of the
4409 molecule relative to the stretch and release rates in the experiments,
4410 respectively. Scaling the molecular data up to sarcomeric dimensions
4411 reproduced many features of the passive force versus extension curve of
4416 author = WKing #" and "# MSu #" and "# GYang,
4417 title = "{M}onte {C}arlo simulation of mechanical unfolding of proteins
4418 based on a simple two-state model",
4422 address = "Department of Physics, Drexel University, 3141
4423 Chestnut Street, Philadelphia, PA 19104, USA.",
4429 alternative_issn = "1879-0003",
4430 doi = "10.1016/j.ijbiomac.2009.12.001",
4431 url = "http://www.sciencedirect.com/science/article/B6T7J-
4432 4XWMND2-1/2/7ef768562b4157fc201d450553e5de5e",
4434 keywords = "Atomic force microscopy;Mechanical unfolding;Monte Carlo
4435 simulation;Worm-like chain;Single molecule methods",
4436 abstract = "Single molecule methods are becoming routine biophysical
4437 techniques for studying biological macromolecules. In mechanical
4438 unfolding of proteins, an externally applied force is used to induce
4439 the unfolding of individual protein molecules. Such experiments have
4440 revealed novel information that has significantly enhanced our
4441 understanding of the function and folding mechanisms of several types
4442 of proteins. To obtain information on the unfolding kinetics and the
4443 free energy landscape of the protein molecule from mechanical unfolding
4444 data, a Monte Carlo simulation based on a simple two-state kinetic
4445 model is often used. In this paper, we provide a detailed description
4446 of the procedure to perform such simulations and discuss the
4447 approximations and assumptions involved. We show that the appearance of
4448 the force versus extension curves from mechanical unfolding of proteins
4449 is affected by a variety of experimental parameters, such as the length
4450 of the protein polymer and the force constant of the cantilever. We
4451 also analyze the errors associated with different methods of data
4452 pooling and present a quantitative measure of how well the simulation
4453 results fit experimental data. These findings will be helpful in
4454 experimental design, artifact identification, and data analysis for
4455 single molecule studies of various proteins using the mechanical
4459 @article { kleiner07,
4460 author = AKleiner #" and "# EShakhnovich,
4461 title = "The mechanical unfolding of ubiquitin through all-atom Monte Carlo
4462 simulation with a Go-type potential",
4469 pages = "2054--2061",
4471 doi = "10.1529/biophysj.106.081257",
4472 eprint = "http://www.biophysj.org/cgi/reprint/92/6/2054",
4473 url = "http://www.biophysj.org/cgi/content/full/92/6/2054",
4474 keywords = "Computer Simulation; Models, Chemical; Models, Molecular;
4475 Models, Statistical; Monte Carlo Method; Motion; Protein Conformation;
4476 Protein Denaturation; Protein Folding; Ubiquitin",
4477 abstract = "The mechanical unfolding of proteins under a stretching force
4478 has an important role in living systems and is a logical extension of
4479 the more general protein folding problem. Recent advances in
4480 experimental methodology have allowed the stretching of single
4481 molecules, thus rendering this process ripe for computational study. We
4482 use all-atom Monte Carlo simulation with a G?-type potential to study
4483 the mechanical unfolding pathway of ubiquitin. A detailed, robust,
4484 well-defined pathway is found, confirming existing results in this vein
4485 though using a different model. Additionally, we identify the protein's
4486 fundamental stabilizing secondary structure interactions in the
4487 presence of a stretching force and show that this fundamental
4488 stabilizing role does not persist in the absence of mechanical stress.
4489 The apparent success of simulation methods in studying ubiquitin's
4490 mechanical unfolding pathway indicates their potential usefulness for
4491 future study of the stretching of other proteins and the relationship
4492 between protein structure and the response to mechanical deformation."
4495 @article { klimov00,
4496 author = DKlimov #" and "# DThirumalai,
4497 title = "Native topology determines force-induced unfolding pathways in
4505 pages = "7254--7259",
4507 doi = "10.1073/pnas.97.13.7254",
4508 eprint = "http://www.pnas.org/cgi/reprint/97/13/7254.pdf",
4509 url = "http://www.pnas.org/cgi/content/abstract/97/13/7254",
4510 keywords = "Animals; Humans; Protein Folding; Proteins; Spectrin",
4511 abstract = "Single-molecule manipulation techniques reveal that stretching
4512 unravels individually folded domains in the muscle protein titin and
4513 the extracellular matrix protein tenascin. These elastic proteins
4514 contain tandem repeats of folded domains with beta-sandwich
4515 architecture. Herein, we propose by stretching two model sequences (S1
4516 and S2) with four-stranded beta-barrel topology that unfolding forces
4517 and pathways in folded domains can be predicted by using only the
4518 structure of the native state. Thermal refolding of S1 and S2 in the
4519 absence of force proceeds in an all-or-none fashion. In contrast, phase
4520 diagrams in the force-temperature (f,T) plane and steered Langevin
4521 dynamics studies of these sequences, which differ in the native
4522 registry of the strands, show that S1 unfolds in an allor-none fashion,
4523 whereas unfolding of S2 occurs via an obligatory intermediate. Force-
4524 induced unfolding is determined by the native topology. After proving
4525 that the simulation results for S1 and S2 can be calculated by using
4526 native topology alone, we predict the order of unfolding events in Ig
4527 domain (Ig27) and two fibronectin III type domains ((9)FnIII and
4528 (10)FnIII). The calculated unfolding pathways for these proteins, the
4529 location of the transition states, and the pulling speed dependence of
4530 the unfolding forces reflect the differences in the way the strands are
4531 arranged in the native states. We also predict the mechanisms of force-
4532 induced unfolding of the coiled-coil spectrin (a three-helix bundle
4533 protein) for all 20 structures deposited in the Protein Data Bank. Our
4534 approach suggests a natural way to measure the phase diagram in the
4535 (f,C) plane, where C is the concentration of denaturants.",
4536 note = {Simulated unfolding time scales for Ig27-like S1 and S2 domains.},
4539 @article { klimov99,
4540 author = DKlimov #" and "# DThirumalai,
4541 title = "Stretching single-domain proteins: Phase diagram and kinetics of
4542 force-induced unfolding",
4549 pages = "6166--6170",
4551 keywords = "Amino Acid Sequence;Kinetics;Models, Chemical;Protein
4552 Denaturation;Protein Folding;Proteins;Thermodynamics;Time Factors",
4553 abstract = "Single-molecule force spectroscopy reveals unfolding of domains
4554 in titin on stretching. We provide a theoretical framework for these
4555 experiments by computing the phase diagrams for force-induced unfolding
4556 of single-domain proteins using lattice models. The results show that
4557 two-state folders (at zero force) unravel cooperatively, whereas
4558 stretching of non-two-state folders occurs through intermediates. The
4559 stretching rates of individual molecules show great variations
4560 reflecting the heterogeneity of force-induced unfolding pathways. The
4561 approach to the stretched state occurs in a stepwise ``quantized''
4562 manner. Unfolding dynamics and forces required to stretch proteins
4563 depend sensitively on topology. The unfolding rates increase
4564 exponentially with force f till an optimum value, which is determined
4565 by the barrier to unfolding when f = 0. A mapping of these results to
4566 proteins shows qualitative agreement with force-induced unfolding of
4567 Ig-like domains in titin. We show that single-molecule force
4568 spectroscopy can be used to map the folding free energy landscape of
4569 proteins in the absence of denaturants."
4572 @article { kosztin06,
4573 author = IKosztin #" and "# BBarz #" and "# LJanosi,
4574 title = "Calculating potentials of mean force and diffusion coefficients
4575 from nonequilibrium processes without Jarzynski's equality",
4583 doi = "10.1063/1.2166379",
4584 url = "http://link.aip.org/link/?JCPSA6/124/064106/1"
4587 @article { kramers40,
4589 title = "Brownian motion in a field of force and the diffusion model of
4590 chemical reactions",
4598 doi = "10.1016/S0031-8914(40)90098-2",
4599 url = "http://dx.doi.org/10.1016/S0031-8914(40)90098-2",
4600 abstract = "A particle which is caught in a potential hole and which,
4601 through the shuttling action of Brownian motion, can escape over a
4602 potential barrier yields a suitable model for elucidating the
4603 applicability of the transition state method for calculating the rate
4604 of chemical reactions.",
4605 note = "Seminal paper on thermally activated barrier crossings."
4608 @article { krammer99,
4609 author = AKrammer #" and "# HLu #" and "# BIsralewitz #" and "# KSchulten
4611 title = "Forced unfolding of the fibronectin type {III} module reveals a
4612 tensile molecular recognition switch",
4619 pages = "1351--1356",
4621 keywords = "Amino Acid Sequence;Binding Sites;Computer
4622 Simulation;Crystallography, X-Ray;Disulfides;Fibronectins;Hydrogen
4623 Bonding;Integrins;Models, Molecular;Oligopeptides;Protein
4624 Conformation;Protein Denaturation;Protein Folding;Protein Structure,
4625 Secondary;Protein Structure, Tertiary;Software;Tensile Strength",
4626 abstract = "The 10th type III module of fibronectin possesses a beta-
4627 sandwich structure consisting of seven beta-strands (A-G) that are
4628 arranged in two antiparallel sheets. It mediates cell adhesion to
4629 surfaces via its integrin binding motif, Arg78, Gly79, and Asp80 (RGD),
4630 which is placed at the apex of the loop connecting beta-strands F and
4631 G. Steered molecular dynamics simulations in which tension is applied
4632 to the protein's terminal ends reveal that the beta-strand G is the
4633 first to break away from the module on forced unfolding whereas the
4634 remaining fold maintains its structural integrity. The separation of
4635 strand G from the remaining fold results in a gradual shortening of the
4636 distance between the apex of the RGD-containing loop and the module
4637 surface, which potentially reduces the loop's accessibility to surface-
4638 bound integrins. The shortening is followed by a straightening of the
4639 RGD-loop from a tight beta-turn into a linear conformation, which
4640 suggests a further decrease of affinity and selectivity to integrins.
4641 The RGD-loop therefore is located strategically to undergo strong
4642 conformational changes in the early stretching stages of the module and
4643 thus constitutes a mechanosensitive control of ligand recognition."
4646 @article { kreuzer01,
4647 author = HJKreuzer #" and "# SHPayne,
4648 title = "Stretching a macromolecule in an atomic force microscope:
4649 statistical mechanical analysis",
4658 eprint = "http://www.biophysj.org/cgi/reprint/80/6/2505.pdf",
4659 url = "http://www.biophysj.org/cgi/content/abstract/80/6/2505",
4660 keywords = "Biophysics;Macromolecular Substances;Microscopy, Atomic
4661 Force;Models, Statistical;Models, Theoretical;Statistics as Topic",
4662 abstract = "We formulate the proper statistical mechanics to describe the
4663 stretching of a macromolecule under a force provided by the cantilever
4664 of an atomic force microscope. In the limit of a soft cantilever the
4665 generalized ensemble of the coupled molecule/cantilever system reduces
4666 to the Gibbs ensemble for an isolated molecule subject to a constant
4667 force in which the extension is fluctuating. For a stiff cantilever we
4668 obtain the Helmholtz ensemble for an isolated molecule held at a fixed
4669 extension with the force fluctuating. Numerical examples are given for
4670 poly (ethylene glycol) chains."
4674 author = KKroy #" and "# JGlaser,
4675 title = "The glassy wormlike chain",
4681 doi = "10.1088/1367-2630/9/11/416",
4682 eprint = "http://www.iop.org/EJ/article/1367-2630/9/11/416/njp7_11_416.pdf",
4683 url = "http://stacks.iop.org/1367-2630/9/416",
4684 abstract = "We introduce a new model for the dynamics of a wormlike chain
4685 (WLC) in an environment that gives rise to a rough free energy
4686 landscape, which we name the glassy WLC. It is obtained from the common
4687 WLC by an exponential stretching of the relaxation spectrum of its
4688 long-wavelength eigenmodes, controlled by a single parameter
4689 \\boldsymbol{\\cal E} . Predictions for pertinent observables such as
4690 the dynamic structure factor and the microrheological susceptibility
4691 exhibit the characteristics of soft glassy rheology and compare
4692 favourably with experimental data for reconstituted cytoskeletal
4693 networks and live cells. We speculate about the possible microscopic
4694 origin of the stretching, implications for the nonlinear rheology, and
4695 the potential physiological significance of our results.",
4696 note = "Has short section on WLC relaxation time in the weakly bending
4700 @article { labeit03,
4701 author = DLabeit #" and "# KWatanabe #" and "# CWitt #" and "# HFujita #"
4702 and "# YWu #" and "# SLahmers #" and "# TFunck #" and "# SLabeit #" and
4704 title = "Calcium-dependent molecular spring elements in the giant protein
4710 pages = "13716--13721",
4711 doi = "10.1073/pnas.2235652100",
4712 eprint = "http://www.pnas.org/cgi/reprint/100/23/13716.pdf",
4713 url = "http://www.pnas.org/cgi/content/abstract/100/23/13716",
4714 abstract = "Titin (also known as connectin) is a giant protein with a wide
4715 range of cellular functions, including providing muscle cells with
4716 elasticity. Its physiological extension is largely derived from the
4717 PEVK segment, rich in proline (P), glutamate (E), valine (V), and
4718 lysine (K) residues. We studied recombinant PEVK molecules containing
4719 the two conserved elements: {approx}28-residue PEVK repeats and E-rich
4720 motifs. Single molecule experiments revealed that calcium-induced
4721 conformational changes reduce the bending rigidity of the PEVK
4722 fragments, and site-directed mutagenesis identified four glutamate
4723 residues in the E-rich motif that was studied (exon 129), as critical
4724 for this process. Experiments with muscle fibers showed that titin-
4725 based tension is calcium responsive. We propose that the PEVK segment
4726 contains E-rich motifs that render titin a calcium-dependent molecular
4727 spring that adapts to the physiological state of the cell."
4731 author = SLabeit #" and "# BKolmerer,
4732 title = "Titins: Giant proteins in charge of muscle ultrastructure
4738 address = "European Molecular Biology Laboratory, Heidelberg, Germany.",
4742 keywords = "Actin Cytoskeleton",
4743 keywords = "Amino Acid Sequence",
4744 keywords = "Animals",
4745 keywords = "DNA, Complementary",
4746 keywords = "Elasticity",
4747 keywords = "Fibronectins",
4748 keywords = "Humans",
4749 keywords = "Immunoglobulins",
4750 keywords = "Molecular Sequence Data",
4751 keywords = "Muscle Contraction",
4752 keywords = "Muscle Proteins",
4753 keywords = "Muscle, Skeletal",
4754 keywords = "Myocardium",
4755 keywords = "Protein Kinases",
4756 keywords = "Rabbits",
4757 keywords = "Repetitive Sequences, Nucleic Acid",
4758 keywords = "Sarcomeres",
4759 abstract = "In addition to thick and thin filaments, vertebrate
4760 striated muscle contains a third filament system formed by the
4761 giant protein titin. Single titin molecules extend from Z discs to
4762 M lines and are longer than 1 micrometer. The titin filament
4763 contributes to muscle assembly and resting tension, but more
4764 details are not known because of the large size of the
4765 protein. The complete complementary DNA sequence of human cardiac
4766 titin was determined. The 82-kilobase complementary DNA predicts a
4767 3-megadalton protein composed of 244 copies of immunoglobulin and
4768 fibronectin type III (FN3) domains. The architecture of sequences
4769 in the A band region of titin suggests why thick filament
4770 structure is conserved among vertebrates. In the I band region,
4771 comparison of titin sequences from muscles of different passive
4772 tension identifies two elements that correlate with tissue
4773 stiffness. This suggests that titin may act as two springs in
4774 series. The differential expression of the springs provides a
4775 molecular explanation for the diversity of sarcomere length and
4776 resting tension in vertebrate striated muscles.",
4778 URL = "http://www.ncbi.nlm.nih.gov/pubmed/7569978",
4783 author = RLaw #" and "# GLiao #" and "# SHarper #" and "# GYang #" and "#
4784 DSpeicher #" and "# DDischer,
4785 title = "Pathway shifts and thermal softening in temperature-coupled forced
4786 unfolding of spectrin domains",
4787 address = "Biophysical Engineering Lab, Institute for Medicine and
4788 Engineering, and School of Engineering and Applied Science,
4789 University of Pennsylvania, Philadelphia, Pennsylvania
4796 pages = "3286--3293",
4798 keywords = "Circular Dichroism;Elasticity;Heat;Microscopy, Atomic
4799 Force;Physical Stimulation;Protein Conformation;Protein
4800 Denaturation;Protein Folding;Protein Structure,
4801 Tertiary;Spectrin;Stress, Mechanical;Temperature",
4802 abstract = "Pathways of unfolding a protein depend in principle on the
4803 perturbation-whether it is temperature, denaturant, or even forced
4804 extension. Widely-shared, helical-bundle spectrin repeats are known to
4805 melt at temperatures as low as 40-45 degrees C and are also known to
4806 unfold via multiple pathways as single molecules in atomic force
4807 microscopy. Given the varied roles of spectrin family proteins in cell
4808 deformability, we sought to determine the coupled effects of
4809 temperature on forced unfolding. Bimodal distributions of unfolding
4810 intervals are seen at all temperatures for the four-repeat beta(1-4)
4811 spectrin-an alpha-actinin homolog. The major unfolding length
4812 corresponds to unfolding of a single repeat, and a minor peak at twice
4813 the length corresponds to tandem repeats. Increasing temperature shows
4814 fewer tandem events but has no effect on unfolding intervals. As T
4815 approaches T(m), however, mean unfolding forces in atomic force
4816 microscopy also decrease; and circular dichroism studies demonstrate a
4817 nearly proportional decrease of helical content in solution. The
4818 results imply a thermal softening of a helical linker between repeats
4819 which otherwise propagates a helix-to-coil transition to adjacent
4820 repeats. In sum, structural changes with temperature correlate with
4821 both single-molecule unfolding forces and shifts in unfolding
4823 doi = "10.1016/S0006-3495(03)74747-X",
4824 URL = "http://www.ncbi.nlm.nih.gov/pubmed/14581229",
4828 @article { levinthal68,
4829 author = CLevinthal,
4830 title = "Are there pathways for protein folding?",
4837 "http://www.biochem.wisc.edu/courses/biochem704/Reading/Levinthal1968.p
4839 note = "\emph{Not} Levinthal's paradox."
4842 @inproceedings { levinthal69,
4843 editor = PDebrunner #" and "# JCMTsibris #" and "# EMunck,
4844 author = CLevinthal,
4845 title = "How to Fold Graciously.",
4846 booktitle = "Mossbauer Spectroscopy in Biological Systems",
4849 publisher = UIP:Urbana,
4850 address = "Allerton House, Monticello, IL",
4851 url = "http://www-miller.ch.cam.ac.uk/levinthal/levinthal.html"
4855 author = RLevy #" and "# MMaaloum,
4856 title = "Measuring the spring constant of atomic force microscope
4857 cantilevers: Thermal fluctuations and other methods",
4863 doi = "10.1088/0957-4484/13/1/307",
4864 url = "http://stacks.iop.org/0957-4484/13/33",
4865 abstract = "Knowledge of the interaction forces between surfaces gained
4866 using an atomic force microscope (AFM) is crucial in a variety of
4867 industrial and scientific applications and necessitates a precise
4868 knowledge of the cantilever spring constant. Many methods have been
4869 devised to experimentally determine the spring constants of AFM
4870 cantilevers. The thermal fluctuation method is elegant but requires a
4871 theoretical model of the bending modes. For a rectangular cantilever,
4872 this model is available (Butt and Jaschke). Detailed thermal
4873 fluctuation measurements of a series of AFM cantilever beams have been
4874 performed in order to test the validity and accuracy of the recent
4875 theoretical models. The spring constant of rectangular cantilevers can
4876 also be determined easily with the method of Sader and White. We found
4877 very good agreement between the two methods. In the case of the
4878 V-shaped cantilever, we have shown that the thermal fluctuation method
4879 is a valid and accurate approach to the evaluation of the spring
4880 constant. A comparison between this method and those of Sader-
4881 Neumeister and of Ducker has been established. In some cases, we found
4882 disagreement between these two methods; the effect of non-conservation
4883 of material properties over all cantilevers from a single chip is
4884 qualitatively invoked.",
4885 note = "Good review of thermal calibration to 2002, but not much on the
4886 derviation of the Lorentzian fit.",
4887 project = "Cantilever Calibration"
4891 author = HLi #" and "# AOberhauser #" and "# SFowler #" and "# JClarke #"
4893 title = "Atomic force microscopy reveals the mechanical design of a modular
4899 pages = "6527--6531",
4900 doi = "10.1073/pnas.120048697",
4901 eprint = "http://www.pnas.org/cgi/reprint/97/12/6527.pdf",
4902 url = "http://www.pnas.org/cgi/content/abstract/97/12/6527",
4904 note = "Unfolding order not from protein-surface interactions. Mechanical
4905 unfolding of a chain of interleaved domains $ABABAB\ldots$ yielded a
4906 run of $A$ unfoldings followed by a run of $B$ unfoldings."
4910 author = HLi #" and "# AOberhauser #" and "# SRedick #" and "#
4911 MCarrionVazquez #" and "# HErickson #" and "# JFernandez,
4912 title = "Multiple conformations of {PEVK} proteins detected by single-
4913 molecule techniques",
4918 pages = "10682--10686",
4919 doi = "10.1073/pnas.191189098",
4920 eprint = "http://www.pnas.org/cgi/reprint/98/19/10682.pdf",
4921 url = "http://www.pnas.org/cgi/content/abstract/98/19/10682",
4922 abstract = "An important component of muscle elasticity is the PEVK region
4923 of titin, so named because of the preponderance of these amino acids.
4924 However, the PEVK region, similar to other elastomeric proteins, is
4925 thought to form a random coil and therefore its structure cannot be
4926 determined by standard techniques. Here we combine single-molecule
4927 electron microscopy and atomic force microscopy to examine the
4928 conformations of the human cardiac titin PEVK region. In contrast to a
4929 simple random coil, we have found that cardiac PEVK shows a wide range
4930 of elastic conformations with end-to-end distances ranging from 9 to 24
4931 nm and persistence lengths from 0.4 to 2.5 nm. Individual PEVK
4932 molecules retained their distinctive elastic conformations through many
4933 stretch-relaxation cycles, consistent with the view that these PEVK
4934 conformers cannot be interconverted by force. The multiple elastic
4935 conformations of cardiac PEVK may result from varying degrees of
4936 proline isomerization. The single-molecule techniques demonstrated here
4937 may help elucidate the conformation of other proteins that lack a well-
4942 author = HLi #" and "# JFernandez,
4943 title = "Mechanical design of the first proximal Ig domain of human cardiac
4944 titin revealed by single molecule force spectroscopy",
4953 doi = "10.1016/j.jmb.2003.09.036",
4954 keywords = "Amino Acid Sequence;Disulfides;Humans;Immunoglobulins;Models,
4955 Molecular;Molecular Sequence Data;Muscle Proteins;Myocardium;Protein
4956 Denaturation;Protein Engineering;Protein Kinases;Protein Structure,
4957 Tertiary;Spectrum Analysis",
4958 abstract = "The elastic I-band part of muscle protein titin contains two
4959 tandem immunoglobulin (Ig) domain regions of distinct mechanical
4960 properties. Until recently, the only known structure was that of the
4961 I27 module of the distal region, whose mechanical properties have been
4962 reported in detail. Recently, the structure of the first proximal
4963 domain, I1, has been resolved at 2.1A. In addition to the
4964 characteristic beta-sandwich structure of all titin Ig domains, the
4965 crystal structure of I1 showed an internal disulfide bridge that was
4966 proposed to modulate its mechanical extensibility in vivo. Here, we use
4967 single molecule force spectroscopy and protein engineering to examine
4968 the mechanical architecture of this domain. In contrast to the
4969 predictions made from the X-ray crystal structure, we find that the
4970 formation of a disulfide bridge in I1 is a relatively rare event in
4971 solution, even under oxidative conditions. Furthermore, our studies of
4972 the mechanical stability of I1 modules engineered with point mutations
4973 reveal significant differences between the mechanical unfolding of the
4974 I1 and I27 modules. Our study illustrates the varying mechanical
4975 architectures of the titin Ig modules."
4979 author = LeLi #" and "# HHuang #" and "# CBadilla #" and "# JFernandez,
4980 title = "Mechanical unfolding intermediates observed by single-molecule
4981 force spectroscopy in a fibronectin type {III} module",
4990 doi = "10.1016/j.jmb.2004.11.021",
4991 keywords = "Fibronectins;Kinetics;Microscopy, Atomic Force;Models,
4992 Molecular;Mutagenesis, Site-Directed;Protein Denaturation;Protein
4993 Folding;Protein Structure, Tertiary;Recombinant Fusion Proteins",
4994 abstract = "Domain 10 of type III fibronectin (10FNIII) is known to play a
4995 pivotal role in the mechanical interactions between cell surface
4996 integrins and the extracellular matrix. Recent molecular dynamics
4997 simulations have predicted that 10FNIII, when exposed to a stretching
4998 force, unfolds along two pathways, each with a distinct, mechanically
4999 stable intermediate. Here, we use single-molecule force spectroscopy
5000 combined with protein engineering to test these predictions by probing
5001 the mechanical unfolding pathway of 10FNIII. Stretching single
5002 polyproteins containing the 10FNIII module resulted in sawtooth
5003 patterns where 10FNIII was seen unfolding in two consecutive steps. The
5004 native state unfolded at 100(+/-20) pN, elongating (10)FNIII by
5005 12(+/-2) nm and reaching a clearly marked intermediate that unfolded at
5006 50(+/-20) pN. Unfolding of the intermediate completed the elongation of
5007 the molecule by extending another 19(+/-2) nm. Site-directed
5008 mutagenesis of residues in the A and B beta-strands (E9P and L19P)
5009 resulted in sawtooth patterns with all-or-none unfolding events that
5010 elongated the molecule by 19(+/-2) nm. In contrast, mutating residues
5011 in the G beta-strand gave results that were dependent on amino acid
5012 position. The mutation I88P in the middle of the G beta-strand resulted
5013 in native like unfolding sawtooth patterns showing an intact
5014 intermediate state. The mutation Y92P, which is near the end of G beta-
5015 strand, produced sawtooth patterns with all-or-none unfolding events
5016 that lengthened the molecule by 17(+/-2) nm. These results are
5017 consistent with the view that 10FNIII can unfold in two different ways.
5018 Along one pathway, the detachment of the A and B beta-strands from the
5019 body of the folded module constitute the first unfolding event,
5020 followed by the unfolding of the remaining beta-sandwich structure.
5021 Along the second pathway, the detachment of the G beta-strands is
5022 involved in the first unfolding event. These results are in excellent
5023 agreement with the sequence of events predicted by molecular dynamics
5024 simulations of the 10FNIII module."
5028 author = MSLi #" and "# CKHu #" and "# DKlimov #" and "# DThirumalai,
5029 title = "Multiple stepwise refolding of immunoglobulin domain {I27} upon
5030 force quench depends on initial conditions",
5036 doi = "10.1073/pnas.0503758103",
5037 eprint = "http://www.pnas.org/cgi/reprint/103/1/93.pdf",
5038 url = "http://www.pnas.org/cgi/content/abstract/103/1/93",
5039 abstract = "Mechanical folding trajectories for polyproteins starting from
5040 initially stretched conformations generated by single-molecule atomic
5041 force microscopy experiments [Fernandez, J. M. & Li, H. (2004) Science
5042 303, 1674-1678] show that refolding, monitored by the end-to-end
5043 distance, occurs in distinct multiple stages. To clarify the molecular
5044 nature of folding starting from stretched conformations, we have probed
5045 the folding dynamics, upon force quench, for the single I27 domain from
5046 the muscle protein titin by using a C{alpha}-Go model. Upon temperature
5047 quench, collapse and folding of I27 are synchronous. In contrast,
5048 refolding from stretched initial structures not only increases the
5049 folding and collapse time scales but also decouples the two kinetic
5050 processes. The increase in the folding times is associated primarily
5051 with the stretched state to compact random coil transition.
5052 Surprisingly, force quench does not alter the nature of the refolding
5053 kinetics, but merely increases the height of the free-energy folding
5054 barrier. Force quench refolding times scale as f1.gif, where {Delta}xf
5055 {approx} 0.6 nm is the location of the average transition state along
5056 the reaction coordinate given by end-to-end distance. We predict that
5057 {tau}F and the folding mechanism can be dramatically altered by the
5058 initial and/or final values of force. The implications of our results
5059 for design and analysis of experiments are discussed."
5064 title = "Divergence measures based on the {S}hannon entropy",
5072 doi = "10.1109/18.61115",
5073 url = "http://ieeexplore.ieee.org/xpl/freeabs_all.jsp?isnumber=2227&arnumbe
5074 r=61115&count=35&index=9",
5075 keywords = "divergence;dissimilarity measure;discrimintation
5076 information;entropy;probability of error bounds",
5077 abstract = "A novel class of information-theoretic divergence measures
5078 based on the Shannon entropy is introduced. Unlike the well-known
5079 Kullback divergences, the new measures do not require the condition of
5080 absolute continuity to be satisfied by the probability distributions
5081 involved. More importantly, their close relationship with the
5082 variational distance and the probability of misclassification error are
5083 established in terms of bounds. These bounds are crucial in many
5084 applications of divergence measures. The measures are also well
5085 characterized by the properties of nonnegativity, finiteness,
5086 semiboundedness, and boundedness."
5090 author = WALinke #" and "# AGrutzner,
5091 title = "Pulling single molecules of titin by {AFM}--recent advances and
5092 physiological implications",
5101 doi = "10.1007/s00424-007-0389-x",
5102 abstract = "Perturbation of a protein away from its native state by
5103 mechanical stress is a physiological process immanent to many cells.
5104 The mechanical stability and conformational diversity of proteins under
5105 force therefore are important parameters in nature. Molecular-level
5106 investigations of ``mechanical proteins'' have enjoyed major
5107 breakthroughs over the last decade, a development to which atomic force
5108 microscopy (AFM) force spectroscopy has been instrumental. The giant
5109 muscle protein titin continues to be a paradigm model in this field. In
5110 this paper, we review how single-molecule mechanical measurements of
5111 titin using AFM have served to elucidate key aspects of protein
5112 unfolding-refolding and mechanisms by which biomolecular elasticity is
5113 attained. We outline recent work combining protein engineering and AFM
5114 force spectroscopy to establish the mechanical behavior of titin
5115 domains using molecular ``fingerprinting.'' Furthermore, we summarize
5116 AFM force-extension data demonstrating different mechanical stabilities
5117 of distinct molecular-spring elements in titin, compare AFM force-
5118 extension to novel force-ramp/force-clamp studies, and elaborate on
5119 exciting new results showing that AFM force clamp captures the
5120 unfolding and refolding trajectory of single mechanical proteins. Along
5121 the way, we discuss the physiological implications of the findings, not
5122 least with respect to muscle mechanics. These studies help us
5123 understand how proteins respond to forces in cells and how
5124 mechanosensing and mechanosignaling events may proceed in vivo."
5127 @article { linke98a,
5128 author = WALinke #" and "# MRStockmeier #" and "# MIvemeyer #" and "#
5129 HHosser #" and "# PMundel,
5130 title = "Characterizing titin's {I}-band {Ig} domain region as an entropic
5135 volume = "111 (Pt 11)",
5136 pages = "1567--1574",
5139 eprint = "http://jcs.biologists.org/cgi/reprint/111/11/1567",
5140 url = "http://jcs.biologists.org/cgi/content/abstract/111/11/1567",
5141 keywords = "Animals;Elasticity;Immunoglobulins;Male;Muscle Proteins;Muscle,
5142 Skeletal;Protein Kinases;Rats;Rats, Wistar;Structure-Activity
5144 abstract = "The poly-immunoglobulin domain region of titin, located within
5145 the elastic section of this giant muscle protein, determines the
5146 extensibility of relaxed myofibrils mainly at shorter physiological
5147 lengths. To elucidate this region's contribution to titin elasticity,
5148 we measured the elastic properties of the N-terminal I-band Ig region
5149 by using immunofluorescence/immunoelectron microscopy and myofibril
5150 mechanics and tried to simulate the results with a model of entropic
5151 polymer elasticity. Rat psoas myofibrils were stained with titin-
5152 specific antibodies flanking the Ig region at the N terminus and C
5153 terminus, respectively, to record the extension behaviour of that titin
5154 segment. The segment's end-to-end length increased mainly at small
5155 stretch, reaching approximately 90\% of the native contour length of
5156 the Ig region at a sarcomere length of 2.8 microm. At this extension,
5157 the average force per single titin molecule, deduced from the steady-
5158 state passive length-tension relation of myofibrils, was approximately
5159 5 or 2.5 pN, depending on whether we assumed a number of 3 or 6 titins
5160 per half thick filament. When the force-extension curve constructed for
5161 the Ig region was simulated by the wormlike chain model, best fits were
5162 obtained for a persistence length, a measure of the chain's bending
5163 rigidity, of 21 or 42 nm (for 3 or 6 titins/half thick filament), which
5164 correctly reproduced the curve for sarcomere lengths up to 3.4 microm.
5165 Systematic deviations between data and fits above that length indicated
5166 that forces of >30 pN per titin strand may induce unfolding of Ig
5167 modules. We conclude that stretches of at least 5-6 Ig domains, perhaps
5168 coinciding with known super repeat patterns of these titin modules in
5169 the I-band, may represent the unitary lengths of the wormlike chain.
5170 The poly-Ig regions might thus act as compliant entropic springs that
5171 determine the minute levels of passive tension at low extensions of a
5175 @article { linke98b,
5176 author = WALinke #" and "# MIvemeyer #" and "# PMundel #" and "#
5177 MRStockmeier #" and "# BKolmerer,
5178 title = "Nature of {PEVK}-titin elasticity in skeletal muscle",
5185 pages = "8052--8057",
5187 keywords = "Animals;Elasticity;Fluorescent Antibody
5188 Technique;Male;Microscopy, Immunoelectron;Muscle Proteins;Muscle,
5189 Skeletal;Protein Kinases;Rats;Rats, Wistar;Stress, Mechanical",
5190 abstract = "A unique sequence within the giant titin molecule, the PEVK
5191 domain, has been suggested to greatly contribute to passive force
5192 development of relaxed skeletal muscle during stretch. To explore the
5193 nature of PEVK elasticity, we used titin-specific antibodies to stain
5194 both ends of the PEVK region in rat psoas myofibrils and determined the
5195 region's force-extension relation by combining immunofluorescence and
5196 immunoelectron microscopy with isolated myofibril mechanics. We then
5197 tried to fit the results with recent models of polymer elasticity. The
5198 PEVK segment elongated substantially at sarcomere lengths above 2.4
5199 micro(m) and reached its estimated contour length at approximately 3.5
5200 micro(m). In immunofluorescently labeled sarcomeres stretched and
5201 released repeatedly above 3 micro(m), reversible PEVK lengthening could
5202 be readily visualized. At extensions near the contour length, the
5203 average force per titin molecule was calculated to be approximately 45
5204 pN. Attempts to fit the force-extension curve of the PEVK segment with
5205 a standard wormlike chain model of entropic elasticity were successful
5206 only for low to moderate extensions. In contrast, the experimental data
5207 also could be correctly fitted at high extensions with a modified
5208 wormlike chain model that incorporates enthalpic elasticity. Enthalpic
5209 contributions are likely to arise from electrostatic stiffening, as
5210 evidenced by the ionic-strength dependency of titin-based myofibril
5211 stiffness; at high stretch, hydrophobic effects also might become
5212 relevant. Thus, at physiological muscle lengths, the PEVK region does
5213 not function as a pure entropic spring. Rather, PEVK elasticity may
5214 have both entropic and enthalpic origins characterizable by a polymer
5215 persistence length and a stretch modulus."
5219 author = WLiu #" and "# VMontana #" and "# EChapman #" and "# UMohideen #"
5221 title = "Botulinum toxin type {B} micromechanosensor",
5226 pages = "13621--13625",
5227 doi = "10.1073/pnas.2233819100",
5228 eprint = "http://www.pnas.org/cgi/reprint/100/23/13621.pdf",
5229 url = "http://www.pnas.org/cgi/content/abstract/100/23/13621",
5230 abstract = "Botulinum neurotoxin (BoNT) types A, B, E, and F are toxic to
5231 humans; early and rapid detection is essential for adequate medical
5232 treatment. Presently available tests for detection of BoNTs, although
5233 sensitive, require hours to days. We report a BoNT-B sensor whose
5234 properties allow detection of BoNT-B within minutes. The technique
5235 relies on the detection of an agarose bead detachment from the tip of a
5236 micromachined cantilever resulting from BoNT-B action on its
5237 substratum, the synaptic protein synaptobrevin 2, attached to the
5238 beads. The mechanical resonance frequency of the cantilever is
5239 monitored for the detection. To suspend the bead off the cantilever we
5240 use synaptobrevin's molecular interaction with another synaptic
5241 protein, syntaxin 1A, that was deposited onto the cantilever tip.
5242 Additionally, this bead detachment technique is general and can be used
5243 in any displacement reaction, such as in receptor-ligand pairs, where
5244 the introduction of one chemical leads to the displacement of another.
5245 The technique is of broad interest and will find uses outside
5250 author = GLois #" and "# JBlawzdziewicz #" and "# CSOHern,
5251 title = "Reliable protein folding on complex energy landscapes: the free
5252 energy reaction path",
5259 pages = "2692--2701",
5261 doi = "10.1529/biophysj.108.133132",
5262 abstract = "A theoretical framework is developed to study the dynamics of
5263 protein folding. The key insight is that the search for the native
5264 protein conformation is influenced by the rate r at which external
5265 parameters, such as temperature, chemical denaturant, or pH, are
5266 adjusted to induce folding. A theory based on this insight predicts
5267 that 1), proteins with complex energy landscapes can fold reliably to
5268 their native state; 2), reliable folding can occur as an equilibrium or
5269 out-of-equilibrium process; and 3), reliable folding only occurs when
5270 the rate r is below a limiting value, which can be calculated from
5271 measurements of the free energy. We test these predictions against
5272 numerical simulations of model proteins with a single energy scale."
5276 author = HLu #" and "# AKrammer #" and "# BIsralewitz #" and "# VVogel #"
5278 title = "Computer modeling of force-induced titin domain unfolding",
5280 journal = AdvExpMedBiol,
5284 url = {http://www.ncbi.nlm.nih.gov/pubmed/10987071},
5285 keywords = "Amino Acid Sequence;Animals;Computer
5286 Simulation;Elasticity;Fibronectins;Humans;Hydrogen
5287 Bonding;Immunoglobulins;Models, Molecular;Muscle Proteins;Muscle,
5288 Skeletal;Myofibrils;Protein Conformation;Protein Denaturation;Protein
5290 abstract = "Titin, a 1 micron long protein found in striated muscle
5291 myofibrils, possesses unique elastic and extensibility properties, and
5292 is largely composed of a PEVK region and beta-sandwich immunoglobulin
5293 (Ig) and fibronectin type III (FnIII) domains. The extensibility
5294 behavior of titin has been shown in atomic force microscope and optical
5295 tweezer experiments to partially depend on the reversible unfolding of
5296 individual Ig and FnIII domains. We performed steered molecular
5297 dynamics simulations to stretch single titin Ig domains in solution
5298 with pulling speeds of 0.1-1.0 A/ps, and FnIII domains with a pulling
5299 speed of 0.5 A/ps. Resulting force-extension profiles exhibit a single
5300 dominant peak for each domain unfolding, consistent with the
5301 experimentally observed sequential, as opposed to concerted, unfolding
5302 of Ig and FnIII domains under external stretching forces. The force
5303 peaks can be attributed to an initial burst of a set of backbone
5304 hydrogen bonds connected to the domains' terminal beta-strands.
5305 Constant force stretching simulations, applying 500-1000 pN of force,
5306 were performed on Ig domains. The resulting domain extensions are
5307 halted at an initial extension of 10 A until the set of all six
5308 hydrogen bonds connecting terminal beta-strands break simultaneously.
5309 This behavior is accounted for by a barrier separating folded and
5310 unfolded states, the shape of which is consistent with AFM and chemical
5311 denaturation data.",
5312 note = "discussion in journal on pages 161--2"
5316 author = HLu #" and "# KSchulten,
5317 title = "The key event in force-induced unfolding of Titin's immunoglobulin
5326 doi = {10.1016/S0006-3495(00)76273-4},
5327 url = {http://www.cell.com/biophysj/abstract/S0006-3495%2800%2976273-4},
5328 eprint = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1300915/pdf/10866937.pdf},
5329 keywords = "Amino Acid Sequence;Computer Simulation;Double Bind
5330 Interaction;Hydrogen Bonding;Immunoglobulins;Microscopy, Atomic
5331 Force;Models, Chemical;Models, Molecular;Molecular Sequence Data;Muscle
5332 Proteins;Protein Folding;Protein Kinases;Protein Structure,
5333 Tertiary;Stress, Mechanical;Water",
5334 abstract = "Steered molecular dynamics simulation of force-induced titin
5335 immunoglobulin domain I27 unfolding led to the discovery of a
5336 significant potential energy barrier at an extension of approximately
5337 14 A on the unfolding pathway that protects the domain against
5338 stretching. Previous simulations showed that this barrier is due to the
5339 concurrent breaking of six interstrand hydrogen bonds (H-bonds) between
5340 beta-strands A' and G that is preceded by the breaking of two to three
5341 hydrogen bonds between strands A and B, the latter leading to an
5342 unfolding intermediate. The simulation results are supported by
5343 Angstrom-resolution atomic force microscopy data. Here we perform a
5344 structural and energetic analysis of the H-bonds breaking. It is
5345 confirmed that H-bonds between strands A and B break rapidly. However,
5346 the breaking of the H-bond between strands A' and G needs to be
5347 assisted by fluctuations of water molecules. In nanosecond simulations,
5348 water molecules are found to repeatedly interact with the protein
5349 backbone atoms, weakening individual interstrand H-bonds until all six
5350 A'-G H-bonds break simultaneously under the influence of external
5351 stretching forces. Only when those bonds are broken can the generic
5352 unfolding take place, which involves hydrophobic interactions of the
5353 protein core and exerts weaker resistance against stretching than the
5358 author = HLu #" and "# BIsralewitz #" and "# AKrammer #" and "# VVogel #"
5360 title = "Unfolding of titin immunoglobulin domains by steered molecular
5361 dynamics simulation",
5369 doi = "10.1016/S0006-3495(98)77556-3",
5370 eprint = "http://download.cell.com/biophysj/pdf/PIIS0006349598775563.pdf",
5371 url = "http://www.cell.com/biophysj/abstract/S0006-3495(98)77556-3",
5372 keywords = "Amino Acid Sequence;Animals;Computer Simulation;Glutamic
5373 Acid;Immunoglobulins;Lysine;Macromolecular Substances;Models,
5374 Molecular;Molecular Sequence Data;Muscle
5375 Proteins;Myocardium;Proline;Protein Denaturation;Protein
5376 Folding;Protein Kinases;Protein Structure, Secondary;Sequence
5377 Alignment;Sequence Homology, Amino Acid;Valine",
5378 abstract = "Titin, a 1-microm-long protein found in striated muscle
5379 myofibrils, possesses unique elastic and extensibility properties in
5380 its I-band region, which is largely composed of a PEVK region (70\%
5381 proline, glutamic acid, valine, and lysine residue) and seven-strand
5382 beta-sandwich immunoglobulin-like (Ig) domains. The behavior of titin
5383 as a multistage entropic spring has been shown in atomic force
5384 microscope and optical tweezer experiments to partially depend on the
5385 reversible unfolding of individual Ig domains. We performed steered
5386 molecular dynamics simulations to stretch single titin Ig domains in
5387 solution with pulling speeds of 0.5 and 1.0 A/ps. Resulting force-
5388 extension profiles exhibit a single dominant peak for each Ig domain
5389 unfolding, consistent with the experimentally observed sequential, as
5390 opposed to concerted, unfolding of Ig domains under external stretching
5391 forces. This force peak can be attributed to an initial burst of
5392 backbone hydrogen bonds, which takes place between antiparallel beta-
5393 strands A and B and between parallel beta-strands A' and G. Additional
5394 features of the simulations, including the position of the force peak
5395 and relative unfolding resistance of different Ig domains, can be
5396 related to experimental observations."
5400 author = HLu #" and "# KSchulten,
5401 title = "Steered molecular dynamics simulations of force-induced protein
5411 doi = "10.1002/(SICI)1097-0134(19990601)35:4<453::AID-PROT9>3.0.CO;2-M",
5412 eprint = "http://www3.interscience.wiley.com/cgi-bin/fulltext/65000328/PDFSTART",
5413 url = "http://www3.interscience.wiley.com/journal/65000328/abstract",
5414 keywords = "Computer Simulation;Fibronectins;Hydrogen Bonding;Microscopy,
5415 Atomic Force;Models, Molecular;Protein Denaturation",
5416 abstract = "Steered molecular dynamics (SMD), a computer simulation method
5417 for studying force-induced reactions in biopolymers, has been applied
5418 to investigate the response of protein domains to stretching apart of
5419 their terminal ends. The simulations mimic atomic force microscopy and
5420 optical tweezer experiments, but proceed on much shorter time scales.
5421 The simulations on different domains for 0.6 nanosecond each reveal two
5422 types of protein responses: the first type, arising in certain beta-
5423 sandwich domains, exhibits nanosecond unfolding only after a force
5424 above 1,500 pN is applied; the second type, arising in a wider class of
5425 protein domain structures, requires significantly weaker forces for
5426 nanosecond unfolding. In the first case, strong forces are needed to
5427 concertedly break a set of interstrand hydrogen bonds which protect the
5428 domains against unfolding through stretching; in the second case,
5429 stretching breaks backbone hydrogen bonds one by one, and does not
5430 require strong forces for this purpose. Stretching of beta-sandwich
5431 (immunoglobulin) domains has been investigated further revealing a
5432 specific relationship between response to mechanical strain and the
5433 architecture of beta-sandwich domains."
5436 @article { makarov01,
5437 author = DEMakarov #" and "# PHansma #" and "# HMetiu,
5438 title = "Kinetic Monte Carlo simulation of titin unfolding",
5444 pages = "9663--9673",
5446 doi = "10.1063/1.1369622",
5447 eprint = "http://hansmalab.physics.ucsb.edu/pdf/297%20-%20Makarov,%20D.E._J
5448 .Chem.Phys._2001.pdf",
5449 url = "http://link.aip.org/link/?JCP/114/9663/1",
5450 keywords = "proteins; hydrogen bonds; digital simulation; Monte Carlo
5451 methods; molecular biophysics; intramolecular mechanics;
5452 macromolecules; atomic force microscopy"
5456 author = JFMarko #" and "# EDSiggia,
5457 title = "Stretching {DNA}",
5463 pages = "8759--8770",
5465 eprint = "http://pubs.acs.org/cgi-
5466 bin/archive.cgi/mamobx/1995/28/i26/pdf/ma00130a008.pdf",
5468 "http://pubs3.acs.org/acs/journals/doilookup?in_doi=10.1021/ma00130a008
5471 note = "Derivation of the Worm-like Chain interpolation function."
5474 @article { marszalek02,
5475 author = PMarszalek #" and "# HLi #" and "# AOberhauser #" and "#
5477 title = "Chair-boat transitions in single polysaccharide molecules observed
5478 with force-ramp {AFM}",
5483 pages = "4278--4283",
5484 doi = "10.1073/pnas.072435699",
5485 eprint = "http://www.pnas.org/cgi/reprint/99/7/4278.pdf",
5486 url = "http://www.pnas.org/cgi/content/abstract/99/7/4278",
5487 abstract = "Under a stretching force, the sugar ring of polysaccharide
5488 molecules switches from the chair to the boat-like or inverted chair
5489 conformation. This conformational change can be observed by stretching
5490 single polysaccharide molecules with an atomic force microscope. In
5491 those early experiments, the molecules were stretched at a constant
5492 rate while the resulting force changed over wide ranges. However,
5493 because the rings undergo force-dependent transitions, an experimental
5494 arrangement where the force is the free variable introduces an
5495 undesirable level of complexity in the results. Here we demonstrate the
5496 use of force-ramp atomic force microscopy to capture the conformational
5497 changes in single polysaccharide molecules. Force-ramp atomic force
5498 microscopy readily captures the ring transitions under conditions where
5499 the entropic elasticity of the molecule is separated from its
5500 conformational transitions, enabling a quantitative analysis of the
5501 data with a simple two-state model. This analysis directly provides the
5502 physico-chemical characteristics of the ring transitions such as the
5503 width of the energy barrier, the relative energy of the conformers, and
5504 their enthalpic elasticity. Our experiments enhance the ability of
5505 single-molecule force spectroscopy to make high-resolution measurements
5506 of the conformations of single polysaccharide molecules under a
5507 stretching force, making an important addition to polysaccharide
5511 @article { marszalek99,
5512 author = PMarszalek #" and "# HLu #" and "# HLi #" and "# MCarrionVazquez
5513 #" and "# AOberhauser #" and "# KSchulten #" and "# JFernandez,
5514 title = "Mechanical unfolding intermediates in titin modules",
5523 doi = "10.1038/47083",
5524 eprint = "http://www.nature.com/nature/journal/v402/n6757/pdf/402100a0.pdf",
5525 url = "http://www.nature.com/nature/journal/v402/n6757/abs/402100a0.html",
5526 keywords = "Biomechanics;Computer Simulation;Humans;Hydrogen
5527 Bonding;Microscopy, Atomic Force;Models, Molecular;Muscle
5528 Proteins;Myocardium;Protein Folding;Protein Kinases;Recombinant
5530 abstract = "The modular protein titin, which is responsible for the passive
5531 elasticity of muscle, is subjected to stretching forces. Previous work
5532 on the experimental elongation of single titin molecules has suggested
5533 that force causes consecutive unfolding of each domain in an all-or-
5534 none fashion. To avoid problems associated with the heterogeneity of
5535 the modular, naturally occurring titin, we engineered single proteins
5536 to have multiple copies of single immunoglobulin domains of human
5537 cardiac titin. Here we report the elongation of these molecules using
5538 the atomic force microscope. We find an abrupt extension of each domain
5539 by approximately 7 A before the first unfolding event. This fast
5540 initial extension before a full unfolding event produces a reversible
5541 'unfolding intermediate' Steered molecular dynamics simulations show
5542 that the rupture of a pair of hydrogen bonds near the amino terminus of
5543 the protein domain causes an extension of about 6 A, which is in good
5544 agreement with our observations. Disruption of these hydrogen bonds by
5545 site-directed mutagenesis eliminates the unfolding intermediate. The
5546 unfolding intermediate extends titin domains by approximately 15\% of
5547 their slack length, and is therefore likely to be an important
5548 previously unrecognized component of titin elasticity."
5551 @article { mcpherson01,
5552 author = JDMcPherson #" and "# MMarra #" and "# LHillier #" and "#
5553 RHWaterston #" and "# AChinwalla #" and "# JWallis #" and "# MSekhon #"
5554 and "# KWylie #" and "# ERMardis #" and "# RKWilson #" and "# RFulton
5555 #" and "# TAKucaba #" and "# CWagner-McPherson #" and "# WBBarbazuk #"
5556 and "# SGGregory #" and "# SJHumphray #" and "# LFrench #" and "#
5557 RSEvans #" and "# GBethel #" and "# AWhittaker #" and "# JLHolden #"
5558 and "# OTMcCann #" and "# ADunham #" and "# CSoderlund #" and "#
5559 CEScott #" and "# DRBentley #" and "# GSchuler #" and "# HCChen #" and
5560 "# WJang #" and "# EDGreen #" and "# JRIdol #" and "# VVMaduro #" and
5561 "# KTMontgomery #" and "# ELee #" and "# AMiller #" and "# SEmerling #"
5562 and "# Kucherlapati #" and "# RGibbs #" and "# SScherer #" and "#
5563 JHGorrell #" and "# ESodergren #" and "# KClerc-Blankenburg #" and "#
5564 PTabor #" and "# SNaylor #" and "# DGarcia #" and "# PJdeJong #" and "#
5565 JJCatanese #" and "# NNowak #" and "# KOsoegawa #" and "# SQin #" and
5566 "# LRowen #" and "# AMadan #" and "# MDors #" and "# LHood #" and "#
5567 BTrask #" and "# CFriedman #" and "# HMassa #" and "# VGCheung #" and
5568 "# IRKirsch #" and "# TReid #" and "# RYonescu #" and "# JWeissenbach
5569 #" and "# TBruls #" and "# RHeilig #" and "# EBranscomb #" and "#
5570 AOlsen #" and "# NDoggett #" and "# JFCheng #" and "# THawkins #" and
5571 "# RMMyers #" and "# JShang #" and "# LRamirez #" and "# JSchmutz #"
5572 and "# OVelasquez #" and "# KDixon #" and "# NEStone #" and "# DRCox #"
5573 and "# DHaussler #" and "# WJKent #" and "# TFurey #" and "# SRogic #"
5574 and "# SKennedy #" and "# SJones #" and "# ARosenthal #" and "# GWen #"
5575 and "# MSchilhabel #" and "# GGloeckner #" and "# GNyakatura #" and "#
5576 RSiebert #" and "# BSchlegelberger #" and "# JKorenberg #" and "#
5577 XNChen #" and "# AFujiyama #" and "# MHattori #" and "# AToyoda #" and
5578 "# TYada #" and "# HSPark #" and "# YSakaki #" and "# NShimizu #" and
5579 "# SAsakawa #" and "# KKawasaki #" and "# TSasaki #" and "# AShintani
5580 #" and "# AShimizu #" and "# KShibuya #" and "# JKudoh #" and "#
5581 SMinoshima #" and "# JRamser #" and "# PSeranski #" and "# CHoff #" and
5582 "# APoustka #" and "# RReinhardt #" and "# HLehrach,
5583 title = "A physical map of the human genome.",
5592 doi = "10.1038/35057157",
5593 eprint = "http://www.nature.com/nature/journal/v409/n6822/pdf/409934a0.pdf",
5594 url = "http://www.nature.com/nature/journal/v409/n6822/full/409934a0.html",
5595 keywords = "Chromosomes, Artificial, Bacterial;Cloning, Molecular;Contig
5596 Mapping;DNA Fingerprinting;Gene Duplication;Genome, Human;Humans;In
5597 Situ Hybridization, Fluorescence;Repetitive Sequences, Nucleic Acid",
5598 abstract = "The human genome is by far the largest genome to be sequenced,
5599 and its size and complexity present many challenges for sequence
5600 assembly. The International Human Genome Sequencing Consortium
5601 constructed a map of the whole genome to enable the selection of clones
5602 for sequencing and for the accurate assembly of the genome sequence.
5603 Here we report the construction of the whole-genome bacterial
5604 artificial chromosome (BAC) map and its integration with previous
5605 landmark maps and information from mapping efforts focused on specific
5606 chromosomal regions. We also describe the integration of sequence data
5611 author = CCMello #" and "# DBarrick,
5612 title = "An experimentally determined protein folding energy landscape",
5619 pages = "14102--14107",
5621 doi = "10.1073/pnas.0403386101",
5622 keywords = "Animals; Ankyrin Repeat; Circular Dichroism; Drosophila
5623 Proteins; Drosophila melanogaster; Gene Deletion; Models, Chemical;
5624 Models, Molecular; Protein Denaturation; Protein Folding; Protein
5625 Structure, Tertiary; Spectrometry, Fluorescence; Thermodynamics; Urea",
5626 abstract = "Energy landscapes have been used to conceptually describe and
5627 model protein folding but have been difficult to measure
5628 experimentally, in large part because of the myriad of partly folded
5629 protein conformations that cannot be isolated and thermodynamically
5630 characterized. Here we experimentally determine a detailed energy
5631 landscape for protein folding. We generated a series of overlapping
5632 constructs containing subsets of the seven ankyrin repeats of the
5633 Drosophila Notch receptor, a protein domain whose linear arrangement of
5634 modular structural units can be fragmented without disrupting
5635 structure. To a good approximation, stabilities of each construct can
5636 be described as a sum of energy terms associated with each repeat. The
5637 magnitude of each energy term indicates that each repeat is
5638 intrinsically unstable but is strongly stabilized by interactions with
5639 its nearest neighbors. These linear energy terms define an equilibrium
5640 free energy landscape, which shows an early free energy barrier and
5641 suggests preferred low-energy routes for folding."
5644 @article { merkel99,
5645 author = RMerkel #" and "# PNassoy #" and "# ALeung #" and "# KRitchie #"
5647 title = "Energy landscapes of receptor-ligand bonds explored with dynamic
5648 force spectroscopy",
5657 doi = "10.1038/16219",
5658 url = "http://www.nature.com/nature/journal/v397/n6714/full/397050a0.html",
5659 keywords = "Biotin;Microscopy, Atomic Force;Protein Binding;Streptavidin",
5660 abstract = "Atomic force microscopy (AFM) has been used to measure the
5661 strength of bonds between biological receptor molecules and their
5662 ligands. But for weak noncovalent bonds, a dynamic spectrum of bond
5663 strengths is predicted as the loading rate is altered, with the
5664 measured strength being governed by the prominent barriers traversed in
5665 the energy landscape along the force-driven bond-dissociation pathway.
5666 In other words, the pioneering early AFM measurements represent only a
5667 single point in a continuous spectrum of bond strengths, because theory
5668 predicts that these will depend on the rate at which the load is
5669 applied. Here we report the strength spectra for the bonds between
5670 streptavidin (or avidin) and biotins-the prototype of receptor-ligand
5671 interactions used in earlier AFM studies, and which have been modelled
5672 by molecular dynamics. We have probed bond formation over six orders of
5673 magnitude in loading rate, and find that the bond survival time
5674 diminished from about 1 min to 0.001 s with increasing loading rate
5675 over this range. The bond strength, meanwhile, increased from about 5
5676 pN to 170 pN. Thus, although they are among the strongest noncovalent
5677 linkages in biology (affinity of 10(13) to 10(15) M(-1)), these bonds
5678 in fact appear strong or weak depending on how fast they are loaded. We
5679 are also able to relate the activation barriers derived from our
5680 strength spectra to the shape of the energy landscape derived from
5681 simulations of the biotin-avidin complex."
5684 @article { metropolis87,
5685 author = NMetropolis,
5686 title = "The Beginning of the {M}onte {C}arlo Method",
5692 url = "http://library.lanl.gov/cgi-bin/getfile?15-12.pdf"
5695 @article { mickler07,
5696 author = MMickler #" and "# RDima #" and "# HDietz #" and "# CHyeon #" and
5697 "# DThirumalai #" and "# MRief,
5698 title = "Revealing the bifurcation in the unfolding pathways of {GFP} by
5699 using single-molecule experiments and simulations",
5704 pages = "20268--20273",
5705 doi = "10.1073/pnas.0705458104",
5706 eprint = "http://www.pnas.org/cgi/reprint/104/51/20268.pdf",
5707 url = "http://www.pnas.org/cgi/content/abstract/104/51/20268",
5708 keywords = "AFM experiments, coarse-grained simulations, cross-link
5709 mutants, pathway bifurcation, plasticity of energy landscape",
5710 abstract = "Nanomanipulation of biomolecules by using single-molecule
5711 methods and computer simulations has made it possible to visualize the
5712 energy landscape of biomolecules and the structures that are sampled
5713 during the folding process. We use simulations and single-molecule
5714 force spectroscopy to map the complex energy landscape of GFP that is
5715 used as a marker in cell biology and biotechnology. By engineering
5716 internal disulfide bonds at selected positions in the GFP structure,
5717 mechanical unfolding routes are precisely controlled, thus allowing us
5718 to infer features of the energy landscape of the wild-type GFP. To
5719 elucidate the structures of the unfolding pathways and reveal the
5720 multiple unfolding routes, the experimental results are complemented
5721 with simulations of a self-organized polymer (SOP) model of GFP. The
5722 SOP representation of proteins, which is a coarse-grained description
5723 of biomolecules, allows us to perform forced-induced simulations at
5724 loading rates and time scales that closely match those used in atomic
5725 force microscopy experiments. By using the combined approach, we show
5726 that forced unfolding of GFP involves a bifurcation in the pathways to
5727 the stretched state. After detachment of an N-terminal {alpha}-helix,
5728 unfolding proceeds along two distinct pathways. In the dominant
5729 pathway, unfolding starts from the detachment of the primary N-terminal
5730 -strand, while in the minor pathway rupture of the last, C-terminal
5731 -strand initiates the unfolding process. The combined approach has
5732 allowed us to map the features of the complex energy landscape of GFP
5733 including a characterization of the structures, albeit at a coarse-
5734 grained level, of the three metastable intermediates.",
5735 note = {Hiccup in unfolding leg corresponds to unfolding
5736 intermediate (\fref{figure}{2}). The unfolding time scale in GFP
5737 is about $6\U{ms}$.},
5741 author = RNevo #" and "# CStroh #" and "# FKienberger #" and "# DKaftan #"
5742 and "# VBrumfeld #" and "# MElbaum #" and "# ZReich #" and "#
5744 title = "A molecular switch between alternative conformational states in
5745 the complex of {Ran} and importin beta1",
5753 doi = "10.1038/nsb940",
5754 eprint = "http://www.nature.com/nsmb/journal/v10/n7/pdf/nsb940.pdf",
5755 url = "http://www.nature.com/nsmb/journal/v10/n7/abs/nsb940.html",
5756 keywords = "Guanosine Diphosphate; Guanosine Triphosphate; Microscopy,
5757 Atomic Force; Protein Binding; Protein Conformation; beta Karyopherins;
5758 ran GTP-Binding Protein",
5759 abstract = "Several million macromolecules are exchanged each minute
5760 between the nucleus and cytoplasm by receptor-mediated transport. Most
5761 of this traffic is controlled by the small GTPase Ran, which regulates
5762 assembly and disassembly of the receptor-cargo complexes in the
5763 appropriate cellular compartment. Here we applied dynamic force
5764 spectroscopy to study the interaction of Ran with the nuclear import
5765 receptor importin beta1 (impbeta) at the single-molecule level. We
5766 found that the complex alternates between two distinct conformational
5767 states of different adhesion strength. The application of an external
5768 mechanical force shifts equilibrium toward one of these states by
5769 decreasing the height of the interstate activation energy barrier. The
5770 other state can be stabilized by a functional Ran mutant that increases
5771 this barrier. These results support a model whereby functional control
5772 of Ran-impbeta is achieved by a population shift between pre-existing
5773 alternative conformations."
5777 author = RNevo #" and "# VBrumfeld #" and "# MElbaum #" and "#
5778 PHinterdorfer #" and "# ZReich,
5779 title = "Direct discrimination between models of protein activation by
5780 single-molecule force measurements",
5786 pages = "2630--2634",
5788 doi = "10.1529/biophysj.104.041889",
5789 eprint = "http://www.biophysj.org/cgi/reprint/87/4/2630.pdf",
5790 url = "http://www.biophysj.org/cgi/content/abstract/87/4/2630",
5791 keywords = "Elasticity; Enzyme Activation; Micromanipulation; Microscopy,
5792 Atomic Force; Models, Chemical; Models, Molecular; Multiprotein
5793 Complexes; Nuclear Proteins; Physical Stimulation; Protein Binding;
5794 Stress, Mechanical; Structure-Activity Relationship; beta Karyopherins;
5795 ran GTP-Binding Protein",
5796 abstract = "The limitations imposed on the analyses of complex chemical and
5797 biological systems by ensemble averaging can be overcome by single-
5798 molecule experiments. Here, we used a single-molecule technique to
5799 discriminate between two generally accepted mechanisms of a key
5800 biological process--the activation of proteins by molecular effectors.
5801 The two mechanisms, namely induced-fit and population-shift, are
5802 normally difficult to discriminate by ensemble approaches. As a model,
5803 we focused on the interaction between the nuclear transport effector,
5804 RanBP1, and two related complexes consisting of the nuclear import
5805 receptor, importin beta, and the GDP- or GppNHp-bound forms of the
5806 small GTPase, Ran. We found that recognition by the effector proceeds
5807 through either an induced-fit or a population-shift mechanism,
5808 depending on the substrate, and that the two mechanisms can be
5809 differentiated by the data."
5813 author = RNevo #" and "# VBrumfeld #" and "# RKapon #" and "# PHinterdorfer
5815 title = "Direct measurement of protein energy landscape roughness",
5823 doi = "10.1038/sj.embor.7400403",
5824 eprint = "http://www.nature.com/embor/journal/v6/n5/pdf/7400403.pdf",
5825 url = "http://www.nature.com/embor/journal/v6/n5/abs/7400403.html",
5826 keywords = "Models, Molecular; Protein Binding; Protein Folding; Spectrum
5827 Analysis; Thermodynamics; beta Karyopherins; ran GTP-Binding Protein",
5828 abstract = "The energy landscape of proteins is thought to have an
5829 intricate, corrugated structure. Such roughness should have important
5830 consequences on the folding and binding kinetics of proteins, as well
5831 as on their equilibrium fluctuations. So far, no direct measurement of
5832 protein energy landscape roughness has been made. Here, we combined a
5833 recent theory with single-molecule dynamic force spectroscopy
5834 experiments to extract the overall energy scale of roughness epsilon
5835 for a complex consisting of the small GTPase Ran and the nuclear
5836 transport receptor importin-beta. The results gave epsilon > 5k(B)T,
5837 indicating a bumpy energy surface, which is consistent with the ability
5838 of importin-beta to accommodate multiple conformations and to interact
5839 with different, structurally distinct ligands.",
5840 note = "Applies \citet{hyeon03} to ligand-receptor binding.",
5841 project = "Energy Landscape Roughness"
5845 author = SNg #" and "# KBillings #" and "# TOhashi #" and "# MAllen #" and
5846 "# RBest #" and "# LRandles #" and "# HErickson #" and "# JClarke,
5847 title = "Designing an extracellular matrix protein with enhanced mechanical
5855 pages = "9633--9637",
5856 doi = "10.1073/pnas.0609901104",
5857 eprint = "http://www.pnas.org/cgi/reprint/104/23/9633.pdf",
5858 url = "http://www.pnas.org/cgi/content/abstract/104/23/9633",
5859 abstract = "The extracellular matrix proteins tenascin and fibronectin
5860 experience significant mechanical forces in vivo. Both contain a number
5861 of tandem repeating homologous fibronectin type III (fnIII) domains,
5862 and atomic force microscopy experiments have demonstrated that the
5863 mechanical strength of these domains can vary significantly. Previous
5864 work has shown that mutations in the core of an fnIII domain from human
5865 tenascin (TNfn3) reduce the unfolding force of that domain
5866 significantly: The composition of the core is apparently crucial to the
5867 mechanical stability of these proteins. Based on these results, we have
5868 used rational redesign to increase the mechanical stability of the 10th
5869 fnIII domain of human fibronectin, FNfn10, which is directly involved
5870 in integrin binding. The hydrophobic core of FNfn10 was replaced with
5871 that of the homologous, mechanically stronger TNfn3 domain. Despite the
5872 extensive substitution, FNoTNc retains both the three-dimensional
5873 structure and the cell adhesion activity of FNfn10. Atomic force
5874 microscopy experiments reveal that the unfolding forces of the
5875 engineered protein FNoTNc increase by {approx}20% to match those of
5876 TNfn3. Thus, we have specifically designed a protein with increased
5877 mechanical stability. Our results demonstrate that core engineering can
5878 be used to change the mechanical strength of proteins while retaining
5879 functional surface interactions."
5883 author = SNg #" and "# JClarke,
5884 title = "Experiments Suggest that Simulations May Overestimate
5885 Electrostatic Contributions to the Mechanical Stability of a
5886 Fibronectin Type {III} Domain",
5890 pages = "851–854",
5895 doi = "10.1016/j.jmb.2007.06.015",
5896 url = "http://www.sciencedirect.com/science/article/pii/S0022283607007966",
5898 keywords = "MD simulations",
5900 keywords = "forced unfolding",
5901 keywords = "extracellular matrix",
5902 abstract = "Steered molecular dynamics simulations have previously
5903 been used to investigate the mechanical properties of the
5904 extracellular matrix protein fibronectin. The simulations
5905 suggest that the mechanical stability of the tenth type III
5906 domain from fibronectin (FNfn10) is largely determined by a
5907 number of critical hydrogen bonds in the peripheral
5908 strands. Interestingly, the simulations predict that lowering
5909 the pH from 7 to ∼4.7 will increase the mechanical stability
5910 of FNfn10 significantly (by ∼33 %) due to the protonation of a
5911 few key acidic residues in the A and B strands. To test this
5912 simulation prediction, we used single-molecule atomic force
5913 microscopy (AFM) to investigate the mechanical stability of
5914 FNfn10 at neutral pH and at lower pH where these key residues
5915 have been shown to be protonated. Our AFM experimental results
5916 show no difference in the mechanical stability of FNfn10 at
5917 these different pH values. These results suggest that some
5918 simulations may overestimate the role played by electrostatic
5919 interactions in determining the mechanical stability of
5924 author = RNome #" and "# JZhao #" and "# WHoff #" and "# NScherer,
5925 title = "Axis-dependent anisotropy in protein unfolding from integrated
5926 nonequilibrium single-molecule experiments, analysis, and simulation",
5933 pages = "20799--20804",
5935 doi = "10.1073/pnas.0701281105",
5936 eprint = "http://www.pnas.org/cgi/reprint/104/52/20799.pdf",
5937 url = "http://www.pnas.org/cgi/content/abstract/104/52/20799",
5938 keywords = "Anisotropy; Bacterial Proteins; Biophysics; Computer
5939 Simulation; Cysteine; Halorhodospira halophila; Hydrogen Bonding;
5940 Kinetics; Luminescent Proteins; Microscopy, Atomic Force; Molecular
5941 Conformation; Protein Binding; Protein Conformation; Protein
5942 Denaturation; Protein Folding; Protein Structure, Secondary",
5943 abstract = "We present a comprehensive study that integrates experimental
5944 and theoretical nonequilibrium techniques to map energy landscapes
5945 along well defined pull-axis specific coordinates to elucidate
5946 mechanisms of protein unfolding. Single-molecule force-extension
5947 experiments along two different axes of photoactive yellow protein
5948 combined with nonequilibrium statistical mechanical analysis and
5949 atomistic simulation reveal energetic and mechanistic anisotropy.
5950 Steered molecular dynamics simulations and free-energy curves
5951 constructed from the experimental results reveal that unfolding along
5952 one axis exhibits a transition-state-like feature where six hydrogen
5953 bonds break simultaneously with weak interactions observed during
5954 further unfolding. The other axis exhibits a constant (unpeaked) force
5955 profile indicative of a noncooperative transition, with enthalpic
5956 (e.g., H-bond) interactions being broken throughout the unfolding
5957 process. Striking qualitative agreement was found between the force-
5958 extension curves derived from steered molecular dynamics calculations
5959 and the equilibrium free-energy curves obtained by JarzynskiHummerSzabo
5960 analysis of the nonequilibrium work data. The anisotropy persists
5961 beyond pulling distances of more than twice the initial dimensions of
5962 the folded protein, indicating a rich energy landscape to the
5963 mechanically fully unfolded state. Our findings challenge the notion
5964 that cooperative unfolding is a universal feature in protein
5970 title = "Handbook of Molecular Force Spectroscopy",
5972 isbn = "978-0-387-49987-1",
5973 publisher = SPRINGER,
5974 note = "The first book about force spectroscopy. Discusses the scaffold
5975 effect in section 8.4.1."
5978 @article { nummela07,
5979 author = JNummela #" and "# IAndricioaei,
5980 title = "{Exact Low-Force Kinetics from High-Force Single-Molecule
5986 pages = "3373--3381",
5987 doi = "10.1529/biophysj.107.111658",
5988 eprint = "http://www.biophysj.org/cgi/reprint/93/10/3373.pdf",
5989 url = "http://www.biophysj.org/cgi/content/abstract/93/10/3373",
5990 abstract = "Mechanical forces play a key role in crucial cellular processes
5991 involving force-bearing biomolecules, as well as in novel single-
5992 molecule pulling experiments. We present an exact method that enables
5993 one to extrapolate, to low (or zero) forces, entire time-correlation
5994 functions and kinetic rate constants from the conformational dynamics
5995 either simulated numerically or measured experimentally at a single,
5996 relatively higher, external force. The method has twofold relevance:
5997 1), to extrapolate the kinetics at physiological force conditions from
5998 molecular dynamics trajectories generated at higher forces that
5999 accelerate conformational transitions; and 2), to extrapolate unfolding
6000 rates from experimental force-extension single-molecule curves. The
6001 theoretical formalism, based on stochastic path integral weights of
6002 Langevin trajectories, is presented for the constant-force, constant
6003 loading rate, and constant-velocity modes of the pulling experiments.
6004 For the first relevance, applications are described for simulating the
6005 conformational isomerization of alanine dipeptide; and for the second
6006 relevance, the single-molecule pulling of RNA is considered. The
6007 ability to assign a weight to each trace in the single-molecule data
6008 also suggests a means to quantitatively compare unfolding pathways
6009 under different conditions."
6012 @article { oberhauser01,
6013 author = AOberhauser #" and "# PHansma #" and "# MCarrionVazquez #" and "#
6015 title = "Stepwise unfolding of titin under force-clamp atomic force
6022 doi = "10.1073/pnas.021321798",
6023 eprint = "http://www.pnas.org/cgi/reprint/98/2/468.pdf",
6024 url = "http://www.pnas.org/cgi/content/abstract/98/2/468",
6030 title = "Cantilever spring constant calibration using laser Doppler
6040 doi = "10.1063/1.2743272",
6041 url = "http://link.aip.org/link/?RSI/78/063701/1",
6042 keywords = "calibration; vibration measurement; measurement by laser beam;
6043 Doppler measurement; measurement uncertainty; atomic force microscopy",
6044 note = "Excellent review of thermal calibration to 2007, but nothing in the
6045 way of derivations. Compares thermal tune and Sader method with laser
6046 Doppler vibrometry.",
6047 project = "Cantilever Calibration"
6050 @article { olshansky97,
6051 author = SJOlshansky #" and "# BACarnes,
6052 title = "Ever since {G}ompertz",
6055 journal = Demography,
6060 url = "http://www.jstor.org/stable/2061656",
6061 keywords = "Aging;Biometry;History, 19th Century;History, 20th
6062 Century;Humans;Life Tables;Mortality;Sexual Maturation",
6063 abstract = "In 1825 British actuary Benjamin Gompertz made a simple but
6064 important observation that a law of geometrical progression pervades
6065 large portions of different tables of mortality for humans. The simple
6066 formula he derived describing the exponential rise in death rates
6067 between sexual maturity and old age is commonly, referred to as the
6068 Gompertz equation-a formula that remains a valuable tool in demography
6069 and in other scientific disciplines. Gompertz's observation of a
6070 mathematical regularity in the life table led him to believe in the
6071 presence of a low of mortality that explained why common age patterns
6072 of death exist. This law of mortality has captured the attention of
6073 scientists for the past 170 years because it was the first among what
6074 are now several reliable empirical tools for describing the dying-out
6075 process of many living organisms during a significant portion of their
6076 life spans. In this paper we review the literature on Gompertz's law of
6077 mortality and discuss the importance of his observations and insights
6078 in light of research on aging that has taken place since then.",
6079 note = "Hardly any actual math, but the references might be interesting.
6080 I'll look into them if I have the time. Available through several
6084 @article { onuchic96,
6085 author = JNOnuchic #" and "# NDSocci #" and "# ZLuthey-Schulten #" and "#
6087 title = "Protein folding funnels: the nature of the transition state
6095 keywords = "Animals; Cytochrome c Group; Humans; Infant; Protein Folding",
6096 abstract = "BACKGROUND: Energy landscape theory predicts that the folding
6097 funnel for a small fast-folding alpha-helical protein will have a
6098 transition state half-way to the native state. Estimates of the
6099 position of the transition state along an appropriate reaction
6100 coordinate can be obtained from linear free energy relationships
6101 observed for folding and unfolding rate constants as a function of
6102 denaturant concentration. The experimental results of Huang and Oas for
6103 lambda repressor, Fersht and collaborators for C12, and Gray and
6104 collaborators for cytochrome c indicate a free energy barrier midway
6105 between the folded and unfolded regions. This barrier arises from an
6106 entropic bottleneck for the folding process. RESULTS: In keeping with
6107 the experimental results, lattice simulations based on the folding
6108 funnel description show that the transition state is not just a single
6109 conformation, but rather an ensemble of a relatively large number of
6110 configurations that can be described by specific values of one or a few
6111 order parameters (e.g. the fraction of native contacts). Analysis of
6112 this transition state or bottleneck region from our lattice simulations
6113 and from atomistic models for small alpha-helical proteins by Boczko
6114 and Brooks indicates a broad distribution for native contact
6115 participation in the transition state ensemble centered around 50\%.
6116 Importantly, however, the lattice-simulated transition state ensemble
6117 does include some particularly hot contacts, as seen in the
6118 experiments, which have been termed by others a folding nucleus.
6119 CONCLUSIONS: Linear free energy relations provide a crude spectroscopy
6120 of the transition state, allowing us to infer the values of a reaction
6121 coordinate based on the fraction of native contacts. This bottleneck
6122 may be thought of as a collection of delocalized nuclei where different
6123 native contacts will have different degrees of participation. The
6124 agreement between the experimental results and the theoretical
6125 predictions provides strong support for the landscape analysis."
6129 author = COpitz #" and "# MKulke #" and "# MLeake #" and "# CNeagoe #" and
6130 "# HHinssen #" and "# RHajjar #" and "# WALinke,
6131 title = "Damped elastic recoil of the titin spring in myofibrils of human
6137 pages = "12688--12693",
6138 doi = "10.1073/pnas.2133733100",
6139 eprint = "http://www.pnas.org/cgi/reprint/100/22/12688.pdf",
6140 url = "http://www.pnas.org/cgi/content/abstract/100/22/12688",
6141 abstract = "The giant protein titin functions as a molecular spring in
6142 muscle and is responsible for most of the passive tension of
6143 myocardium. Because the titin spring is extended during diastolic
6144 stretch, it will recoil elastically during systole and potentially may
6145 influence the overall shortening behavior of cardiac muscle. Here,
6146 titin elastic recoil was quantified in single human heart myofibrils by
6147 using a high-speed charge-coupled device-line camera and a
6148 nanonewtonrange force sensor. Application of a slack-test protocol
6149 revealed that the passive shortening velocity (Vp) of nonactivated
6150 cardiomyofibrils depends on: (i) initial sarcomere length, (ii)
6151 release-step amplitude, and (iii) temperature. Selective digestion of
6152 titin, with low doses of trypsin, decelerated myofibrillar passive
6153 recoil and eventually stopped it. Selective extraction of actin
6154 filaments with a Ca2+-independent gelsolin fragment greatly reduced the
6155 dependency of Vp on release-step size and temperature. These results
6156 are explained by the presence of viscous forces opposing myofibrillar
6157 passive recoil that are caused mainly by weak actin-titin interactions.
6158 Thus, Vp is determined by two distinct factors: titin elastic recoil
6159 and internal viscous drag forces. The recoil could be modeled as that
6160 of a damped entropic spring consisting of independent worm-like chains.
6161 The functional importance of myofibrillar elastic recoil was addressed
6162 by comparing instantaneous Vp to unloaded shortening velocity, which
6163 was measured in demembranated, fully Ca2+-activated, human cardiac
6164 fibers. Titin-driven passive recoil was much faster than active
6165 unloaded shortening velocity in early phases of isotonic contraction.
6166 Damped myofibrillar elastic recoil could help accelerate active
6167 contraction speed of human myocardium during early systolic
6171 @article { oroudjev02,
6172 author = EOroudjev #" and "# JSoares #" and "# SArcidiacono #" and "#
6173 JThompson #" and "# SFossey #" and "# HHansma,
6174 title = "Segmented nanofibers of spider dragline silk: Atomic force
6175 microscopy and single-molecule force spectroscopy",
6180 pages = "6460--6465",
6181 doi = "10.1073/pnas.082526499",
6182 eprint = "http://www.pnas.org/cgi/reprint/99/suppl_2/6460.pdf",
6183 url = "http://www.pnas.org/cgi/content/abstract/99/suppl_2/6460",
6184 abstract = "Despite its remarkable materials properties, the structure of
6185 spider dragline silk has remained unsolved. Results from two probe
6186 microscopy techniques provide new insights into the structure of spider
6187 dragline silk. A soluble synthetic protein from dragline silk
6188 spontaneously forms nanofibers, as observed by atomic force microscopy.
6189 These nanofibers have a segmented substructure. The segment length and
6190 amino acid sequence are consistent with a slab-like shape for
6191 individual silk protein molecules. The height and width of nanofiber
6192 segments suggest a stacking pattern of slab-like molecules in each
6193 nanofiber segment. This stacking pattern produces nano-crystals in an
6194 amorphous matrix, as observed previously by NMR and x-ray diffraction
6195 of spider dragline silk. The possible importance of nanofiber formation
6196 to native silk production is discussed. Force spectra for single
6197 molecules of the silk protein demonstrate that this protein unfolds
6198 through a number of rupture events, indicating a modular substructure
6199 within single silk protein molecules. A minimal unfolding module size
6200 is estimated to be around 14 nm, which corresponds to the extended
6201 length of a single repeated module, 38 amino acids long. The structure
6202 of this spider silk protein is distinctly different from the structures
6203 of other proteins that have been analyzed by single-molecule force
6204 spectroscopy, and the force spectra show correspondingly novel
6209 author = EPaci #" and "# MKarplus,
6210 title = "Unfolding proteins by external forces and temperature: The
6211 importance of topology and energetics",
6216 pages = "6521--6526",
6217 doi = "10.1073/pnas.100124597",
6218 eprint = "http://www.pnas.org/cgi/reprint/97/12/6521.pdf",
6219 url = "http://www.pnas.org/cgi/content/abstract/97/12/6521"
6223 author = EPaci #" and "# MKarplus,
6224 title = "Forced unfolding of fibronectin type 3 modules: an analysis by
6225 biased molecular dynamics simulations",
6234 doi = "10.1006/jmbi.1999.2670",
6235 keywords = "Dimerization;Fibronectins;Humans;Hydrogen Bonding;Microscopy,
6236 Atomic Force;Protein Denaturation;Protein Folding",
6237 abstract = "Titin, an important constituent of vertebrate muscles, is a
6238 protein of the order of a micrometer in length in the folded state.
6239 Atomic force microscopy and laser tweezer experiments have been used to
6240 stretch titin molecules to more than ten times their folded lengths. To
6241 explain the observed relation between force and extension, it has been
6242 suggested that the immunoglobulin and fibronectin domains unfold one at
6243 a time in an all-or-none fashion. We use molecular dynamics simulations
6244 to study the forced unfolding of two different fibronectin type 3
6245 domains (the ninth, 9Fn3, and the tenth, 10Fn3, from human fibronectin)
6246 and of their heterodimer of known structure. An external biasing
6247 potential on the N to C distance is employed and the protein is treated
6248 in the polar hydrogen representation with an implicit solvation model.
6249 The latter provides an adiabatic solvent response, which is important
6250 for the nanosecond unfolding simulation method used here. A series of
6251 simulations is performed for each system to obtain meaningful results.
6252 The two different fibronectin domains are shown to unfold in the same
6253 way along two possible pathways. These involve the partial separation
6254 of the ``beta-sandwich'', an essential structural element, and the
6255 unfolding of the individual sheets in a stepwise fashion. The biasing
6256 potential results are confirmed by constant force unfolding
6257 simulations. For the two connected domains, there is complete unfolding
6258 of one domain (9Fn3) before major unfolding of the second domain
6259 (10Fn3). Comparison of different models for the potential energy
6260 function demonstrates that the dominant cohesive element in both
6261 proteins is due to the attractive van der Waals interactions;
6262 electrostatic interactions play a structural role but appear to make
6263 only a small contribution to the stabilization of the domains, in
6264 agreement with other studies of beta-sheet stability. The unfolding
6265 forces found in the simulations are of the order of those observed
6266 experimentally, even though the speed of the former is more than six
6267 orders of magnitude greater than that used in the latter."
6271 author = QPeng #" and "# HLi,
6272 title = "Atomic force microscopy reveals parallel mechanical unfolding
6273 pathways of T4 lysozyme: Evidence for a kinetic partitioning mechanism",
6278 pages = "1885--1890",
6279 doi = "10.1073/pnas.0706775105",
6280 eprint = "http://www.pnas.org/cgi/reprint/105/6/1885.pdf",
6281 url = "http://www.pnas.org/cgi/content/abstract/105/6/1885",
6282 abstract = "Kinetic partitioning is predicted to be a general mechanism for
6283 proteins to fold into their well defined native three-dimensional
6284 structure from unfolded states following multiple folding pathways.
6285 However, experimental evidence supporting this mechanism is still
6286 limited. By using single-molecule atomic force microscopy, here we
6287 report experimental evidence supporting the kinetic partitioning
6288 mechanism for mechanical unfolding of T4 lysozyme, a small protein
6289 composed of two subdomains. We observed that on stretching from its N
6290 and C termini, T4 lysozyme unfolds by multiple distinct unfolding
6291 pathways: the majority of T4 lysozymes unfold in an all-or-none fashion
6292 by overcoming a dominant unfolding kinetic barrier; and a small
6293 fraction of T4 lysozymes unfold in three-state fashion involving
6294 unfolding intermediate states. The three-state unfolding pathways do
6295 not follow well defined routes, instead they display variability and
6296 diversity in individual unfolding pathways. The unfolding intermediate
6297 states are local energy minima along the mechanical unfolding pathways
6298 and are likely to result from the residual structures present in the
6299 two subdomains after crossing the main unfolding barrier. These results
6300 provide direct evidence for the kinetic partitioning of the mechanical
6301 unfolding pathways of T4 lysozyme, and the complex unfolding behaviors
6302 reflect the stochastic nature of kinetic barrier rupture in mechanical
6303 unfolding processes. Our results demonstrate that single-molecule
6304 atomic force microscopy is an ideal tool to investigate the
6305 folding/unfolding dynamics of complex multimodule proteins that are
6306 otherwise difficult to study using traditional methods."
6310 author = WPress #" and "# STeukolsky #" and "# WVetterling #" and "#
6312 title = "Numerical Recipies in {C}: The Art of Scientific Computing",
6316 address = "New York",
6317 eprint = "http://www.nrbook.com/a/bookcpdf.php",
6318 note = "See Sections 12.0, 12.1, 12.3, and 13.4 for a good introduction to
6319 Fourier transforms and power spectrum estimation.",
6320 project = "Cantilever Calibration"
6323 @article { puchner08,
6324 author = EPuchner #" and "# GFranzen #" and "# MGautel #" and "# HEGaub,
6325 title = "Comparing proteins by their unfolding pattern.",
6333 doi = "10.1529/biophysj.108.129999",
6334 eprint = "http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2426622/pdf/426.pdf",
6335 url = "http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2426622/",
6336 keywords = "Algorithms;Computer Simulation;Microscopy, Atomic Force;Models,
6337 Chemical;Models, Molecular;Protein Denaturation;Protein
6339 abstract = "Single molecule force spectroscopy has evolved into an
6340 important and extremely powerful technique for investigating the
6341 folding potentials of biomolecules. Mechanical tension is applied to
6342 individual molecules, and the subsequent, often stepwise unfolding is
6343 recorded in force extension traces. However, because the energy
6344 barriers of the folding potentials are often close to the thermal
6345 energy, both the extensions and the forces at which these barriers are
6346 overcome are subject to marked fluctuations. Therefore, force extension
6347 traces are an inadequate representation despite widespread use
6348 particularly when large populations of proteins need to be compared and
6349 analyzed. We show in this article that contour length, which is
6350 independent of fluctuations and alterable experimental parameters, is a
6351 more appropriate variable than extension. By transforming force
6352 extension traces into contour length space, histograms are obtained
6353 that directly represent the energy barriers. In contrast to force
6354 extension traces, such barrier position histograms can be averaged to
6355 investigate details of the unfolding potential. The cross-superposition
6356 of barrier position histograms allows us to detect and visualize the
6357 order of unfolding events. We show with this approach that in contrast
6358 to the sequential unfolding of bacteriorhodopsin, two main steps in the
6359 unfolding of the enzyme titin kinase are independent of each other. The
6360 potential of this new method for accurate and automated analysis of
6361 force spectroscopy data and for novel automated screening techniques is
6362 shown with bacteriorhodopsin and with protein constructs containing GFP
6364 note = {Contour length space and barrier position fingerprinting.
6365 There are errors in \fref{equation}{3}, propagated from
6366 \citet{livadaru03}. I contacted Elias Puchner and pointed out the
6367 typos, and he revised his FRC fit parameters from $\gamma=22\dg$
6368 and $b=0.4\U{nm}$ to $\gamma=41\dg$ and $b=0.11\U{nm}$. The
6369 combined effect on \fref{figure}{3} of fixing the equation typos
6370 and adjusting the fit parameters was small, so their conclusions
6374 @article { raible04,
6375 author = MRaible #" and "# MEvstigneev #" and "# PReimann #" and "#
6376 FWBartels #" and "# RRos,
6377 title = "Theoretical analysis of dynamic force spectroscopy experiments on
6378 ligand-receptor complexes",
6387 doi = "10.1016/j.jbiotec.2004.04.017",
6388 keywords = "Binding Sites;Computer Simulation;DNA;DNA-Binding
6389 Proteins;Elasticity;Ligands;Macromolecular
6390 Substances;Micromanipulation;Microscopy, Atomic Force;Models,
6391 Chemical;Molecular Biology;Nucleic Acid Conformation;Physical
6392 Stimulation;Protein Binding;Protein Conformation;Stress, Mechanical",
6393 abstract = "The forced rupture of single chemical bonds in biomolecular
6394 compounds (e.g. ligand-receptor systems) as observed in dynamic force
6395 spectroscopy experiments is addressed. Under the assumption that the
6396 probability of bond rupture depends only on the instantaneously acting
6397 force, a data collapse onto a single master curve is predicted. For
6398 rupture data obtained experimentally by dynamic AFM force spectroscopy
6399 of a ligand-receptor bond between a DNA and a regulatory protein we do
6400 not find such a collapse. We conclude that the above mentioned,
6401 generally accepted assumption is not satisfied and we discuss possible
6405 @article { raible06,
6406 author = MRaible #" and "# MEvstigneev #" and "# FWBartels #" and "# REckel
6407 #" and "# MNguyen-Duong #" and "# RMerkel #" and "# RRos #" and "#
6408 DAnselmetti #" and "# PReimann,
6409 title = "Theoretical analysis of single-molecule force spectroscopy
6410 experiments: heterogeneity of chemical bonds",
6417 pages = "3851--3864",
6419 doi = "10.1529/biophysj.105.077099",
6420 eprint = "http://www.biophysj.org/cgi/reprint/90/11/3851.pdf",
6421 url = "http://www.biophysj.org/cgi/content/abstract/90/11/3851",
6422 keywords = "Biomechanics;Microscopy, Atomic Force;Models,
6423 Molecular;Statistical Distributions;Thermodynamics",
6424 abstract = "We show that the standard theoretical framework in single-
6425 molecule force spectroscopy has to be extended to consistently describe
6426 the experimental findings. The basic amendment is to take into account
6427 heterogeneity of the chemical bonds via random variations of the force-
6428 dependent dissociation rates. This results in a very good agreement
6429 between theory and rupture data from several different experiments."
6432 @article{ bartels03,
6433 author = FWBartels #" and "# BBaumgarth #" and "# DAnselmetti
6434 #" and "# RRos #" and "# ABecker,
6435 title = "Specific binding of the regulatory protein Exp{G} to
6436 promoter regions of the galactoglucan biosynthesis gene cluster of
6437 Sinorhizobium meliloti--a combined molecular biology and force
6438 spectroscopy investigation.",
6439 journal = JStructBiol,
6442 address = "Experimentelle Biophysik, Fakult{\"a}t f{\"u}r Physik,
6443 Universit{\"a}t Bielefeld, 33615 Bielefeld, Germany.",
6447 keywords = "Base Sequence",
6448 keywords = "Binding Sites",
6449 keywords = "Conserved Sequence",
6450 keywords = "Fungal Proteins",
6451 keywords = "Galactans",
6452 keywords = "Glucans",
6453 keywords = "Kinetics",
6454 keywords = "Microscopy, Atomic Force",
6455 keywords = "Multigene Family",
6456 keywords = "Polysaccharides, Bacterial",
6457 keywords = "Promoter Regions, Genetic",
6458 keywords = "Protein Binding",
6459 keywords = "Sinorhizobium meliloti",
6460 keywords = "Trans-Activators",
6461 abstract = "Specific protein-DNA interaction is fundamental for all
6462 aspects of gene transcription. We focus on a regulatory
6463 DNA-binding protein in the Gram-negative soil bacterium
6464 Sinorhizobium meliloti 2011, which is capable of fixing molecular
6465 nitrogen in a symbiotic interaction with alfalfa plants. The ExpG
6466 protein plays a central role in regulation of the biosynthesis of
6467 the exopolysaccharide galactoglucan, which promotes the
6468 establishment of symbiosis. ExpG is a transcriptional activator of
6469 exp gene expression. We investigated the molecular mechanism of
6470 binding of ExpG to three associated target sequences in the exp
6471 gene cluster with standard biochemical methods and single molecule
6472 force spectroscopy based on the atomic force microscope
6473 (AFM). Binding of ExpG to expA1, expG-expD1, and expE1 promoter
6474 fragments in a sequence specific manner was demonstrated, and a 28
6475 bp conserved region was found. AFM force spectroscopy experiments
6476 confirmed the specific binding of ExpG to the promoter regions,
6477 with unbinding forces ranging from 50 to 165 pN in a logarithmic
6478 dependence from the loading rates of 70-79000 pN/s. Two different
6479 regimes of loading rate-dependent behaviour were
6480 identified. Thermal off-rates in the range of k(off)=(1.2+/-1.0) x
6481 10(-3)s(-1) were derived from the lower loading rate regime for
6482 all promoter regions. In the upper loading rate regime, however,
6483 these fragments exhibited distinct differences which are
6484 attributed to the molecular binding mechanism.",
6486 URL = "http://www.ncbi.nlm.nih.gov/pubmed/12972351",
6491 author = MRief #" and "# HGrubmuller,
6492 title = "Force spectroscopy of single biomolecules",
6501 doi = "10.1002/1439-7641(20020315)3:3<255::AID-CPHC255>3.0.CO;2-M",
6502 url = "http://www3.interscience.wiley.com/journal/91016383/abstract",
6503 keywords = "Ligands;Microscopy, Atomic Force;Polysaccharides;Protein
6504 Denaturation;Proteins",
6505 abstract = "Many processes in the body are effected and regulated by highly
6506 specialized protein molecules: These molecules certainly deserve the
6507 name ``biochemical nanomachines''. Recent progress in single-molecule
6508 experiments and corresponding simulations with supercomputers enable us
6509 to watch these ``nanomachines'' at work, revealing a host of astounding
6510 mechanisms. Examples are the fine-tuned movements of the binding pocket
6511 of a receptor protein locking into its ligand molecule and the forced
6512 unfolding of titin, which acts as a molecular shock absorber to protect
6513 muscle cells. At present, we are not capable of designing such high
6514 precision machines, but we are beginning to understand their working
6515 principles and to simulate and predict their function.",
6516 note = "Nice, general review of force spectroscopy to 2002, but not much
6522 title = "Fundamentals of Statistical and Thermal Physics",
6524 publisher = McGraw-Hill,
6525 address = "New York",
6526 note = "Thermal noise for simple harmonic oscillators, in Chapter
6527 15, Sections 6 and 10.",
6528 project = "Cantilever Calibration"
6532 author = MRief #" and "# MGautel #" and "# FOesterhelt #" and "# JFernandez
6534 title = "Reversible Unfolding of Individual Titin Immunoglobulin Domains by
6540 pages = "1109--1112",
6541 doi = "10.1126/science.276.5315.1109",
6542 eprint = "http://www.sciencemag.org/cgi/reprint/276/5315/1109.pdf",
6543 url = "http://www.sciencemag.org/cgi/content/abstract/276/5315/1109",
6544 note = "Seminal paper for force spectroscopy on Titin. Cited by
6545 \citet{dietz04} (ref 9) as an example of how unfolding large proteins
6546 is easily interpreted (vs.\ confusing unfolding in bulk), but Titin is
6547 a rather simple example of that, because of its globular-chain
6549 project = "Energy Landscape Roughness"
6553 author = MRief #" and "# FOesterhelt #" and "# BHeymann #" and "# HEGaub,
6554 title = "Single Molecule Force Spectroscopy on Polysaccharides by Atomic
6562 pages = "1295--1297",
6564 doi = "10.1126/science.275.5304.1295",
6565 eprint = "http://www.sciencemag.org/cgi/reprint/275/5304/1295.pdf",
6566 url = "http://www.sciencemag.org/cgi/content/abstract/275/5304/1295",
6567 abstract = "Recent developments in piconewton instrumentation allow the
6568 manipulation of single molecules and measurements of intermolecular as
6569 well as intramolecular forces. Dextran filaments linked to a gold
6570 surface were probed with the atomic force microscope tip by vertical
6571 stretching. At low forces the deformation of dextran was found to be
6572 dominated by entropic forces and can be described by the Langevin
6573 function with a 6 angstrom Kuhn length. At elevated forces the strand
6574 elongation was governed by a twist of bond angles. At higher forces the
6575 dextran filaments underwent a distinct conformational change. The
6576 polymer stiffened and the segment elasticity was dominated by the
6577 bending of bond angles. The conformational change was found to be
6578 reversible and was corroborated by molecular dynamics calculations."
6582 author = MRief #" and "# JFernandez #" and "# HEGaub,
6583 title = "Elastically Coupled Two-Level Systems as a Model for Biopolymer
6590 pages = "4764--4767",
6593 doi = "10.1103/PhysRevLett.81.4764",
6594 eprint = "http://prola.aps.org/pdf/PRL/v81/i21/p4764_1",
6595 url = "http://prola.aps.org/abstract/PRL/v81/i21/p4764_1",
6596 note = "Original details on mechanical unfolding analysis via Monte Carlo
6601 author = MRief #" and "# HClausen-Schaumann #" and "# HEGaub,
6602 title = "Sequence-dependent mechanics of single {DNA} molecules",
6610 doi = "10.1038/7582",
6611 eprint = "http://www.nature.com/nsmb/journal/v6/n4/pdf/nsb0499_346.pdf",
6612 url = "http://www.nature.com/nsmb/journal/v6/n4/abs/nsb0499_346.html",
6613 keywords = "Bacteriophage lambda;Base Pairing;DNA;DNA, Single-Stranded;DNA,
6614 Viral;Gold;Mechanics;Microscopy, Atomic Force;Nucleotides;Spectrum
6615 Analysis;Thermodynamics",
6616 abstract = "Atomic force microscope-based single-molecule force
6617 spectroscopy was employed to measure sequence-dependent mechanical
6618 properties of DNA by stretching individual DNA double strands attached
6619 between a gold surface and an AFM tip. We discovered that in lambda-
6620 phage DNA the previously reported B-S transition, where 'S' represents
6621 an overstretched conformation, at 65 pN is followed by a nonequilibrium
6622 melting transition at 150 pN. During this transition the DNA is split
6623 into single strands that fully recombine upon relaxation. The sequence
6624 dependence was investigated in comparative studies with poly(dG-dC) and
6625 poly(dA-dT) DNA. Both the B-S and the melting transition occur at
6626 significantly lower forces in poly(dA-dT) compared to poly(dG-dC). We
6627 made use of the melting transition to prepare single poly(dG-dC) and
6628 poly(dA-dT) DNA strands that upon relaxation reannealed into hairpins
6629 as a result of their self-complementary sequence. The unzipping of
6630 these hairpins directly revealed the base pair-unbinding forces for G-C
6631 to be 20 +/- 3 pN and for A-T to be 9 +/- 3 pN."
6634 @article{ schmitt00,
6635 author = LSchmitt #" and "# MLudwig #" and "# HEGaub #" and "# RTampe,
6636 title = "A metal-chelating microscopy tip as a new toolbox for
6637 single-molecule experiments by atomic force microscopy.",
6641 address = "Institut f{\"u}r Physiologische Chemie,
6642 Philipps-Universit{\"a}t Marburg, 35033 Marburg,
6643 Germany. schmittl@mailer.uni-marburg.de",
6646 pages = "3275--3285",
6647 keywords = "Chelating Agents",
6648 keywords = "Edetic Acid",
6649 keywords = "Histidine",
6650 keywords = "Metals",
6651 keywords = "Microscopy, Atomic Force",
6652 keywords = "Nitrilotriacetic Acid",
6653 keywords = "Peptides",
6654 keywords = "Recombinant Fusion Proteins",
6655 abstract = "In recent years, the atomic force microscope (AFM) has
6656 contributed much to our understanding of the molecular forces
6657 involved in various high-affinity receptor-ligand
6658 systems. However, a universal anchor system for such measurements
6659 is still required. This would open up new possibilities for the
6660 study of biological recognition processes and for the
6661 establishment of high-throughput screening applications. One such
6662 candidate is the N-nitrilo-triacetic acid (NTA)/His-tag system,
6663 which is widely used in molecular biology to isolate and purify
6664 histidine-tagged fusion proteins. Here the histidine tag acts as a
6665 high-affinity recognition site for the NTA chelator. Accordingly,
6666 we have investigated the possibility of using this approach in
6667 single-molecule force measurements. Using a histidine-peptide as a
6668 model system, we have determined the binding force for various
6669 metal ions. At a loading rate of 0.5 microm/s, the determined
6670 forces varied from 22 +/- 4 to 58 +/- 5 pN. Most importantly, no
6671 interaction was detected for Ca(2+) and Mg(2+) up to
6672 concentrations of 10 mM. Furthermore, EDTA and a metal ion
6673 reloading step demonstrated the reversibility of the
6674 approach. Here the molecular interactions were turned off (EDTA)
6675 and on (metal reloading) in a switch-like fashion. Our results
6676 show that the NTA/His-tag system will expand the ``molecular
6677 toolboxes'' with which receptor-ligand systems can be investigated
6678 at the single-molecule level.",
6680 doi = "10.1016/S0006-3495(00)76863-9",
6681 URL = "http://www.ncbi.nlm.nih.gov/pubmed/10828003",
6685 @article { roters96,
6686 author = ARoters #" and "# DJohannsmann,
6687 title = "Distance-dependent noise measurements in scanning force
6693 pages = "7561-7577",
6694 doi = "10.1088/0953-8984",
6695 eprint = "http://www.iop.org/EJ/article/0953-8984/8/41/006/c64103.pdf",
6696 url = "http://stacks.iop.org/0953-8984/8/7561",
6697 abstract = "The changes in the thermal noise spectrum of a scanning-force-
6698 microscope cantilever upon approach of the tip to the sample were used
6699 to investigate the interactions between the cantilever and the sample.
6700 The investigation of thermal noise is the natural choice for dynamic
6701 measurements with little disturbance of the sample. In particular, the
6702 small amplitudes involved ensure linear dynamic response. It is
6703 possible to discriminate between viscous coupling, elastic coupling and
6704 changes in the effective mass. The technique is versatile in terms of
6705 substrates and environments. Hydrodynamic long-range interactions
6706 depending on the sample, the geometry and the ambient medium are
6707 observed. The dependence of hydrodynamic interaction on various
6708 parameters such as the viscosity and the density of the medium is
6709 described. For sufficiently soft surfaces, the method is sensitive to
6710 viscoelastic properties of the surface. For example, the viscous
6711 coupling to the surface is strongly increased when the surface is
6712 covered with a swollen `polymer brush'.",
6713 note = "They actually write down a Lagrangian formula and give a decent
6714 derivation of PSD, but don't show or work out the integrals.",
6715 project = "Cantilever Calibration"
6718 @article { ryckaert77,
6719 author = JPRyckaert #" and "# GCiccotti #" and "# HJCBerendsen,
6720 title = "Numerical integration of the cartesian equations of motion of a
6721 system with constraints: molecular dynamics of n-alkanes",
6728 doi = "10.1016/0021-9991(77)90098-5",
6729 url = "http://dx.doi.org/10.1016/0021-9991(77)90098-5",
6730 abstract = "A numerical algorithm integrating the 3N Cartesian equations of
6731 motion of a system of N points subject to holonomic constraints is
6732 formulated. The relations of constraint remain perfectly fulfilled at
6733 each step of the trajectory despite the approximate character of
6734 numerical integration. The method is applied to a molecular dynamics
6735 simulation of a liquid of 64 n-butane molecules and compared to a
6736 simulation using generalized coordinates. The method should be useful
6737 for molecular dynamics calculations on large molecules with internal
6738 degrees of freedom.",
6739 note = "Entry-level explaination of MD with rigid constraints. Explicit
6740 Verlet integrator example."
6743 @article { sarkar04,
6744 author = ASarkar #" and "# RRobertson #" and "# JFernandez,
6745 title = "Simultaneous atomic force microscope and fluorescence measurements
6746 of protein unfolding using a calibrated evanescent wave",
6751 pages = "12882--12886",
6752 doi = "10.1073/pnas.0403534101",
6753 eprint = "http://www.pnas.org/cgi/reprint/101/35/12882.pdf",
6754 url = "http://www.pnas.org/cgi/content/abstract/101/35/12882",
6755 abstract = "Fluorescence techniques for monitoring single-molecule dynamics
6756 in the vertical dimension currently do not exist. Here we use an atomic
6757 force microscope to calibrate the distance-dependent intensity decay of
6758 an evanescent wave. The measured evanescent wave transfer function was
6759 then used to convert the vertical motions of a fluorescent particle
6760 into displacement ($SD =< 1$ nm). We demonstrate the use of the
6761 calibrated evanescent wave to resolve the 20.1 {+/-} 0.5-nm step
6762 increases in the length of the small protein ubiquitin during forced
6763 unfolding. The experiments that we report here make an important
6764 contribution to fluorescence microscopy by demonstrating the
6765 unambiguous optical tracking of a single molecule with a resolution
6766 comparable to that of an atomic force microscope."
6770 author = TSato #" and "# MEsaki #" and "# JFernandez #" and "# TEndo,
6771 title = "{Comparison of the protein-unfolding pathways between
6772 mitochondrial protein import and atomic-force microscopy measurements}",
6777 pages = "17999--18004",
6778 doi = "10.1073/pnas.0504495102",
6779 eprint = "http://www.pnas.org/cgi/reprint/102/50/17999.pdf",
6780 url = "http://www.pnas.org/cgi/content/abstract/102/50/17999",
6781 abstract = "Many newly synthesized proteins have to become unfolded during
6782 translocation across biological membranes. We have analyzed the effects
6783 of various stabilization/destabilization mutations in the Ig-like
6784 module of the muscle protein titin upon its import from the N terminus
6785 or C terminus into mitochondria. The effects of mutations on the import
6786 of the titin module from the C terminus correlate well with those on
6787 forced mechanical unfolding in atomic-force microscopy (AFM)
6788 measurements. On the other hand, as long as turnover of the
6789 mitochondrial Hsp70 system is not rate-limiting for the import, import
6790 of the titin module from the N terminus is sensitive to mutations in
6791 the N-terminal region but not the ones in the C-terminal region that
6792 affect resistance to global unfolding in AFM experiments. We propose
6793 that the mitochondrial-import system can catalyze precursor-unfolding
6794 by reducing the stability of unfolding intermediates."
6797 @article { schlierf04,
6798 author = MSchlierf #" and "# HLi #" and "# JFernandez,
6799 title = "The unfolding kinetics of ubiquitin captured with single-molecule
6800 force-clamp techniques",
6807 pages = "7299--7304",
6809 doi = "10.1073/pnas.0400033101",
6810 eprint = "http://www.pnas.org/cgi/reprint/101/19/7299.pdf",
6811 url = "http://www.pnas.org/cgi/content/abstract/101/19/7299",
6812 keywords = "Kinetics;Microscopy, Atomic Force;Probability;Ubiquitin",
6813 abstract = "We use single-molecule force spectroscopy to study the kinetics
6814 of unfolding of the small protein ubiquitin. Upon a step increase in
6815 the stretching force, a ubiquitin polyprotein extends in discrete steps
6816 of 20.3 +/- 0.9 nm marking each unfolding event. An average of the time
6817 course of these unfolding events was well described by a single
6818 exponential, which is a necessary condition for a memoryless Markovian
6819 process. Similar ensemble averages done at different forces showed that
6820 the unfolding rate was exponentially dependent on the stretching force.
6821 Stretching a ubiquitin polyprotein with a force that increased at a
6822 constant rate (force-ramp) directly measured the distribution of
6823 unfolding forces. This distribution was accurately reproduced by the
6824 simple kinetics of an all-or-none unfolding process. Our force-clamp
6825 experiments directly demonstrate that an ensemble average of ubiquitin
6826 unfolding events is well described by a two-state Markovian process
6827 that obeys the Arrhenius equation. However, at the single-molecule
6828 level, deviant behavior that is not well represented in the ensemble
6829 average is readily observed. Our experiments make an important addition
6830 to protein spectroscopy by demonstrating an unambiguous method of
6831 analysis of the kinetics of protein unfolding by a stretching force."
6834 @article { schlierf06,
6835 author = MSchlierf #" and "# MRief,
6836 title = "Single-molecule unfolding force distributions reveal a funnel-
6837 shaped energy landscape",
6846 doi = "10.1529/biophysj.105.077982",
6847 url = "http://www.biophysj.org/cgi/content/abstract/90/4/L33",
6848 keywords = "Models, Molecular; Protein Folding; Proteins; Thermodynamics",
6849 abstract = "The protein folding process is described as diffusion on a
6850 high-dimensional energy landscape. Experimental data showing details of
6851 the underlying energy surface are essential to understanding folding.
6852 So far in single-molecule mechanical unfolding experiments a simplified
6853 model assuming a force-independent transition state has been used to
6854 extract such information. Here we show that this so-called Bell model,
6855 although fitting well to force velocity data, fails to reproduce full
6856 unfolding force distributions. We show that by applying Kramers'
6857 diffusion model, we were able to reconstruct a detailed funnel-like
6858 curvature of the underlying energy landscape and establish full
6859 agreement with the data. We demonstrate that obtaining spatially
6860 resolved details of the unfolding energy landscape from mechanical
6861 single-molecule protein unfolding experiments requires models that go
6862 beyond the Bell model.",
6863 note = {The inspiration behind my sawtooth simulation. Bell model
6864 fit to $f_{unfold}(v)$, but Kramers model fit to unfolding
6865 distribution for a given $v$. \fref{equation}{3} in the
6866 supplement is \xref{evans99}{equation}{2}, but it is just
6867 $[\text{dying percent}] \cdot [\text{surviving population}]
6869 $\nu \equiv k$ is the force/time-dependent off rate. The Kramers'
6870 rate equation (on page L34, the second equation in the paper) is
6871 \xref{hanggi90}{equation}{4.56b} (page 275) and
6872 \xref{socci96}{equation}{2} but \citet{schlierf06} gets the minus
6873 sign wrong in the exponent. $U_F(x=0)\gg 0$ and
6874 $U_F(x_\text{max})\ll 0$ (\cf~\xref{schlierf06}{figure}{1}).
6875 Schlierf's integral (as written) contains
6876 $\exp{-U_F(x_\text{max})}\cdot\exp{U_F(0)}$, which is huge, when
6877 it should contain $\exp{U_F(x_\text{max})}\cdot\exp{-U_F(0)}$,
6878 which is tiny. For more details and a picture of the peak that
6879 forms the bulk of the integrand, see
6880 \cref{eq:kramers,fig:kramers:integrand}. I pointed out this
6881 problem to Michael Schlierf, but he was unconvinced.},
6884 @article { schwaiger04,
6885 author = ISchwaiger #" and "# AKardinal #" and "# MSchleicher #" and "#
6886 AANoegel #" and "# MRief,
6887 title = "A mechanical unfolding intermediate in an actin-crosslinking
6897 doi = "10.1038/nsmb705",
6898 eprint = "http://www.nature.com/nsmb/journal/v11/n1/pdf/nsmb705.pdf",
6899 url = "http://www.nature.com/nsmb/journal/v11/n1/full/nsmb705.html",
6900 keywords = "Actins; Animals; Contractile Proteins; Cross-Linking Reagents;
6901 Dictyostelium; Dimerization; Microfilament Proteins; Microscopy, Atomic
6902 Force; Mutagenesis, Site-Directed; Protein Denaturation; Protein
6903 Folding; Protein Structure, Tertiary; Protozoan Proteins",
6904 abstract = "Many F-actin crosslinking proteins consist of two actin-binding
6905 domains separated by a rod domain that can vary considerably in length
6906 and structure. In this study, we used single-molecule force
6907 spectroscopy to investigate the mechanics of the immunoglobulin (Ig)
6908 rod domains of filamin from Dictyostelium discoideum (ddFLN). We find
6909 that one of the six Ig domains unfolds at lower forces than do those of
6910 all other domains and exhibits a stable unfolding intermediate on its
6911 mechanical unfolding pathway. Amino acid inserts into various loops of
6912 this domain lead to contour length changes in the single-molecule
6913 unfolding pattern. These changes allowed us to map the stable core of
6914 approximately 60 amino acids that constitutes the unfolding
6915 intermediate. Fast refolding in combination with low unfolding forces
6916 suggest a potential in vivo role for this domain as a mechanically
6917 extensible element within the ddFLN rod.",
6918 note = "ddFLN unfolding with WLC params for sacrificial domains. Gives
6919 persistence length $p = 0.5\mbox{ nm}$ in ``high force regime'', $p =
6920 0.9\mbox{ nm}$ in ``low force regime'', with a transition at $F =
6922 project = "sawtooth simulation"
6925 @article { schwaiger05,
6926 author = ISchwaiger #" and "# MSchleicher #" and "# AANoegel #" and "#
6928 title = "The folding pathway of a fast-folding immunoglobulin domain
6929 revealed by single-molecule mechanical experiments",
6937 doi = "10.1038/sj.embor.7400317",
6938 eprint = "http://www.nature.com/embor/journal/v6/n1/pdf/7400317.pdf",
6939 url = "http://www.nature.com/embor/journal/v6/n1/index.html",
6940 keywords = "Animals; Contractile Proteins; Dictyostelium; Immunoglobulins;
6941 Kinetics; Microfilament Proteins; Models, Molecular; Protein Folding;
6942 Protein Structure, Tertiary",
6943 abstract = "The F-actin crosslinker filamin from Dictyostelium discoideum
6944 (ddFLN) has a rod domain consisting of six structurally similar
6945 immunoglobulin domains. When subjected to a stretching force, domain 4
6946 unfolds at a lower force than all the other domains in the chain.
6947 Moreover, this domain shows a stable intermediate along its mechanical
6948 unfolding pathway. We have developed a mechanical single-molecule
6949 analogue to a double-jump stopped-flow experiment to investigate the
6950 folding kinetics and pathway of this domain. We show that an obligatory
6951 and productive intermediate also occurs on the folding pathway of the
6952 domain. Identical mechanical properties suggest that the unfolding and
6953 refolding intermediates are closely related. The folding process can be
6954 divided into two consecutive steps: in the first step 60 C-terminal
6955 amino acids form an intermediate at the rate of 55 s(-1); and in the
6956 second step the remaining 40 amino acids are packed on this core at the
6957 rate of 179 s(-1). This division increases the overall folding rate of
6958 this domain by a factor of ten compared with all other homologous
6959 domains of ddFLN that lack the folding intermediate."
6962 @article { sharma07,
6963 author = DSharma #" and "# OPerisic #" and "# QPeng #" and "# YCao #" and
6964 "# CLam #" and "# HLu #" and "# HLi,
6965 title = "Single-molecule force spectroscopy reveals a mechanically stable
6966 protein fold and the rational tuning of its mechanical stability",
6971 pages = "9278--9283",
6972 doi = "10.1073/pnas.0700351104",
6973 eprint = "http://www.pnas.org/cgi/reprint/104/22/9278.pdf",
6974 url = "http://www.pnas.org/cgi/content/abstract/104/22/9278",
6975 abstract = "It is recognized that shear topology of two directly connected
6976 force-bearing terminal [beta]-strands is a common feature among the
6977 vast majority of mechanically stable proteins known so far. However,
6978 these proteins belong to only two distinct protein folds, Ig-like
6979 [beta] sandwich fold and [beta]-grasp fold, significantly hindering
6980 delineating molecular determinants of mechanical stability and rational
6981 tuning of mechanical properties. Here we combine single-molecule atomic
6982 force microscopy and steered molecular dynamics simulation to reveal
6983 that the de novo designed Top7 fold [Kuhlman B, Dantas G, Ireton GC,
6984 Varani G, Stoddard BL, Baker D (2003) Science 302:13641368] represents
6985 a mechanically stable protein fold that is distinct from Ig-like [beta]
6986 sandwich and [beta]-grasp folds. Although the two force-bearing [beta]
6987 strands of Top7 are not directly connected, Top7 displays significant
6988 mechanical stability, demonstrating that the direct connectivity of
6989 force-bearing [beta] strands in shear topology is not mandatory for
6990 mechanical stability. This finding broadens our understanding of the
6991 design of mechanically stable proteins and expands the protein fold
6992 space where mechanically stable proteins can be screened. Moreover, our
6993 results revealed a substructure-sliding mechanism for the mechanical
6994 unfolding of Top7 and the existence of two possible unfolding pathways
6995 with different height of energy barrier. Such insights enabled us to
6996 rationally tune the mechanical stability of Top7 by redesigning its
6997 mechanical unfolding pathway. Our study demonstrates that computational
6998 biology methods (including de novo design) offer great potential for
6999 designing proteins of defined topology to achieve significant and
7000 tunable mechanical properties in a rational and systematic fashion."
7004 author = YJSheng #" and "# SJiang #" and "# HKTsao,
7005 title = "Forced Kramers escape in single-molecule pulling experiments",
7015 doi = "10.1063/1.2046632",
7016 url = "http://link.aip.org/link/?JCP/123/091102/1",
7017 keywords = "molecular biophysics; bonds (chemical); proteins",
7018 note = "Gives appropriate Einstein-S... relation for diffusion to damping",
7019 project = "sawtooth simulation"
7022 @article { shillcock98,
7023 author = JShillcock #" and "# USeifert,
7024 title = "Escape from a metastable well under a time-ramped force",
7030 pages = "7301--7304",
7033 doi = "10.1103/PhysRevE.57.7301",
7034 eprint = "http://prola.aps.org/pdf/PRE/v57/i6/p7301_1",
7035 url = "http://link.aps.org/abstract/PRE/v57/p7301",
7036 project = "sawtooth simulation"
7040 author = GESims #" and "# SRJun #" and "# GAWu #" and "# SHKim,
7041 title = "Alignment-free genome comparison with feature frequency profiles
7042 ({FFP}) and optimal resolutions",
7049 pages = "2677--2682",
7051 doi = "10.1073/pnas.0813249106",
7052 eprint = "http://www.pnas.org/cgi/reprint/106/31/12826",
7053 url = "http://www.pnas.org/content/106/8/2677",
7054 keywords = "Genome;Introns;Phylogeny",
7055 abstract = "For comparison of whole-genome (genic + nongenic) sequences,
7056 multiple sequence alignment of a few selected genes is not appropriate.
7057 One approach is to use an alignment-free method in which feature (or
7058 l-mer) frequency profiles (FFP) of whole genomes are used for
7059 comparison-a variation of a text or book comparison method, using word
7060 frequency profiles. In this approach it is critical to identify the
7061 optimal resolution range of l-mers for the given set of genomes
7062 compared. The optimum FFP method is applicable for comparing whole
7063 genomes or large genomic regions even when there are no common genes
7064 with high homology. We outline the method in 3 stages: (i) We first
7065 show how the optimal resolution range can be determined with English
7066 books which have been transformed into long character strings by
7067 removing all punctuation and spaces. (ii) Next, we test the robustness
7068 of the optimized FFP method at the nucleotide level, using a mutation
7069 model with a wide range of base substitutions and rearrangements. (iii)
7070 Finally, to illustrate the utility of the method, phylogenies are
7071 reconstructed from concatenated mammalian intronic genomes; the FFP
7072 derived intronic genome topologies for each l within the optimal range
7073 are all very similar. The topology agrees with the established
7074 mammalian phylogeny revealing that intron regions contain a similar
7075 level of phylogenic signal as do coding regions."
7079 author = SBSmith #" and "# LFinzi #" and "# CBustamante,
7080 title = "Direct mechanical measurements of the elasticity of single {DNA}
7081 molecules by using magnetic beads",
7088 pages = "1122--1126",
7090 doi = "10.1126/science.1439819",
7091 eprint = "http://www.sciencemag.org/cgi/reprint/258/5085/1122.pdf",
7092 url = "http://www.sciencemag.org/cgi/content/abstract/258/5085/1122",
7093 keywords = "Chemistry,
7094 Physical;Cisplatin;DNA;Elasticity;Ethidium;Glass;Indoles;Intercalating
7095 Agents;Magnetics;Mathematics;Microspheres",
7096 abstract = "Single DNA molecules were chemically attached by one end to a
7097 glass surface and by their other end to a magnetic bead. Equilibrium
7098 positions of the beads were observed in an optical microscope while the
7099 beads were acted on by known magnetic and hydrodynamic forces.
7100 Extension versus force curves were obtained for individual DNA
7101 molecules at three different salt concentrations with forces between
7102 10(-14) and 10(-11) newtons. Deviations from the force curves predicted
7103 by the freely jointed chain model suggest that DNA has significant
7104 local curvature in solution. Ethidium bromide and
7105 4',6-diamidino-2-phenylindole had little effect on the elastic response
7106 of the molecules, but their extent of intercalation was directly
7107 measured. Conversely, the effect of bend-inducing cis-
7108 diamminedichloroplatinum (II) was large and supports the hypothesis of
7109 natural curvature in DNA."
7113 author = SBSmith #" and "# YCui #" and "# CBustamante,
7114 title = "Overstretching {B}-{DNA}: the elastic response of individual
7115 double-stranded and single-stranded {DNA} molecules",
7124 keywords = "Base Composition;Chemistry, Physical;DNA;DNA, Single-
7125 Stranded;Elasticity;Nucleic Acid Conformation;Osmolar
7126 Concentration;Thermodynamics",
7127 abstract = "Single molecules of double-stranded DNA (dsDNA) were stretched
7128 with force-measuring laser tweezers. Under a longitudinal stress of
7129 approximately 65 piconewtons (pN), dsDNA molecules in aqueous buffer
7130 undergo a highly cooperative transition into a stable form with 5.8
7131 angstroms rise per base pair, that is, 70\% longer than B form dsDNA.
7132 When the stress was relaxed below 65 pN, the molecules rapidly and
7133 reversibly contracted to their normal contour lengths. This transition
7134 was affected by changes in the ionic strength of the medium and the
7135 water activity or by cross-linking of the two strands of dsDNA.
7136 Individual molecules of single-stranded DNA were also stretched giving
7137 a persistence length of 7.5 angstroms and a stretch modulus of 800 pN.
7138 The overstretched form may play a significant role in the energetics of
7143 author = NDSocci #" and "# JNOnuchic #" and "# PGWolynes,
7144 title = "Diffusive dynamics of the reaction coordinate for protein folding
7151 pages = "5860--5868",
7153 doi = "10.1063/1.471317",
7154 eprint = "http://arxiv.org/pdf/cond-mat/9601091",
7155 url = "http://link.aip.org/link/?JCP/104/5860/1",
7156 keywords = "PROTEINS; FOLDS; DIFFUSION; MONTE CARLO METHOD; SIMULATION;
7158 abstract = "The quantitative description of model protein folding kinetics
7159 using a diffusive collective reaction coordinate is examined. Direct
7160 folding kinetics, diffusional coefficients and free energy profiles are
7161 determined from Monte Carlo simulations of a 27-mer, 3 letter code
7162 lattice model, which corresponds roughly to a small helical protein.
7163 Analytic folding calculations, using simple diffusive rate theory,
7164 agree extremely well with the full simulation results. Folding in this
7165 system is best seen as a diffusive, funnel-like process.",
7166 note = "A nice introduction to some quantitative ramifications of the
7167 funnel energy landscape. There's also a bit of Kramers' theory and
7168 graph theory thrown in for good measure."
7172 author = NDSocci #" and "# JNOnuchic #" and "# PGWolynes,
7173 title = "Stretching lattice models of protein folding",
7180 pages = "2031--2035",
7182 keywords = "Amino Acid Sequence;Drug Stability;Kinetics;Models,
7183 Theoretical;Molecular Sequence Data;Peptides;Protein
7184 Denaturation;Protein Folding",
7185 abstract = "A new class of experiments that probe folding of individual
7186 protein domains uses mechanical stretching to cause the transition. We
7187 show how stretching forces can be incorporated in lattice models of
7188 folding. For fast folding proteins, the analysis suggests a complex
7189 relation between the force dependence and the reaction coordinate for
7193 @article { staple08,
7194 author = DBStaple #" and "# SHPayne #" and "# ALCReddin #" and "# HJKreuzer,
7195 title = "Model for stretching and unfolding the giant multidomain muscle
7196 protein using single-molecule force spectroscopy.",
7205 doi = "10.1103/PhysRevLett.101.248301",
7206 url = "http://dx.doi.org/10.1103/PhysRevLett.101.248301",
7207 keywords = "Kinetics;Microscopy, Atomic Force;Models, Chemical;Muscle
7208 Proteins;Protein Conformation;Protein Folding;Protein Kinases;Protein
7209 Structure, Tertiary;Thermodynamics",
7210 abstract = "Single-molecule manipulation has allowed the forced unfolding
7211 of multidomain proteins. Here we outline a theory that not only
7212 explains these experiments but also points out a number of difficulties
7213 in their interpretation and makes suggestions for further experiments.
7214 For titin we reproduce force-extension curves, the dependence of break
7215 force on pulling speed, and break-force distributions and also validate
7216 two common experimental views: Unfolding titin Ig domains can be
7217 explained as stepwise increases in contour length, and increasing force
7218 peaks in native Ig sequences represent a hierarchy of bond strengths.
7219 Our theory is valid for essentially any molecule that can be unfolded
7220 in atomic force microscopy; as a further example, we present force-
7221 extension curves for the unfolding of RNA hairpins."
7225 author = RStark #" and "# TDrobek #" and "# WHeckl,
7226 title = "Thermomechanical noise of a free v-shaped cantilever for atomic-
7235 doi = "http://dx.doi.org/10.1016/S0304-3991(00)00077-2",
7236 abstract = "We have calculated the thermal noise of a v-shaped AFM
7237 cantilever (Microlever, Type E, Thermomicroscopes) by means of a finite
7238 element analysis. The modal shapes of the first 10 eigenmodes are
7239 displayed as well as the numerical constants, which are needed for the
7240 calibration using the thermal noise method. In the first eigenmode,
7241 values for the thermomechanical noise of the z-displacement at 22
7242 degrees C temperature of square root of u2(1) = A/square root of
7243 c(cant) and the photodiode signal (normal-force) of S2(1) = A/square
7244 root of c(cant) were obtained. The results also indicate a systematic
7245 deviation ofthe spectral density of the thermomechanical noise of
7246 v-shaped cantilevers as compared to rectangular beam-shaped
7248 note = "Higher mode adjustments for v-shaped cantilevers from simulation.",
7249 project = "Cantilever Calibration"
7252 @article { strick96,
7253 author = TRStrick #" and "# JFAllemand #" and "# DBensimon #" and "#
7254 ABensimon #" and "# VCroquette,
7255 title = "The elasticity of a single supercoiled {DNA} molecule",
7262 pages = "1835--1837",
7264 keywords = "Bacteriophage lambda;DNA, Superhelical;DNA,
7265 Viral;Elasticity;Magnetics;Nucleic Acid Conformation;Temperature",
7266 abstract = "Single linear DNA molecules were bound at multiple sites at one
7267 extremity to a treated glass cover slip and at the other to a magnetic
7268 bead. The DNA was therefore torsionally constrained. A magnetic field
7269 was used to rotate the beads and thus to coil and pull the DNA. The
7270 stretching force was determined by analysis of the Brownian
7271 fluctuations of the bead. Here the elastic behavior of individual
7272 lambda DNA molecules over- and underwound by up to 500 turns was
7273 studied. A sharp transition was discovered from a low to a high
7274 extension state at a force of approximately 0.45 piconewtons for
7275 underwound molecules and at a force of approximately 3 piconewtons for
7276 overwound ones. These transitions, probably reflecting the formation of
7277 alternative structures in stretched coiled DNA molecules, might be
7278 relevant for DNA transcription and replication."
7281 @article { strunz99,
7282 author = TStrunz #" and "# KOroszlan #" and "# RSchafer #" and "#
7284 title = "Dynamic force spectroscopy of single {DNA} molecules",
7289 pages = "11277--11282",
7290 doi = "10.1073/pnas.96.20.11277",
7291 eprint = "http://www.pnas.org/cgi/reprint/96/20/11277.pdf",
7292 url = "http://www.pnas.org/cgi/content/abstract/96/20/11277"
7296 author = ASzabo #" and "# KSchulten #" and "# ZSchulten,
7297 title = "First passage time approach to diffusion controlled reactions",
7303 pages = "4350--4357",
7305 doi = "10.1063/1.439715",
7306 url = "http://link.aip.org/link/?JCP/72/4350/1",
7307 keywords = "DIFFUSION; CHEMICAL REACTIONS; CHEMICAL REACTION KINETICS;
7308 PROBABILITY; DIFFERENTIAL EQUATIONS"
7311 @article { talaga00,
7312 author = DTalaga #" and "# WLau #" and "# HRoder #" and "# JTang #" and "#
7313 YJia #" and "# WDeGrado #" and "# RHochstrasser,
7314 title = "Dynamics and folding of single two-stranded coiled-coil peptides
7315 studied by fluorescent energy transfer confocal microscopy",
7320 pages = "13021--13026",
7321 doi = "10.1073/pnas.97.24.13021",
7322 eprint = "http://www.pnas.org/cgi/reprint/97/24/13021.pdf",
7323 url = "http://www.pnas.org/cgi/content/abstract/97/24/13021"
7326 @article { thirumalai05,
7327 author = DThirumalai #" and "# CHyeon,
7328 title = "{RNA} and Protein Folding: Common Themes and Variations",
7329 affiliation = "Biophysics Program, and Department of Chemistry and
7330 Biochemistry, Institute for Physical Science and Technology, University
7331 of Maryland, College Park, Maryland 20742",
7336 pages = "4957--4970",
7339 "http://pubs3.acs.org/acs/journals/doilookup?in_doi=10.1021/bi047314+",
7340 abstract = "Visualizing the navigation of an ensemble of unfolded molecules
7341 through the bumpy energy landscape in search of the native state gives
7342 a pictorial view of biomolecular folding. This picture, when combined
7343 with concepts in polymer theory, provides a unified theory of RNA and
7344 protein folding. Just as for proteins, the major folding free energy
7345 barrier for RNA scales sublinearly with the number of nucleotides,
7346 which allows us to extract the elusive prefactor for RNA folding.
7347 Several folding scenarios can be anticipated by considering variations
7348 in the energy landscape that depend on sequence, native topology, and
7349 external conditions. RNA and protein folding mechanism can be described
7350 by the kinetic partitioning mechanism (KPM) according to which a
7351 fraction () of molecules reaches the native state directly, whereas the
7352 remaining fraction gets kinetically trapped in metastable
7353 conformations. For two-state folders 1. Molecular chaperones are
7354 recruited to assist protein folding whenever is small. We show that the
7355 iterative annealing mechanism, introduced to describe chaperonin-
7356 mediated folding, can be generalized to understand protein-assisted RNA
7357 folding. The major differences between the folding of proteins and RNA
7358 arise in the early stages of folding. For RNA, folding can only begin
7359 after the polyelectrolyte problem is solved, whereas protein collapse
7360 requires burial of hydrophobic residues. Cross-fertilization of ideas
7361 between the two fields should lead to an understanding of how RNA and
7362 proteins solve their folding problems.",
7363 note = "unfolding-refolding"
7367 author = SThornton #" and "# JMarion,
7368 title = "Classical Dynamics of Particles and Systems",
7371 isbn = "0-534-40896-6",
7372 publisher = BrooksCole,
7373 address = "Belmont, CA"
7376 @article { tlusty98,
7377 author = TTlusty #" and "# AMeller #" and "# RBar-Ziv,
7378 title = "Optical Gradient Forces of Strongly Localized Fields",
7384 pages = "1738--1741",
7387 doi = "10.1103/PhysRevLett.81.1738",
7388 eprint = "http://prola.aps.org/pdf/PRL/v81/i8/p1738_1",
7390 \url{http://nanoscience.bu.edu/papers/p1738_1_Meller.pdf}.
7391 Cited by \citet{grossman05} for derivation of thermal response
7392 functions. However, I only see a referenced thermal energy when
7393 they list the likelyhood of a small partical (radius $<R_c$)
7394 escaping due to thermal energy, where $R_c$ is roughly $R_c \sim
7395 (k_B T / \alpha I_0)^{1/3}$, $\alpha$ is a dielectric scaling
7396 term, and $I_0$ is the maximum beam energy density. I imagine
7397 Grossman and Stout mixed up this reference.",
7398 project = "Cantilever Calibration"
7401 @article { tshiprut08,
7402 author = ZTshiprut #" and "# JKlafter #" and "# MUrbakh,
7403 title = "Single-molecule pulling experiments: when the stiffness of the
7404 pulling device matters",
7413 doi = "10.1529/biophysj.108.141580",
7414 eprint = "http://www.biophysj.org/cgi/reprint/95/6/L42.pdf",
7415 abstract = "Using Langevin modeling, we investigate the role of the
7416 experimental setup on the unbinding forces measured in single-molecule
7417 pulling experiments. We demonstrate that the stiffness of the pulling
7418 device, K(eff), may influence the unbinding forces through its effect
7419 on the barrier heights for both unbinding and rebinding processes.
7420 Under realistic conditions the effect of K(eff) on the rebinding
7421 barrier is shown to play the most important role. This results in a
7422 significant increase of the mean unbinding force with the stiffness for
7423 a given loading rate. Thus, in contrast to the phenomenological Bell
7424 model, we find that the loading rate (the multiplicative value K(eff)V,
7425 V being the pulling velocity) is not the only control parameter that
7426 determines the mean unbinding force. If interested in intrinsic
7427 properties of a molecular system, we recommend probing the system in
7428 the parameter range corresponding to a weak spring and relatively high
7429 loading rates where rebinding is negligible.",
7430 note = "Cites \citet{dudko03} for Kramers' description of irreversible
7431 rupture, and claims it is required to explain the deviations in
7432 $\avg{F}$ at the same loading rate. Proposes Moese equation as an
7433 example potential. Cites \citet{walton08} for experimental evidence of
7434 $\avg{F}$ increasing with linker stiffness."
7437 @article { uniprot10,
7438 author = UniProtConsort,
7440 title = "The Universal Protein Resource (UniProt) in 2010.",
7446 number = "Database issue",
7447 pages = "D142--D148",
7449 doi = "10.1093/nar/gkp846",
7450 url = "http://nar.oxfordjournals.org/cgi/content/abstract/38/suppl_1/D142",
7451 keywords = "Algorithms;Animals;Computational Biology;Databases, Nucleic
7452 Acid;Databases, Protein;Europe;Genome, Fungal;Genome,
7453 Viral;Humans;Information Storage and Retrieval;Internet;Protein
7454 Isoforms;Proteome;Proteomics;Software",
7455 abstract = "The primary mission of UniProt is to support biological
7456 research by maintaining a stable, comprehensive, fully classified,
7457 richly and accurately annotated protein sequence knowledgebase, with
7458 extensive cross-references and querying interfaces freely accessible to
7459 the scientific community. UniProt is produced by the UniProt Consortium
7460 which consists of groups from the European Bioinformatics Institute
7461 (EBI), the Swiss Institute of Bioinformatics (SIB) and the Protein
7462 Information Resource (PIR). UniProt is comprised of four major
7463 components, each optimized for different uses: the UniProt Archive, the
7464 UniProt Knowledgebase, the UniProt Reference Clusters and the UniProt
7465 Metagenomic and Environmental Sequence Database. UniProt is updated and
7466 distributed every 3 weeks and can be accessed online for searches or
7467 download at http://www.uniprot.org."
7470 @misc { uniprot:STRAV,
7471 key = "uniprot:STRAV",
7472 url = "http://www.uniprot.org/uniprot/P22629"
7475 @book { vanKampen07,
7476 author = NGvanKampen,
7477 title = "Stochastic Processes in Physics and Chemistry",
7481 address = "Amsterdam",
7483 project = "sawtooth simulation"
7486 @article { venter01,
7487 author = JCVenter #" and "# MDAdams #" and "# EWMyers #" and "# PWLi #" and
7488 "# RJMural #" and "# GGSutton #" and "# HOSmith #" and "# MYandell #"
7489 and "# CAEvans #" and "# RAHolt #" and "# JDGocayne #" and "#
7490 PAmanatides #" and "# RMBallew #" and "# DHHuson #" and "# JRWortman #"
7491 and "# QZhang #" and "# CDKodira #" and "# XHZheng #" and "# LChen #"
7492 and "# MSkupski #" and "# GSubramanian #" and "# PDThomas #" and "#
7493 JZhang #" and "# GLGaborMiklos #" and "# CNelson #" and "# SBroder #"
7494 and "# AGClark #" and "# JNadeau #" and "# VAMcKusick #" and "# NZinder
7495 #" and "# AJLevine #" and "# RJRoberts #" and "# MSimon #" and "#
7496 CSlayman #" and "# MHunkapiller #" and "# RBolanos #" and "# ADelcher
7497 #" and "# IDew #" and "# DFasulo #" and "# MFlanigan #" and "# LFlorea
7498 #" and "# AHalpern #" and "# SHannenhalli #" and "# SKravitz #" and "#
7499 SLevy #" and "# CMobarry #" and "# KReinert #" and "# KRemington #" and
7500 "# JAbu-Threideh #" and "# EBeasley #" and "# KBiddick #" and "#
7501 VBonazzi #" and "# RBrandon #" and "# MCargill #" and "#
7502 IChandramouliswaran #" and "# RCharlab #" and "# KChaturvedi #" and "#
7503 ZDeng #" and "# VDiFrancesco #" and "# PDunn #" and "# KEilbeck #" and
7504 "# CEvangelista #" and "# AEGabrielian #" and "# WGan #" and "# WGe #"
7505 and "# FGong #" and "# ZGu #" and "# PGuan #" and "# TJHeiman #" and "#
7506 MEHiggins #" and "# RRJi #" and "# ZKe #" and "# KAKetchum #" and "#
7507 ZLai #" and "# YLei #" and "# ZLi #" and "# JLi #" and "# YLiang #" and
7508 "# XLin #" and "# FLu #" and "# GVMerkulov #" and "# NMilshina #" and
7509 "# HMMoore #" and "# AKNaik #" and "# VANarayan #" and "# BNeelam #"
7510 and "# DNusskern #" and "# DBRusch #" and "# SSalzberg #" and "# WShao
7511 #" and "# BShue #" and "# JSun #" and "# ZWang #" and "# AWang #" and
7512 "# XWang #" and "# JWang #" and "# MWei #" and "# RWides #" and "#
7513 CXiao #" and "# CYan #" and "# AYao #" and "# JYe #" and "# MZhan #"
7514 and "# WZhang #" and "# HZhang #" and "# QZhao #" and "# LZheng #" and
7515 "# FZhong #" and "# WZhong #" and "# SZhu #" and "# SZhao #" and "#
7516 DGilbert #" and "# SBaumhueter #" and "# GSpier #" and "# CCarter #"
7517 and "# ACravchik #" and "# TWoodage #" and "# FAli #" and "# HAn #" and
7518 "# AAwe #" and "# DBaldwin #" and "# HBaden #" and "# MBarnstead #" and
7519 "# IBarrow #" and "# KBeeson #" and "# DBusam #" and "# ACarver #" and
7520 "# ACenter #" and "# MLCheng #" and "# LCurry #" and "# SDanaher #" and
7521 "# LDavenport #" and "# RDesilets #" and "# SDietz #" and "# KDodson #"
7522 and "# LDoup #" and "# SFerriera #" and "# NGarg #" and "# AGluecksmann
7523 #" and "# BHart #" and "# JHaynes #" and "# CHaynes #" and "# CHeiner
7524 #" and "# SHladun #" and "# DHostin #" and "# JHouck #" and "# THowland
7525 #" and "# CIbegwam #" and "# JJohnson #" and "# FKalush #" and "#
7526 LKline #" and "# SKoduru #" and "# ALove #" and "# FMann #" and "# DMay
7527 #" and "# SMcCawley #" and "# TMcIntosh #" and "# IMcMullen #" and "#
7528 MMoy #" and "# LMoy #" and "# BMurphy #" and "# KNelson #" and "#
7529 CPfannkoch #" and "# EPratts #" and "# VPuri #" and "# HQureshi #" and
7530 "# MReardon #" and "# RRodriguez #" and "# YHRogers #" and "# DRomblad
7531 #" and "# BRuhfel #" and "# RScott #" and "# CSitter #" and "#
7532 MSmallwood #" and "# EStewart #" and "# RStrong #" and "# ESuh #" and
7533 "# RThomas #" and "# NNTint #" and "# STse #" and "# CVech #" and "#
7534 GWang #" and "# JWetter #" and "# SWilliams #" and "# MWilliams #" and
7535 "# SWindsor #" and "# EWinn-Deen #" and "# KWolfe #" and "# JZaveri #"
7536 and "# KZaveri #" and "# JFAbril #" and "# RGuigo #" and "# MJCampbell
7537 #" and "# KVSjolander #" and "# BKarlak #" and "# AKejariwal #" and "#
7538 HMi #" and "# BLazareva #" and "# THatton #" and "# ANarechania #" and
7539 "# KDiemer #" and "# AMuruganujan #" and "# NGuo #" and "# SSato #" and
7540 "# VBafna #" and "# SIstrail #" and "# RLippert #" and "# RSchwartz #"
7541 and "# BWalenz #" and "# SYooseph #" and "# DAllen #" and "# ABasu #"
7542 and "# JBaxendale #" and "# LBlick #" and "# MCaminha #" and "#
7543 JCarnes-Stine #" and "# PCaulk #" and "# YHChiang #" and "# MCoyne #"
7544 and "# CDahlke #" and "# AMays #" and "# MDombroski #" and "# MDonnelly
7545 #" and "# DEly #" and "# SEsparham #" and "# CFosler #" and "# HGire #"
7546 and "# SGlanowski #" and "# KGlasser #" and "# AGlodek #" and "#
7547 MGorokhov #" and "# KGraham #" and "# BGropman #" and "# MHarris #" and
7548 "# JHeil #" and "# SHenderson #" and "# JHoover #" and "# DJennings #"
7549 and "# CJordan #" and "# JJordan #" and "# JKasha #" and "# LKagan #"
7550 and "# CKraft #" and "# ALevitsky #" and "# MLewis #" and "# XLiu #"
7551 and "# JLopez #" and "# DMa #" and "# WMajoros #" and "# JMcDaniel #"
7552 and "# SMurphy #" and "# MNewman #" and "# TNguyen #" and "# NNguyen #"
7553 and "# MNodell #" and "# SPan #" and "# JPeck #" and "# MPeterson #"
7554 and "# WRowe #" and "# RSanders #" and "# JScott #" and "# MSimpson #"
7555 and "# TSmith #" and "# ASprague #" and "# TStockwell #" and "# RTurner
7556 #" and "# EVenter #" and "# MWang #" and "# MWen #" and "# DWu #" and
7557 "# MWu #" and "# AXia #" and "# AZandieh #" and "# XZhu,
7558 title = "The sequence of the human genome.",
7565 pages = "1304--1351",
7567 doi = "10.1126/science.1058040",
7568 eprint = "http://www.sciencemag.org/cgi/content/pdf/291/5507/1304",
7569 url = "http://www.sciencemag.org/cgi/content/short/291/5507/1304",
7570 keywords = "Algorithms;Animals;Chromosome Banding;Chromosome
7571 Mapping;Chromosomes, Artificial, Bacterial;Computational
7572 Biology;Consensus Sequence;CpG Islands;DNA, Intergenic;Databases,
7573 Factual;Evolution, Molecular;Exons;Female;Gene
7574 Duplication;Genes;Genetic Variation;Genome, Human;Human Genome
7575 Project;Humans;Introns;Male;Phenotype;Physical Chromosome
7576 Mapping;Polymorphism, Single Nucleotide;Proteins;Pseudogenes;Repetitive
7577 Sequences, Nucleic Acid;Retroelements;Sequence Analysis, DNA;Species
7579 abstract = "A 2.91-billion base pair (bp) consensus sequence of the
7580 euchromatic portion of the human genome was generated by the whole-
7581 genome shotgun sequencing method. The 14.8-billion bp DNA sequence was
7582 generated over 9 months from 27,271,853 high-quality sequence reads
7583 (5.11-fold coverage of the genome) from both ends of plasmid clones
7584 made from the DNA of five individuals. Two assembly strategies-a whole-
7585 genome assembly and a regional chromosome assembly-were used, each
7586 combining sequence data from Celera and the publicly funded genome
7587 effort. The public data were shredded into 550-bp segments to create a
7588 2.9-fold coverage of those genome regions that had been sequenced,
7589 without including biases inherent in the cloning and assembly procedure
7590 used by the publicly funded group. This brought the effective coverage
7591 in the assemblies to eightfold, reducing the number and size of gaps in
7592 the final assembly over what would be obtained with 5.11-fold coverage.
7593 The two assembly strategies yielded very similar results that largely
7594 agree with independent mapping data. The assemblies effectively cover
7595 the euchromatic regions of the human chromosomes. More than 90\% of the
7596 genome is in scaffold assemblies of 100,000 bp or more, and 25\% of the
7597 genome is in scaffolds of 10 million bp or larger. Analysis of the
7598 genome sequence revealed 26,588 protein-encoding transcripts for which
7599 there was strong corroborating evidence and an additional approximately
7600 12,000 computationally derived genes with mouse matches or other weak
7601 supporting evidence. Although gene-dense clusters are obvious, almost
7602 half the genes are dispersed in low G+C sequence separated by large
7603 tracts of apparently noncoding sequence. Only 1.1\% of the genome is
7604 spanned by exons, whereas 24\% is in introns, with 75\% of the genome
7605 being intergenic DNA. Duplications of segmental blocks, ranging in size
7606 up to chromosomal lengths, are abundant throughout the genome and
7607 reveal a complex evolutionary history. Comparative genomic analysis
7608 indicates vertebrate expansions of genes associated with neuronal
7609 function, with tissue-specific developmental regulation, and with the
7610 hemostasis and immune systems. DNA sequence comparisons between the
7611 consensus sequence and publicly funded genome data provided locations
7612 of 2.1 million single-nucleotide polymorphisms (SNPs). A random pair of
7613 human haploid genomes differed at a rate of 1 bp per 1250 on average,
7614 but there was marked heterogeneity in the level of polymorphism across
7615 the genome. Less than 1\% of all SNPs resulted in variation in
7616 proteins, but the task of determining which SNPs have functional
7617 consequences remains an open challenge."
7620 @article { verdier70,
7622 title = "Relaxation Behavior of the Freely Jointed Chain",
7628 pages = "5512--5517",
7630 doi = "10.1063/1.1672818",
7631 url = "http://link.aip.org/link/?JCP/52/5512/1"
7634 @article { walther07,
7635 author = KWalther #" and "# FGrater #" and "# LDougan #" and "# CBadilla #"
7636 and "# BBerne #" and "# JFernandez,
7637 title = "Signatures of hydrophobic collapse in extended proteins captured
7638 with force spectroscopy",
7643 pages = "7916--7921",
7644 doi = "10.1073/pnas.0702179104",
7645 eprint = "http://www.pnas.org/cgi/reprint/104/19/7916.pdf",
7646 url = "http://www.pnas.org/cgi/content/abstract/104/19/7916",
7647 abstract = "We unfold and extend single proteins at a high force and then
7648 linearly relax the force to probe their collapse mechanisms. We observe
7649 a large variability in the extent of their recoil. Although chain
7650 entropy makes a small contribution, we show that the observed
7651 variability results from hydrophobic interactions with randomly varying
7652 magnitude from protein to protein. This collapse mechanism is common to
7653 highly extended proteins, including nonfolding elastomeric proteins
7654 like PEVK from titin. Our observations explain the puzzling differences
7655 between the folding behavior of highly extended proteins, from those
7656 folding after chemical or thermal denaturation. Probing the collapse of
7657 highly extended proteins with force spectroscopy allows separation of
7658 the different driving forces in protein folding."
7661 @article { walton08,
7662 author = EBWalton #" and "# SLee #" and "# KJVanVliet,
7663 title = "Extending {B}ell's model: How force transducer stiffness alters
7664 measured unbinding forces and kinetics of molecular complexes",
7671 pages = "2621--2630",
7673 doi = "10.1529/biophysj.107.114454",
7674 keywords = "Biotin;Computer
7675 Simulation;Elasticity;Kinetics;Mechanotransduction, Cellular;Models,
7676 Chemical;Models, Molecular;Molecular Motor
7677 Proteins;Motion;Streptavidin;Stress, Mechanical;Transducers",
7678 abstract = "Forced unbinding of complementary macromolecules such as
7679 ligand-receptor complexes can reveal energetic and kinetic details
7680 governing physiological processes ranging from cellular adhesion to
7681 drug metabolism. Although molecular-level experiments have enabled
7682 sampling of individual ligand-receptor complex dissociation events,
7683 disparities in measured unbinding force F(R) among these methods lead
7684 to marked variation in inferred binding energetics and kinetics at
7685 equilibrium. These discrepancies are documented for even the ubiquitous
7686 ligand-receptor pair, biotin-streptavidin. We investigated these
7687 disparities and examined atomic-level unbinding trajectories via
7688 steered molecular dynamics simulations, as well as via molecular force
7689 spectroscopy experiments on biotin-streptavidin. In addition to the
7690 well-known loading rate dependence of F(R) predicted by Bell's model,
7691 we find that experimentally accessible parameters such as the effective
7692 stiffness of the force transducer k can significantly perturb the
7693 energy landscape and the apparent unbinding force of the complex for
7694 sufficiently stiff force transducers. Additionally, at least 20\%
7695 variation in unbinding force can be attributed to minute differences in
7696 initial atomic positions among energetically and structurally
7697 comparable complexes. For force transducers typical of molecular force
7698 spectroscopy experiments and atomistic simulations, this energy barrier
7699 perturbation results in extrapolated energetic and kinetic parameters
7700 of the complex that depend strongly on k. We present a model that
7701 explicitly includes the effect of k on apparent unbinding force of the
7702 ligand-receptor complex, and demonstrate that this correction enables
7703 prediction of unbinding distances and dissociation rates that are
7704 decoupled from the stiffness of actual or simulated molecular linkers.",
7705 note = "Some detailed estimates at U(x)."
7708 @article { walton86,
7710 title = "The Abbe theory of imaging: an alternative derivation of the
7717 url = "http://stacks.iop.org/0143-0807/7/62"
7720 @article { watanabe05,
7721 author = HWatanabe #" and "# TInoue,
7722 title = "Conformational dynamics of Rouse chains during creep/recovery
7723 processes: a review",
7728 pages = "R607--R636",
7729 doi = "10.1088/0953-8984/17/19/R01",
7730 eprint = "http://www.iop.org/EJ/article/0953-8984/17/19/R01/cm5_19_R01.pdf",
7731 url = "http://stacks.iop.org/0953-8984/17/R607",
7732 abstract = "The Rouse model is a well-established model for non-entangled
7733 polymer chains and also serves as a fundamental model for entangled
7734 chains. The dynamic behaviour of this model under strain-controlled
7735 conditions has been fully analysed in the literature. However, despite
7736 the importance of the Rouse model, no analysis has been made so far of
7737 the orientational anisotropy of the Rouse eigenmodes during the stress-
7738 controlled, creep and recovery processes. For completeness of the
7739 analysis of the model, the Rouse equation of motion is solved to
7740 calculate this anisotropy for monodisperse chains and their binary
7741 blends during the creep/recovery processes. The calculation is simple
7742 and straightforward, but the result is intriguing in the sense that
7743 each Rouse eigenmode during these processes has a distribution in the
7744 retardation times. This behaviour, reflecting the interplay/correlation
7745 among the Rouse eigenmodes of different orders (and for different
7746 chains in the blends) under the constant stress condition, is quite
7747 different from the behaviour under rate-controlled flow (where each
7748 eigenmode exhibits retardation/relaxation associated with a single
7749 characteristic time). Furthermore, the calculation indicates that the
7750 Rouse chains exhibit affine deformation on sudden imposition/removal of
7751 the stress and the magnitude of this deformation is inversely
7752 proportional to the number of bond vectors per chain. In relation to
7753 these results, a difference between the creep and relaxation properties
7754 is also discussed for chains obeying multiple relaxation mechanisms
7755 (Rouse and reptation mechanisms).",
7756 note = "Middly-detailed Rouse model review."
7760 author = AWiita #" and "# SAinavarapu #" and "# HHuang #" and "# JFernandez,
7761 title = "From the Cover: Force-dependent chemical kinetics of disulfide
7762 bond reduction observed with single-molecule techniques",
7767 pages = "7222--7227",
7768 doi = "10.1073/pnas.0511035103",
7769 eprint = "http://www.pnas.org/cgi/reprint/103/19/7222.pdf",
7770 url = "http://www.pnas.org/cgi/content/abstract/103/19/7222",
7771 abstract = "The mechanism by which mechanical force regulates the kinetics
7772 of a chemical reaction is unknown. Here, we use single-molecule force-
7773 clamp spectroscopy and protein engineering to study the effect of force
7774 on the kinetics of thiol/disulfide exchange. Reduction of disulfide
7775 bonds through the thiol/disulfide exchange chemical reaction is crucial
7776 in regulating protein function and is known to occur in mechanically
7777 stressed proteins. We apply a constant stretching force to single
7778 engineered disulfide bonds and measure their rate of reduction by DTT.
7779 Although the reduction rate is linearly dependent on the concentration
7780 of DTT, it is exponentially dependent on the applied force, increasing
7781 10-fold over a 300-pN range. This result predicts that the disulfide
7782 bond lengthens by 0.34 A at the transition state of the thiol/disulfide
7783 exchange reaction. Our work at the single bond level directly
7784 demonstrates that thiol/disulfide exchange in proteins is a force-
7785 dependent chemical reaction. Our findings suggest that mechanical force
7786 plays a role in disulfide reduction in vivo, a property that has never
7787 been explored by traditional biochemistry. Furthermore, our work also
7788 indicates that the kinetics of any chemical reaction that results in
7789 bond lengthening will be force-dependent."
7792 @article { wilcox05,
7793 author = AWilcox #" and "# JChoy #" and "# CBustamante #" and "#
7795 title = "Effect of protein structure on mitochondrial import",
7800 pages = "15435--15440",
7801 doi = "10.1073/pnas.0507324102",
7802 eprint = "http://www.pnas.org/cgi/reprint/102/43/15435.pdf",
7803 url = "http://www.pnas.org/cgi/content/abstract/102/43/15435",
7804 abstract = "Most proteins that are to be imported into the mitochondrial
7805 matrix are synthesized as precursors, each composed of an N-terminal
7806 targeting sequence followed by a mature domain. Precursors are
7807 recognized through their targeting sequences by receptors at the
7808 mitochondrial surface and are then threaded through import channels
7809 into the matrix. Both the targeting sequence and the mature domain
7810 contribute to the efficiency with which proteins are imported into
7811 mitochondria. Precursors must be in an unfolded conformation during
7812 translocation. Mitochondria can unfold some proteins by changing their
7813 unfolding pathways. The effectiveness of this unfolding mechanism
7814 depends on the local structure of the mature domain adjacent to the
7815 targeting sequence. This local structure determines the extent to which
7816 the unfolding pathway can be changed and, therefore, the unfolding rate
7817 increased. Atomic force microscopy studies find that the local
7818 structures of proteins near their N and C termini also influence their
7819 resistance to mechanical unfolding. Thus, protein unfolding during
7820 import resembles mechanical unfolding, and the specificity of import is
7821 determined by the resistance of the mature domain to unfolding as well
7822 as by the properties of the targeting sequence."
7825 @article { wolfsberg01,
7826 author = TGWolfsberg #" and "# JMcEntyre #" and "# GDSchuler,
7827 title = "Guide to the draft human genome.",
7836 doi = "10.1038/35057000",
7837 eprint = "http://www.nature.com/nature/journal/v409/n6822/pdf/409824a0.pdf",
7838 url = "http://www.nature.com/nature/journal/v409/n6822/full/409824a0.html",
7839 keywords = "Amino Acid Sequence;Chromosome Mapping;Computational
7840 Biology;Genes;Genetic Variation;Genome, Human;Human Genome
7841 Project;Humans;Internet;Molecular Sequence Data;Sequence Analysis, DNA",
7842 abstract = "There are a number of ways to investigate the structure,
7843 function and evolution of the human genome. These include examining the
7844 morphology of normal and abnormal chromosomes, constructing maps of
7845 genomic landmarks, following the genetic transmission of phenotypes and
7846 DNA sequence variations, and characterizing thousands of individual
7847 genes. To this list we can now add the elucidation of the genomic DNA
7848 sequence, albeit at 'working draft' accuracy. The current challenge is
7849 to weave together these disparate types of data to produce the
7850 information infrastructure needed to support the next generation of
7851 biomedical research. Here we provide an overview of the different
7852 sources of information about the human genome and how modern
7853 information technology, in particular the internet, allows us to link
7858 author = JWWu #" and "# WLHung #" and "# CHTsai,
7859 title = "Estimation of parameters of the {G}ompertz distribution using the
7860 least squares method",
7869 doi = "10.1016/j.amc.2003.08.086",
7870 url = "http://dx.doi.org/10.1016/j.amc.2003.08.086",
7871 keywords = "Gompertz distribution; Least squares estimate; Maximum
7872 likelihood estimate; First failure-censored; Series system",
7873 abstract = "The Gompertz distribution has been used to describe human
7874 mortality and establish actuarial tables. Recently, this distribution
7875 has been again studied by some authors. The maximum likelihood
7876 estimates for the parameters of the Gompertz distribution has been
7877 discussed by Garg et al. [J. R. Statist. Soc. C 19 (1970) 152]. The
7878 purpose of this paper is to propose unweighted and weighted least
7879 squares estimates for parameters of the Gompertz distribution under the
7880 complete data and the first failure-censored data (series systems; see
7881 [J. Statist. Comput. Simulat. 52 (1995) 337]). A simulation study is
7882 carried out to compare the proposed estimators and the maximum
7883 likelihood estimators. Results of the simulation studies show that the
7884 performance of the weighted least squares estimators is acceptable."
7888 author = GYang #" and "# CCecconi #" and "# WBaase #" and "# IVetter #" and
7889 "# WBreyer #" and "# JHaack #" and "# BMatthews #" and "# FDahlquist #"
7891 title = "Solid-state synthesis and mechanical unfolding of polymers of {T4}
7898 doi = "10.1073/pnas.97.1.139",
7899 eprint = "http://www.pnas.org/cgi/reprint/97/1/139.pdf",
7900 url = "http://www.pnas.org/cgi/content/abstract/97/1/139"
7904 author = YYang #" and "# FCLin #" and "# GYang,
7905 title = "Temperature control device for single molecule measurements using
7906 the atomic force microscope",
7916 doi = "10.1063/1.2204580",
7917 url = "http://link.aip.org/link/?RSI/77/063701/1",
7918 keywords = "temperature control; atomic force microscopy; thermocouples;
7920 note = "Introduces our temperature control system",
7921 project = "Energy Landscape Roughness"
7925 author = WYu #" and "# JLamb #" and "# FHan #" and "# JBirchler,
7926 title = "Telomere-mediated chromosomal truncation in maize",
7931 pages = "17331--17336",
7932 doi = "10.1073/pnas.0605750103",
7933 eprint = "http://www.pnas.org/cgi/reprint/103/46/17331.pdf",
7934 url = "http://www.pnas.org/cgi/content/abstract/103/46/17331",
7935 abstract = "Direct repeats of Arabidopsis telomeric sequence were
7936 constructed to test telomere-mediated chromosomal truncation in maize.
7937 Two constructs with 2.6 kb of telomeric sequence were used to transform
7938 maize immature embryos by Agrobacterium-mediated transformation. One
7939 hundred seventy-six transgenic lines were recovered in which 231
7940 transgene loci were revealed by a FISH analysis. To analyze chromosomal
7941 truncations that result in transgenes located near chromosomal termini,
7942 Southern hybridization analyses were performed. A pattern of smear in
7943 truncated lines was seen as compared with discrete bands for internal
7944 integrations, because telomeres in different cells are elongated
7945 differently by telomerase. When multiple restriction enzymes were used
7946 to map the transgene positions, the size of the smears shifted in
7947 accordance with the locations of restriction sites on the construct.
7948 This result demonstrated that the transgene was present at the end of
7949 the chromosome immediately before the integrated telomere sequence.
7950 Direct evidence for chromosomal truncation came from the results of
7951 FISH karyotyping, which revealed broken chromosomes with transgene
7952 signals at the ends. These results demonstrate that telomere-mediated
7953 chromosomal truncation operates in plant species. This technology will
7954 be useful for chromosomal engineering in maize as well as other plant
7959 author = JZhao #" and "# HLee #" and "# RNome #" and "# SMajid #" and "#
7960 NScherer #" and "# WHoff,
7961 title = "Single-molecule detection of structural changes during
7962 {P}er-{A}rnt-{S}im ({PAS}) domain activation",
7967 pages = "11561--11566",
7968 doi = "10.1073/pnas.0601567103",
7969 eprint = "http://www.pnas.org/cgi/reprint/103/31/11561.pdf",
7970 url = "http://www.pnas.org/cgi/content/abstract/103/31/11561",
7971 abstract = "The Per-Arnt-Sim (PAS) domain is a ubiquitous protein module
7972 with a common three-dimensional fold involved in a wide range of
7973 regulatory and sensory functions in all domains of life. The activation
7974 of these functions is thought to involve partial unfolding of N- or
7975 C-terminal helices attached to the PAS domain. Here we use atomic force
7976 microscopy to probe receptor activation in single molecules of
7977 photoactive yellow protein (PYP), a prototype of the PAS domain family.
7978 Mechanical unfolding of Cys-linked PYP multimers in the presence and
7979 absence of illumination reveals that, in contrast to previous studies,
7980 the PAS domain itself is extended by {approx}3 nm (at the 10-pN
7981 detection limit of the measurement) and destabilized by {approx}30% in
7982 the light-activated state of PYP. Comparative measurements and steered
7983 molecular dynamics simulations of two double-Cys PYP mutants that probe
7984 different regions of the PAS domain quantify the anisotropy in
7985 stability and changes in local structure, thereby demonstrating the
7986 partial unfolding of their PAS domain upon activation. These results
7987 establish a generally applicable single-molecule approach for mapping
7988 functional conformational changes to selected regions of a protein. In
7989 addition, the results have profound implications for the molecular
7990 mechanism of PAS domain activation and indicate that stimulus-induced
7991 partial protein unfolding can be used as a signaling mechanism."
7994 @article { zhuang06,
7995 author = WZhuang #" and "# DAbramavicius #" and "# SMukamel,
7996 title = "Two-dimensional vibrational optical probes for peptide fast
7997 folding investigation",
8002 pages = "18934--18938",
8003 doi = "10.1073/pnas.0606912103",
8004 eprint = "http://www.pnas.org/cgi/reprint/103/50/18934.pdf",
8005 url = "http://www.pnas.org/cgi/content/abstract/103/50/18934",
8006 abstract = "A simulation study shows that early protein folding events may
8007 be investigated by using a recently developed family of nonlinear
8008 infrared techniques that combine the high temporal and spatial
8009 resolution of multidimensional spectroscopy with the chirality-specific
8010 sensitivity of amide vibrations to structure. We demonstrate how the
8011 structural sensitivity of cross-peaks in two-dimensional correlation
8012 plots of chiral signals of an {alpha} helix and a [beta] hairpin may be
8013 used to clearly resolve structural and dynamical details undetectable
8014 by one-dimensional techniques (e.g. circular dichroism) and identify
8015 structures indistinguishable by NMR."
8018 @article { zinober02,
8019 author = RCZinober #" and "# DJBrockwell #" and "# GSBeddard #" and "#
8020 AWBlake #" and "# PDOlmsted #" and "# SERadford #" and "# DASmith,
8021 title = "Mechanically unfolding proteins: the effect of unfolding history
8022 and the supramolecular scaffold",
8028 pages = "2759--2765",
8030 doi = "10.1110/ps.0224602",
8031 eprint = "http://www.proteinscience.org/cgi/reprint/11/12/2759.pdf",
8032 url = "http://www.proteinscience.org/cgi/content/abstract/11/12/2759",
8033 keywords = "Computer Simulation; Models, Molecular; Monte Carlo Method;
8034 Protein Folding; Protein Structure, Tertiary; Proteins",
8035 abstract = "The mechanical resistance of a folded domain in a polyprotein
8036 of five mutant I27 domains (C47S, C63S I27)(5)is shown to depend on the
8037 unfolding history of the protein. This observation can be understood on
8038 the basis of competition between two effects, that of the changing
8039 number of domains attempting to unfold, and the progressive increase in
8040 the compliance of the polyprotein as domains unfold. We present Monte
8041 Carlo simulations that show the effect and experimental data that
8042 verify these observations. The results are confirmed using an
8043 analytical model based on transition state theory. The model and
8044 simulations also predict that the mechanical resistance of a domain
8045 depends on the stiffness of the surrounding scaffold that holds the
8046 domain in vivo, and on the length of the unfolded domain. Together,
8047 these additional factors that influence the mechanical resistance of
8048 proteins have important consequences for our understanding of natural
8049 proteins that have evolved to withstand force.",
8050 note = "Introduces unfolding-order \emph{scaffold effect} on average
8052 project = "sawtooth simulation"
8055 @article { zwanzig92,
8056 author = RZwanzig #" and "# ASzabo #" and "# BBagchi,
8057 title = "Levinthal's paradox.",
8067 "http://www.ncbi.nlm.nih.gov/pmc/articles/PMC48166/pdf/pnas01075-0036.p
8069 url = "http://www.ncbi.nlm.nih.gov/pmc/articles/PMC48166/",
8070 keywords = "Mathematics;Models, Theoretical;Protein Conformation;Proteins",
8071 abstract = "Levinthal's paradox is that finding the native folded state of
8072 a protein by a random search among all possible configurations can take
8073 an enormously long time. Yet proteins can fold in seconds or less.
8074 Mathematical analysis of a simple model shows that a small and
8075 physically reasonable energy bias against locally unfavorable
8076 configurations, of the order of a few kT, can reduce Levinthal's time
8077 to a biologically significant size."
8081 author = XHong #" and "# XChu #" and "# PZou #" and "# YLiu
8083 title = "Magnetic-field-assisted rapid ultrasensitive
8084 immunoassays using Fe3{O4}/Zn{O}/Au nanorices as Raman
8090 address = "Centre for Advanced Optoelectronic Functional
8091 Materials Research, Key Laboratory for UV
8092 Light-Emitting Materials and Technology of Ministry of
8093 Education, Northeast Normal University, Changchun
8098 keywords = "Biosensing Techniques",
8099 keywords = "Electromagnetic Fields",
8100 keywords = "Equipment Design",
8101 keywords = "Equipment Failure Analysis",
8102 keywords = "Immunoassay",
8103 keywords = "Magnetite Nanoparticles",
8104 keywords = "Spectrum Analysis, Raman",
8105 keywords = "Zinc Oxide",
8106 abstract = "Rapid and ultrasensitive immunoassays were developed
8107 by using biofunctional Fe3O4/ZnO/Au nanorices as Raman
8108 probes. Taking advantage of the superparamagnetic
8109 property of the nanorices, the labeled proteins can
8110 rapidly be separated and purified with a commercial
8111 permanent magnet. The unsusceptible multiphonon
8112 resonant Raman scattering of the nanorices provided a
8113 characteristic spectroscopic fingerprint function,
8114 which allowed an accurate detection of the analyte.
8115 High specificity and selectivity of the assay were
8116 demonstrated. It was found that the diffusion barriers
8117 and the boundary layer effects had a great influence on
8118 the detection limit. Manipulation of the nanorice
8119 probes using an external magnetic field can enhance the
8120 assay sensitivity by several orders of magnitude, and
8121 reduce the detection time from 1 h to 3 min. This
8122 magnetic-field-assisted rapid and ultrasensitive
8123 immunoassay based on the resonant Raman scatting of
8124 semiconductor shows significant value for potential
8125 applications in biomedicine, food safety, and
8126 environmental defence.",
8128 doi = "10.1016/j.bios.2010.06.066",
8129 URL = "http://www.ncbi.nlm.nih.gov/pubmed/20667438",
8134 author = LZhao #" and "# ABulhassan #" and "# GYang #" and "#
8136 title = "Real-time detection of the morphological change in
8137 cellulose by a nanomechanical sensor.",
8142 address = "Department of Physics, Drexel University,
8143 Philadelphia, Pennsylvania, USA.",
8147 keywords = "Cellulose",
8148 keywords = "Computer Systems",
8149 keywords = "Equipment Design",
8150 keywords = "Equipment Failure Analysis",
8151 keywords = "Micro-Electrical-Mechanical Systems",
8152 keywords = "Molecular Conformation",
8153 keywords = "Nanotechnology",
8154 keywords = "Transducers",
8155 abstract = "Up to now, experimental limitations have prevented
8156 researchers from achieving the molecular-level
8157 understanding for the initial steps of the enzymatic
8158 hydrolysis of cellulose, where cellulase breaks down
8159 the crystal structure on the surface region of
8160 cellulose and exposes cellulose chains for the
8161 subsequent hydrolysis by cellulase. Because one of
8162 these non-hydrolytic enzymatic steps could be the
8163 rate-limiting step for the entire enzymatic hydrolysis
8164 of crystalline cellulose by cellulase, being able to
8165 analyze and understand these steps is instrumental in
8166 uncovering novel leads for improving the efficiency of
8167 cellulase. In this communication, we report an
8168 innovative application of the microcantilever technique
8169 for a real-time assessment of the morphological change
8170 of cellulose induced by a treatment of sodium chloride.
8171 This sensitive nanomechanical approach to define
8172 changes in surface structure of cellulose has the
8173 potential to permit a real-time assessment of the
8174 effect of the non-hydrolytic activities of cellulase on
8175 cellulose and thereby to provide a comprehensive
8176 understanding of the initial steps of the enzymatic
8177 hydrolysis of cellulose.",
8179 doi = "10.1002/bit.22754",
8180 URL = "http://www.ncbi.nlm.nih.gov/pubmed/20653025",
8185 author = RLiu #" and "# MRoman #" and "# GYang,
8186 title = "Correction of the viscous drag induced errors in
8187 macromolecular manipulation experiments using atomic
8192 address = "Department of Physics, Drexel University,
8193 Philadelphia, Pennsylvania 19104, USA.",
8197 keywords = "Algorithms",
8198 keywords = "Artifacts",
8199 keywords = "Macromolecular Substances",
8200 keywords = "Mechanical Processes",
8201 keywords = "Microscopy, Atomic Force",
8202 keywords = "Models, Theoretical",
8203 keywords = "Motion",
8204 keywords = "Protein Folding",
8205 keywords = "Signal Processing, Computer-Assisted",
8206 keywords = "Viscosity",
8207 abstract = "We describe a method to correct the errors induced by
8208 viscous drag on the cantilever in macromolecular
8209 manipulation experiments using the atomic force
8210 microscope. The cantilever experiences a viscous drag
8211 force in these experiments because of its motion
8212 relative to the surrounding liquid. This viscous force
8213 superimposes onto the force generated by the
8214 macromolecule under study, causing ambiguity in the
8215 experimental data. To remove this artifact, we analyzed
8216 the motions of the cantilever and the liquid in
8217 macromolecular manipulation experiments, and developed
8218 a novel model to treat the viscous drag on the
8219 cantilever as the superposition of the viscous force on
8220 a static cantilever in a moving liquid and that on a
8221 bending cantilever in a static liquid. The viscous
8222 force was measured under both conditions and the
8223 results were used to correct the viscous drag induced
8224 errors from the experimental data. The method will be
8225 useful for many other cantilever based techniques,
8226 especially when high viscosity and high cantilever
8227 speed are involved.",
8229 doi = "10.1063/1.3436646",
8230 URL = "http://www.ncbi.nlm.nih.gov/pubmed/20590242",
8234 @phdthesis { roman12,
8236 title = "Macromolecular crowding effects in the mechanical unfolding
8237 forces of proteins",
8241 url = "http://hdl.handle.net/1860/3854",
8242 eprint = "http://idea.library.drexel.edu/bitstream/1860/3854/1/Roman_Marisa.pdf",
8243 keywords = "Physics",
8244 keywords = "Biophysics",
8245 keywords = "Protein folding",
8246 abstract = "Macromolecules can occupy a large fraction of the volume
8247 of a cell and this crowded environment influences the behavior and
8248 properties of the proteins, such as mechanical unfolding forces,
8249 thermal stability and rates of folding and diffusion. Although
8250 much is already known about molecular crowding, it is not well
8251 understood how it affects a protein’s resistance to mechanical
8252 stress in a crowded environment and how the size of the crowders
8253 affect those changes. An atomic force microscope-based single
8254 molecule method was used to measure the effects of the crowding on
8255 the mechanical stability of a model protein, in this case I-27. As
8256 proteins tend to aggregate, single molecule methods provided a way
8257 to prevent aggregation because of the very low concentration of
8258 proteins in the solution under study. Dextran was used as the
8259 crowding agent with three different molecular weights 6kDa, 10 kDa
8260 and 40 kDa, with concentrations varying from zero to 300 grams per
8261 liter in a pH neutral buffer solution at room temperature. Results
8262 showed that the forces required to unfold biomolecules were
8263 increased when a high concentration of crowder molecules were
8264 added to the buffer solution and that the maximum force required
8265 to unfold a domain was when the crowder size was 10 kDa, which is
8266 comparable to the protein size. Unfolding rates obtained from
8267 Monte Carlo simulations showed that they were also affected in the
8268 presence of crowders. As a consequence, the energy barrier was
8269 also affected. These effects were most notable when the size of
8270 the crowder was 10 kDa, comparable to the size of the protein. On
8271 the other hand, distances to the transition state did not seem to
8272 change when crowders were added to the solution. The effect of
8273 Dextran on the energy barrier was modeled by using established
8274 theories such as Ogston’s and scaled particle theory, neither of
8275 which was completely convincing at describing the results. It can
8276 be hypothesized that the composition of Dextran plays a role in
8277 the deviation of the predicted behavior with respect to the
8278 experimental data.",
8282 @article { measey09,
8283 author = TMeasey #" and "# KBSmith #" and "# SDecatur #" and "#
8284 LZhao #" and "# GYang #" and "# RSchweitzerStenner,
8285 title = "Self-aggregation of a polyalanine octamer promoted by
8286 its {C}-terminal tyrosine and probed by a strongly
8287 enhanced vibrational circular dichroism signal.",
8292 address = "Department of Chemistry, Drexel University, 3141
8293 Chestnut Street, Philadelphia, Pennsylvania 19104,
8297 pages = "18218--18219",
8298 keywords = "Amyloid",
8299 keywords = "Circular Dichroism",
8300 keywords = "Dimerization",
8301 keywords = "Oligopeptides",
8302 keywords = "Peptides",
8303 keywords = "Protein Conformation",
8304 keywords = "Tyrosine",
8305 abstract = "The eight-residue alanine oligopeptide
8306 Ac-A(4)KA(2)Y-NH(2) (AKY8) was found to form
8307 amyloid-like fibrils upon incubation at room
8308 temperature in acidified aqueous solution at peptide
8309 concentrations >10 mM. The fibril solution exhibits an
8310 enhanced vibrational circular dichroism (VCD) couplet
8311 in the amide I' band region that is nearly 2 orders of
8312 magnitude larger than typical polypeptide/protein
8313 signals in this region. The UV-CD spectrum of the
8314 fibril solution shows CD in the region associated with
8315 the tyrosine side chain absorption. A similar peptide,
8316 Ac-A(4)KA(2)-NH(2) (AK7), which lacks a terminal
8317 tyrosine residue, does not aggregate. These results
8318 suggest a pivotal role for the C-terminal tyrosine
8319 residue in stabilizing the aggregation state of this
8320 peptide. It is speculated that interactions between the
8321 lysine and tyrosine side chains of consecutive strands
8322 in an antiparallel arrangement (e.g., cation-pi
8323 interactions) are responsible for the stabilization of
8324 the resulting fibrils. These results offer
8325 considerations and insight regarding the de novo design
8326 of self-assembling oligopeptides for biomedical and
8327 biotechnological applications and highlight the
8328 usefulness of VCD as a tool for probing amyloid fibril
8331 doi = "10.1021/ja908324m",
8332 URL = "http://www.ncbi.nlm.nih.gov/pubmed/19958029",
8337 author = GShan #" and "# SWang #" and "# XFei #" and "# YLiu
8339 title = "Heterostructured Zn{O}/Au nanoparticles-based resonant
8340 Raman scattering for protein detection.",
8345 address = "Center for Advanced Optoelectronic Functional
8346 Materials Research, Northeast Normal University,
8347 Changchun 130024, P. R. China.",
8350 pages = "1468--1472",
8351 keywords = "Animals",
8353 keywords = "Humans",
8354 keywords = "Immunoglobulin G",
8355 keywords = "Metal Nanoparticles",
8356 keywords = "Microscopy, Electron, Transmission",
8357 keywords = "Spectrum Analysis, Raman",
8358 keywords = "Zinc Oxide",
8359 abstract = "A new method of protein detection was explored on the
8360 resonant Raman scattering signal of ZnO nanoparticles.
8361 A probe for the target protein was constructed by
8362 binding the ZnO/Au nanoparticles to secondary protein
8363 by eletrostatic interaction. The detection of proteins
8364 was achieved by an antibody-based sandwich assay. A
8365 first antibody, which could be specifically recognized
8366 by target protein, was attached to a solid silicon
8367 surface. The ZnO/Au protein probe could specifically
8368 recognize and bind to the complex of the target protein
8369 and first antibody. This method on the resonant Raman
8370 scattering signal of ZnO nanoparticles showed good
8371 selectivity and sensitivity for the target protein.",
8373 doi = "10.1021/jp8046032",
8374 URL = "http://www.ncbi.nlm.nih.gov/pubmed/19138135",
8379 author = JMYuan #" and "# CLChyan #" and "# HXZhou #" and "#
8380 TYChung #" and "# HPeng #" and "# GPing #" and "#
8382 title = "The effects of macromolecular crowding on the
8383 mechanical stability of protein molecules.",
8388 address = "Department of Physics, Drexel University,
8389 Philadelphia, Pennsylvania 19104, USA.",
8392 pages = "2156--2166",
8393 keywords = "Circular Dichroism",
8394 keywords = "Dextrans",
8395 keywords = "Kinetics",
8396 keywords = "Microscopy, Atomic Force",
8397 keywords = "Microscopy, Scanning Probe",
8398 keywords = "Protein Folding",
8399 keywords = "Protein Stability",
8400 keywords = "Protein Structure, Secondary",
8401 keywords = "Thermodynamics",
8402 keywords = "Ubiquitin",
8403 abstract = "Macromolecular crowding, a common phenomenon in the
8404 cellular environments, can significantly affect the
8405 thermodynamic and kinetic properties of proteins. A
8406 single-molecule method based on atomic force microscopy
8407 (AFM) was used to investigate the effects of
8408 macromolecular crowding on the forces required to
8409 unfold individual protein molecules. It was found that
8410 the mechanical stability of ubiquitin molecules was
8411 enhanced by macromolecular crowding from added dextran
8412 molecules. The average unfolding force increased from
8413 210 pN in the absence of dextran to 234 pN in the
8414 presence of 300 g/L dextran at a pulling speed of 0.25
8415 microm/sec. A theoretical model, accounting for the
8416 effects of macromolecular crowding on the native and
8417 transition states of the protein molecule by applying
8418 the scaled-particle theory, was used to quantitatively
8419 explain the crowding-induced increase in the unfolding
8420 force. The experimental results and interpretation
8421 presented could have wide implications for the many
8422 proteins that experience mechanical stresses and
8423 perform mechanical functions in the crowded environment
8426 doi = "10.1110/ps.037325.108",
8427 URL = "http://www.ncbi.nlm.nih.gov/pubmed/18780817",
8432 author = YLiu #" and "# MZhong #" and "# GShan #" and "# YLi
8433 #" and "# BHuang #" and "# GYang,
8434 title = "Biocompatible Zn{O}/Au nanocomposites for
8435 ultrasensitive {DNA} detection using resonance Raman
8441 address = "Centre for Advanced Optoelectronic Functional
8442 Materials Research, Institute of Genetics and Cytology,
8443 Northeast Normal University, Changchun, People's
8444 Republic of China. ycliu@nenu.edu.cn",
8447 pages = "6484--6489",
8448 keywords = "Base Sequence",
8451 keywords = "Microscopy, Electron, Transmission",
8452 keywords = "Nanocomposites",
8453 keywords = "Sensitivity and Specificity",
8454 keywords = "Spectrum Analysis, Raman",
8455 keywords = "Zinc Oxide",
8456 abstract = "A novel method for identifying DNA microarrays based
8457 on ZnO/Au nanocomposites functionalized with
8458 thiol-oligonucleotide as probes is descried here. DNA
8459 labeled with ZnO/Au nanocomposites has a strong Raman
8460 signal even without silver acting as a surface-enhanced
8461 Raman scattering promoter. X-ray photoelectron spectra
8462 confirmed the formation of a three-component sandwich
8463 assay, i.e., constituted DNA and ZnO/Au nanocomposites.
8464 The resonance multiple-phonon Raman signal of the
8465 ZnO/Au nanocomposites as a spectroscopic fingerprint is
8466 used to detect a target sequence of oligonucleotide.
8467 This method exhibits extraordinary sensitivity and the
8468 detection limit is at least 1 fM.",
8470 doi = "10.1021/jp710399d",
8471 URL = "http://www.ncbi.nlm.nih.gov/pubmed/18444675",
8476 author = YGuo #" and "# AMylonakis #" and "# ZZhang #" and "#
8477 GYang #" and "# PLelkes #" and "# SChe #" and "#
8479 title = "Templated synthesis of electroactive periodic
8480 mesoporous organosilica bridged with oligoaniline.",
8483 address = "Department of Chemistry, Drexel University,
8484 Philadelphia, Pennsylvania 19104, USA.",
8487 pages = "2909--2917",
8488 keywords = "Aniline Compounds",
8489 keywords = "Cetrimonium Compounds",
8490 keywords = "Electrochemistry",
8491 keywords = "Hydrolysis",
8492 keywords = "Microscopy, Electron, Transmission",
8493 keywords = "Molecular Structure",
8494 keywords = "Organosilicon Compounds",
8495 keywords = "Particle Size",
8496 keywords = "Porosity",
8497 keywords = "Spectroscopy, Fourier Transform Infrared",
8498 keywords = "Surface Properties",
8499 keywords = "Thermogravimetry",
8500 keywords = "X-Ray Diffraction",
8501 abstract = "The synthesis and characterization of novel
8502 electroactive periodic mesoporous organosilica (PMO)
8503 are reported. The silsesquioxane precursor,
8504 N,N'-bis(4'-(3-triethoxysilylpropylureido)phenyl)-1,4-quinonene-diimine
8505 (TSUPQD), was prepared from the emeraldine base of
8506 amino-capped aniline trimer (EBAT) using a one-step
8507 coupling reaction and was used as an organic silicon
8508 source in the co-condensation with tetraethyl
8509 orthosilicate (TEOS) in proper ratios. By means of a
8510 hydrothermal sol-gel approach with the cationic
8511 surfactant cetyltrimethyl-ammonium bromide (CTAB) as
8512 the structure-directing template and acetone as the
8513 co-solvent for the dissolution of TSUPQD, a series of
8514 novel MCM-41 type siliceous materials (TSU-PMOs) were
8515 successfully prepared under mild alkaline conditions.
8516 The resultant mesoporous organosilica were
8517 characterized by Fourier transform infrared (FT-IR)
8518 spectroscopy, thermogravimetry, X-ray diffraction,
8519 nitrogen sorption, and transmission electron microscopy
8520 (TEM) and showed that this series of TSU-PMOs exhibited
8521 hexagonally patterned mesostructures with pore
8522 diameters of 2.1-2.8 nm. Although the structural
8523 regularity and pore parameters gradually deteriorated
8524 with increasing loading of organic bridges, the
8525 electrochemical behavior of TSU-PMOs monitored by
8526 cyclic voltammetry demonstrated greater
8527 electroactivities for samples with higher concentration
8528 of the incorporated TSU units.",
8530 doi = "10.1002/chem.200701605",
8531 URL = "http://www.ncbi.nlm.nih.gov/pubmed/18224650",
8536 author = LiLi #" and "# BLi #" and "# GYang #" and "# CYLi,
8537 title = "Polymer decoration on carbon nanotubes via physical
8543 address = "A. J. Drexel Nanotechnology Institute and Department
8544 of Materials Science and Engineering, Drexel
8545 University, Philadelphia, Pennsylvania 19104, USA.",
8548 pages = "8522--8525",
8549 keywords = "Microscopy, Atomic Force",
8550 keywords = "Microscopy, Electron, Transmission",
8551 keywords = "Nanotubes, Carbon",
8552 keywords = "Polymers",
8553 keywords = "Surface Properties",
8554 keywords = "Volatilization",
8555 abstract = "The polymer decoration technique has been widely used
8556 to study the chain folding behavior of polymer single
8557 crystals. In this article, we demonstrate that this
8558 method can be successfully adopted to pattern a variety
8559 of polymers on carbon nanotubes (CNTs). The resulting
8560 structure is a two-dimensional nanohybrid shish kebab
8561 (2D NHSK), wherein the CNT forms the shish and the
8562 polymer crystals form the kebabs. 2D NHSKs consisting
8563 of CNTs and polymers such as polyethylene, nylon 66,
8564 polyvinylidene fluoride and poly(L-lysine) have been
8565 achieved. Transmission electron microscopy and atomic
8566 force microscopy were used to study the nanoscale
8567 morphology of these hybrid materials. Relatively
8568 periodic decoration of polymers on both single-walled
8569 and multi-walled CNTs was observed. It is envisaged
8570 that this unique method offers a facile means to
8571 achieve patterned CNTs for nanodevice applications.",
8573 doi = "10.1021/la700480z",
8574 URL = "http://www.ncbi.nlm.nih.gov/pubmed/17602575",
8579 author = MSu #" and "# YYang #" and "# GYang,
8580 title = "Quantitative measurement of hydroxyl radical induced
8581 {DNA} double-strand breaks and the effect of
8582 {N}-acetyl-{L}-cysteine.",
8587 address = "Department of Physics, Drexel University,
8588 Philadelphia, PA 19104, USA.",
8591 pages = "4136--4142",
8592 keywords = "Acetylcysteine",
8593 keywords = "Animals",
8594 keywords = "DNA Damage",
8595 keywords = "Humans",
8596 keywords = "Hydroxyl Radical",
8597 keywords = "Microscopy, Atomic Force",
8598 keywords = "Nucleic Acid Conformation",
8599 keywords = "Plasmids",
8600 abstract = "Reactive oxygen species, such as hydroxyl or
8601 superoxide radicals, can be generated by exogenous
8602 agents as well as from normal cellular metabolism.
8603 Those radicals are known to induce various lesions in
8604 DNA, including strand breaks and base modifications.
8605 These lesions have been implicated in a variety of
8606 diseases such as cancer, arteriosclerosis, arthritis,
8607 neurodegenerative disorders and others. To assess these
8608 oxidative DNA damages and to evaluate the effects of
8609 the antioxidant N-acetyl-L-cysteine (NAC), atomic force
8610 microscopy (AFM) was used to image DNA molecules
8611 exposed to hydroxyl radicals generated via Fenton
8612 chemistry. AFM images showed that the circular DNA
8613 molecules became linear after incubation with hydroxyl
8614 radicals, indicating the development of double-strand
8615 breaks. The occurrence of the double-strand breaks was
8616 found to depend on the concentration of the hydroxyl
8617 radicals and the duration of the reaction. Under the
8618 conditions of the experiments, NAC was found to
8619 exacerbate the free radical-induced DNA damage.",
8621 doi = "10.1016/j.febslet.2006.06.060",
8622 URL = "http://www.ncbi.nlm.nih.gov/pubmed/16828758",
8627 author = LiLi #" and "# YYang #" and "# GYang #" and "# XuChen
8628 #" and "# BHsiao #" and "# BChu #" and "#
8629 JSpanier #" and "# CYLi,
8630 title = "Patterning polyethylene oligomers on carbon nanotubes
8631 using physical vapor deposition.",
8635 address = "A. J. Drexel Nanotechnology Institute and Department
8636 of Materials Science and Engineering, Drexel
8637 University, Philadelphia, Pennsylvania 19104, USA.",
8640 pages = "1007--1012",
8641 keywords = "Microscopy, Atomic Force",
8642 keywords = "Nanotechnology",
8643 keywords = "Nanotubes, Carbon",
8644 keywords = "Polyethylenes",
8645 keywords = "Volatilization",
8646 abstract = "Periodic patterning on one-dimensional (1D) carbon
8647 nanotubes (CNTs) is of great interest from both
8648 scientific and technological points of view. In this
8649 letter, we report using a facile physical vapor
8650 deposition method to achieve periodic polyethylene (PE)
8651 oligomer patterning on individual CNTs. Upon heating
8652 under vacuum, PE degraded into oligomers and
8653 crystallized into rod-shaped single crystals. These PE
8654 rods periodically decorate on CNTs with their long axes
8655 perpendicular to the CNT axes. The formation mechanism
8656 was attributed to ``soft epitaxy'' growth of PE
8657 oligomer crystals on CNTs. Both SWNTs and MWNTs were
8658 decorated successfully with PE rods. The intermediate
8659 state of this hybrid structure, MWNTs absorbed with a
8660 thin layer of PE, was captured successfully by
8661 depositing PE vapor on MWNTs detached from the solid
8662 substrate, and was observed using high-resolution
8663 transmission electron microscopy. Furthermore, this
8664 hybrid structure formation depends critically on CNT
8665 surface chemistry: alkane-modification of the MWNT
8666 surface prohibited the PE single-crystal growth on the
8667 CNTs. We anticipate that this work could open a gateway
8668 for creating complex CNT-based nanoarchitectures for
8669 nanodevice applications.",
8671 doi = "10.1021/nl060276q",
8672 URL = "http://www.ncbi.nlm.nih.gov/pubmed/16683841",
8677 author = MKuhn #" and "# HJanovjak #" and "# MHubain #" and "# DJMuller,
8678 title = {Automated alignment and pattern recognition of
8679 single-molecule force spectroscopy data.},
8682 address = {Division of Computer Science, California Institute of
8683 Technology, Pasadena, California 91125, USA.},
8689 doi = {10.1111/j.1365-2818.2005.01478.x},
8690 URL = {http://www.ncbi.nlm.nih.gov/pubmed/15857374},
8692 keywords = {Algorithms},
8693 keywords = {Bacteriorhodopsins},
8694 keywords = {Data Interpretation, Statistical},
8695 keywords = {Escherichia coli Proteins},
8696 keywords = {Microscopy, Atomic Force},
8697 keywords = {Protein Folding},
8698 keywords = {Sodium-Hydrogen Antiporter},
8699 keywords = {Software},
8700 abstract = {Recently, direct measurements of forces stabilizing
8701 single proteins or individual receptor-ligand bonds became
8702 possible with ultra-sensitive force probe methods like the atomic
8703 force microscope (AFM). In force spectroscopy experiments using
8704 AFM, a single molecule or receptor-ligand pair is tethered between
8705 the tip of a micromachined cantilever and a supporting
8706 surface. While the molecule is stretched, forces are measured by
8707 the deflection of the cantilever and plotted against extension,
8708 yielding a force spectrum characteristic for each biomolecular
8709 system. In order to obtain statistically relevant results, several
8710 hundred to thousand single-molecule experiments have to be
8711 performed, each resulting in a unique force spectrum. We developed
8712 software and algorithms to analyse large numbers of force
8713 spectra. Our algorithms include the fitting polymer extension
8714 models to force peaks as well as the automatic alignment of
8715 spectra. The aligned spectra allowed recognition of patterns of
8716 peaks across different spectra. We demonstrate the capabilities of
8717 our software by analysing force spectra that were recorded by
8718 unfolding single transmembrane proteins such as bacteriorhodopsin
8719 and NhaA. Different unfolding pathways were detected by
8720 classifying peak patterns. Deviant spectra, e.g. those with no
8721 attachment or erratic peaks, can be easily identified. The
8722 software is based on the programming language C++, the GNU
8723 Scientific Library (GSL), the software WaveMetrics IGOR Pro and
8724 available open-source at http://bioinformatics.org/fskit/.},
8725 note = {Development stalled in 2005 after Michael graduated.},
8728 @article{ janovjak05,
8729 author = HJanovjak #" and "# JStruckmeier #" and "# DJMuller,
8730 title = {Hydrodynamic effects in fast {AFM} single-molecule
8731 force measurements.},
8735 address = {BioTechnological Center, University of Technology
8736 Dresden, 01307 Dresden, Germany.},
8742 doi = {10.1007/s00249-004-0430-3},
8743 url = {http://www.ncbi.nlm.nih.gov/pubmed/15257425},
8745 keywords = {Algorithms},
8746 keywords = {Computer Simulation},
8747 keywords = {Elasticity},
8748 keywords = {Microfluidics},
8749 keywords = {Microscopy, Atomic Force},
8750 keywords = {Models, Chemical},
8751 keywords = {Models, Molecular},
8752 keywords = {Physical Stimulation},
8753 keywords = {Protein Binding},
8754 keywords = {Proteins},
8755 keywords = {Stress, Mechanical},
8756 keywords = {Viscosity},
8757 abstract = {Atomic force microscopy (AFM) allows the critical forces
8758 that unfold single proteins and rupture individual receptor-ligand
8759 bonds to be measured. To derive the shape of the energy landscape,
8760 the dynamic strength of the system is probed at different force
8761 loading rates. This is usually achieved by varying the pulling
8762 speed between a few nm/s and a few $\mu$m/s, although for a more
8763 complete investigation of the kinetic properties higher speeds are
8764 desirable. Above 10 $\mu$m/s, the hydrodynamic drag force acting
8765 on the AFM cantilever reaches the same order of magnitude as the
8766 molecular forces. This has limited the maximum pulling speed in
8767 AFM single-molecule force spectroscopy experiments. Here, we
8768 present an approach for considering these hydrodynamic effects,
8769 thereby allowing a correct evaluation of AFM force measurements
8770 recorded over an extended range of pulling speeds (and thus
8771 loading rates). To support and illustrate our theoretical
8772 considerations, we experimentally evaluated the mechanical
8773 unfolding of a multi-domain protein recorded at $30\U{$mu$m/s}$
8778 author = MSandal #" and "# FBenedetti #" and "# MBrucale #" and "#
8779 AGomezCasado #" and "# BSamori,
8780 title = "Hooke: An open software platform for force spectroscopy.",
8785 address = "Department of Biochemistry, University of Bologna,
8786 Bologna, Italy. massimo.sandal@unibo.it",
8789 pages = "1428--1430",
8790 keywords = "Algorithms",
8791 keywords = "Computational Biology",
8792 keywords = "Internet",
8793 keywords = "Microscopy, Atomic Force",
8794 keywords = "Proteome",
8795 keywords = "Proteomics",
8796 keywords = "Software",
8797 abstract = "SUMMARY: Hooke is an open source, extensible software
8798 intended for analysis of atomic force microscope (AFM)-based
8799 single molecule force spectroscopy (SMFS) data. We propose it as a
8800 platform on which published and new algorithms for SMFS analysis
8801 can be integrated in a standard, open fashion, as a general
8802 solution to the current lack of a standard software for SMFS data
8803 analysis. Specific features and support for file formats are coded
8804 as independent plugins. Any user can code new plugins, extending
8805 the software capabilities. Basic automated dataset filtering and
8806 semi-automatic analysis facilities are included. AVAILABILITY:
8807 Software and documentation are available at
8808 (http://code.google.com/p/hooke). Hooke is a free software under
8809 the GNU Lesser General Public License.",
8811 doi = "10.1093/bioinformatics/btp180",
8812 URL = "http://www.ncbi.nlm.nih.gov/pubmed/19336443",
8816 @article{ materassi09,
8817 author = DMaterassi #" and "# PBaschieri #" and "# BTiribilli #" and "#
8818 GZuccheri #" and "# BSamori,
8819 title = {An open source/real-time atomic force microscope
8820 architecture to perform customizable force spectroscopy
8824 address = {Department of Electrical and Computer Engineering,
8825 University of Minnesota, 200 Union St. SE, Minneapolis,
8826 Minnesota 55455, USA. mater013@umn.edu},
8832 doi = "10.1063/1.3194046",
8833 url = "http://www.ncbi.nlm.nih.gov/pubmed/19725671",
8835 keywords = {Algorithms},
8836 keywords = {Animals},
8837 keywords = {Calibration},
8839 keywords = {Microscopy, Atomic Force},
8840 keywords = {Muscle Proteins},
8841 keywords = {Myocardium},
8842 keywords = {Optics and Photonics},
8843 keywords = {Ownership},
8844 keywords = {Protein Kinases},
8845 keywords = {Software},
8846 keywords = {Spectrum Analysis},
8847 keywords = {Time Factors},
8848 abstract = {We describe the realization of an atomic force
8849 microscope architecture designed to perform customizable
8850 experiments in a flexible and automatic way. Novel technological
8851 contributions are given by the software implementation platform
8852 (RTAI-LINUX), which is free and open source, and from a functional
8853 point of view, by the implementation of hard real-time control
8854 algorithms. Some other technical solutions such as a new way to
8855 estimate the optical lever constant are described as well. The
8856 adoption of this architecture provides many degrees of freedom in
8857 the device behavior and, furthermore, allows one to obtain a
8858 flexible experimental instrument at a relatively low cost. In
8859 particular, we show how such a system has been employed to obtain
8860 measures in sophisticated single-molecule force spectroscopy
8861 experiments\citep{fernandez04}. Experimental results on proteins
8862 already studied using the same methodologies are provided in order
8863 to show the reliability of the measure system.},
8864 note = {Although this paper claims to present an open source
8865 experiment control framework (on Linux!), it doesn't actually link
8866 to any source code. This is puzzling and frusterating.},
8869 @article{ aioanei11,
8870 author = DAioanei #" and "# MBrucale #" and "# BSamori,
8871 title = {Open source platform for the execution and analysis of
8872 mechanical refolding experiments.},
8876 address = {Department of Biochemistry G.~Moruzzi,
8877 University of Bologna, Via Irnerio 48, 40126 Bologna, Italy.
8878 aioaneid@gmail.com},
8884 doi = {10.1093/bioinformatics/btq663},
8885 url = {http://www.ncbi.nlm.nih.gov/pubmed/21123222},
8887 keywords = {Computational Biology},
8888 keywords = {Kinetics},
8889 keywords = {Protein Denaturation},
8890 keywords = {Protein Refolding},
8891 keywords = {Software},
8892 abstract = {Single-molecule force spectroscopy has facilitated the
8893 experimental investigation of biomolecular force-coupled kinetics,
8894 from which the kinetics at zero force can be extrapolated via
8895 explicit theoretical models. The atomic force microscope (AFM) in
8896 particular is routinely used to study protein unfolding kinetics,
8897 but only rarely protein folding kinetics. The discrepancy arises
8898 because mechanical protein refolding studies are more technically
8900 note = {\href{http://code.google.com/p/refolding/}{Refolding} is a
8901 suite for performing and analyzing double-pulse refolding
8902 experiments. The experiment-driver is mostly written in Java with
8903 the analysis code in Python. The driver is curious; it uses the
8904 NanoScope scripting interface to drive the experiment through the
8905 NanoScope software by impersonating a mouse-wielding user (like
8906 Selenium does for web browsers). See the
8907 \imint{sh}|RobotNanoDriver.java| code for details. There is also
8908 support for automatic velocity clamp analysis.},
8911 @article{ benedetti11,
8912 author = FBenedetti #" and "# CMicheletti #" and "# GBussi #" and "#
8913 SKSekatskii #" and "# GDietler,
8914 title = {Nonkinetic modeling of the mechanical unfolding of
8915 multimodular proteins: theory and experiments.},
8919 address = {Laboratory of Physics of Living Matter,
8920 Ecole Polytechnique F{\'e}d{\'e}rale de Lausanne,
8921 Lausanne, Switzerland.},
8925 pages = {1504--1512},
8927 doi = {10.1016/j.bpj.2011.07.047},
8928 url = {http://www.ncbi.nlm.nih.gov/pubmed/21943432},
8930 keywords = {Kinetics},
8931 keywords = {Microscopy, Atomic Force},
8932 keywords = {Models, Molecular},
8933 keywords = {Monte Carlo Method},
8934 keywords = {Protein Unfolding},
8935 keywords = {Stochastic Processes},
8936 abstract = {We introduce and discuss a novel approach called
8937 back-calculation for analyzing force spectroscopy experiments on
8938 multimodular proteins. The relationship between the histograms of
8939 the unfolding forces for different peaks, corresponding to a
8940 different number of not-yet-unfolded protein modules, is exploited
8941 in such a manner that the sole distribution of the forces for one
8942 unfolding peak can be used to predict the unfolding forces for
8943 other peaks. The scheme is based on a bootstrap prediction method
8944 and does not rely on any specific kinetic model for multimodular
8945 unfolding. It is tested and validated in both
8946 theoretical/computational contexts (based on stochastic
8947 simulations) and atomic force microscopy experiments on (GB1)(8)
8948 multimodular protein constructs. The prediction accuracy is so
8949 high that the predicted average unfolding forces corresponding to
8950 each peak for the GB1 construct are within only 5 pN of the
8951 averaged directly-measured values. Experimental data are also used
8952 to illustrate how the limitations of standard kinetic models can
8953 be aptly circumvented by the proposed approach.},
8956 @phdthesis{ benedetti12,
8957 author = FBenedetti,
8958 title = {Statistical Study of the Unfolding of Multimodular Proteins
8959 and their Energy Landscape by Atomic Force Microscopy},
8961 address = {Lausanne},
8962 affiliation = {EPFL},
8965 doi = {10.5075/epfl-thesis-5440},
8966 url = {http://infoscience.epfl.ch/record/181215},
8967 eprint = {http://infoscience.epfl.ch/record/181215/files/EPFL_TH5440.pdf},
8968 keywords = {atomic force microscope (AFM); single molecule force
8969 spectrosopy; velocity clamp AFM; Monte carlo simulations; force
8970 modulation spectroscopy; energy barrier model; non kinetic methods
8971 for force spectroscopy},
8972 abstract = {The aim of the present thesis is to investigate several
8973 aspects of: the proteins mechanics, interprotein interactions and
8974 to study also new techniques, theoretical and technical, to obtain
8975 and analyze the force spectroscopy experiments. The first section
8976 is dedicated to the statistical properties of the unfolding forces
8977 in a chain of homomeric multimodular proteins. The basic idea of
8978 this kind of statistic is to divide the peaks observed in a force
8979 extension curve in separate groups and then analyze these groups
8980 considering their position in the force curves. In fact in a
8981 multimodular homomeric protein the unfolding force is related to
8982 the number of not yet unfolded modules (we call it "N"). Such
8983 effect yields to a linear dependence of the most probable
8984 unfolding force of a peak on ln(N). We demonstrate how such
8985 dependence can be used to extract the kinetic parameters and how,
8986 ignoring it, could lead to significant errors. Following this
8987 topic we continue with non kinetic methods that, using the
8988 resampling from the rupture forces of any peak, could reconstruct
8989 the rupture forces for all the other peaks in a chain. Then a
8990 discussion about the Monte Carlo simulation for protein pulling is
8991 present. In fact a theoretical framework for such methodology has
8992 to be introduced to understand the various simulations done. In
8993 this chapter we also introduce a methodology to study the ligand
8994 receptor interactions when we directly functionalize the AFM tip
8995 and the substrate. In fact, in many of our experiments, we see a
8996 "cloud of points" in the force vs loading rate graph. We have
8997 modeled a system composed by "N" parallel springs, and studying
8998 the distribution of forces obtained in the force vs loading rate
8999 graph we have establish a procedure to restore the kinetic
9000 parameters used. Such procedure has then been used to discuss real
9001 experiments similar to biotin-avidin interaction. In the following
9002 chapter we discuss a first order approximation of the Bell-Evans
9003 model where a more explicit form of the potential is
9004 considered. In particular the dependence of the curvature of the
9005 potential on the applied force at the minimum and at the
9006 metastable state is considered. In the well known Bell-Evans model
9007 the prefactors of the transition rate are fixed at any force,
9008 however this is not what happen in nature, where the prefactors
9009 (that are the second local derivative of the interacting energy
9010 with respect to the reaction coordinate in its minimum and
9011 maximum) depend on the force applied. The results obtained with
9012 the force spectroscopy of the Laminin-binding-protein are
9013 discussed, in particular this protein showed a phase transition
9014 when the pH was changed. The behavior of this protein changes,
9015 from a normal WLC behavior to a plateau behavior. The analysis of
9016 the force spectroscopy curves shows a distribution of length where
9017 the maximum of the first prominent peak correspond to the full
9018 length of the protein. However, length that could be associated
9019 with dimers and trymers are also present in this
9020 distribution. Later a new approach to study the lock and key
9021 mechanism, using "handles" with a specific force extension
9022 pattern, is introduced. In particular handles of (I27)3 and
9023 (I27–SNase)3 were biochemically attached to: strept-actin
9024 molecules, biotin molecules, RNase and Angiogenin. The main idea
9025 is to have a system composed by "handle-(molecule A)-(molecule
9026 B)-handle" where the handles are covalently attached to the
9027 respective molecules and the two molecules "A and B" are attached
9028 by secondary bonds. This approach allows a better recognition of
9029 the protein-protein interaction enabling us to filter out spurious
9030 events. Doing a statistic on the rupture forces and comparing this
9031 with the statistic of the detachments of the system of the bare
9032 handles, we are able to extract the information of the interaction
9033 between the molecule A and B. The two last chapters are of more
9034 preliminary character that the previous part of the thesis. A
9035 section is dedicated to the estimation of effective mass and
9036 viscous drag of the cantilevers studied by autocorrelation and
9037 noise power spectrum. Usually the noise power spectrum method is
9038 the most used, however the autocorrelation should give
9039 approximately the same information. The parameters obtained are
9040 important in high frequency modulation techniques. In fact, they
9041 are needed to interpret the results. The results of these two
9042 methods show a good agreement in the estimation of the mass and
9043 the viscous drag of the various cantilever used. Afterwards a
9044 chapter is dedicated to the discussion of the force spectroscopy
9045 experiments using a low frequency modulation of the cantilever
9046 base. Such experiments allow us to record the phase and the
9047 amplitude shift of the modulation signal used. Using the amplitude
9048 channel we managed to restore the static force signal with a lower
9049 level of noise. Moreover these signals give us direct information
9050 about the dynamic stiffness and the lose of energy in the system,
9051 information that, using the standard technique would be difficult
9052 (or even impossible) to obtain.},
9056 author = TKempe #" and "# SBHKent #" and "# FChow #" and "# SMPeterson
9057 #" and "# WSundquist #" and "# JLItalien #" and "# DHarbrecht
9058 #" and "# DPlunkett #" and "# WDeLorbe,
9059 title = "Multiple-copy genes: Production and modification of
9060 monomeric peptides from large multimeric fusion proteins.",
9066 keywords = "Cloning, Molecular",
9067 keywords = "Cyanogen Bromide",
9068 keywords = "DNA, Recombinant",
9069 keywords = "Escherichia coli",
9070 keywords = "Gene Expression Regulation",
9071 keywords = "Genetic Vectors",
9072 keywords = "Humans",
9073 keywords = "Molecular Weight",
9074 keywords = "Peptide Fragments",
9075 keywords = "Plasmids",
9076 keywords = "Substance P",
9077 keywords = "beta-Galactosidase",
9078 abstract = "A vector system has been designed for obtaining high
9079 yields of polypeptides synthesized in Escherichia coli. Multiple
9080 copies of a synthetic gene encoding the neuropeptide substance P
9081 (SP) (Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2) have been
9082 linked and fused to the lacZ gene. Each copy of the SP gene was
9083 flanked by codons for methionine to create sites for cleavage by
9084 cyanogen bromide (CNBr). The isolated multimeric SP fusion
9085 protein was converted to monomers of SP analog, each containing a
9086 carboxyl-terminal homoserine lactone (Hse-lactone) residue
9087 (Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Hse-lactone), upon
9088 treatment with CNBr in formic acid. The Hse-lactone moiety was
9089 subjected to chemical modifications to produce an SP Hse
9090 amide. This method permits synthesis of peptide amide analogs and
9091 other peptide derivatives by combining recombinant DNA techniques
9092 and chemical methods.",
9094 URL = "http://www.ncbi.nlm.nih.gov/pubmed/2419204",
9099 author = MHonda #" and "# YBaba #" and "# NHiaro #" and "# TSekiguchi,
9100 title = "Metal-molecular interface of sulfur-containing amino acid
9101 and thiophene on gold surface",
9106 url = "http://dx.doi.org/10.1088/1742-6596/100/5/052071",
9108 abstract = "Chemical-bonding states of metal-molecular interface
9109 have been investigated for L-cysteine and thiophene on gold by
9110 x-ray photoelectron spectroscopy (XPS) and near edge x-ray
9111 adsorption fine structure (NEXAFS). A remarkable difference in
9112 Au-S bonding states was found between L-cysteine and
9113 thiophene. For mono-layered L-cysteine on gold, the binding energy
9114 of S 1s in XPS and the resonance energy at the S K-edge in NEXAFS
9115 are higher by 8–9 eV than those for multi-layered film (molecular
9116 L-cysteine). In contrast, the S K-edge resonance energy for
9117 mono-layered thiophene on gold was 2475.0 eV, which is the same as
9118 that for molecular L-cysteine. In S 1s XPS for mono-layered
9119 thiophene, two peaks were observed. The higher binging-energy and
9120 more intense peak at 2473.4 eV are identified as gold sulfide. The
9121 binding energy of smaller peak, whose intensity is less than 1/3
9122 of the higher binding energy peak, is 2472.2 eV, which is the same
9123 as that for molecular thiophene. These observations indicate that
9124 Au-S interface behavior shows characteristic chemical bond only
9125 for the Au-S interface of L-cysteine monolayer on gold
9131 title = "Formation and Structure of Self-Assembled Monolayers.",
9136 address = "Department of Chemical Engineering, Chemistry and
9137 Materials Science, and the Herman F. Mark Polymer Research
9138 Institute, Polytechnic University, Six MetroTech Center, Brooklyn,
9142 pages = "1533--1554",
9144 URL = "http://www.ncbi.nlm.nih.gov/pubmed/11848802",
9149 author = GHager #" and "# ABrolo,
9150 title = "Adsorption/desorption behaviour of cysteine and cystine in
9151 neutral and basic media: electrochemical evidence for differing
9152 thiol and disulfide adsorption to a {Au(111)} single crystal
9155 volume = "550--551",
9160 doi = "10.1016/S0022-0728(03)00052-4",
9161 url = "http://www.sciencedirect.com/science/article/pii/S0022072803000524",
9163 keywords = "Disulfide",
9164 keywords = "Thiol adsorption",
9165 keywords = "Self-assembled monolayers",
9166 keywords = "Au(111) single crystal electrode",
9167 keywords = "Cysteine",
9168 keywords = "Cystine",
9169 abstract = "The adsorption/desorption behaviour of the
9170 thiol/disulfide redox couple, cysteine/cystine, was monitored at a
9171 Au(111) single crystal electrode. The monolayers were formed
9172 electrochemically from 0.1 M KClO4 and 0.1 M NaOH solutions
9173 containing either the thiol or the disulfide. Distinct features in
9174 the adsorption potential were noted. An adsorption peak was
9175 observed in the cyclic voltammograms (CVs) from Au(111) in 0.1 M
9176 KClO4 solutions containing cystine at $-0.57$ V vs. saturated
9177 calomel electrode. Under the same conditions, the CVs from
9178 solutions containing cysteine showed an adsorption peak at $-0.43$
9179 V (0.14 V more positive than the corresponding peak from disulfide
9180 solutions). This showed that the thiol and disulfide species have
9181 different adsorption properties. Similar behaviour was observed in
9182 0.1 M NaOH. Cyclic voltammetric and chronocoulometric data were
9183 employed to determine the surface coverage of the different
9184 monolayers. Cysteine solutions prepared in 0.1 M KClO4 provided
9185 coverages of $3.0\times10^{-10}$ and $2.5\times10^{-10}$
9186 mol~cm$^{-2}$ for the L and the D--L species, respectively as
9187 evaluated from the desorption peaks. Desorption of cystine in the
9188 same medium yielded coverages of $1.2\times10^{-10}$ mol~cm$^{-2}$
9189 for both L and D--L solutions (or $2.4\times10^{-10}$
9190 mol~cm$^{-2}$ in cysteine equivalents). Surface coverages obtained
9191 from Au(111) in 0.1 M NaOH corresponded to $3.9\times10^{10}$
9192 mol~cm$^{-2}$ for L-cysteine, and $1.2\times10^{-10}$
9193 mol~cm$^{-2}$ (or $2.4\times10^{-10}$ mol~cm$^{-2}$ cysteine
9194 equivalents) for L and D--L cystine.",
9199 title = "The Nanomechanics of Polycystin-1: A Kidney Mechanosensor",
9203 url = "http://etd.utmb.edu/theses/available/etd-07072010-132038/",
9205 keywords = "Polycystin-1",
9206 keywords = "Missense mutations",
9207 keywords = "Atomic Force Microscopy",
9208 keywords = "Osmolyte",
9209 keywords = "Mechanosensor",
9210 abstract = "Mutations in polycystin-1 (PC1) can cause Autosomal
9211 Dominant Polycystic Kidney Disease (ADPKD), which is a leading
9212 cause of renal failure. The available evidence suggests that PC1
9213 acts as a mechanosensor, receiving signals from the primary cilia,
9214 neighboring cells, and extracellular matrix. PC1 is a large
9215 membrane protein that has a long N-terminal extracellular region
9216 (about 3000 aa) with a multimodular structure including sixteen
9217 Ig-like PKD domains, which are targeted by many naturally
9218 occurring missense mutations. Nothing is known about the effects
9219 of these mutations on the biophysical properties of PKD
9220 domains. In addition, PC1 is expressed along the renal tubule,
9221 where it is exposed to a wide range of concentration of urea. Urea
9222 is known to destabilize proteins. Other osmolytes found in the
9223 kidney such as sorbitol, betaine and TMAO are known to counteract
9224 urea's negative effects on proteins. Nothing is known about how
9225 the mechanical properties of PC1 are affected by these
9226 osmolytes. Here I use nano-mechanical techniques to study the
9227 effects of missense mutations and effects of denaturants and
9228 various osmolytes on the mechanical properties of PKD
9229 domains. Several missense mutations were found to alter the
9230 mechanical stability of PKD domains resulting in distinct
9231 mechanical phenotypes. Based on these findings, I hypothesize that
9232 missense mutations may cause ADPKD by altering the stability of
9233 the PC1 ectodomain, thereby perturbing its ability to sense
9234 mechanical signals. I also found that urea has a significant
9235 impact on both the mechanical stability and refolding rate of PKD
9236 domains. It not only lowers their mechanical stability, but also
9237 slows down their refolding rate. Moreover, several osmolytes were
9238 found to effectively counteract the effects of urea. Our data
9239 provide the evidence that naturally occurring osmolytes can help
9240 to maintain Polycystin-1 mechanical stability and folding
9241 kinetics. This study has the potential to provide new therapeutic
9242 approaches (e.g. through the use of osmolytes or chemical
9243 chaperones) for rescuing destabilized and misfolded PKD domains.",
9247 @article{ sundberg03,
9248 author = MSundberg #" and "# JRosengren #" and "# RBunk
9249 #" and "# JLindahl #" and "# INicholls #" and "# STagerud
9250 #" and "# POmling #" and "# LMontelius #" and "# AMansson,
9251 title = "Silanized surfaces for in vitro studies of actomyosin
9252 function and nanotechnology applications.",
9257 address = "Department of Chemistry and Biomedical Sciences,
9258 University of Kalmar, SE-391 82 Kalmar, Sweden.",
9262 keywords = "Actomyosin",
9263 keywords = "Adsorption",
9264 keywords = "Animals",
9265 keywords = "Collodion",
9266 keywords = "Kinetics",
9267 keywords = "Methods",
9268 keywords = "Movement",
9269 keywords = "Nanotechnology",
9270 keywords = "Rabbits",
9271 keywords = "Silicon",
9272 keywords = "Surface Properties",
9273 keywords = "Trimethylsilyl Compounds",
9274 abstract = "We have previously shown that selective heavy meromyosin
9275 (HMM) adsorption to predefined regions of nanostructured polymer
9276 resist surfaces may be used to produce a nanostructured in vitro
9277 motility assay. However, actomyosin function was of lower quality
9278 than on conventional nitrocellulose films. We have therefore
9279 studied actomyosin function on differently derivatized glass
9280 surfaces with the aim to find a substitute for the polymer
9281 resists. We have found that surfaces derivatized with
9282 trimethylchlorosilane (TMCS) were superior to all other surfaces
9283 tested, including nitrocellulose. High-quality actin filament
9284 motility was observed up to 6 days after incubation with HMM and
9285 the fraction of motile actin filaments and the velocity of smooth
9286 sliding were generally higher on TMCS than on nitrocellulose. The
9287 actomyosin function on TMCS-derivatized glass and nitrocellulose
9288 is considered in relation to roughness and hydrophobicity of these
9289 surfaces. The results suggest that TMCS is an ideal substitute for
9290 polymer resists in the nanostructured in vitro motility
9291 assay. Furthermore, TMCS derivatized glass also seems to offer
9292 several advantages over nitrocellulose for HMM adsorption in the
9293 ordinary in /vitro motility assay.",
9295 URL = "http://www.ncbi.nlm.nih.gov/pubmed/14622967",
9296 doi = "10.1016/j.ab.2003.07.022",
9301 author = HItoh #" and "# ATakahashi #" and "# KAdachi #" and "#
9302 HNoji #" and "# RYasuda #" and "# MYoshida #" and "#
9304 title = "Mechanically driven {ATP} synthesis by {F1}-{ATP}ase.",
9309 address = "Tsukuba Research Laboratory, Hamamatsu Photonics KK,
9310 Joko, Hamamatsu 431-3103, Japan.
9311 hiritoh@hpk.trc-net.co.jp",
9315 keywords = "Adenosine Diphosphate",
9316 keywords = "Adenosine Triphosphate",
9317 keywords = "Bacillus",
9318 keywords = "Catalysis",
9320 keywords = "Magnetics",
9321 keywords = "Microchemistry",
9322 keywords = "Microspheres",
9323 keywords = "Molecular Motor Proteins",
9324 keywords = "Proton-Translocating ATPases",
9325 keywords = "Rotation",
9326 keywords = "Torque",
9327 abstract = "ATP, the main biological energy currency, is synthesized
9328 from ADP and inorganic phosphate by ATP synthase in an
9329 energy-requiring reaction. The F1 portion of ATP synthase, also
9330 known as F1-ATPase, functions as a rotary molecular motor: in
9331 vitro its gamma-subunit rotates against the surrounding
9332 alpha3beta3 subunits, hydrolysing ATP in three separate catalytic
9333 sites on the beta-subunits. It is widely believed that reverse
9334 rotation of the gamma-subunit, driven by proton flow through the
9335 associated F(o) portion of ATP synthase, leads to ATP synthesis in
9336 biological systems. Here we present direct evidence for the
9337 chemical synthesis of ATP driven by mechanical energy. We attached
9338 a magnetic bead to the gamma-subunit of isolated F1 on a glass
9339 surface, and rotated the bead using electrical magnets. Rotation
9340 in the appropriate direction resulted in the appearance of ATP in
9341 the medium as detected by the luciferase-luciferin reaction. This
9342 shows that a vectorial force (torque) working at one particular
9343 point on a protein machine can influence a chemical reaction
9344 occurring in physically remote catalytic sites, driving the
9345 reaction far from equilibrium.",
9347 doi = "10.1038/nature02212",
9348 URL = "http://www.ncbi.nlm.nih.gov/pubmed/14749837",
9353 author = NSakaki #" and "# RShimoKon #" and "# KAdachi
9354 #" and "# HItoh #" and "# SFuruike #" and "# EMuneyuki
9355 #" and "# MYoshida #" and "# KKinosita,
9356 title = "One rotary mechanism for {F1}-{ATP}ase over {ATP}
9357 concentrations from millimolar down to nanomolar.",
9362 address = "Department of Functional Molecular Science, The Graduate
9363 University for Advanced Studies, Nishigonaka 38, Myodaiji, Okazaki
9367 pages = "2047--2056",
9368 keywords = "Adenosine Triphosphate",
9369 keywords = "Hydrolysis",
9370 keywords = "Kinetics",
9371 keywords = "Microchemistry",
9372 keywords = "Molecular Motor Proteins",
9373 keywords = "Nanostructures",
9374 keywords = "Protein Binding",
9375 keywords = "Protein Conformation",
9376 keywords = "Proton-Translocating ATPases",
9377 keywords = "Rotation",
9378 keywords = "Torque",
9379 abstract = "F(1)-ATPase is a rotary molecular motor in which the
9380 central gamma-subunit rotates inside a cylinder made of
9381 alpha(3)beta(3)-subunits. The rotation is driven by ATP hydrolysis
9382 in three catalytic sites on the beta-subunits. How many of the
9383 three catalytic sites are filled with a nucleotide during the
9384 course of rotation is an important yet unsettled question. Here we
9385 inquire whether F(1) rotates at extremely low ATP concentrations
9386 where the site occupancy is expected to be low. We observed under
9387 an optical microscope rotation of individual F(1) molecules that
9388 carried a bead duplex on the gamma-subunit. Time-averaged rotation
9389 rate was proportional to the ATP concentration down to 200 pM,
9390 giving an apparent rate constant for ATP binding of 2 x 10(7)
9391 M(-1)s(-1). A similar rate constant characterized bulk ATP
9392 hydrolysis in solution, which obeyed a simple Michaelis-Menten
9393 scheme between 6 mM and 60 nM ATP. F(1) produced the same torque
9394 of approximately 40 pN.nm at 2 mM, 60 nM, and 2 nM ATP. These
9395 results point to one rotary mechanism governing the entire range
9396 of nanomolar to millimolar ATP, although a switchover between two
9397 mechanisms cannot be dismissed. Below 1 nM ATP, we observed less
9398 regular rotations, indicative of the appearance of another
9401 doi = "10.1529/biophysj.104.054668",
9402 URL = "http://www.ncbi.nlm.nih.gov/pubmed/15626703",
9406 @article{ schmidt02,
9407 author = JSchmidt #" and "# XJiang #" and "# CMontemagno,
9408 title = "Force Tolerances of Hybrid Nanodevices",
9412 pages = "1229--1233",
9414 doi = "10.1021/nl025773v",
9415 URL = "http://pubs.acs.org/doi/abs/10.1021/nl025773v",
9416 eprint = "http://pubs.acs.org/doi/pdf/10.1021/nl025773v",
9417 abstract = "We have created hybrid devices consisting of nanoscale
9418 fabricated inorganic components integrated with and powered by a
9419 genetically engineered motor protein. We wish to increase the
9420 assembly yield and lifetime of these devices through
9421 identification, measurement, and improvement of weak internal
9422 bonds. Using dynamic force spectroscopy, we have measured the bond
9423 rupture force of (histidine)\textsubscript{6} on a number of
9424 different surfaces as a function of loading rate. The bond sizes,
9425 lifetimes, and energy barrier heights were derived from these
9426 measurements. We compare the (His)\textsubscript{6}--nickel bonds
9427 to other bonds composing the hybrid device and describe
9428 preliminary measurements of the force tolerances of the protein
9429 itself. Pathways for improvement of device longevity and
9430 robustness are discussed.",
9434 author = YSLo #" and "# YJZhu #" and "# TBeebe,
9435 title = "Loading-Rate Dependence of Individual Ligand−Receptor
9436 Bond-Rupture Forces Studied by Atomic Force Microscopy",
9440 pages = "3741--3748",
9442 doi = "10.1021/la001569g",
9443 URL = "http://pubs.acs.org/doi/abs/10.1021/la001569g",
9444 eprint = "http://pubs.acs.org/doi/pdf/10.1021/la001569g",
9445 abstract = "It is known that bond strength is a dynamic property
9446 that is dependent upon the force loading rate applied during the
9447 rupturing of a bond. For biotin--avidin and biotin--streptavidin
9448 systems, dynamic force spectra, which are plots of bond strength
9449 vs loge(loading rate), have been acquired in a recent biomembrane
9450 force probe (BFP) study at force loading rates in the range
9451 0.05--60 000 pN/s. In the present study, the dynamic force spectrum
9452 of the biotin--streptavidin bond strength in solution was extended
9453 from loading rates of ∼104 to ∼107 pN/s with the atomic force
9454 microscope (AFM). A Poisson statistical analysis method was
9455 applied to extract the magnitude of individual bond-rupture forces
9456 and nonspecific interactions from the AFM force--distance curve
9457 measurements. The bond strengths were found to scale linearly with
9458 the logarithm of the loading rate. The nonspecific interactions
9459 also exhibited a linear dependence on the logarithm of loading
9460 rate, although not increasing as rapidly as the specific
9461 interactions. The dynamic force spectra acquired here with the AFM
9462 combined well with BFP measurements by Merkel et al. The combined
9463 spectrum exhibited two linear regimes, consistent with the view
9464 that multiple energy barriers are present along the unbinding
9465 coordinate of the biotin--streptavidin complex. This study
9466 demonstrated that unbinding forces measured by different
9467 techniques are in agreement and can be used together to obtain a
9468 dynamic force spectrum covering 9 orders of magnitude in loading
9470 note = "These guys seem to be pretty thorough, give this one another read.",
9474 author = ABaljon #" and "# MRobbins,
9475 title = "Energy Dissipation During Rupture of Adhesive Bonds",
9482 doi = "10.1126/science.271.5248.482",
9483 URL = "http://www.sciencemag.org/content/271/5248/482.abstract",
9484 eprint = "http://www.sciencemag.org/content/271/5248/482.full.pdf",
9485 abstract = "Molecular dynamics simulations were used to study
9486 energy-dissipation mechanisms during the rupture of a thin
9487 adhesive bond formed by short chain molecules. The degree of
9488 dissipation and its velocity dependence varied with the state of
9489 the film. When the adhesive was in a liquid phase, dissipation was
9490 caused by viscous loss. In glassy films, dissipation occurred
9491 during a sequence of rapid structural rearrangements. Roughly
9492 equal amounts of energy were dissipated in each of three types of
9493 rapid motion: cavitation, plastic yield, and bridge rupture. These
9494 mechanisms have similarities to nucleation, plastic flow, and
9495 crazing in commercial polymeric adhesives.",
9498 @article{ fisher99a,
9499 author = TEFisher #" and "# PMarszalek #" and "# AOberhauser
9500 #" and "# MCarrionVazquez #" and "# JFernandez,
9501 title = "The micro-mechanics of single molecules studied with
9502 atomic force microscopy.",
9507 address = "Department of Physiology and Biophysics, Mayo Foundation,
9508 1-117 Medical Sciences Building, Rochester, MN 55905, USA.",
9509 volume = "520 Pt 1",
9511 keywords = "Animals",
9512 keywords = "Extracellular Matrix",
9513 keywords = "Extracellular Matrix Proteins",
9514 keywords = "Humans",
9515 keywords = "Microscopy, Atomic Force",
9516 keywords = "Polysaccharides",
9517 abstract = "The atomic force microscope (AFM) in its force-measuring
9518 mode is capable of effecting displacements on an angstrom scale
9519 (10 A = 1 nm) and measuring forces of a few piconewtons. Recent
9520 experiments have applied AFM techniques to study the mechanical
9521 properties of single biological polymers. These properties
9522 contribute to the function of many proteins exposed to mechanical
9523 strain, including components of the extracellular matrix
9524 (ECM). The force-bearing proteins of the ECM typically contain
9525 multiple tandem repeats of independently folded domains, a common
9526 feature of proteins with structural and mechanical
9527 roles. Polysaccharide moieties of adhesion glycoproteins such as
9528 the selectins are also subject to strain. Force-induced extension
9529 of both types of molecules with the AFM results in conformational
9530 changes that could contribute to their mechanical function. The
9531 force-extension curve for amylose exhibits a transition in
9532 elasticity caused by the conversion of its glucopyranose rings
9533 from the chair to the boat conformation. Extension of multi-domain
9534 proteins causes sequential unraveling of domains, resulting in a
9535 force-extension curve displaying a saw tooth pattern of peaks. The
9536 engineering of multimeric proteins consisting of repeats of
9537 identical domains has allowed detailed analysis of the mechanical
9538 properties of single protein domains. Repetitive extension and
9539 relaxation has enabled direct measurement of rates of domain
9540 unfolding and refolding. The combination of site-directed
9541 mutagenesis with AFM can be used to elucidate the amino acid
9542 sequences that determine mechanical stability. The AFM thus offers
9543 a novel way to explore the mechanical functions of proteins and
9544 will be a useful tool for studying the micro-mechanics of
9547 URL = "http://www.ncbi.nlm.nih.gov/pubmed/10517795",
9551 @article{ fisher99b,
9552 author = TEFisher #" and "# AOberhauser #" and "# MCarrionVazquez
9553 #" and "# PMarszalek #" and "# JFernandez,
9554 title = "The study of protein mechanics with the atomic force microscope.",
9555 journal = "Trends in biochemical sciences",
9558 address = "Dept of Physiology and Biophysics, Mayo Foundation, 1-117
9559 Medical Sciences Building, Rochester, MN 55905, USA.",
9563 keywords = "Entropy",
9564 keywords = "Kinetics",
9565 keywords = "Microscopy, Atomic Force",
9566 keywords = "Protein Binding",
9567 keywords = "Protein Folding",
9568 keywords = "Proteins",
9569 abstract = "The unfolding and folding of single protein molecules
9570 can be studied with an atomic force microscope (AFM). Many
9571 proteins with mechanical functions contain multiple, individually
9572 folded domains with similar structures. Protein engineering
9573 techniques have enabled the construction and expression of
9574 recombinant proteins that contain multiple copies of identical
9575 domains. Thus, the AFM in combination with protein engineering
9576 has enabled the kinetic analysis of the force-induced unfolding
9577 and refolding of individual domains as well as the study of the
9578 determinants of mechanical stability.",
9580 URL = "http://www.ncbi.nlm.nih.gov/pubmed/10500301",
9584 @article{ zlatanova00,
9585 author = JZlatanova #" and "# SLindsay #" and "# SLeuba,
9586 title = "Single molecule force spectroscopy in biology using the
9587 atomic force microscope.",
9590 address = "Biochip Technology Center, Argonne National Laboratory,
9591 9700 South Cass Avenue, Bldg. 202-A253, Argonne, IL 60439,
9592 USA. jzlatano@duke.poly.edu",
9596 keywords = "Biophysics",
9597 keywords = "Cell Adhesion",
9599 keywords = "Elasticity",
9600 keywords = "Microscopy, Atomic Force",
9601 keywords = "Polysaccharides",
9602 keywords = "Proteins",
9603 keywords = "Signal Processing, Computer-Assisted",
9604 keywords = "Viscosity",
9605 abstract = "The importance of forces in biology has been recognized
9606 for quite a while but only in the past decade have we acquired
9607 instrumentation and methodology to directly measure interactive
9608 forces at the level of single biological macromolecules and/or
9609 their complexes. This review focuses on force measurements
9610 performed with the atomic force microscope. A general introduction
9611 to the principle of action is followed by review of the types of
9612 interactions being studied, describing the main results and
9613 discussing the biological implications.",
9615 URL = "http://www.ncbi.nlm.nih.gov/pubmed/11106806",
9617 note = "Lots of great force-clamp cartoons explaining different
9618 approach/retract features.",
9622 author = MViani #" and "# TESchafer #" and "# AChand #" and "# MRief
9623 #" and "# HEGaub #" and "# HHansma,
9624 title = "Small cantilevers for force spectroscopy of single molecules",
9629 pages = "2258--2262",
9630 abstract = "We have used a simple process to fabricate small
9631 rectangular cantilevers out of silicon nitride. They have lengths
9632 of 9--50 $\mu$m, widths of 3--5 $\mu$m, and thicknesses of 86 and
9633 102 nm. We have added metallic reflector pads to some of the
9634 cantilever ends to maximize reflectivity while minimizing
9635 sensitivity to temperature changes. We have characterized small
9636 cantilevers through their thermal spectra and show that they can
9637 measure smaller forces than larger cantilevers with the same
9638 spring constant because they have lower coefficients of viscous
9639 damping. Finally, we show that small cantilevers can be used for
9640 experiments requiring large measurement bandwidths, and have used
9641 them to unfold single titin molecules over an order of magnitude
9642 faster than previously reported with conventional cantilevers.",
9644 issn_online = "1089-7550",
9645 doi = "10.1063/1.371039",
9646 URL = "http://jap.aip.org/resource/1/japiau/v86/i4/p2258_s1",
9650 @article{ capitanio02,
9651 author = MCapitanio #" and "# GRomano #" and "# RBallerini #" and "#
9652 MGiuntini #" and "# FPavone #" and "# DDunlap #" and "# LFinzi,
9653 title = "Calibration of optical tweezers with differential
9654 interference contrast signals",
9659 pages = "1687--1696",
9660 abstract = "A comparison of different calibration methods for
9661 optical tweezers with the differential interference contrast (DIC)
9662 technique was performed to establish the uses and the advantages
9663 of each method. A detailed experimental and theoretical analysis
9664 of each method was performed with emphasis on the anisotropy
9665 involved in the DIC technique and the noise components in the
9666 detection. Finally, a time of flight method that permits the
9667 reconstruction of the optical potential well was demonstrated.",
9669 issn_online = "1089-7623",
9670 doi = "10.1063/1.1460929",
9671 URL = "http://rsi.aip.org/resource/1/rsinak/v73/i4/p1687_s1",
9676 author = GBinnig #" and "# CQuate #" and "# CGerber,
9677 title = "Atomic force microscope",
9685 abstract = "The scanning tunneling microscope is proposed as a
9686 method to measure forces as small as $10^{-18}$ N. As one
9687 application for this concept, we introduce a new type of
9688 microscope capable of investigating surfaces of insulators on an
9689 atomic scale. The atomic force microscope is a combination of the
9690 principles of the scanning tunneling microscope and the stylus
9691 profilometer. It incorporates a probe that does not damage the
9692 surface. Our preliminary results in air demonstrate a lateral
9693 resolution of 30 \AA and a vertical resolution less than 1 \AA.",
9695 doi = "10.1103/PhysRevLett.56.930",
9696 URL = "http://www.ncbi.nlm.nih.gov/pubmed/10033323",
9697 eprint = {http://prl.aps.org/pdf/PRL/v56/i9/p930_1},
9699 note = "Original AFM paper.",
9703 author = BDrake #" and "# CBPrater #" and "# ALWeisenhorn #" and "#
9704 SAGould #" and "# TRAlbrecht #" and "# CQuate #" and "#
9705 DSCannell #" and "# HHansma #" and "# PHansma,
9706 title = {Imaging crystals, polymers, and processes in water with the
9707 atomic force microscope},
9714 pages = {1586--1589},
9715 doi = {10.1126/science.2928794},
9716 url = {http://www.sciencemag.org/content/243/4898/1586.abstract},
9717 eprint = {http://www.sciencemag.org/content/243/4898/1586.full.pdf},
9718 abstract ={The atomic force microscope (AFM) can be used to image
9719 the surface of both conductors and nonconductors even if they are
9720 covered with water or aqueous solutions. An AFM was used that
9721 combines microfabricated cantilevers with a previously described
9722 optical lever system to monitor deflection. Images of mica
9723 demonstrate that atomic resolution is possible on rigid materials,
9724 thus opening the possibility of atomic-scale corrosion experiments
9725 on nonconductors. Images of polyalanine, an amino acid polymer,
9726 show the potential of the AFM for revealing the structure of
9727 molecules important in biology and medicine. Finally, a series of
9728 ten images of the polymerization of fibrin, the basic component of
9729 blood clots, illustrate the potential of the AFM for revealing
9730 subtle details of biological processes as they occur in real
9734 @article{ radmacher92,
9735 author = MRadmacher #" and "# RWTillmann #" and "# MFritz #" and "# HEGaub,
9736 title = {From molecules to cells: imaging soft samples with the
9737 atomic force microscope},
9744 pages = {1900--1905},
9745 doi = {10.1126/science.1411505},
9746 url = {http://www.sciencemag.org/content/257/5078/1900.abstract},
9747 eprint = {http://www.sciencemag.org/content/257/5078/1900.full.pdf},
9748 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.},
9751 @article{ williams86,
9752 author = CCWilliams #" and "# HKWickramasinghe,
9753 title = "Scanning thermal profiler",
9760 pages = "1587--1589",
9761 abstract = "A new high-resolution profilometer has been demonstrated
9762 based upon a noncontacting near-field thermal probe. The thermal
9763 probe consists of a thermocouple sensor with dimensions
9764 approaching 100 nm. Profiling is achieved by scanning the heated
9765 sensor above but close to the surface of a solid. The conduction
9766 of heat between tip and sample via the air provides a means for
9767 maintaining the sample spacing constant during the lateral
9768 scan. The large difference in thermal properties between air and
9769 solids makes the profiling technique essentially independent of
9770 the material properties of the solid. Noncontact profiling of
9771 resist and metal films has shown a lateral resolution of 100 nm
9772 and a depth solution of 3 nm. The basic theory of the new probe is
9773 described and the results presented.",
9775 issn_online = "1077-3118",
9776 doi = "10.1063/1.97288",
9777 URL = "http://apl.aip.org/resource/1/applab/v49/i23/p1587_s1",
9782 author = GMeyer #" and "# NMAmer,
9783 title = "Novel optical approach to atomic force microscopy",
9790 pages = "1045--1047",
9791 abstract = "A sensitive and simple optical method for detecting the
9792 cantilever deflection in atomic force microscopy is described. The
9793 method was incorporated in an atomic force microscope, and imaging
9794 and force measurements, in ultrahigh vacuum, were successfully
9797 issn_online = "1077-3118",
9798 doi = "10.1063/1.100061",
9799 URL = "http://apl.aip.org/resource/1/applab/v53/i12/p1045_s1",
9805 title = {Notes on Structured Programming},
9808 url = {http://www.cs.utexas.edu/users/EWD/ewd02xx/EWD249.PDF},
9809 publisher = THEMath,
9810 note = {T.H. Report 70-WSK-03},
9815 title = {On the Composition of Well-Structured Programs},
9824 doi = {10.1145/356635.356639},
9825 url = {http://doi.acm.org/10.1145/356635.356639},
9827 address = {New York, NY, USA},
9830 @article{ shneiderman79,
9831 author = BShneiderman #" and "# RMayer,
9832 title = {Syntactic/semantic interactions in programmer behavior: A
9833 model and experimental results},
9840 doi = {10.1007/BF00977789},
9841 url = {http://dx.doi.org/10.1007/BF00977789},
9843 keywords = {Programming; programming languages; cognitive models;
9844 program composition; program comprehension; debugging;
9845 modification; learning; education; information processing},
9846 language = {English},
9851 title = {Why Functional Programming Matters},
9857 doi = {10.1093/comjnl/32.2.98},
9858 URL = {http://comjnl.oxfordjournals.org/content/32/2/98.abstract},
9859 eprint = {http://comjnl.oxfordjournals.org/content/32/2/98.full.pdf+html},
9860 abstract ={As software becomes more and more complex, it is more and
9861 more important to structure it well. Well-structured software is
9862 easy to write, easy to debug, and provides a collection of modules
9863 that can be re-used to reduce future programming
9864 costs. Conventional languages place conceptual limits on the way
9865 problems can be modularised. Functional languages push those
9866 limits back. In this paper we show that two features of functional
9867 languages in particular, higher-order functions and lazy
9868 evaluation, can contribute greatly to modularity. As examples, we
9869 manipulate lists and trees, program several numerical algorithms,
9870 and implement the alpha-beta heuristics (an Artificial
9871 Intelligence algorithm used in game-playing programs). Since
9872 modularity is the key to successful programming, functional
9873 languages are vitally important to the real world.},
9876 @article{ hilburn93,
9878 title = {A top-down approach to teaching an introductory computer science course},
9879 journal = ACM:SIGCSE,
9887 doi = {10.1145/169073.169349},
9888 url = {http://doi.acm.org/10.1145/169073.169349},
9891 address = {New York, NY, USA},
9896 title = {The mythical man-month},
9897 edition = {20$^\text{th}$ anniversary},
9899 isbn = {0-201-83595-9},
9901 address = {Boston, MA, USA},
9902 url = {http://dl.acm.org/citation.cfm?id=207583},
9903 note = {First published in 1975},
9906 @inproceedings{ claerbout92,
9907 author = JClaerbout #" and "# MKarrenbach,
9908 title = {Electronic documents give reproducible research a new meaning},
9909 booktitle = {SEG Technical Program Expanded Abstracts 1992},
9913 doi = {10.1190/1.1822162},
9916 url = {http://library.seg.org/doi/abs/10.1190/1.1822162},
9917 eprint = {http://sepwww.stanford.edu/doku.php?id=sep:research:reproducible:seg92},
9920 @incollection{ buckheit95,
9921 author = JBuckheit #" and "# DDonoho,
9922 title = {WaveLab and Reproducible Research},
9923 booktitle = {Wavelets and Statistics},
9924 series = {Lecture Notes in Statistics},
9925 editor = AAntoniadis #" and "# GOppenheim,
9929 isbn = {978-0-387-94564-4},
9930 doi = {10.1007/978-1-4612-2544-7_5},
9931 url = {http://dx.doi.org/10.1007/978-1-4612-2544-7_5},
9932 eprint = {http://www-stat.stanford.edu/~wavelab/Wavelab_850/wavelab.pdf},
9933 publisher = SPRINGER,
9934 language = {English},
9938 author = MSchwab #" and "# MKarrenbach #" and "# JClaerbout,
9939 title = {Making scientific computations reproducible},
9942 month = {November--December},
9946 doi = {10.1109/5992.881708},
9948 keywords = {document handling;file organisation;natural sciences
9949 computing;research and development
9950 management;ReDoc;authors;computational results;reproducible
9951 scientific computations;research paper;software filing
9952 system;standardized rules;Computer
9953 interfaces;Documentation;Electronic
9954 publishing;Laboratories;Organizing;Reproducibility of
9955 results;Software maintenance;Software systems;Software
9956 testing;Technological innovation},
9957 abstract = {To verify a research paper's computational results,
9958 readers typically have to recreate them from scratch. ReDoc is a
9959 simple software filing system for authors that lets readers easily
9960 reproduce computational results using standardized rules and
9964 @article{ wilson06a,
9966 title = {Where's the Real Bottleneck in Scientific Computing?},
9969 month = {January--February},
9972 @article{ wilson06b,
9974 title = {Software Carpentry: Getting Scientists to Write Better
9975 Code by Making Them More Productive},
9978 month = {November--December},
9981 @article{ vandewalle09,
9982 author = PVandewalle #" and "# JKovacevic #" and "# MVetterli ,
9983 title = {Reproducible Research in Signal Processing - What, why, and how},
9990 doi = {10.1109/MSP.2009.932122},
9992 url = {http://rr.epfl.ch/17/},
9993 eprint = {http://rr.epfl.ch/17/1/VandewalleKV09.pdf},
9994 keywords={research and development;signal processing;high-quality
9995 reviewing process;large data set;reproducible research;signal
9996 processing;win-win situation;Advertising;Digital signal
9997 processing;Education;Programming;Reproducibility of
9998 results;Scholarships;Signal processing;Signal processing
9999 algorithms;Testing;Wikipedia},
10000 abstract = {Have you ever tried to reproduce the results presented
10001 in a research paper? For many of our current publications, this
10002 would unfortunately be a challenging task. For a computational
10003 algorithm, details such as the exact data set, initialization or
10004 termination procedures, and precise parameter values are often
10005 omitted in the publication for various reasons, such as a lack of
10006 space, a lack of self-discipline, or an apparent lack of interest
10007 to the readers, to name a few. This makes it difficult, if not
10008 impossible, for someone else to obtain the same results. In our
10009 experience, it is often even worse as even we are not always able
10010 to reproduce our own experiments, making it difficult to answer
10011 questions from colleagues about details. Following are some
10012 examples of e-mails we have received: ``I just read your paper
10013 X. It is very completely described, however I am confused by
10014 Y. Could you provide the implementation code to me for reference
10015 if possible?'' ``Hi! I am also working on a project related to
10016 X. I have implemented your algorithm but cannot get the same
10017 results as described in your paper. Which values should I use for
10018 parameters Y and Z?''},
10021 @article{ aruliah12,
10022 author = DAruliah #" and "# CTBrown #" and "# MPCHong #" and "#
10023 MDavis #" and "# RTGuy #" and "# SHaddock #" and "# KHuff #" and "#
10024 IMitchell #" and "# MPlumbley #" and "# BWaugh #" and "#
10025 EPWhite #" and "# GWilson #" and "# PWilson,
10026 title = {Best Practices for Scientific Computing},
10028 volume = {abs/1210.0530},
10033 url = {http://arxiv.org/abs/1210.0530},
10034 eprint = {http://arxiv.org/pdf/1210.0530v3},
10035 note = {v3: Thu, 29 Nov 2012 19:28:27 GMT},
10038 @article{ ziegler42,
10039 author = JZiegler #" and "# NNichols,
10040 title = {Optimum Settings for Automatic Controllers},
10045 pages = {759--765},
10046 url = {http://www.driedger.ca/Z-N/Z-N.html},
10047 eprint = {http://www.driedger.ca/Z-N/Z-n.pdf},
10051 author = GHCohen #" and "# GACoon,
10052 title = {Theoretical considerations of retarded control},
10056 pages = {827--834},
10060 author = FSWang #" and "# WSJuang #" and "# CTChan,
10061 title = {Optimal tuning of {PID} controllers for single and
10062 cascade control loops},
10068 publisher = GordonBreach,
10069 issn = {0098-6445},
10070 doi = {10.1080/00986449508936294},
10071 url = {http://www.tandfonline.com/doi/abs/10.1080/00986449508936294},
10072 keywords = {process control; cascade control; controller tuning},
10073 abstract = {Design of one parameter tuning of three-mode PID
10074 controller was developed in this present study. The integral time
10075 and the derivative time of the controller were expressed in terms
10076 of the time constant and dead time of the process. Only the
10077 proportional gain was observed to be dependent on the implemented
10078 tunable parameter in which the stable region could be
10079 predetermined by the Routh test. Extension of the concept towards
10080 designing cascade PID controllers was straightforward such that
10081 only two parameters for the inner and outer PID controllers
10082 required to be tuned, respectively. The optimal tuning correlative
10083 formulas of the proportional gain for single and cascade control
10084 systems were obtained by the least square regression method.},
10087 @article{ astrom93,
10088 author = KAstrom #" and "# THagglund #" and "# CCHang #" and "# WKHo,
10089 title = {Automatic tuning and adaptation for {PID} controllers---a survey},
10094 pages = {699--714},
10095 issn = "0967-0661",
10096 doi = "10.1016/0967-0661(93)91394-C",
10097 url = "http://www.sciencedirect.com/science/article/pii/096706619391394C",
10098 keywords = {Adaptive control},
10099 keywords = {automatic tuning},
10100 keywords = {gain scheduling},
10101 keywords = {{PID} control},
10102 abstract = {Adaptive techniques such as gain scheduling, automatic
10103 tuning and continuous adaptation have been used in industrial
10104 single-loop controllers for about ten years. This paper gives a
10105 survey of the different adaptive techniques, the underlying
10106 process models and control designs. An overview of industrial
10107 products is also presented, which includes a fairly detailed
10108 investigation of four different adaptive single-loop
10114 title = {Notes on the use of propagation of error formulas},
10120 pages = {263--273},
10122 issn = {0022-4316},
10123 url = {http://nistdigitalarchives.contentdm.oclc.org/cdm/compoundobject/collection/p13011coll6/id/78003/rec/5},
10124 eprint = {http://nistdigitalarchives.contentdm.oclc.org/utils/getfile/collection/p13011coll6/id/78003/filename/print/page/download},
10125 keywords = {Approximation; error; formula; imprecision; law of
10126 error; products; propagation of error; random; ratio; systematic;
10128 abstract = {The ``law of propagation of error'' is a tool that
10129 physical scientists have conveniently and frequently used in their
10130 work for many years, yet an adequate reference is difficult to
10131 find. In this paper an expository review of this topic is
10132 presented, particularly in the light of current practices and
10133 interpretations. Examples on the accuracy of the approximations
10134 are given. The reporting of the uncertainties of final results is
10138 @article{ livadaru03,
10139 author = LLivadaru #" and "# RRNetz #" and "# HJKreuzer,
10140 title = {Stretching Response of Discrete Semiflexible Polymers},
10144 journal = Macromol,
10147 pages = {3732--3744},
10148 doi = {10.1021/ma020751g},
10149 URL = {http://pubs.acs.org/doi/abs/10.1021/ma020751g},
10150 eprint = {http://pubs.acs.org/doi/pdf/10.1021/ma020751g},
10151 abstract = {We demonstrate that semiflexible polymer chains
10152 (characterized by a persistence length $l$) made up of discrete
10153 segments or bonds of length $b$ show at large stretching forces a
10154 crossover from the standard wormlike chain (WLC) behavior to a
10155 discrete-chain (DC) behavior. In the DC regime, the stretching
10156 response is independent of the persistence length and shows a
10157 different force dependence than in the WLC regime. We perform
10158 extensive transfer-matrix calculations for the force-response of a
10159 freely rotating chain (FRC) model as a function of varying bond
10160 angle $\gamma$ (and thus varying persistence length) and chain
10161 length. The FRC model is a first step toward the understanding of
10162 the stretching behavior of synthetic polymers, denatured proteins,
10163 and single-stranded DNA under large tensile forces. We also
10164 present scaling results for the force response of the elastically
10165 jointed chain (EJC) model, that is, a chain made up of freely
10166 jointed bonds that are connected by joints with some bending
10167 stiffness; this is the discretized version of the continuum WLC
10168 model. The EJC model might be applicable to stiff biopolymers such
10169 as double-stranded DNA or Actin. Both models show a similar
10170 crossover from the WLC to the DC behavior, which occurs at a force
10171 $f/k_BT\sim l/b^2$ and is thus (for polymers with a moderately
10172 large persistence length) in the piconewton range probed in many
10173 AFM experiments. We also give a heuristic simple function for the
10174 force--distance relation of a FRC, valid in the global force
10175 range, which can be used to fit experimental data. Our findings
10176 might help to resolve the discrepancies encountered when trying to
10177 fit experimental data for the stretching response of polymers in a
10178 broad force range with a single effective persistence length.},
10179 note = {There are two typos in \fref{equation}{46}.
10180 \citet{livadaru03} have
10182 \frac{R_z}{L} = \begin{cases}
10183 \frac{fa}{3k_BT} & \frac{fb}{k_BT} < \frac{b}{l} \\
10184 1 - \p({\frac{fl}{4k_BT}})^{-0.5}
10185 & \frac{b}{l} < \frac{fb}{k_BT} < \frac{l}{b} \\
10186 1 - \p({\frac{fb}{ck_BT}})^{-1} & \frac{1}{b} < \frac{fb}{k_BT} \;,
10189 but the correct formula is
10191 \frac{R_z}{L} = \begin{cases}
10192 \frac{fa}{3k_BT} & \frac{fb}{k_BT} < \frac{b}{l} \\
10193 1 - \p({\frac{4fl}{k_BT}})^{-0.5}
10194 & \frac{b}{l} < \frac{fb}{k_BT} < \frac{l}{b} \\
10195 1 - \p({\frac{cfb}{k_BT}})^{-1} & \frac{1}{b} < \frac{fb}{k_BT} \;,
10198 with both the $4$ and the $c$ moved into their respective
10199 numerators. I pointed these errors out to Roland Netz in 2012,
10200 along with the fact that even with the corrected formula there is
10201 a discontinuity between the low- and moderate-force regimes. Netz
10202 confirmed the errors, and pointed out that the discontinuity is
10203 because \fref{equation}{46} only accounts for the scaling (without
10204 prefactors). Unfortunately, there does not seem to be a published
10205 erratum pointing out the error and at least \citet{puchner08} have
10206 quoted the incorrect form.},
10210 author = PCarl #" and "# PDalhaimer,
10211 title = {{PUNIAS}: Protein Unfolding and Nano-indentation Analysis
10216 note = {4 Int. Workshop, Scanning Probe Microscopy in Life Sciences},
10217 address = {Berlin},
10218 url = {http://punias.voila.net/},
10222 author = PCarl #" and "# HSchillers,
10223 title = {Elasticity measurement of living cells with an atomic force
10224 microscope: data acquisition and processing.},
10228 address = {Institute of Physiology II, University of M{\"u}nster,
10229 Robert-Koch-Str. 27b, 48149, M{\"u}nster, Germany.},
10233 pages = {551--559},
10234 issn = {0031-6768},
10235 doi = {10.1007/s00424-008-0524-3},
10236 url = {http://www.ncbi.nlm.nih.gov/pubmed/18481081},
10238 keywords = {Animals},
10239 keywords = {Biomechanics},
10240 keywords = {CHO Cells},
10241 keywords = {Cricetinae},
10242 keywords = {Cricetulus},
10243 keywords = {Cystic Fibrosis Transmembrane Conductance Regulator},
10244 keywords = {Elastic Modulus},
10245 keywords = {Equipment Design},
10246 keywords = {Microscopy, Atomic Force},
10247 keywords = {Models, Biological},
10248 keywords = {Reproducibility of Results},
10249 keywords = {Signal Processing, Computer-Assisted},
10250 keywords = {Transfection},
10251 abstract = {Elasticity of living cells is a parameter of increasing
10252 importance in cellular physiology, and the atomic force microscope
10253 is a suitable instrument to quantitatively measure it. The
10254 principle of an elasticity measurement is to physically indent a
10255 cell with a probe, to measure the applied force, and to process
10256 this force-indentation data using an appropriate model. It is
10257 crucial to know what extent the geometry of the indenting probe
10258 influences the result. Therefore, we indented living Chinese
10259 hamster ovary cells at 37 degrees C with sharp tips and colloidal
10260 probes (spherical particle tips) of different sizes and
10261 materials. We furthermore developed an implementation of the Hertz
10262 model, which simplifies the data processing. Our results show (a)
10263 that the size of the colloidal probe does not influence the result
10264 over a wide range (radii $0.5$-$26\U{$\mu$m}$) and (b) indenting
10265 cells with sharp tips results in higher Young's moduli
10266 (approximately $1,300\U{Pa}$) than using colloidal probes
10267 (approximately $400\U{Pa}$).},
10268 note = {Mentions \citetalias{punias} as if it was in-house software,
10269 which makes sense because Philippe Carl seems to be a major author.},
10272 @article{ struckmeier08,
10273 author = JStruckmeier #" and "# RWahl #" and "# MLeuschner #" and "#
10274 JNunes #" and "# HJanovjak #" and "# UGeisler #" and "#
10275 GHofmann #" and "# TJahnke #" and "# DJMuller,
10276 title = {Fully automated single-molecule force spectroscopy for
10277 screening applications},
10281 address = {Cellular Machines, Biotechnology Center,
10282 Technische Universit{\"a}t Dresden, Tatzberg 47, D-01307
10288 issn = {0957-4484},
10289 doi = {10.1088/0957-4484/19/38/384020},
10290 url = {http://www.ncbi.nlm.nih.gov/pubmed/21832579},
10292 abstract = {With the introduction of single-molecule force
10293 spectroscopy (SMFS) it has become possible to directly access the
10294 interactions of various molecular systems. A bottleneck in
10295 conventional SMFS is collecting the large amount of data required
10296 for statistically meaningful analysis. Currently, atomic force
10297 microscopy (AFM)-based SMFS requires the user to tediously `fish'
10298 for single molecules. In addition, most experimental and
10299 environmental conditions must be manually adjusted. Here, we
10300 developed a fully automated single-molecule force
10301 spectroscope. The instrument is able to perform SMFS while
10302 monitoring and regulating experimental conditions such as buffer
10303 composition and temperature. Cantilever alignment and calibration
10304 can also be automatically performed during experiments. This,
10305 combined with in-line data analysis, enables the instrument, once
10306 set up, to perform complete SMFS experiments autonomously.},
10307 note = {An advertisement for JPK's \citetalias{force-robot}.},
10310 @article{ andreopoulos11,
10311 author = BAndreopoulos #" and "# DLabudde,
10312 title = {Efficient unfolding pattern recognition in single molecule
10313 force spectroscopy data},
10317 address = {Department of Bioinformatics, Biotechnological Center,
10318 University of Technology Dresden, Dresden, Germany.
10319 williama@biotec.tu-dresden.de},
10324 issn = {1748-7188},
10325 doi = {10.1186/1748-7188-6-16},
10326 url = {http://www.ncbi.nlm.nih.gov/pubmed/21645400},
10328 abstract = {Single-molecule force spectroscopy (SMFS) is a technique
10329 that measures the force necessary to unfold a protein. SMFS
10330 experiments generate Force-Distance (F-D) curves. A statistical
10331 analysis of a set of F-D curves reveals different unfolding
10332 pathways. Information on protein structure, conformation,
10333 functional states, and inter- and intra-molecular interactions can
10338 editor = HWTurnbull,
10340 title = {The correspondence of Isaac Newton},
10345 url = {http://books.google.com/books?id=pr8WAQAAMAAJ},
10346 note = {The ``Giants'' quote is on page 416, in a letter to Robert
10347 Hooke dated February 5, 1676.},
10350 @book{ whitehead11,
10351 author = ANWhitehead,
10352 title = {An introduction to mathematics},
10356 address = {London},
10357 url = {http://archive.org/details/introductiontoma00whitiala},
10358 note = {The ``civilization'' quote is on page 61.},
10362 author = NJMlot #" and "# CATovey #" and "# DLHu,
10363 title = {Fire ants self-assemble into waterproof rafts to survive floods},
10367 address = {Schools of Mechanical Engineering, Industrial and
10368 Systems Engineering, and Biology,
10369 Georgia Institute of Technology, Atlanta, GA 30318, USA.},
10373 pages = {7669--7673},
10374 issn = {1091-6490},
10375 doi = {10.1073/pnas.1016658108},
10376 url = {http://www.ncbi.nlm.nih.gov/pubmed/21518911},
10378 keywords = {Animals},
10380 keywords = {Behavior, Animal},
10381 keywords = {Biophysical Phenomena},
10382 keywords = {Floods},
10383 keywords = {Hydrophobic and Hydrophilic Interactions},
10384 keywords = {Microscopy, Electron, Scanning},
10385 keywords = {Models, Biological},
10386 keywords = {Social Behavior},
10387 keywords = {Surface Properties},
10388 keywords = {Time-Lapse Imaging},
10389 keywords = {Video Recording},
10390 keywords = {Water},
10391 abstract = {Why does a single fire ant \species{Solenopsis invicta}
10392 struggle in water, whereas a group can float effortlessly for
10393 days? We use time-lapse photography to investigate how fire ants
10394 \species{S.~invicta} link their bodies together to build
10395 waterproof rafts. Although water repellency in nature has been
10396 previously viewed as a static material property of plant leaves
10397 and insect cuticles, we here demonstrate a self-assembled
10398 hydrophobic surface. We find that ants can considerably enhance
10399 their water repellency by linking their bodies together, a process
10400 analogous to the weaving of a waterproof fabric. We present a
10401 model for the rate of raft construction based on observations of
10402 ant trajectories atop the raft. Central to the construction
10403 process is the trapping of ants at the raft edge by their
10404 neighbors, suggesting that some ``cooperative'' behaviors may rely
10406 note = {Higher resolution pictures are available at
10407 \url{http://antlab.gatech.edu/antlab/The_Ant_Raft.html}.},
10410 @article{ chauhan97,
10411 author = VPChauhan #" and "# IRay #" and "# AChauhan #" and "#
10412 JWegiel #" and "# HMWisniewski,
10413 title = {Metal cations defibrillize the amyloid beta-protein fibrils.},
10416 address = {New York State Institute for Basic Research in
10417 Developmental Disabilities, Staten Island 10314-6399,
10422 pages = {805--809},
10423 issn = {0364-3190},
10424 url = {http://www.ncbi.nlm.nih.gov/pubmed/9232632},
10425 doi = {10.1023/A:1022079709085},
10427 keywords = {Alzheimer Disease},
10428 keywords = {Amyloid beta-Peptides},
10429 keywords = {Drug Evaluation, Preclinical},
10430 keywords = {Humans},
10431 keywords = {Metals},
10432 keywords = {Peptide Fragments},
10433 keywords = {Solubility},
10434 abstract = {Amyloid beta-protein (A beta) is the major constituent
10435 of amyloid fibrils composing beta-amyloid plaques and
10436 cerebrovascular amyloid in Alzheimer's disease (AD). We studied
10437 the effect of metal cations on preformed fibrils of synthetic A
10438 beta by Thioflavin T (ThT) fluorescence spectroscopy and
10439 electronmicroscopy (EM) in negative staining. The amount of cross
10440 beta-pleated sheet structure of A beta 1-40 fibrils was found to
10441 decrease by metal cations in a concentration-dependent manner as
10442 measured by ThT fluorescence spectroscopy. The order of
10443 defibrillization of A beta 1-40 fibrils by metal cations was: Ca2+
10444 and Zn2+ (IC50 = 100 microM) > Mg3+ (IC50 = 300 microM) > Al3+
10445 (IC50 = 1.1 mM). EM analysis in negative staining showed that A
10446 beta 1-40 fibrils in the absence of cations were organized in a
10447 fine network with a little or no amorphous material. The addition
10448 of Ca2+, Mg2+, and Zn2+ to preformed A beta 1-40 fibrils
10449 defibrillized the fibrils or converted them into short rods or to
10450 amorphous material. Al3+ was less effective, and reduced the
10451 fibril network by about 80\% of that in the absence of any metal
10452 cation. Studies with A beta 1-42 showed that this peptide forms
10453 more dense network of fibrils as compared to A beta 1-40. Both ThT
10454 fluorescence spectroscopy and EM showed that similar to A beta
10455 1-40, A beta 1-42 fibrils are also defibrillized in the presence
10456 of millimolar concentrations of Ca2+. These studies suggest that
10457 metal cations can defibrillize the fibrils of synthetic A beta.},
10458 note = {From page 806, ``The exact mechanism by which these metal
10459 ions affect the fibrillization of A$\beta$ is not known.''},
10462 @article{ friedman05,
10463 author = RFriedman #" and "# ENachliel #" and "# MGutman,
10464 title = {Molecular dynamics of a protein surface: ion-residues
10469 address = {Laser Laboratory for Fast Reactions in Biology,
10470 Department of Biochemistry, The George S. Wise Faculty
10471 for Life Sciences, Tel Aviv University, Israel.},
10475 pages = {768--781},
10476 issn = {0006-3495},
10477 doi = {10.1529/biophysj.105.058917},
10478 url = {http://www.ncbi.nlm.nih.gov/pubmed/15894639},
10480 keywords = {Amino Acids},
10481 keywords = {Binding Sites},
10482 keywords = {Chlorine},
10483 keywords = {Computer Simulation},
10485 keywords = {Models, Chemical},
10486 keywords = {Models, Molecular},
10487 keywords = {Motion},
10488 keywords = {Protein Binding},
10489 keywords = {Protein Conformation},
10490 keywords = {Ribosomal Protein S6},
10491 keywords = {Sodium},
10492 keywords = {Solutions},
10493 keywords = {Static Electricity},
10494 keywords = {Surface Properties},
10495 keywords = {Water},
10496 abstract = {Time-resolved measurements indicated that protons could
10497 propagate on the surface of a protein or a membrane by a special
10498 mechanism that enhanced the shuttle of the proton toward a
10499 specific site. It was proposed that a suitable location of
10500 residues on the surface contributes to the proton shuttling
10501 function. In this study, this notion was further investigated by
10502 the use of molecular dynamics simulations, where Na(+) and Cl(-)
10503 are the ions under study, thus avoiding the necessity for quantum
10504 mechanical calculations. Molecular dynamics simulations were
10505 carried out using as a model a few Na(+) and Cl(-) ions enclosed
10506 in a fully hydrated simulation box with a small globular protein
10507 (the S6 of the bacterial ribosome). Three independent 10-ns-long
10508 simulations indicated that the ions and the protein's surface were
10509 in equilibrium, with rapid passage of the ions between the
10510 protein's surface and the bulk. However, it was noted that close
10511 to some domains the ions extended their duration near the surface,
10512 thus suggesting that the local electrostatic potential hindered
10513 their diffusion to the bulk. During the time frame in which the
10514 ions were detained next to the surface, they could rapidly shuttle
10515 between various attractor sites located under the electrostatic
10516 umbrella. Statistical analysis of the molecular dynamics and
10517 electrostatic potential/entropy consideration indicated that the
10518 detainment state is an energetic compromise between attractive
10519 forces and entropy of dilution. The similarity between the motion
10520 of free ions next to a protein and the proton transfer on the
10521 protein's surface are discussed.},
10524 @article{ friedman11,
10525 author = RFriedman,
10526 title = {Ions and the protein surface revisited: extensive molecular
10527 dynamics simulations and analysis of protein structures in
10528 alkali-chloride solutions.},
10532 address = {School of Natural Sciences, Linn{\ae}us University,
10533 391 82 Kalmar, Sweden. ran.friedman@lnu.se},
10537 pages = {9213--9223},
10538 issn = {1520-5207},
10539 doi = {10.1021/jp112155m},
10540 URL = {http://www.ncbi.nlm.nih.gov/pubmed/21688775},
10542 keywords = {Alkalies},
10543 keywords = {Amyloid},
10544 keywords = {Chlorides},
10545 keywords = {Databases, Protein},
10546 keywords = {Fungal Proteins},
10547 keywords = {HIV Protease},
10548 keywords = {Humans},
10549 keywords = {Molecular Dynamics Simulation},
10550 keywords = {Protein Multimerization},
10551 keywords = {Protein Structure, Secondary},
10552 keywords = {Proteins},
10553 keywords = {Ribosomal Protein S6},
10554 keywords = {Solutions},
10555 keywords = {Solvents},
10556 keywords = {Surface Properties},
10557 abstract = {Proteins interact with ions in various ways. The surface
10558 of proteins has an innate capability to bind ions, and it is also
10559 influenced by the screening of the electrostatic potential owing
10560 to the presence of salts in the bulk solution. Alkali metal ions
10561 and chlorides interact with the protein surface, but such
10562 interactions are relatively weak and often transient. In this
10563 paper, computer simulations and analysis of protein structures are
10564 used to characterize the interactions between ions and the protein
10565 surface. The results show that the ion-binding properties of
10566 protein residues are highly variable. For example, alkali metal
10567 ions are more often associated with aspartate residues than with
10568 glutamates, whereas chlorides are most likely to be located near
10569 arginines. When comparing NaCl and KCl solutions, it was found
10570 that certain surface residues attract the anion more strongly in
10571 NaCl. This study demonstrates that protein-salt interactions
10572 should be accounted for in the planning and execution of
10573 experiments and simulations involving proteins, particularly if
10574 subtle structural details are sought after.},
10578 author = YZhang #" and "# PSCremer,
10579 title = {Interactions between macromolecules and ions: The
10580 {H}ofmeister series.},
10584 address = {Department of Chemistry, Texas A\&M University,
10585 College Station, TX 77843, USA.},
10589 pages = {658--663},
10590 issn = {1367-5931},
10591 doi = {10.1016/j.cbpa.2006.09.020},
10592 url = {http://www.ncbi.nlm.nih.gov/pubmed/17035073},
10594 keywords = {Acrylamides},
10595 keywords = {Biopolymers},
10596 keywords = {Solubility},
10597 keywords = {Thermodynamics},
10598 keywords = {Water},
10599 abstract = {The Hofmeister series, first noted in 1888, ranks the
10600 relative influence of ions on the physical behavior of a wide
10601 variety of aqueous processes ranging from colloidal assembly to
10602 protein folding. Originally, it was thought that an ion's
10603 influence on macromolecular properties was caused at least in part
10604 by `making' or `breaking' bulk water structure. Recent
10605 time-resolved and thermodynamic studies of water molecules in salt
10606 solutions, however, demonstrate that bulk water structure is not
10607 central to the Hofmeister effect. Instead, models are being
10608 developed that depend upon direct ion-macromolecule interactions
10609 as well as interactions with water molecules in the first
10610 hydration shell of the macromolecule.},
10611 note = {A quick pass through Hofmeister history, but no discussion
10612 of cations (``A complete picture will inevitably involve an
10613 integrated understanding of the role of cations (including
10614 guanidinium ions) and osmolytes (such as urea and tri-methylamine
10615 N-oxide) as well. There has been some progress in these fields,
10616 although such subjects are generally beyond the scope of this
10617 short review.'').},
10620 @article{ isaacs06,
10621 author = AMIsaacs #" and "# DBSenn #" and "# MYuan #" and "#
10622 JPShine #" and "# BAYankner,
10623 title = {Acceleration of amyloid beta-peptide aggregation by
10624 physiological concentrations of calcium.},
10628 address = {Department of Neurology and Division of Neuroscience,
10629 The Children's Hospital, Harvard Medical School,
10630 Boston, Massachusetts 02115, USA.},
10634 pages = {27916--27923},
10635 issn = {0021-9258},
10636 doi = {10.1074/jbc.M602061200},
10637 url = {http://www.ncbi.nlm.nih.gov/pubmed/16870617},
10639 keywords = {Alzheimer Disease},
10640 keywords = {Amyloid},
10641 keywords = {Amyloid beta-Peptides},
10642 keywords = {Animals},
10643 keywords = {Calcium},
10644 keywords = {Cells, Cultured},
10645 keywords = {Copper},
10646 keywords = {Neurons},
10649 abstract = {Alzheimer disease is characterized by the accumulation
10650 of aggregated amyloid beta-peptide (Abeta) in the brain. The
10651 physiological mechanisms and factors that predispose to Abeta
10652 aggregation and deposition are not well understood. In this
10653 report, we show that calcium can predispose to Abeta aggregation
10654 and fibril formation. Calcium increased the aggregation of early
10655 forming protofibrillar structures and markedly increased
10656 conversion of protofibrils to mature amyloid fibrils. This
10657 occurred at levels 20-fold below the calcium concentration in the
10658 extracellular space of the brain, the site at which amyloid plaque
10659 deposition occurs. In the absence of calcium, protofibrils can
10660 remain stable in vitro for several days. Using this approach, we
10661 directly compared the neurotoxicity of protofibrils and mature
10662 amyloid fibrils and demonstrate that both species are inherently
10663 toxic to neurons in culture. Thus, calcium may be an important
10664 predisposing factor for Abeta aggregation and toxicity. The high
10665 extracellular concentration of calcium in the brain, together with
10666 impaired intraneuronal calcium regulation in the aging brain and
10667 Alzheimer disease, may play an important role in the onset of
10668 amyloid-related pathology.},
10669 note = {Physiological levels of \NaCl\ are $\sim 150\U{mM}$. \Ca\
10670 is $\sim 2\U{mM}$.},
10674 author = AItkin #" and "# VDupres #" and "# YFDufrene #" and "#
10675 BBechinger #" and "# JMRuysschaert #" and "# VRaussens,
10676 title = {Calcium ions promote formation of amyloid $\beta$-peptide
10677 (1-40) oligomers causally implicated in neuronal toxicity of
10678 {A}lzheimer's disease.},
10682 address = {Laboratory of Structure and Function of Biological
10683 Membranes, Center for Structural Biology and
10684 Bioinformatics, Universit{\'e} Libre de Bruxelles,
10685 Brussels, Belgium.},
10686 journal = PLOS:ONE,
10690 keywords = {Alzheimer Disease},
10691 keywords = {Amyloid beta-Peptides},
10692 keywords = {Blotting, Western},
10693 keywords = {Calcium},
10694 keywords = {Fluorescence},
10695 keywords = {Humans},
10697 keywords = {Models, Biological},
10698 keywords = {Mutant Proteins},
10699 keywords = {Neurons},
10700 keywords = {Protein Structure, Quaternary},
10701 keywords = {Protein Structure, Secondary},
10702 keywords = {Spectroscopy, Fourier Transform Infrared},
10703 keywords = {Thiazoles},
10704 ISSN = {1932-6203},
10705 doi = {10.1371/journal.pone.0018250},
10706 URL = {http://www.ncbi.nlm.nih.gov/pubmed/21464905},
10708 abstract = {Amyloid $\beta$-peptide (A$\beta$) is directly linked to
10709 Alzheimer's disease (AD). In its monomeric form, A$\beta$
10710 aggregates to produce fibrils and a range of oligomers, the latter
10711 being the most neurotoxic. Dysregulation of Ca(2+) homeostasis in
10712 aging brains and in neurodegenerative disorders plays a crucial
10713 role in numerous processes and contributes to cell dysfunction and
10714 death. Here we postulated that calcium may enable or accelerate
10715 the aggregation of A$\beta$. We compared the aggregation pattern
10716 of A$\beta$(1-40) and that of A$\beta$(1-40)E22G, an amyloid
10717 peptide carrying the Arctic mutation that causes early onset of
10718 the disease. We found that in the presence of Ca(2+),
10719 A$\beta$(1-40) preferentially formed oligomers similar to those
10720 formed by A$\beta$(1-40)E22G with or without added Ca(2+), whereas
10721 in the absence of added Ca(2+) the A$\beta$(1-40) aggregated to
10722 form fibrils. Morphological similarities of the oligomers were
10723 confirmed by contact mode atomic force microscopy imaging. The
10724 distribution of oligomeric and fibrillar species in different
10725 samples was detected by gel electrophoresis and Western blot
10726 analysis, the results of which were further supported by
10727 thioflavin T fluorescence experiments. In the samples without
10728 Ca(2+), Fourier transform infrared spectroscopy revealed
10729 conversion of oligomers from an anti-parallel $\beta$-sheet to the
10730 parallel $\beta$-sheet conformation characteristic of
10731 fibrils. Overall, these results led us to conclude that calcium
10732 ions stimulate the formation of oligomers of A$\beta$(1-40), that
10733 have been implicated in the pathogenesis of AD.},
10734 note = {$2\U{mM}$ of \Ca\ is the \emph{extracellular} concentration.
10735 Cytosol concetrations are in the $\mu$M range.},
10739 author = JZidar #" and "# FMerzel,
10740 title = {Probing amyloid-beta fibril stability by increasing ionic
10745 address = {National Institute of Chemistry, Hajdrihova 19,
10746 SI-1000 Ljubljana, Slovenia.},
10750 pages = {2075--2081},
10751 issn = {1520-5207},
10752 doi = {10.1021/jp109025b},
10753 URL = {http://www.ncbi.nlm.nih.gov/pubmed/21329333},
10755 keywords = {Amyloid beta-Peptides},
10756 keywords = {Entropy},
10757 keywords = {Hydrogen Bonding},
10758 keywords = {Molecular Dynamics Simulation},
10759 keywords = {Osmolar Concentration},
10760 keywords = {Protein Multimerization},
10761 keywords = {Protein Stability},
10762 keywords = {Protein Structure, Secondary},
10763 keywords = {Solvents},
10764 keywords = {Vibration},
10765 abstract = {Previous experimental studies have demonstrated changing
10766 the ionic strength of the solvent to have a great impact on the
10767 mechanism of aggregation of amyloid-beta (A$\beta$) protein
10768 leading to distinct fibril morphology at high and low ionic
10769 strength. Here, we use molecular dynamics simulations to elucidate
10770 the ionic strength-dependent effects on the structure and dynamics
10771 of the model A$\beta$ fibril. The change in ionic strength was
10772 brought forth by varying the NaCl concentration in the environment
10773 surrounding the A$\beta$ fibril. Comparison of the calculated
10774 vibrational spectra of A$\beta$ derived from 40 ns all-atom
10775 molecular dynamics simulations at different ionic strength reveals
10776 the fibril structure to be stiffer with increasing ionic
10777 strength. This finding is further corroborated by the calculation
10778 of the stretching force constants. Decomposition of binding and
10779 dynamical properties into contributions from different structural
10780 segments indicates the elongation of the fibril at low ionic
10781 strength is most likely promoted by hydrogen bonding between
10782 N-terminal parts of the fibril, whereas aggregation at higher
10783 ionic strength is suggested to be driven by the hydrophobic
10785 note = {Only study \NaCl\ over the range to $308\U{mM}$, but show a
10786 general decreased hydrogen bonding as concentration increases.},
10790 author = LMiao #" and "# HQin #" and "# PKoehl #" and "# JSong,
10791 title = {Selective and specific ion binding on proteins at
10792 physiologically-relevant concentrations.},
10796 address = {Department of Biological Sciences, Faculty of Science,
10797 National University of Singapore, Singapore.},
10801 pages = {3126--3132},
10802 issn = {1873-3468},
10803 doi = {10.1016/j.febslet.2011.08.048},
10804 url = {http://www.ncbi.nlm.nih.gov/pubmed/21907714},
10806 keywords = {Amino Acid Sequence},
10807 keywords = {Ephrin-B2},
10809 keywords = {Models, Molecular},
10810 keywords = {Molecular Sequence Data},
10811 keywords = {Nuclear Magnetic Resonance, Biomolecular},
10812 keywords = {Protein Binding},
10813 keywords = {Protein Folding},
10814 keywords = {Protein Structure, Tertiary},
10815 keywords = {Salts},
10816 keywords = {Solutions},
10817 keywords = {Thermodynamics},
10818 keywords = {Water},
10819 abstract = {Insoluble proteins dissolved in unsalted water appear to
10820 have no well-folded tertiary structures. This raises a fundamental
10821 question as to whether being unstructured is due to the absence of
10822 salt ions. To address this issue, we solubilized the insoluble
10823 ephrin-B2 cytoplasmic domain in unsalted water and first confirmed
10824 using NMR spectroscopy that it is only partially folded. Using NMR
10825 HSQC titrations with 14 different salts, we further demonstrate
10826 that the addition of salt triggers no significant folding of the
10827 protein within physiologically relevant ion concentrations. We
10828 reveal however that their 8 anions bind to the ephrin-B2 protein
10829 with high affinity and specificity at biologically-relevant
10830 concentrations. Interestingly, the binding is found to be both
10831 salt- and residue-specific.},
10832 note = {They suggest that for low concentrations ($<100\U{mM}$),
10833 protein-ion interactions are mostly electrostatic. The Hofmeister
10834 effects only kick in at higher consentrations.},
10838 author = HJDyson #" and "# PEWright,
10839 title = {Intrinsically unstructured proteins and their functions.},
10843 address = {Department of Molecular Biology and Skaggs Institute
10844 for Chemical Biology, The Scripps Research Institute,
10845 10550 North Torrey Pines Road, La Jolla, California
10846 92037, USA. dyson@scripps.edu},
10849 pages = {197--208},
10850 issn = {1471-0072},
10851 doi = {10.1038/nrm1589},
10852 url = {http://www.ncbi.nlm.nih.gov/pubmed/15738986},
10854 keywords = {CREB-Binding Protein},
10855 keywords = {Humans},
10856 keywords = {Nuclear Proteins},
10857 keywords = {Nucleic Acids},
10858 keywords = {Protein Binding},
10859 keywords = {Protein Processing, Post-Translational},
10860 keywords = {Protein Structure, Tertiary},
10861 keywords = {Proteins},
10862 keywords = {Trans-Activators},
10863 keywords = {Tumor Suppressor Protein p53},
10864 abstract = {Many gene sequences in eukaryotic genomes encode entire
10865 proteins or large segments of proteins that lack a well-structured
10866 three-dimensional fold. Disordered regions can be highly conserved
10867 between species in both composition and sequence and, contrary to
10868 the traditional view that protein function equates with a stable
10869 three-dimensional structure, disordered regions are often
10870 functional, in ways that we are only beginning to discover. Many
10871 disordered segments fold on binding to their biological targets
10872 (coupled folding and binding), whereas others constitute flexible
10873 linkers that have a role in the assembly of macromolecular
10877 @article{ cleland64,
10878 author = WWCleland,
10879 title = {Dithiothreitol, a New Protective Reagent for SH Groups},
10885 pages = {480--482},
10886 keywords = {Alcohols},
10887 keywords = {Chromatography},
10888 keywords = {Coenzyme A},
10889 keywords = {Oxidation-Reduction},
10890 keywords = {Research},
10891 keywords = {Sulfhydryl Compounds},
10892 keywords = {Sulfides},
10893 keywords = {Ultraviolet Rays},
10894 issn = {0006-2960},
10895 doi = {10.1021/bi00892a002},
10896 url = {http://www.ncbi.nlm.nih.gov/pubmed/14192894},
10897 eprint = {http://pubs.acs.org/doi/pdf/10.1021/bi00892a002},