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{\o}rensen, Kirstine"}
94 @string{EBergantino = "Bergantino, Elisabetta"}
95 @string{DBerk = "Berk, D."}
96 @string{FBerkemeier = "Berkemeier, Felix"}
97 @string{BBerne = "Berne, Bruce J."}
98 @string{MBertz = "Bertz, Morten"}
99 @string{RBest = "Best, Robert B."}
100 @string{GBethel = "Bethel, G."}
101 @string{NBhasin = "Bhasin, Nishant"}
102 @string{KBiddick = "Biddick, K."}
103 @string{KBillings = "Billings, Kate S."}
104 @string{GBinnig = "Binnig, Gerd"}
105 @string{BCBPRC = "Biochemical and Biophysical Research Communications"}
106 @string{Biochem = "Biochemistry"}
107 @string{BBABE = "Biochimica et Biophysica Acta (BBA) - Bioenergetics"}
108 @string{BIOINFO = "Bioinformatics (Oxford, England)"}
109 @string{Biomet = "Biometrika"}
110 @string{BPJ = "Biophysical Journal"}
111 %string{BPJ = "Biophys. J."}
112 @string{BIOSENSE = "Biosensors and Bioelectronics"}
113 @string{BIOTECH = "Biotechnology and Bioengineering"}
114 @string{JBirchler = "Birchler, James A."}
115 @string{AWBlake = "Blake, Anthony W."}
116 @string{JBlawzdziewicz = "Blawzdziewicz, Jerzy"}
117 @string{LBlick = "Blick, L."}
118 @string{RBolanos = "Bolanos, R."}
119 @string{VBonazzi = "Bonazzi, V."}
120 @string{Borgia = "Borgia"}
121 @string{MBorkovec = "Borkovec, Michal"}
122 @string{RBrandon = "Brandon, R."}
123 @string{EBranscomb = "Branscomb, E."}
124 @string{EBraverman = "Braverman, Elena"}
125 @string{WBreyer = "Breyer, Wendy A."}
126 @string{FBrochard-Wyart = "Brochard-Wyart, F."}
127 @string{DJBrockwell = "Brockwell, David J."}
128 @string{SBroder = "Broder, S."}
129 @string{SBroedel = "Broedel, Sheldon E."}
130 @string{ABrolo = "Brolo, Alexandre G."}
131 @string{FBrooks = "Brooks, Jr., Frederick P."}
132 @string{BrooksCole = "Brooks/Cole"}
133 @string{BDBrowerToland = "Brower-Toland, Brent D."}
134 @string{CTBrown = "Brown, C. Titus"}
135 @string{MBrucale = "Brucale, Marco"}
136 @string{TBruls = "Bruls, T."}
137 @string{VBrumfeld = "Brumfeld, Vlad"}
138 @string{JDBryngelson = "Bryngelson, J. D."}
139 @string{LBubacco = "Bubacco, Luigi"}
140 @string{JBuckheit = "Buckheit, Jonathan B."}
141 @string{ABuguin = "Buguin, A."}
142 @string{ABulhassan = "Bulhassan, Ahmed"}
143 @string{BBullard = "Bullard, Belinda"}
144 @string{RBunk = "Bunk, Richard"}
145 @string{NABurnham = "Burnham, N.~A."}
146 @string{DBusam = "Busam, D."}
147 @string{GBussi = "Bussi, Giovanni"}
148 @string{CBustamante = "Bustamante, Carlos"}
149 @string{YBustanji = "Bustanji, Yasser"}
150 @string{HJButt = {Butt, Hans-J\"urgen}}
151 @string{CUP = "Cambridge University Press"}
152 @string{MCaminha = "Caminha, M."}
153 @string{ICampbell = "Campbell, Iain D."}
154 @string{MJCampbell = "Campbell, M. J."}
155 @string{DSCannell = "Cannell, D.~S."}
156 @string{YCao = "Cao, Yi"}
157 @string{MCapitanio = "Capitanio, M."}
158 @string{MCargill = "Cargill, M."}
159 @string{PCarl = "Carl, Philippe"}
160 @string{BACarnes = "Carnes, B. A."}
161 @string{JCarnes-Stine = "Carnes-Stine, J."}
162 @string{MCarrionVazquez = "Carrion-Vazquez, Mariano"}
163 @string{CCarter = "Carter, C."}
164 @string{ACarver = "Carver, A."}
165 @string{JJCatanese = "Catanese, J.~J."}
166 @string{PCaulk = "Caulk, P."}
167 @string{CCecconi = "Cecconi, Ciro"}
168 @string{ACenter = "Center, A."}
169 @string{CTChan = "Chan, C.~T."}
170 @string{HSChan = "Chan, H.~S."}
171 @string{AChand = "Chand, Ami"}
172 @string{IChandramouliswaran = "Chandramouliswaran, I."}
173 @string{CHChang = "Chang, Chung-Hung"}
174 @string{EChapman = "Chapman, Edwin R."}
175 @string{RCharlab = "Charlab, R."}
176 @string{KChaturvedi = "Chaturvedi, K."}
177 @string{AChauhan = "Chauhan, A."}
178 @string{VPChauhan = "Chauhan, V.~P."}
179 @string{CChauzy = "Chauzy, C."}
180 @string{SChe = "Che, Shunai"}
181 @string{CEC = "Chemical Engineering Communications"}
182 @string{CHEMREV = "Chemical reviews"}
183 @string{CHEM = "Chemistry (Weinheim an der Bergstrasse, Germany)"}
184 @string{CPC = "Chemphyschem"}
185 @string{HCChen = "Chen, H. C."}
186 @string{LChen = "Chen, L."}
187 @string{XNChen = "Chen, X. N."}
188 @string{XiChen = "Chen, Xinyong"}
189 @string{XuChen = "Chen, Xuming"}
190 @string{JFCheng = "Cheng, J. F."}
191 @string{MLCheng = "Cheng, M. L."}
192 @string{VGCheung = "Cheung, V. G."}
193 @string{YHChiang = "Chiang, Y. H."}
194 @string{AChinwalla = "Chinwalla, A."}
195 @string{FChow = "Chow, Flora"}
196 @string{JChoy = "Choy, Jason"}
197 @string{BChu = "Chu, Benjamin"}
198 @string{XChu = "Chu, Xueying"}
199 @string{TYChung = "Chung, Tse-Yu"}
200 @string{CLChyan = "Chyan, Chia-Lin"}
201 @string{GCiccotti = "Ciccotti, Giovanni"}
202 @string{JClaerbout = "Claerbout, Jon F."}
203 @string{AGClark = "Clark, A. G."}
204 @string{Clarke = "Clarke"}
205 @string{JClarke = "Clarke, Jane"}
206 @string{JClarkson = "Clarkson, John"}
207 @string{HClausen-Schaumann = "Clausen-Schaumann, H."}
208 @string{JMClaverie = "Claverie, J. M."}
209 @string{WWCleland = "Cleland, W.~W."}
210 @string{KClerc-Blankenburg = "Clerc-Blankenburg, K."}
211 @string{NJCobb = "Cobb, Nathan J."}
212 @string{GHCohen = "Cohen, G.~H."}
213 @string{FSCollins = "Collins, Francis S."}
214 @string{CUP = "Columbia University Press"}
215 @string{CPR = "Computer Physics Reports"}
216 @string{CSE = "Computing in Science \& Engineering"}
217 @string{UniProtConsort = "Consortium, The UniProt"}
218 @string{MConti = "Conti, Matteo"}
219 @string{CEP = "Control Engineering Practice"}
220 @string{GACoon = "Coon, G.~A."}
221 @string{PVCornish = "Cornish, Peter V."}
222 @string{MNCourel = "Courel, M. N."}
223 @string{GCowan = "Cowan, Glen"}
224 @string{DRCox = "Cox, D. R."}
225 @string{MCoyne = "Coyne, M."}
226 @string{DCraig = "Craig, David"}
227 @string{ACravchik = "Cravchik, A."}
228 @string{PSCremer = "Cremer, Paul S."}
229 @string{CCroarkin = "Croarkin, Carroll"}
230 @string{VCroquette = "Croquette, Vincent"}
231 @string{YCui = "Cui, Y."}
232 @string{COSB = "Current Opinion in Structural Biology"}
233 @string{COCB = "Current Opinion in Chemical Biology"}
234 @string{LCurry = "Curry, L."}
235 @string{CDahlke = "Dahlke, C."}
236 @string{FDahlquist = "Dahlquist, Frederick W."}
237 @string{PDalhaimer = "Dalhaimer, Paul"}
238 @string{SDanaher = "Danaher, S."}
239 @string{LDavenport = "Davenport, L."}
240 @string{MCDavies = "Davies, M.~C."}
241 @string{MDavis = "Davis, Matt"}
242 @string{SDecatur = "Decatur, Sean M."}
243 @string{WDeGrado = "DeGrado, William F."}
244 @string{PDebrunner = "Debrunner, P."}
245 @string{ADelcher = "Delcher, A."}
246 @string{WDeLorbe = "DeLorbe, William J."}
247 @string{BDelpech = "Delpech, B."}
248 @string{Demography = "Demography"}
249 @string{ZDeng = "Deng, Z."}
250 @string{RDesilets = "Desilets, R."}
251 @string{IDew = "Dew, I."}
252 @string{CDewhurst = "Dewhurst, Charles"}
253 @string{VDiFrancesco = "Di Francesco, V."}
254 @string{KDiemer = "Diemer, K."}
255 @string{GDietler = "Dietler, Giovanni"}
256 @string{HDietz = "Dietz, Hendrik"}
257 @string{SDietz = "Dietz, S."}
258 @string{EDijkstra = "Dijkstra, Edsger Wybe"}
259 @string{KADill = "Dill, K. A."}
260 @string{RDima = "Dima, Ruxandra I."}
261 @string{DDischer = "Discher, Dennis E."}
262 @string{KDixon = "Dixon, K."}
263 @string{KDodson = "Dodson, K."}
264 @string{NDoggett = "Doggett, N."}
265 @string{MDombroski = "Dombroski, M."}
266 @string{MDonnelly = "Donnelly, M."}
267 @string{DDonoho = "Donoho, David L."}
268 @string{CDornmair = "Dornmair, C."}
269 @string{MDors = "Dors, M."}
270 @string{LDougan = "Dougan, Lorna"}
271 @string{LDoup = "Doup, L."}
272 @string{BDrake = "Drake, B."}
273 @string{TDrobek = "Drobek, T."}
274 @string{Drexel = "Drexel University"}
275 @string{OKDudko = "Dudko, Olga K."}
276 @string{YFDufrene = "Dufr{\^e}ne, Yves F."}
277 @string{ADunham = "Dunham, A."}
278 @string{DDunlap = "Dunlap, D."}
279 @string{PDunn = "Dunn, P."}
280 @string{VDupres = "Dupres, Vincent"}
281 @string{HJDyson = "Dyson, H.~Jane"}
282 @string{EMBORep = "EMBO Rep"}
283 @string{EMBO = "EMBO Rep."}
284 @string{REckel = "Eckel, R."}
285 @string{KEilbeck = "Eilbeck, K."}
286 @string{MElbaum = "Elbaum, Michael"}
287 @string{E:NHPL = "Elsevier, North-Holland Personal Library"}
288 @string{DEly = "Ely, D."}
289 @string{SEmerling = "Emerling, S."}
290 @string{TEndo = "Endo, Toshiya"}
291 @string{SWEnglander = "Englander, S. Walter"}
292 @string{HErickson = "Erickson, Harold P."}
293 @string{MEsaki = "Esaki, Masatoshi"}
294 @string{SEsparham = "Esparham, S."}
295 @string{EBJ = "European Biophysics Journal"}
296 @string{EJP = "European Journal of Physics"}
297 @string{EPL = "Europhysics Letters"}
298 @string{CEvangelista = "Evangelista, C."}
299 @string{CAEvans = "Evans, C. A."}
300 @string{EEvans = "Evans, E."}
301 @string{RSEvans = "Evans, R. S."}
302 @string{MEvstigneev = "Evstigneev, M."}
303 @string{DFasulo = "Fasulo, D."}
304 @string{FEBS = "FEBS letters"}
305 @string{XFei = "Fei, Xiaofang"}
306 @string{JFernandez = "Fernandez, Julio M."}
307 @string{SFerriera = "Ferriera, S."}
308 @string{AEFilippov = "Filippov, A. E."}
309 @string{LFinzi = "Finzi, L."}
310 @string{TEFisher = "Fisher, T. E."}
311 @string{MFlanigan = "Flanigan, M."}
312 @string{BFlannery = "Flannery, B."}
313 @string{LFlorea = "Florea, L."}
314 @string{ELFlorin = "Florin, Ernst-Ludwig"}
315 @string{HFlyvbjerg = "Flyvbjerg, Henrik"}
316 @string{FoldDes = "Fold Des"}
317 @string{NRForde = "Forde, Nancy R."}
318 @string{CFosler = "Fosler, C."}
319 @string{SFossey = "Fossey, S. A."}
320 @string{SFowler = "Fowler, Susan B."}
321 @string{GFranzen = "Franzen, Gereon"}
322 @string{SFreitag = "Freitag, S."}
323 @string{LFrench = "French, L."}
324 @string{RWFriddle = "Friddle, Raymond W."}
325 @string{CFriedman = "Friedman, C."}
326 @string{RFriedman = "Friedman, Ran"}
327 @string{MFritz = "Fritz, M."}
328 @string{HFuchs = "Fuchs, Harald"}
329 @string{TFujii = "Fujii, Tadashi"}
330 @string{HFujita = "Fujita, Hideaki"}
331 @string{AFujiyama = "Fujiyama, A."}
332 @string{RFulton = "Fulton, R."}
333 @string{TFunck = "Funck, Theodor"}
334 @string{TFurey = "Furey, T."}
335 @string{SFuruike = "Furuike, Shou"}
336 @string{GLGaborMiklos = "Gabor Miklos, G. L."}
337 @string{AEGabrielian = "Gabrielian, A. E."}
338 @string{WGan = "Gan, W."}
339 @string{DNGanchev = "Ganchev, Dragomir N."}
340 @string{MGao = "Gao, Mu"}
341 @string{DGarcia = "Garcia, D."}
342 @string{TGarcia = "Garcia, Tzintzuni"}
343 @string{NGarg = "Garg, N."}
344 @string{HEGaub = "Gaub, Hermann E."}
345 @string{MGautel = "Gautel, Mathias"}
346 @string{LAGavrilov = "Gavrilov, L. A."}
347 @string{NSGavrilova = "Gavrilova, N. S."}
348 @string{WGe = "Ge, W."}
349 @string{UGeisler = "Geisler, Ulrich"}
350 @string{GENE = "Gene"}
351 @string{CGerber = "Gerber, Christoph"}
352 @string{CGergely = "Gergely, C."}
353 @string{RGibbs = "Gibbs, R."}
354 @string{DGilbert = "Gilbert, D."}
355 @string{HGire = "Gire, H."}
356 @string{MGiuntini = "Giuntini, M."}
357 @string{FGittes = "Gittes, Frederick"}
358 @string{SGlanowski = "Glanowski, S."}
359 @string{JGlaser = "Glaser, Jens"}
360 @string{KGlasser = "Glasser, K."}
361 @string{AGlodek = "Glodek, A."}
362 @string{GGloeckner = "Gloeckner, G."}
363 @string{AGluecksmann = "Gluecksmann, A."}
364 @string{JDGocayne = "Gocayne, J. D."}
365 @string{AGomezCasado = "Gomez-Casado, Alberto"}
366 @string{BGompertz = "Gompertz, Benjamin"}
367 @string{FGong = "Gong, F."}
368 @string{GordonBreach = "Gordon Breach Scientific Publishing Ltd."}
369 @string{MGorokhov = "Gorokhov, M."}
370 @string{JHGorrell = "Gorrell, J. H."}
371 @string{SAGould = "Gould, S.~A."}
372 @string{KGraham = "Graham, K."}
373 @string{HLGranzier = "Granzier, Henk L."}
374 @string{FGrater = "Gr{\"a}ter, Frauke"}
375 @string{EDGreen = "Green, E. D."}
376 @string{SGGregory = "Gregory, S. G."}
377 @string{BGropman = "Gropman, B."}
378 @string{CGrossman = "Grossman, C."}
379 @string{HGrubmuller = {Grubm\"uller, Helmut}}
380 @string{AGrutzner = {Gr\"utzner, Anika}}
381 @string{ZGu = "Gu, Z."}
382 @string{PGuan = "Guan, P."}
383 @string{RGuigo = "Guig\'o, R."}
384 @string{EJGumbel = "Gumbel, Emil Julius"}
385 @string{HJGuntherodt = "Guntherodt, Hans-Joachim"}
386 @string{NGuo = "Guo, N."}
387 @string{YGuo = "Guo, Yi"}
388 @string{MGutman = "Gutman, Menachem"}
389 @string{RTGuy = "Guy, Richard T."}
390 @string{PHanggi = {H\"anggi, Peter}}
391 @string{THa = "Ha, Taekjip"}
392 @string{JHaack = "Haack, Julie A."}
393 @string{SHaddock = "Haddock, Steven H.~D."}
394 @string{GHager = "Hager, Gabriele"}
395 @string{THagglund = "H{\"a}gglund, T."}
396 @string{RHajjar = "Hajjar, Roger J."}
397 @string{AHalpern = "Halpern, A."}
398 @string{KHalvorsen = "Halvorsen, Ken"}
399 @string{FHan = "Han, Fangpu"}
400 @string{CCHang = "Hang, C.~C."}
401 @string{SHannenhalli = "Hannenhalli, S."}
402 @string{HHansma = "Hansma, H. G."}
403 @string{PHansma = "Hansma, Paul K."}
404 @string{DHarbrecht = "Harbrecht, Douglas"}
405 @string{SHarper = "Harper, Sandy"}
406 @string{MHarris = "Harris, M."}
407 @string{BHart = "Hart, B."}
408 @string{DPHart = "Hart, D.P."}
409 @string{JWHatfield = "Hatfield, John William"}
410 @string{THatton = "Hatton, T."}
411 @string{MHattori = "Hattori, M."}
412 @string{DHaussler = "Haussler, D."}
413 @string{THawkins = "Hawkins, T."}
414 @string{CHaynes = "Haynes, C."}
415 @string{JHaynes = "Haynes, J."}
416 @string{WHeckl = "Heckl, W. M."}
417 @string{CVHeer = "Heer, C.~V."}
418 @string{JHeil = "Heil, J."}
419 @string{RHeilig = "Heilig, R."}
420 @string{TJHeiman = "Heiman, T. J."}
421 @string{CHeiner = "Heiner, C."}
422 @string{MHelmes = "Helmes, M."}
423 @string{JHemmerle = "Hemmerle, J."}
424 @string{SHenderson = "Henderson, S."}
425 @string{BHeymann = "Heymann, Berthold"}
426 @string{NHiaro = "Hiaro, N."}
427 @string{MEHiggins = "Higgins, M. E."}
428 @string{THilburn = "Hilburn, Thomas B."}
429 @string{LHillier = "Hillier, L."}
430 @string{HHinssen = "Hinssen, Horst"}
431 @string{PHinterdorfer = "Hinterdorfer, Peter"}
432 @string{HistochemJ = "Histochem J"}
433 @string{SHladun = "Hladun, S."}
434 @string{WKHo = "Ho, W.~K."}
435 @string{RHochstrasser = "Hochstrasser, Robin M."}
436 @string{CSHodges = "Hodges, C.~S."}
437 @string{CHoff = "Hoff, C."}
438 @string{WHoff = "Hoff, Wouter D."}
439 @string{JLHolden = "Holden, J. L."}
440 @string{RAHolt = "Holt, R. A."}
441 @string{GHofmann = "Hofmann, Gerd"}
442 @string{MHonda = "Honda, M."}
443 @string{NPCHong = "Hong, Neil P. Chue"}
444 @string{XHong = "Hong, Xia"}
445 @string{LHood = "Hood, L."}
446 @string{JHoover = "Hoover, J."}
447 @string{JHorber = "Horber, J. K. H."}
448 @string{HHosser = "Hosser, H."}
449 @string{DHostin = "Hostin, D."}
450 @string{JHouck = "Houck, J."}
451 @string{AHoumeida = "Houmeida, Ahmed"}
452 @string{JHoward = "Howard, J."}
453 @string{THowland = "Howland, T."}
454 @string{BHsiao = "Hsiao, Benjamin S."}
455 @string{CKHu = "Hu, Chin-Kun"}
456 @string{DLHu = "Hu, David L."}
457 @string{BHuang = "Huang, Baiqu"}
458 @string{HHuang = "Huang, Hector Han-Li"}
459 @string{MHubain = "Hubain, Maurice"}
460 @string{AJHudspeth = "Hudspeth, A.~J."}
461 @string{KHuff = "Huff, Katy"}
462 @string{JHughes = "Hughes, John"}
463 @string{GHummer = "Hummer, Gerhard"}
464 @string{SJHumphray = "Humphray, S. J."}
465 @string{WLHung = "Hung, Wen-Liang"}
466 @string{MHunkapiller = "Hunkapiller, M."}
467 @string{DHHuson = "Huson, D. H."}
468 @string{JHutter = "Hutter, Jeffrey L."}
469 @string{CHyeon = "Hyeon, Changbong"}
470 @string{IEEE:TIT = "IEEE Transactions on Information Theory"}
471 @string{IEEE:SPM = "IEEE Signal Processing Magazine"}
472 @string{CIbegwam = "Ibegwam, C."}
473 @string{JRIdol = "Idol, J. R."}
474 @string{SImprota = "Improta, S."}
475 @string{TInoue = "Inoue, Tadashi"}
476 @string{IJBMM = "International Journal of Biological Macromolecules"}
477 @string{IJCIS = "International Journal of Computer \& Information Sciences"}
478 @string{AItkin = "Itkin, Anna"}
479 @string{HItoh = "Itoh, Hiroyasu"}
480 @string{AIrback = "Irback, Anders"}
481 @string{AMIsaacs = "Isaacs, Adrian M."}
482 @string{BIsralewitz = "Isralewitz, B."}
483 @string{SIstrail = "Istrail, S."}
484 @string{MIvemeyer = "Ivemeyer, M."}
485 @string{DIzhaky = "Izhaky, David"}
486 @string{SIzrailev = "Izrailev, S."}
487 @string{TJahnke = "J{\"a}hnke, Torsten"}
488 @string{WJang = "Jang, W."}
489 @string{HJanovjak = "Janovjak, Harald"}
490 @string{LJanosi = "Janosi, Lorant"}
491 @string{AJanshoff = "Janshoff, Andreas"}
492 @string{JJAP = "Japanese Journal of Applied Physics"}
493 @string{MJaschke = "Jaschke, Manfred"}
494 @string{DJennings = "Jennings, D."}
495 @string{HFJi = "Ji, Hai-Feng"}
496 @string{RRJi = "Ji, R. R."}
497 @string{YJia = "Jia, Yiwei"}
498 @string{SJiang = "Jiang, Shaoyi"}
499 @string{XJiang = "Jiang, Xingqun"}
500 @string{DJohannsmann = "Johannsmann, Diethelm"}
501 @string{CJohnson = "Johnson, Colin P."}
502 @string{JJohnson = "Johnson, J."}
503 @string{AJollymore = "Jollymore, Ashlee"}
504 @string{REJones = "Jones, R.E."}
505 @string{SJones = "Jones, S."}
506 @string{CJordan = "Jordan, C."}
507 @string{JJordan = "Jordan, J."}
508 %string{JACS = "J Am Chem Soc"}
509 @string{JACS = "Journal of the American Chemical Society"}
510 @string{JASA = "Journal of the American Statistical Association"}
511 @string{JAP = "Journal of Applied Physics"}
512 @string{JBM = "J Biomech"}
513 @string{JBT = "J Biotechnol"}
514 @string{JCPPCB = "Journal de Chimie Physique et de Physico-Chimie Biologique"}
515 @string{JCS = "Journal of Cell Science"}
516 @string{JCompP = "Journal of Computational Physics"}
517 @string{JEChem = "Journal of Electroanalytical Chemistry"}
518 @string{JMathBiol = "J Math Biol"}
519 @string{JMicro = "Journal of Microscopy"}
520 @string{JPhysio = "Journal of Physiology"}
521 @string{JStructBiol = "Journal of Structural Biology"}
522 @string{JTB = "J Theor Biol"}
523 @string{JMB = "Journal of Molecular Biology"}
524 @string{JP:CM = "Journal of Physics: Condensed Matter"}
525 @string{JP:CON = "Journal of Physics: Conference Series"}
526 @string{JRNBS:C = "Journal of Research of the National Bureau of Standards. Section C: Engineering and Instrumentation"}
527 @string{WSJuang = "Juang, F.~S."}
528 @string{DAJuckett = "Juckett, D. A."}
529 @string{SRJun = "Jun, Se-Ran"}
530 @string{DKaftan = "Kaftan, David"}
531 @string{LKagan = "Kagan, L."}
532 @string{FKalush = "Kalush, F."}
533 @string{ELKaplan = "Kaplan, E. L."}
534 @string{RKapon = "Kapon, Ruti"}
535 @string{AKardinal = "Kardinal, Angelika"}
536 @string{BKarlak = "Karlak, B."}
537 @string{MKarplus = "Karplus, Martin"}
538 @string{MKarrenbach = "Karrenbach, Martin"}
539 @string{JKasha = "Kasha, J."}
540 @string{KKawasaki = "Kawasaki, K."}
541 @string{ZKe = "Ke, Z."}
542 @string{AKejariwal = "Kejariwal, A."}
543 @string{MSKellermayer = "Kellermayer, Mikl\'os S. Z."}
544 @string{TKempe = "Kempe, Thomas"}
545 @string{SKennedy = "Kennedy, S."}
546 @string{SBHKent = "Kent, Stephen B. H."}
547 @string{WJKent = "Kent, W. J."}
548 @string{KAKetchum = "Ketchum, K. A."}
549 @string{FKienberger = "Kienberger, Ferry"}
550 @string{SHKim = "Kim, Sung-Hou"}
551 @string{WKing = "King, William Trevor"}
552 @string{KKinosita = "{Kinosita Jr.}, Kazuhiko"}
553 @string{IRKirsch = "Kirsch, I. R."}
554 @string{JKlafter = "Klafter, J."}
555 @string{AKleiner = "Kleiner, Ariel"}
556 @string{DKlimov = "Klimov, Dmitri K."}
557 @string{LKline = "Kline, L."}
558 @string{LKlumb = "Klumb, L."}
559 @string{KAPPP = "Kluwer Academic Publishers--Plenum Publishers"}
560 @string{CDKodira = "Kodira, C. D."}
561 @string{SKoduru = "Koduru, S."}
562 @string{PKoehl = "Koehl, Patrice"}
563 @string{BKolmerer = "Kolmerer, B."}
564 @string{JKorenberg = "Korenberg, J."}
565 @string{IKosztin = "Kosztin, Ioan"}
566 @string{JKovacevic = "Kovacevic, Jelena"}
567 @string{CKraft = "Kraft, C."}
568 @string{HAKramers = "Kramers, H. A."}
569 @string{AKrammer = "Krammer, Andre"}
570 @string{SKravitz = "Kravitz, S."}
571 @string{HJKreuzer = {Kreuzer, Hans J\"urgen}}
572 @string{MMGKrishna = "Krishna, Mallela M. G."}
573 @string{KKroy = "Kroy, Klaus"}
574 @string{HHKu = "Ku, H.~H."}
575 @string{TAKucaba = "Kucaba, T. A."}
576 @string{Kucherlapati = "Kucherlapati"}
577 @string{JKudoh = "Kudoh, J."}
578 @string{MKuhn = "Kuhn, Michael"}
579 @string{MKulke = "Kulke, Michael"}
580 @string{CKwok = "Kwok, Carol H."}
581 @string{RLevy = "L\'evy, R"}
582 @string{DLabeit = "Labeit, Dietmar"}
583 @string{SLabeit = "Labeit, Siegfried"}
584 @string{DLabudde = "Labudde, Dirk"}
585 @string{SLahmers = "Lahmers, Sunshine"}
586 @string{ZLai = "Lai, Z."}
587 @string{CLam = "Lam, Canaan"}
588 @string{JLamb = "Lamb, Jonathan C."}
589 @string{LANG = "Langmuir"}
590 % "Langmuir : the ACS journal of surfaces and colloids",
591 @string{WLau = "Lau, Wai Leung"}
592 @string{RLaw = "Law, Richard"}
593 @string{BLazareva = "Lazareva, B."}
594 @string{MLeake = "Leake, Mark C."}
595 @string{ELee = "Lee, E."}
596 @string{HLee = "Lee, Haeshin"}
597 @string{SLee = "Lee, Sunyoung"}
598 @string{HLehmann = "Lehmann, H."}
599 @string{HLehrach = "Lehrach, H."}
600 @string{YLei = "Lei, Y."}
601 @string{PLelkes = "Lelkes, Peter I."}
602 @string{OLequin = "Lequin, Olivier"}
603 @string{CLethias = "Lethias, Claire"}
604 @string{SLeuba = "Leuba, Sanford H."}
605 @string{ALeung = "Leung, A."}
606 @string{MLeuschner = "Leuschner, Mirko"}
607 @string{AJLevine = "Levine, A. J."}
608 @string{CLevinthal = "Levinthal, Cyrus"}
609 @string{ALevitsky = "Levitsky, A."}
610 @string{SLevy = "Levy, S."}
611 @string{MLewis = "Lewis, M."}
612 @string{JLItalien = "L'Italien, James J."}
613 @string{BLi = "Li, Bing"}
614 @string{CYLi = "Li, Christopher Y."}
615 @string{HLi = "Li, Hongbin"}
616 @string{JLi = "Li, J."}
617 @string{LeLi = "Li, Lewyn"}
618 @string{LiLi = "Li, Lingyu"}
619 @string{MSLi = "Li, Mai Suan"}
620 @string{PWLi = "Li, P. W."}
621 @string{YLi = "Li, Yajun"}
622 @string{ZLi = "Li, Z."}
623 @string{YLiang = "Liang, Y."}
624 @string{GLiao = "Liao, George"}
625 @string{FCLin = "Lin, Fan-Chi"}
626 @string{JLin = "Lin, Jianhua"}
627 @string{SHLin = "Lin, Sheng-Hsien"}
628 @string{XLin = "Lin, X."}
629 @string{JLindahl = "Lindahl, Joakim"}
630 @string{SLindsay = "Lindsay, Stuart M."}
631 @string{WALinke = "Linke, Wolfgang A."}
632 @string{RLippert = "Lippert, R."}
633 @string{JLis = "Lis, John T."}
634 @string{RLiu = "Liu, Runcong"}
635 @string{WLiu = "Liu, W."}
636 @string{XLiu = "Liu, X."}
637 @string{YLiu = "Liu, Yichun"}
638 @string{LLivadaru = "Livadaru, L."}
639 @string{YSLo = "Lo, Yu-Shiu"}
640 @string{GLois = "Lois, Gregg"}
641 @string{JLopez = "Lopez, J."}
642 @string{LANL = "Los Alamos National Laboratory"}
643 @string{LAS = "Los Alamos Science"}
644 @string{ALove = "Love, A."}
645 @string{FLu = "Lu, F."}
646 @string{HLu = "Lu, Hui"}
647 @string{QLu = "Lu, Qinghua"}
648 @string{MLudwig = "Ludwig, Markus"}
649 @string{ZPLuo = "Luo, Zong-Ping"}
650 @string{ZLuthey-Schulten = "Luthey-Schulten, Z."}
651 @string{EMunck = {M\"unck, E.}}
652 @string{DMa = "Ma, D."}
653 @string{LMa = "Ma, Liang"}
654 @string{MMaaloum = "Maaloum, Mounir"}
655 @string{Macromol = "Macromolecules"}
656 @string{AMadan = "Madan, A."}
657 @string{VVMaduro = "Maduro, V. V."}
658 @string{CMaingonnat = "Maingonnat, C."}
659 @string{SMajid = "Majid, Sophia"}
660 @string{WMajoros = "Majoros, W."}
661 @string{DEMakarov = "Makarov, Dmitrii E."}
662 @string{RMamdani = "Mamdani, Reneeta"}
663 @string{SMammi = "Mammi, Stefano"}
664 @string{EMandello = "Mandello, Enrico"}
665 @string{GManderson = "Manderson, Gavin"}
666 @string{FMann = "Mann, F."}
667 @string{AMansson = "M{\aa}nsson, Alf"}
668 @string{ERMardis = "Mardis, E. R."}
669 @string{JMarion = "Marion, J."}
670 @string{JFMarko = "Marko, John F."}
671 @string{MMarra = "Marra, M."}
672 @string{PMarszalek = "Marszalek, Piotr E."}
673 @string{MMartin = "Martin, M. J."}
674 @string{YMartin = "Martin, Y."}
675 @string{HMassa = "Massa, H."}
676 @string{MIT = "Massachusetts Institute of Technology"}
677 @string{GAMatei = "Matei, G.~A."}
678 @string{DMaterassi = "Materassi, Donatello"}
679 @string{JMathe = "Math\'e, J\'er\^ome"}
680 @string{AMatouschek = "Matouschek, Andreas"}
681 @string{BMatthews = "Matthews, Brian W."}
682 @string{DMay = "May, D."}
683 @string{RMayer = "Mayer, Richard"}
684 @string{LMayne = "Mayne, Leland"}
685 @string{AMays = "Mays, A."}
686 @string{OTMcCann = "McCann, O. T."}
687 @string{SMcCawley = "McCawley, S."}
688 @string{JMcDaniel = "McDaniel, J."}
689 @string{JMcEntyre = "McEntyre, J."}
690 @string{McGraw-Hill = "McGraw-Hill"}
691 @string{TMcIntosh = "McIntosh, T."}
692 @string{VAMcKusick = "McKusick, V. A."}
693 @string{IMcMullen = "McMullen, I."}
694 @string{JDMcPherson = "McPherson, J. D."}
695 @string{TMeasey = "Measey, Thomas J."}
696 @string{MAD = "Mech Ageing Dev"}
697 @string{PMeier = "Meier, Paul"}
698 @string{AMeller = "Meller, Amit"}
699 @string{CCMello = "Mello, Cecilia C."}
700 @string{RMerkel = "Merkel, R."}
701 @string{GVMerkulov = "Merkulov, G. V."}
702 @string{FMerzel = "Merzel, Franci"}
703 @string{HMetiu = "Metiu, Horia"}
704 @string{NMetropolis = "Metropolis, Nicholas"}
705 @string{GMeyer = "Meyer, Gerhard"}
706 @string{HMi = "Mi, H."}
707 @string{LMiao = "Miao, Linlin"}
708 @string{CMicheletti = "Micheletti, Cristian"}
709 @string{MMickler = "Mickler, Moritz"}
710 @string{AMiller = "Miller, A."}
711 @string{NMilshina = "Milshina, N."}
712 @string{SMinoshima = "Minoshima, S."}
713 @string{IMitchell = "Mitchell, Ian"}
714 @string{SMitternacht = "Mitternacht, Simon"}
715 @string{NJMlot = "Mlot, Nathan J."}
716 @string{CMobarry = "Mobarry, C."}
717 @string{NMohandas = "Mohandas, N."}
718 @string{SMohanty = "Mohanty, Sandipan"}
719 @string{UMohideen = "Mohideen, U."}
720 @string{PJMohr = "Mohr, Peter J."}
721 @string{VMontana = "Montana, Vedrana"}
722 @string{LMontanaro = "Montanaro, Lucio"}
723 @string{LMontelius = "Montelius, Lars"}
724 @string{CMontemagno = "Montemagno, Carlo D."}
725 @string{KTMontgomery = "Montgomery, K. T."}
726 @string{HMMoore = "Moore, H. M."}
727 @string{MMorgan = "Morgan, Michael"}
728 @string{LMoy = "Moy, L."}
729 @string{MMoy = "Moy, M."}
730 @string{VMoy = "Moy, Vincent T."}
731 @string{SMukamel = "Mukamel, Shaul"}
732 @string{DJMuller = "M{\"u}ller, Daniel J."}
733 @string{PMundel = "Mundeol, P."}
734 @string{EMuneyuki = "Muneyuki, Eiro"}
735 @string{RJMural = "Mural, R. J."}
736 @string{BMurphy = "Murphy, B."}
737 @string{SMurphy = "Murphy, S."}
738 @string{AMuruganujan = "Muruganujan, A."}
739 @string{FMusiani = "Musiani, Francesco"}
740 @string{EWMyers = "Myers, E. W."}
741 @string{RMMyers = "Myers, R. M."}
742 @string{AMylonakis = "Mylonakis, Andreas"}
743 @string{ENachliel = "Nachliel, Esther"}
744 @string{JNadeau = "Nadeau, J."}
745 @string{AKNaik = "Naik, A. K."}
746 @string{NANO = "Nano letters"}
747 @string{NT = "Nanotechnology"}
748 @string{VANarayan = "Narayan, V. A."}
749 @string{ANarechania = "Narechania, A."}
750 @string{PNassoy = "Nassoy, P."}
751 @string{NBS = "National Bureau of Standards"}
752 @string{NAT = "Nature"}
753 @string{NSB = "Nature Structural Biology"}
754 @string{NSMB = "Nature Structural Molecular Biology"}
755 @string{NRMCB = "Nature Reviews Molecular Cell Biology"}
756 @string{SNaylor = "Naylor, S."}
757 @string{CNeagoe = "Neagoe, Ciprian"}
758 @string{BNeelam = "Neelam, B."}
759 @string{MNeitzert = "Neitzert, Marcus"}
760 @string{CNelson = "Nelson, C."}
761 @string{KNelson = "Nelson, K."}
762 @string{RRNetz = "Netz, R.~R."}
763 @string{NR = "Neurochemical research"}
764 @string{NEURON = "Neuron"}
765 @string{RNevo = "Nevo, Reinat"}
766 @string{NJP = "New Journal of Physics"}
767 @string{DBNewell = "Newell, David B."}
768 @string{MNewman = "Newman, M."}
769 @string{INewton = "Newton, Isaac"}
770 @string{SNg = "Ng, Sean P."}
771 @string{NNguyen = "Nguyen, N."}
772 @string{TNguyen = "Nguyen, T."}
773 @string{MNguyen-Duong = "Nguyen-Duong, M."}
774 @string{INicholls = "Nicholls, Ian A."}
775 @string{NNichols = "Nichols, N.~B."}
776 @string{SNie = "Nie, S."}
777 @string{MNodell = "Nodell, M."}
778 @string{AANoegel = "Noegel, Angelika A."}
779 @string{HNoji = "Noji, Hiroyuki"}
780 @string{RNome = "Nome, Rene A."}
781 @string{NNowak = "Nowak, N."}
782 @string{ANoy = "Noy, Aleksandr"}
783 @string{NAR = "Nucleic Acids Research"}
784 @string{JNummela = "Nummela, Jeremiah"}
785 @string{JNunes = "Nunes, Joao"}
786 @string{DNusskern = "Nusskern, D."}
787 @string{GNyakatura = "Nyakatura, G."}
788 @string{CSOHern = "O'Hern, Corey S."}
789 @string{YOberdorfer = {Oberd\"orfer, York}}
790 @string{AOberhauser = "Oberhauser, Andres F."}
791 @string{FOesterhelt = "Oesterhelt, Filipp"}
792 @string{TOhashi = "Ohashi, Tomoo"}
793 @string{BOhler = "Ohler, Benjamin"}
794 @string{PDOlmsted = "Olmsted, Peter D."}
795 @string{AOlsen = "Olsen, A."}
796 @string{SJOlshansky = "Olshansky, S. J."}
797 @string{POmling = {Omlink, P{\"a}r}}
798 @string{JNOnuchic = "Onuchic, J. N."}
799 @string{YOono = "Oono, Y."}
800 @string{GOppenheim = "Oppenheim, Georges"}
801 @string{COpitz = "Optiz, Christiane A."}
802 @string{KOroszlan = "Oroszlan, Krisztina"}
803 @string{EOroudjev = "Oroudjev, E."}
804 @string{KOsoegawa = "Osoegawa, K."}
805 @string{OUP = "Oxford University Press"}
806 @string{EPaci = "Paci, Emanuele"}
807 @string{SPan = "Pan, S."}
808 @string{HSPark = "Park, H. S."}
809 @string{VParpura = "Parpura, Vladimir"}
810 @string{APastore = "Pastore, A."}
811 @string{APatrinos = "Patrinos, Aristides"}
812 @string{FPavone = "Pavone, F. S."}
813 @string{SHPayne = "Payne, Stephen H."}
814 @string{JPeck = "Peck, J."}
815 @string{HPeng = "Peng, Haibo"}
816 @string{QPeng = "Peng, Qing"}
817 @string{RNPerham = "Perham, Richard N."}
818 @string{OPerisic = "Perisic, Ognjen"}
819 @string{CPeterson = "Peterson, Craig L."}
820 @string{MPeterson = "Peterson, M."}
821 @string{SMPeterson = "Peterson, Susan M."}
822 @string{CPfannkoch = "Pfannkoch, C."}
823 @string{PA = "Pfl{\"u}gers Archiv: European journal of physiology"}
824 @string{PTRSL = "Philosophical Transactions of the Royal Society of London"}
825 @string{PR:E = "Phys Rev E Stat Nonlin Soft Matter Phys"}
826 @string{PRL = "Physical Review Letters"}
827 %string{PRL = "Phys Rev Lett"}
828 @string{Physica = "Physica"}
829 @string{GPing = "Ping, Guanghui"}
830 @string{NPinotsis = "Pinotsis, Nikos"}
831 @string{MPlumbley = "Plumbley, Mark"}
832 @string{PLOS:ONE = "PLOS ONE"}
833 %string{PLOS:ONE = "Public Library of Science ONE"}
834 @string{PLOS:BIO = "PLOS Biology"}
835 @string{DPlunkett = "Plunkett, David"}
836 @string{PPodsiadlo = "Podsiadlo, Paul"}
837 @string{ASPolitou = "Politou, A. S."}
838 @string{APoustka = "Poustka, A."}
839 @string{CBPrater = "Prater, C.~B."}
840 @string{GPratesi = "Pratesi, G."}
841 @string{EPratts = "Pratts, E."}
842 @string{WPress = "Press, W."}
843 @string{PNAS = "Proceedings of the National Academy of Sciences of the
844 United States of America"}
845 @string{PBPMB = "Progress in Biophysics and Molecular Biology"}
846 @string{PS = "Protein Science"}
847 @string{PROT = "Proteins"}
848 @string{RSUP = "Published for the Royal Society at the University Press"}
849 @string{EPuchner = "Puchner, Elias M."}
850 @string{VPuri = "Puri, V."}
851 @string{WPyckhout-Hintzen = "Pyckhout-Hintzen, Wim"}
852 @string{HQin = "Qin, Haina"}
853 @string{SQin = "Qin, S."}
854 @string{SRQuake = "Quake, Stephen R."}
855 @string{CQuate = "Quate, Calvin F."}
856 @string{HQureshi = "Qureshi, H."}
857 @string{SERadford = "Radford, Sheena E."}
858 @string{MRadmacher = "Radmacher, M."}
859 @string{MRaible = "Raible, M."}
860 @string{LRamirez = "Ramirez, L."}
861 @string{JRamser = "Ramser, J."}
862 @string{LRandles = "Randles, Lucy G."}
863 @string{VRaussens = "Raussens, Vincent"}
864 @string{IRay = "Ray, I."}
865 @string{MReardon = "Reardon, M."}
866 @string{ALCReddin = "Reddin, Andrew L. C."}
867 @string{SRedick = "Redick, Sambra D."}
868 @string{ZReich = "Reich, Ziv"}
869 @string{TReid = "Reid, T."}
870 @string{PReimann = "Reimann, P."}
871 @string{KReinert = "Reinert, K."}
872 @string{RReinhardt = "Reinhardt, R."}
873 @string{KRemington = "Remington, K."}
874 @string{RMP = "Rev. Mod. Phys."}
875 @string{RSI = "Review of Scientific Instruments"}
876 @string{FRief = "Rief, Frederick"}
877 @string{MRief = "Rief, Matthias"}
878 @string{KRitchie = "Ritchie, K."}
879 @string{MRobbins = "Robbins, Mark O."}
880 @string{CJRoberts = "Roberts, C.~J."}
881 @string{RJRoberts = "Roberts, R. J."}
882 @string{RRobertson = "Robertson, Ragan B."}
883 @string{HRoder = "Roder, Heinrich"}
884 @string{RRodriguez = "Rodriguez, R."}
885 @string{YHRogers = "Rogers, Y. H."}
886 @string{SRogic = "Rogic, S."}
887 @string{MRoman = "Roman, Marisa B."}
888 @string{GRomano = "Romano, G."}
889 @string{DRomblad = "Romblad, D."}
890 @string{RRos = "Ros, Robert"}
891 @string{BRosenberg = "Rosenberg, B."}
892 @string{JRosengren = "Rosengren, Jenny P."}
893 @string{ARosenthal = "Rosenthal, A."}
894 @string{ARoters = "Roters, Andreas"}
895 @string{WRowe = "Rowe, W."}
896 @string{LRowen = "Rowen, L."}
897 @string{BRuhfel = "Ruhfel, B."}
898 @string{DBRusch = "Rusch, D. B."}
899 @string{JMRuysschaert = "Ruysschaert, Jean-Marie"}
900 @string{JPRyckaert = "Ryckaert, Jean-Paul"}
901 @string{NSakaki = "Sakaki, Naoyoshi"}
902 @string{YSakaki = "Sakaki, Y."}
903 @string{SSalzberg = "Salzberg, S."}
904 @string{BSamori = "Samor{\`i}, Bruno"}
905 @string{MSandal = "Sandal, Massimo"}
906 @string{RSanders = "Sanders, R."}
907 @string{ASarkar = "Sarkar, Atom"}
908 @string{TSasaki = "Sasaki, T."}
909 @string{SSato = "Sato, S."}
910 @string{TSato = "Sato, Takehiro"}
911 @string{PSchaaf = "Schaaf, P."}
912 @string{RSchafer = "Schafer, Rolf"}
913 @string{TESchafer = "Sch{\"a}fer, Tilman E."}
914 @string{NScherer = "Scherer, Norbert F."}
915 @string{SScherer = "Scherer, S."}
916 @string{MSchilhabel = "Schilhabel, M."}
917 @string{HSchillers = "Schillers, Hermann"}
918 @string{BSchlegelberger = "Schlegelberger, B."}
919 @string{MSchleicher = "Schleicher, Michael"}
920 @string{MSchlierf = "Schlierf, Michael"}
921 @string{CFSchmidt = "Schmidt, Christoph F."}
922 @string{JSchmidt = "Schmidt, Jacob J."}
923 @string{LSchmitt = "Schmitt, Lutz"}
924 @string{JSchmutz = "Schmutz, J."}
925 @string{GSchuler = "Schuler, G."}
926 @string{GDSchuler = "Schuler, G. D."}
927 @string{KSchulten = "Schulten, Klaus"}
928 @string{ZSchulten = "Schulten, Zan"}
929 @string{MSchwab = "Schwab, M."}
930 @string{ISchwaiger = "Schwaiger, Ingo"}
931 @string{RSchwartz = "Schwartz, R."}
932 @string{RSchweitzerStenner = "Scheitzer-Stenner, Reinhard"}
933 @string{SCI = "Science"}
934 @string{CEScott = "Scott, C. E."}
935 @string{JScott = "Scott, J."}
936 @string{RScott = "Scott, R."}
937 @string{USeifert = "Seifert, Udo"}
938 @string{SKSekatskii = "Sekatskii, Sergey K."}
939 @string{MSekhon = "Sekhon, M."}
940 @string{TSekiguchi = "Sekiguchi, T."}
941 @string{BSenger = "Senger, B."}
942 @string{DBSenn = "Senn, David B."}
943 @string{PSeranski = "Seranski, P."}
944 @string{RSesboue = {Sesbo\"u\'e, R.}}
945 @string{EShakhnovich = "Shakhnovich, Eugene"}
946 @string{GShan = "Shan, Guiye"}
947 @string{JShang = "Shang, J."}
948 @string{WShao = "Shao, W."}
949 @string{DSharma = "Sharma, Deepak"}
950 @string{YJSheng = "Sheng, Yu-Jane"}
951 @string{KShibuya = "Shibuya, K."}
952 @string{JShillcock = "Shillcock, Julian"}
953 @string{AShimizu = "Shimizu, A."}
954 @string{NShimizu = "Shimizu, N."}
955 @string{RShimoKon = "Shimo-Kon, Rieko"}
956 @string{JPShine = "Shine, James P."}
957 @string{AShintani = "Shintani, A."}
958 @string{BShneiderman = "Shneiderman, Ben"}
959 @string{BShue = "Shue, B."}
960 @string{RSiebert = "Siebert, R."}
961 @string{EDSiggia = "Siggia, Eric D."}
962 @string{MSimon = "Simon, M."}
963 @string{MSimpson = "Simpson, M."}
964 @string{GESims = "Sims, Gregory E."}
965 @string{CSitter = "Sitter, C."}
966 @string{KVSjolander = "Sjolander, K. V."}
967 @string{MSkupski = "Skupski, M."}
968 @string{CSlayman = "Slayman, C."}
969 @string{MSmallwood = "Smallwood, M."}
970 @string{CSmith = "Smith, Corey L."}
971 @string{DASmith = "Smith, D. Alastair"}
972 @string{HOSmith = "Smith, H. O."}
973 @string{KBSmith = "Smith, Kathryn B."}
974 @string{SSmith = "Smith, S."}
975 @string{SBSmith = "Smith, S. B."}
976 @string{TSmith = "Smith, T."}
977 @string{JSoares = "Soares, J."}
978 @string{NDSocci = "Socci, N. D."}
979 @string{SEG = "Society of Exploration Geophysicists"}
980 @string{ESodergren = "Sodergren, E."}
981 @string{CSoderlund = "Soderlund, C."}
982 @string{JSong = "Song, Jianxing"}
983 @string{JSpanier = "Spanier, Jonathan E."}
984 @string{DSpeicher = "Speicher, David W."}
985 @string{GSpier = "Spier, G."}
986 @string{ASprague = "Sprague, A."}
987 @string{SPRINGER = "Springer Science + Business Media, LLC"}
988 @string{SPRINGER:V = "Springer-Verlag"}
989 @string{DBStaple = "Staple, Douglas B."}
990 @string{RStark = "Stark, R. W."}
991 @string{PSStayton = "Stayton, P. S."}
992 @string{REStenkamp = "Stenkamp, R. E."}
993 @string{SStepaniants = "Stepaniants, S."}
994 @string{EStewart = "Stewart, E."}
995 @string{MRStockmeier = "Stockmeier, M. R."}
996 @string{TStockwell = "Stockwell, T."}
997 @string{NEStone = "Stone, N. E."}
998 @string{AStout = "Stout, A."}
999 @string{TRStrick = "Strick, T. R."}
1000 @string{CStroh = "Stroh, Cordula"}
1001 @string{RStrong = "Strong, R."}
1002 @string{JStruckmeier = "Struckmeier, Jens"}
1003 @string{STR = "Structure"}
1004 @string{TStrunz = "Strunz, Torsten"}
1005 @string{MSu = "Su, Meihong"}
1006 @string{GSubramanian = "Subramanian, G."}
1007 @string{ESuh = "Suh, E."}
1008 @string{JSun = "Sun, J."}
1009 @string{YLSun = "Sun, Yu-Long"}
1010 @string{MSundberg = "Sundberg, Mark"}
1011 @string{WSundquist = "Sundquist, Wesley I."}
1012 @string{KSurewicz = "Surewicz, Krystyna"}
1013 @string{WKSurewicz = "Surewicz, Witold K."}
1014 @string{GGSutton = "Sutton, G. G."}
1015 @string{ASzabo = "Szabo, Attila"}
1016 @string{STagerud = "T{\aa}gerud, Sven"}
1017 @string{PTabor = "Tabor, P."}
1018 @string{ATakahashi = "Takahashi, Akiri"}
1019 @string{DTalaga = "Talaga, David S."}
1020 @string{PTalkner = "Talkner, Peter"}
1021 @string{RTampe = "Tamp{\'e}, Robert"}
1022 @string{JTang = "Tang, Jianyong"}
1023 @string{PTavan = "Tavan, P."}
1024 @string{BNTaylor = "Taylor, Barry N."}
1025 @string{THEMath = "Technische Hogeschool Eindhoven, Nederland,
1026 Onderafdeling der Wiskunde"}
1027 @string{SJBTendler = "Tendler, S.~J.~B."}
1028 @string{ITessari = "Tessari, Isabella"}
1029 @string{STeukolsky = "Teukolsky, S."}
1030 @string{CJ = "The Computer Journal"}
1031 @string{JBC = "The Journal of Biological Chemistry"}
1032 @string{JCP = "The Journal of Chemical Physics"}
1033 @string{JPC:B = "The Journal of Physical Chemistry B"}
1034 @string{JPC:C = "The Journal of Physical Chemistry C"}
1035 @string{RS = "The Royal Society"}
1036 @string{DThirumalai = "Thirumalai, Devarajan"}
1037 @string{PDThomas = "Thomas, P. D."}
1038 @string{RThomas = "Thomas, R."}
1039 @string{JThompson = "Thompson, J. B."}
1040 @string{EJThoreson = "Thoreson, E.~J."}
1041 @string{SThornton = "Thornton, S."}
1042 @string{RWTillmann = "Tillmann, R.~W."}
1043 @string{NNTint = "Tint, N. N."}
1044 @string{BTiribilli = "Tiribilli, Bruno"}
1045 @string{TTlusty = "Tlusty, Tsvi"}
1046 @string{PTobias = "Tobias, Paul"}
1047 @string{JTocaHerrera = "Toca-Herrera, Jose L."}
1048 @string{CATovey = "Tovey, Craig A."}
1049 @string{AToyoda = "Toyoda, A."}
1050 @string{TASME = "Transactions of the American Society of Mechanical Engineers"}
1051 @string{BTrask = "Trask, B."}
1052 @string{TBI = "Tribology International"}
1053 @string{JTrinick = "Trinick, John"}
1054 @string{KTrombitas = "Trombit\'as, K."}
1055 @string{ILTrong = "Trong, I. Le"}
1056 @string{CHTsai = "Tsai, Chih-Hui"}
1057 @string{HKTsao = "Tsao, Heng-Kwong"}
1058 @string{STse = "Tse, S."}
1059 @string{ZTshiprut = "Tshiprut, Z."}
1060 @string{JCMTsibris = "Tsibris, J.C.M."}
1061 @string{LTskhovrebova = "Tskhovrebova, Larissa"}
1062 @string{HWTurnbull = "Turnbull, Herbert Westren"}
1063 @string{RTurner = "Turner, R."}
1064 @string{AUlman = "Ulman, Abraham"}
1065 @string{UltraMic = "Ultramicroscopy"}
1066 @string{UIP:Urbana = "University of Illinois Press, Urbana"}
1067 @string{UTMB = "University of Texas Medical Branch"}
1068 @string{MUrbakh = "Urbakh, M."}
1069 @string{FValle = "Valle, Francesco"}
1070 @string{KJVanVliet = "Van Vliet, Krystyn J."}
1071 @string{PVandewalle = "Vandewalle, Patrick"}
1072 @string{CVech = "Vech, C."}
1073 @string{OVelasquez = "Velasquez, O."}
1074 @string{EVenter = "Venter, E."}
1075 @string{JCVenter = "Venter, J. C."}
1076 @string{PHVerdier = "Verdier, Peter H."}
1077 @string{IVetter = "Vetter, Ingrid R."}
1078 @string{MVetterli = "Vetterli, Martin"}
1079 @string{WVetterling = "Vetterling, W."}
1080 @string{MViani = "Viani, Mario B."}
1081 @string{JCVoegel = "Voegel, J.-C."}
1082 @string{VVogel = "Vogel, Viola"}
1083 @string{CWagner-McPherson = "Wagner-McPherson, C."}
1084 @string{RWahl = "Wahl, Reiner"}
1085 @string{TAWaigh = "Waigh, Thomas A."}
1086 @string{BWalenz = "Walenz, B."}
1087 @string{JWallis = "Wallis, J."}
1088 @string{KWalther = "Walther, Kirstin A."}
1089 @string{AJWalton = "Walton, Alan J"}
1090 @string{EBWalton = "Walton, Emily B."}
1091 @string{AWang = "Wang, A."}
1092 @string{FSWang = "Wang, F.~S."}
1093 @string{GWang = "Wang, G."}
1094 @string{JWang = "Wang, J."}
1095 @string{MWang = "Wang, M."}
1096 @string{MDWang = "Wang, Michelle D."}
1097 @string{SWang = "Wang, Shuang"}
1098 @string{XWang = "Wang, X."}
1099 @string{ZWang = "Wang, Z."}
1100 @string{HWatanabe = "Watanabe, Hiroshi"}
1101 @string{KWatanabe = "Watanabe, Kaori"}
1102 @string{RHWaterston = "Waterston, R. H."}
1103 @string{BWaugh = "Waugh, Ben"}
1104 @string{JWegiel = "Wegiel, J."}
1105 @string{MWei = "Wei, M."}
1106 @string{YWei = "Wei, Yen"}
1107 @string{ALWeisenhorn = "Weisenhorn, A.~L."}
1108 @string{JWeissenbach = "Weissenbach, J."}
1109 @string{BLWelch = "Welch, Bernard Lewis"}
1110 @string{GWen = "Wen, G."}
1111 @string{MWen = "Wen, M."}
1112 @string{JWetter = "Wetter, J."}
1113 @string{EPWhite = "White, Ethan P."}
1114 @string{ANWhitehead = "Whitehead, Alfred North"}
1115 @string{AWhittaker = "Whittaker, A."}
1116 @string{HKWickramasinghe = "Wickramasinghe, H. K."}
1117 @string{RWides = "Wides, R."}
1118 @string{AWiita = "Wiita, Arun P."}
1119 @string{MWilchek = "Wilchek, Meir"}
1120 @string{AWilcox = "Wilcox, Alexander J."}
1121 @string{Williams = "Williams"}
1122 @string{CCWilliams = "Williams, C. C."}
1123 @string{MWilliams = "Williams, M."}
1124 @string{SWilliams = "Williams, S."}
1125 @string{WN = "Williams \& Norgate"}
1126 @string{MWilmanns = "Wilmanns, Matthias"}
1127 @string{GWilson = "Wilson, Greg"}
1128 @string{PWilson = "Wilson, Paul"}
1129 @string{RKWilson = "Wilson, R. K."}
1130 @string{SWilson = "Wilson, Scott"}
1131 @string{SWindsor = "Windsor, S."}
1132 @string{EWinn-Deen = "Winn-Deen, E."}
1133 @string{NWirth = "Wirth, Niklaus"}
1134 @string{HMWisniewski = "Wisniewski, H.~M."}
1135 @string{CWitt = "Witt, Christian"}
1136 @string{KWolfe = "Wolfe, K."}
1137 @string{TGWolfsberg = "Wolfsberg, T. G."}
1138 @string{PGWolynes = "Wolynes, P. G."}
1139 @string{WPWong = "Wong, Wesley P."}
1140 @string{TWoodage = "Woodage, T."}
1141 @string{GRWoodcock = "Woodcock, Glenna R."}
1142 @string{JRWortman = "Wortman, J. R."}
1143 @string{PEWright = "Wright, Peter E."}
1144 @string{DWu = "Wu, D."}
1145 @string{GAWu = "Wu, Guohong A."}
1146 @string{JWWu = "Wu, Jong-Wuu"}
1147 @string{MWu = "Wu, M."}
1148 @string{YWu = "Wu, Yiming"}
1149 @string{GJLWuite = "Wuite, Gijs J. L."}
1150 @string{KWylie = "Wylie, K."}
1151 @string{JXi = "Xi, Jun"}
1152 @string{AXia = "Xia, A."}
1153 @string{CXiao = "Xiao, C."}
1154 @string{SXiao = "Xiao, Senbo"}
1155 @string{TYada = "Yada, T."}
1156 @string{CYan = "Yan, C."}
1157 @string{MYandell = "Yandell, M."}
1158 @string{GYang = "Yang, Guoliang"}
1159 @string{YYang = "Yang, Yao"}
1160 @string{BAYankner = "Yankner, Bruce A."}
1161 @string{AYao = "Yao, A."}
1162 @string{RYasuda = "Yaduso, Ryohei"}
1163 @string{JYe = "Ye, J."}
1164 @string{RYeh = "Yeh, Richard C."}
1165 @string{RYonescu = "Yonescu, R."}
1166 @string{SYooseph = "Yooseph, S."}
1167 @string{MYoshida = "Yoshida, Masasuke"}
1168 @string{WYu = "Yu, Weichang"}
1169 @string{JMYuan = "Yuan, Jian-Min"}
1170 @string{MYuan = "Yuan, Menglan"}
1171 @string{AZandieh = "Zandieh, A."}
1172 @string{JZaveri = "Zaveri, J."}
1173 @string{KZaveri = "Zaveri, K."}
1174 @string{MZhan = "Zhan, M."}
1175 @string{HZhang = "Zhang, H."}
1176 @string{JZhang = "Zhang, J."}
1177 @string{QZhang = "Zhang, Q."}
1178 @string{WZhang = "Zhang, W."}
1179 @string{YZhang = "Zhang, Yanjie"}
1180 @string{ZZhang = "Zhang, Zongtao"}
1181 @string{JZhao = "Zhao, Jason Ming"}
1182 @string{LZhao = "Zhao, Liming"}
1183 @string{QZhao = "Zhao, Q."}
1184 @string{SZhao = "Zhao, S."}
1185 @string{LZheng = "Zheng, L."}
1186 @string{XHZheng = "Zheng, X. H."}
1187 @string{FZhong = "Zhong, F."}
1188 @string{MZhong = "Zhong, Mingya"}
1189 @string{WZhong = "Zhong, W."}
1190 @string{HXZhou = "Zhou, Huan-Xiang"}
1191 @string{SZhu = "Zhu, S."}
1192 @string{XZhu = "Zhu, X."}
1193 @string{YJZhu = "Zhu, Ying-Jie"}
1194 @string{WZhuang = "Zhuang, Wei"}
1195 @string{JZidar = "Zidar, Jernej"}
1196 @string{JZiegler = "Ziegler, J.G."}
1197 @string{NZinder = "Zinder, N."}
1198 @string{RCZinober = "Zinober, Rebecca C."}
1199 @string{JZlatanova = "Zlatanova, Jordanka"}
1200 @string{PZou = "Zou, Peng"}
1201 @string{GZuccheri = "Zuccheri, Giampaolo"}
1202 @string{RZwanzig = "Zwanzig, R."}
1203 @string{arXiv = "arXiv"}
1204 @string{PGdeGennes = "de Gennes, P. G."}
1205 @string{PJdeJong = "de Jong, P. J."}
1206 @string{NGvanKampen = "van Kampen, N.G."}
1207 @string{NIST:SEMATECH = "{NIST/SEMATECH}"}
1208 @string{EDCola = "{\uppercase{d}}i Cola, Emanuela"}
1210 @inbook{ NIST:chi-square,
1211 crossref = {NIST:ESH},
1212 chapter = {1.3.5.15: Chi-Square Goodness-of-Fit Test},
1216 url = {http://www.itl.nist.gov/div898/handbook/eda/section3/eda35f.htm},
1219 @inbook{ NIST:gumbel,
1220 crossref = {NIST:ESH},
1221 chapter = {1.3.6.6.16: Extreme Value Type {I} Distribution},
1225 url = {http://www.itl.nist.gov/div898/handbook/eda/section3/eda366g.htm},
1229 editor = CCroarkin #" and "# PTobias,
1230 author = NIST:SEMATECH,
1231 title = {e-{H}andbook of Statistical Methods},
1234 publisher = NIST:SEMATECH,
1235 address = {Boulder, Colorado},
1236 url = {http://www.itl.nist.gov/div898/handbook/},
1237 note = {This manual was developed from seed material produced by
1241 @misc{ wikipedia:gumbel,
1242 author = "Wikipedia",
1243 title = "Gumbel distribution --- {W}ikipedia{,} The Free Encyclopedia",
1245 url = "http://en.wikipedia.org/wiki/Gumbel_distribution",
1250 title = "Statistics of Extremes",
1253 address = "New York",
1254 wtk_note = "Find and read",
1257 @misc{ wikipedia:GEV,
1258 author = "Wikipedia",
1259 title = "Generalized extreme value distribution --- {W}ikipedia{,}
1260 The Free Encyclopedia",
1262 url = "http://en.wikipedia.org/wiki/Generalized_extreme_value_distribution",
1265 @misc{ wikipedia:gompertz,
1266 author = "Wikipedia",
1267 title = "Gompertz distribution --- {W}ikipedia{,} The Free Encyclopedia",
1269 url = "http://en.wikipedia.org/wiki/Gompertz_distribution",
1272 @misc{ wikipedia:gumbel-t1,
1273 author = "Wikipedia",
1274 title = "Type-1 Gumbel distribution --- {W}ikipedia{,} The Free
1277 url = "http://en.wikipedia.org/wiki/Type-1_Gumbel_distribution",
1280 @misc{ wikipedia:gumbel-t2,
1281 author = "Wikipedia",
1282 title = "Type-2 Gumbel distribution --- {W}ikipedia{,} The Free
1285 url = "http://en.wikipedia.org/wiki/Type-2_Gumbel_distribution",
1288 @article { allemand03,
1289 author = JFAllemand #" and "# DBensimon #" and "# VCroquette,
1290 title = "Stretching {DNA} and {RNA} to probe their interactions with
1299 keywords = "DNA;DNA-Binding
1300 Proteins;Isomerases;Micromanipulation;Microscopy, Atomic Force;Nucleic
1301 Acid Conformation;Nucleotidyltransferases",
1302 abstract = "When interacting with a single stretched DNA, many proteins
1303 modify its end-to-end distance. This distance can be monitored in real
1304 time using various micromanipulation techniques that were initially
1305 used to determine the elastic properties of bare nucleic acids and
1306 their mechanically induced structural transitions. These methods are
1307 currently being applied to the study of DNA enzymes such as DNA and RNA
1308 polymerases, topoisomerases and structural proteins such as RecA. They
1309 permit the measurement of the probability distributions of the rate,
1310 processivity, on-time, affinity and efficiency for a large variety of
1311 DNA-based molecular motors."
1315 author = RAlon #" and "# EABayer #" and "# MWilchek,
1316 title = "Streptavidin contains an {RYD} sequence which mimics the {RGD}
1317 receptor domain of fibronectin",
1324 pages = "1236--1241",
1326 doi = "10.1016/0006-291X(90)90526-S",
1327 url = "http://dx.doi.org/10.1016/0006-291X(90)90526-S",
1328 keywords = "Amino Acid Sequence;Animals;Bacterial Proteins;Binding
1329 Sites;Cell Line;Cell Membrane;Cricetinae;Fibronectins;Molecular
1330 Sequence Data;Streptavidin",
1331 abstract = "Streptavidin binds at low levels and high affinity to cell
1332 surfaces, the cause of which can be traced to the occurrence of a
1333 sequence containing RYD (Arg-Tyr-Asp) in the protein molecule. This
1334 binding is enhanced in the presence of biotin. Cell-bound streptavidin
1335 can be displaced by fibronectin, as well as by RGD- and RYD-containing
1336 peptides. In addition, streptavidin can displace fibronectin from cell
1337 surfaces. The RYD sequence of streptavidin thus mimics RGD (Arg-Gly-
1338 Asp), the universal recognition domain present in fibronectin and other
1339 adhesion-related molecules. The observed adhesion to cells has no
1340 relevance to biotin-binding since the RYD sequence is not part of the
1341 biotin-binding site of streptavidin. Since the use of streptavidin in
1342 avidin-biotin technology is based on its biotin-binding properties,
1343 researchers are hereby warned against its indiscriminate use in
1344 histochemical and cytochemical studies.",
1345 note = "Biological role of streptavidin."
1348 @article { balsera97,
1349 author = MBalsera #" and "# SStepaniants #" and "# SIzrailev #" and "#
1350 YOono #" and "# KSchulten,
1351 title = "Reconstructing potential energy functions from simulated force-
1352 induced unbinding processes",
1358 pages = "1281--1287",
1360 eprint = "http://www.biophysj.org/cgi/reprint/73/3/1281.pdf",
1361 url = "http://www.biophysj.org/cgi/content/abstract/73/3/1281",
1362 keywords = "Binding Sites;Biopolymers;Kinetics;Ligands;Microscopy, Atomic
1363 Force;Models, Chemical;Molecular Conformation;Protein
1364 Conformation;Proteins;Reproducibility of Results;Stochastic
1365 Processes;Thermodynamics",
1366 abstract = "One-dimensional stochastic models demonstrate that molecular
1367 dynamics simulations of a few nanoseconds can be used to reconstruct
1368 the essential features of the binding potential of macromolecules. This
1369 can be accomplished by inducing the unbinding with the help of external
1370 forces applied to the molecules, and discounting the irreversible work
1371 performed on the system by these forces. The fluctuation-dissipation
1372 theorem sets a fundamental limit on the precision with which the
1373 binding potential can be reconstructed by this method. The uncertainty
1374 in the resulting potential is linearly proportional to the irreversible
1375 component of work performed on the system during the simulation. These
1376 results provide an a priori estimate of the energy barriers observable
1377 in molecular dynamics simulations."
1380 @article { baneyx02,
1381 author = GBaneyx #" and "# LBaugh #" and "# VVogel,
1382 title = "Supramolecular Chemistry And Self-assembly Special Feature:
1383 Fibronectin extension and unfolding within cell matrix fibrils
1384 controlled by cytoskeletal tension",
1389 pages = "5139--5143",
1390 doi = "10.1073/pnas.072650799",
1391 eprint = "http://www.pnas.org/cgi/reprint/99/8/5139.pdf",
1392 url = "http://www.pnas.org/cgi/content/abstract/99/8/5139",
1393 abstract = "Evidence is emerging that mechanical stretching can alter the
1394 functional states of proteins. Fibronectin (Fn) is a large,
1395 extracellular matrix protein that is assembled by cells into elastic
1396 fibrils and subjected to contractile forces. Assembly into fibrils
1397 coincides with expression of biological recognition sites that are
1398 buried in Fn's soluble state. To investigate how supramolecular
1399 assembly of Fn into fibrillar matrix enables cells to mechanically
1400 regulate its structure, we used fluorescence resonance energy transfer
1401 (FRET) as an indicator of Fn conformation in the fibrillar matrix of
1402 NIH 3T3 fibroblasts. Fn was randomly labeled on amine residues with
1403 donor fluorophores and site-specifically labeled on cysteine residues
1404 in modules FnIII7 and FnIII15 with acceptor fluorophores.
1405 Intramolecular FRET was correlated with known structural changes of Fn
1406 in denaturing solution, then applied in cell culture as an indicator of
1407 Fn conformation within the matrix fibrils of NIH 3T3 fibroblasts. Based
1408 on the level of FRET, Fn in many fibrils was stretched by cells so that
1409 its dimer arms were extended and at least one FnIII module unfolded.
1410 When cytoskeletal tension was disrupted using cytochalasin D, FRET
1411 increased, indicating refolding of Fn within fibrils. These results
1412 suggest that cell-generated force is required to maintain Fn in
1413 partially unfolded conformations. The results support a model of Fn
1414 fibril elasticity based on unraveling and refolding of FnIII modules.
1415 We also observed variation of FRET between and along single fibrils,
1416 indicating variation in the degree of unfolding of Fn in fibrils.
1417 Molecular mechanisms by which mechanical force can alter the structure
1418 of Fn, converting tensile forces into biochemical cues, are discussed."
1421 @article { basche01,
1422 author = TBasche #" and "# SNie #" and "# JFernandez,
1423 title = "Single molecules",
1428 pages = "10527--10528",
1429 doi = "10.1073/pnas.191365898",
1430 eprint = "http://www.pnas.org/cgi/reprint/98/19/10527.pdf",
1431 url = "http://www.pnas.org/cgi/content/abstract/98/19/10527",
1432 note = "Mini summary of single-molecule techniques and look to future.
1433 Focuses on AFM, but mentions others."
1436 @article { bechhoefer02,
1437 author = JBechhoefer #" and "# SWilson,
1438 title = "Faster, cheaper, safer optical tweezers for the undergraduate
1447 doi = "10.1119/1.1445403",
1448 url = "http://link.aip.org/link/?AJP/70/393/1",
1449 keywords = "student experiments; safety; radiation pressure; laser beam
1451 note = {Good discussion of the effect of correlation time on
1452 calibration. References work on deconvolving thermal noise from
1453 other noise\citep{cowan98}. Excellent detail on power spectrum
1454 derivation and thermal noise for extremely overdamped
1455 oscillators in Appendix A (references \citet{rief65}), except
1456 that their equation A12 is missing a factor of $1/\pi$. I
1457 pointed this out to John Bechhoefer and he confirmed the
1459 project = "Cantilever Calibration"
1462 @article{ berg-sorensen04,
1463 author = KBergSorensen #" and "# HFlyvbjerg,
1464 title = {Power spectrum analysis for optical tweezers},
1471 url = {http://rsi.aip.org/resource/1/rsinak/v75/i3/p594_s1},
1472 doi = {10.1063/1.1645654},
1474 keywords = {radiation pressure, Brownian motion, spectral analysis,
1475 dielectric bodies, measurement by laser beam, flow measurement},
1476 abstract = {The force exerted by an optical trap on a dielectric
1477 bead in a fluid is often found by fitting a Lorentzian to the
1478 power spectrum of Brownian motion of the bead in the trap. We
1479 present explicit functions of the experimental power spectrum that
1480 give the values of the parameters fitted, including error bars and
1481 correlations, for the best such $\chi^2$ fit in a given frequency
1482 range. We use these functions to determine the information
1483 content of various parts of the power spectrum, and find, at odds
1484 with lore, much information at relatively high frequencies.
1485 Applying the method to real data, we obtain perfect fits and
1486 calibrate tweezers with less than 1\% error when the trapping
1487 force is not too strong. Relatively strong traps have power
1488 spectra that cannot be fitted properly with any Lorentzian, we
1489 find. This underscores the need for better understanding of the
1490 power spectrum than the Lorentzian provides. This is achieved
1491 using old and new theory for Brownian motion in an incompressible
1492 fluid, and new results for a popular photodetection system. The
1493 trap and photodetection system are then calibrated simultaneously
1494 in a manner that makes optical tweezers a tool of precision for
1495 force spectroscopy, local viscometry, and probably other
1499 @article{ berg-sorensen05,
1500 author = KBergSorensen #" and "# HFlyvbjerg,
1501 title = {The colour of thermal noise in classical Brownian motion: a
1502 feasibility study of direct experimental observation},
1510 doi = {10.1088/1367-2630/7/1/038},
1511 url = {http://stacks.iop.org/1367-2630/7/i=1/a=038},
1512 eprint = {http://iopscience.iop.org/1367-2630/7/1/038/pdf/1367-2630_7_1_038.pdf},
1513 abstract = {One hundred years after Einstein modelled Brownian
1514 motion, a central aspect of this motion in incompressible fluids
1515 has not been verified experimentally: the thermal noise that
1516 drives the Brownian particle, is not white, as in Einstein's
1517 simple theory. It is slightly coloured, due to hydrodynamics and
1518 the fluctuation--dissipation theorem. This theoretical result from
1519 the 1970s was prompted by computer simulation results in apparent
1520 violation of Einstein's theory. We discuss how a direct
1521 experimental observation of this colour might be carried out by
1522 using optical tweezers to separate the thermal noise from the
1523 particle's dynamic response to it. Since the thermal noise is
1524 almost white, very good statistics is necessary to resolve its
1525 colour. That requires stable equipment and long recording times,
1526 possibly making this experiment one for the future only. We give
1527 results for experimental requirements and for stochastic errors as
1528 functions of experimental window and measurement time, and discuss
1529 some potential sources of systematic errors.},
1532 @article { bedard08,
1533 author = SBedard #" and "# MMGKrishna #" and "# LMayne #" and "#
1535 title = "Protein folding: Independent unrelated pathways or predetermined
1536 pathway with optional errors.",
1543 pages = "7182--7187",
1545 doi = "10.1073/pnas.0801864105",
1546 eprint = "http://www.pnas.org/content/105/20/7182.full.pdf",
1547 url = "http://www.pnas.org/content/105/20/7182.full",
1548 keywords = "Biochemistry;Guanidine;Kinetics;Micrococcal Nuclease;Models,
1549 Biological;Models, Chemical;Models, Theoretical;Protein
1550 Conformation;Protein Denaturation;Protein Folding;Protein Structure,
1551 Secondary;Proteins;Proteomics;Reproducibility of
1552 Results;Thermodynamics",
1553 abstract = "The observation of heterogeneous protein folding kinetics has
1554 been widely interpreted in terms of multiple independent unrelated
1555 pathways (IUP model), both experimentally and in theoretical
1556 calculations. However, direct structural information on folding
1557 intermediates and their properties now indicates that all of a protein
1558 population folds through essentially the same stepwise pathway,
1559 determined by cooperative native-like foldon units and the way that the
1560 foldons fit together in the native protein. It is essential to decide
1561 between these fundamentally different folding mechanisms. This article
1562 shows, contrary to previous supposition, that the heterogeneous folding
1563 kinetics observed for the staphylococcal nuclease protein (SNase) does
1564 not require alternative parallel pathways. SNase folding kinetics can
1565 be fit equally well by a single predetermined pathway that allows for
1566 optional misfolding errors, which are known to occur ubiquitously in
1567 protein folding. Structural, kinetic, and thermodynamic information for
1568 the folding intermediates and pathways of many proteins is consistent
1569 with the predetermined pathway-optional error (PPOE) model but contrary
1570 to the properties implied in IUP models."
1575 title = "Models for the specific adhesion of cells to cells",
1584 url = "http://www.jstor.org/stable/1746930",
1585 keywords = "Antigen-Antibody Reactions; Cell Adhesion; Cell Membrane;
1586 Chemistry, Physical; Electrophysiology; Enzymes; Glycoproteins;
1587 Kinetics; Ligands; Membrane Proteins; Models, Biological; Receptors,
1589 abstract = "A theoretical framework is proposed for the analysis of
1590 adhesion between cells or of cells to surfaces when the adhesion is
1591 mediated by reversible bonds between specific molecules such as antigen
1592 and antibody, lectin and carbohydrate, or enzyme and substrate. From a
1593 knowledge of the reaction rates for reactants in solution and of their
1594 diffusion constants both in solution and on membranes, it is possible
1595 to estimate reaction rates for membrane-bound reactants. Two models are
1596 developed for predicting the rate of bond formation between cells and
1597 are compared with experiments. The force required to separate two cells
1598 is shown to be greater than the expected electrical forces between
1599 cells, and of the same order of magnitude as the forces required to
1600 pull gangliosides and perhaps some integral membrane proteins out of
1601 the cell membrane.",
1602 note = "The Bell model and a fair bit of cell bonding background.",
1603 project = "sawtooth simulation"
1607 author = DBerk #" and "# EEvans,
1608 title = "Detachment of agglutinin-bonded red blood cells. {III}. Mechanical
1609 analysis for large contact areas",
1617 keywords = "Cell Adhesion;Erythrocyte Membrane;Erythrocytes;Hemagglutinatio
1618 n;Hemagglutinins;Humans;Kinetics;Mathematics;Models,
1619 Biological;Pressure",
1620 abstract = "An experimental method and analysis are introduced which
1621 provide direct quantitation of the strength of adhesive contact for
1622 large agglutinin-bonded regions between macroscopically smooth membrane
1623 capsules (e.g., red blood cells). The approach yields intrinsic
1624 properties for separation of adherent regions independent of mechanical
1625 deformation of the membrane capsules during detachment. Conceptually,
1626 the micromechanical method involves one rigid test-capsule surface (in
1627 the form of a perfect sphere) held fixed by a micropipette and a second
1628 deformable capsule maneuvered with another micropipette to force
1629 contact with the test capsule. Only the test capsule is bound with
1630 agglutinin so that the maximum number of cross-bridges can be formed
1631 without steric interference. Following formation of a large adhesion
1632 region by mechanical impingement, the deformable capsule is detached
1633 from the rigid capsule surface by progressive aspiration into the
1634 micropipette. For the particular case modeled here, the deformable
1635 capsule is assumed to be a red blood cell which is preswollen by slight
1636 osmotic hydration before the test. The caliber of the detachment
1637 pipette is chosen so that the capsule will form a smooth cylindrical
1638 ``piston'' inside the pipette as it is aspirated. Because of the high
1639 flexibility of the membrane, the capsule naturally seals against the
1640 tube wall by pressurization even though it does not adhere to the
1641 glass. This arrangement maintains perfect axial symmetry and prevents
1642 the membrane from folding or buckling. Hence, it is possible to
1643 rigorously analyze the mechanics of deformation of the cell body to
1644 obtain the crucial ``transducer'' relation between pipette suction
1645 force and the membrane tension applied directly at the perimeter of the
1646 adhesive contact. Further, the geometry of the cell throughout the
1647 detachment process is predicted which provides accurate specification
1648 of the contact angle theta c between surfaces at the perimeter of the
1649 contact. A full analysis of red cell capsules during detachment has
1650 been carried out; however, it is shown that the shear rigidity of the
1651 red cell membrane can often be neglected so that the red cell can be
1652 treated as if it were an underfilled lipid bilayer vesicle. From the
1653 analysis, the mechanical leverage factor (1-cos theta c) and the
1654 membrane tension at the contact perimeter are determined to provide a
1655 complete description of the local mechanics of membrane separation as
1656 functions of large-scale experimental variables (e.g., suction force,
1657 contact diameter, overall cell length).(ABSTRACT TRUNCATED AT 400
1662 author = RBest #" and "# SFowler #" and "# JTocaHerrera #" and "# JClarke,
1663 title = "A simple method for probing the mechanical unfolding pathway of
1664 proteins in detail",
1669 pages = "12143--12148",
1670 doi = "10.1073/pnas.192351899",
1671 eprint = "http://www.pnas.org/cgi/reprint/99/19/12143.pdf",
1672 url = "http://www.pnas.org/cgi/content/abstract/99/19/12143",
1673 abstract = "Atomic force microscopy is an exciting new single-molecule
1674 technique to add to the toolbox of protein (un)folding methods.
1675 However, detailed analysis of the unfolding of proteins on application
1676 of force has, to date, relied on protein molecular dynamics simulations
1677 or a qualitative interpretation of mutant data. Here we describe how
1678 protein engineering {Phi} value analysis can be adapted to characterize
1679 the transition states for mechanical unfolding of proteins. Single-
1680 molecule studies also have an advantage over bulk experiments, in that
1681 partial {Phi} values arising from partial structure in the transition
1682 state can be clearly distinguished from those averaged over alternate
1683 pathways. We show that unfolding rate constants derived in the standard
1684 way by using Monte Carlo simulations are not reliable because of the
1685 errors involved. However, it is possible to circumvent these problems,
1686 providing the unfolding mechanism is not changed by mutation, either by
1687 a modification of the Monte Carlo procedure or by comparing mutant and
1688 wild-type data directly. The applicability of the method is tested on
1689 simulated data sets and experimental data for mutants of titin I27.",
1690 note = "Points out order-of-magnitude errors in $k_{u0}$ estimation from
1691 fitting Monte Carlo simulations."
1695 author = RBest #" and "# GHummer,
1696 title = "Protein folding kinetics under force from molecular simulation.",
1703 pages = "3706--3707",
1705 doi = "10.1021/ja0762691",
1706 keywords = "Computer Simulation;Kinetics;Models, Chemical;Protein
1707 Folding;Stress, Mechanical;Ubiquitin",
1708 abstract = "Despite a large number of studies on the mechanical unfolding
1709 of proteins, there are still relatively few successful attempts to
1710 refold proteins in the presence of a stretching force. We explore
1711 refolding kinetics under force using simulations of a coarse-grained
1712 model of ubiquitin. The effects of force on the folding kinetics can be
1713 fitted by a one-dimensional Kramers theory of diffusive barrier
1714 crossing, resulting in physically meaningful parameters for the height
1715 and location of the folding activation barrier. By comparing parameters
1716 obtained from pulling in different directions, we find that the
1717 unfolded state plays a dominant role in the refolding kinetics. Our
1718 findings explain why refolding becomes very slow at even moderate
1719 pulling forces and suggest how it could be practically observed in
1720 experiments at higher forces."
1724 author = RBest #" and "# EPaci #" and "# GHummer #" and "# OKDudko,
1725 title = "Pulling direction as a reaction coordinate for the mechanical
1726 unfolding of single molecules.",
1733 pages = "5968--5976",
1735 doi = "10.1021/jp075955j",
1736 keywords = "Computer Simulation;Kinetics;Models, Molecular;Protein
1737 Folding;Protein Structure, Tertiary;Time Factors;Ubiquitin",
1738 abstract = "The folding and unfolding kinetics of single molecules, such as
1739 proteins or nucleic acids, can be explored by mechanical pulling
1740 experiments. Determining intrinsic kinetic information, at zero
1741 stretching force, usually requires an extrapolation by fitting a
1742 theoretical model. Here, we apply a recent theoretical approach
1743 describing molecular rupture in the presence of force to unfolding
1744 kinetic data obtained from coarse-grained simulations of ubiquitin.
1745 Unfolding rates calculated from simulations over a broad range of
1746 stretching forces, for different pulling directions, reveal a
1747 remarkable ``turnover'' from a force-independent process at low force
1748 to a force-dependent process at high force, akin to the ``roll-over''
1749 in unfolding rates sometimes seen in studies using chemical denaturant.
1750 While such a turnover in rates is unexpected in one dimension, we
1751 demonstrate that it can occur for dynamics in just two dimensions. We
1752 relate the turnover to the quality of the pulling direction as a
1753 reaction coordinate for the intrinsic folding mechanism. A novel
1754 pulling direction, designed to be the most relevant to the intrinsic
1755 folding pathway, results in the smallest turnover. Our results are in
1756 accord with protein engineering experiments and simulations which
1757 indicate that the unfolding mechanism at high force can differ from the
1758 intrinsic mechanism. The apparent similarity between extrapolated and
1759 intrinsic rates in experiments, unexpected for different unfolding
1760 barriers, can be explained if the turnover occurs at low forces."
1763 @article { borgia08,
1764 author = Borgia #" and "# Williams #" and "# Clarke,
1765 title = "Single-Molecule Studies of Protein Folding",
1773 doi = "10.1146/annurev.biochem.77.060706.093102",
1774 eprint = "http://arjournals.annualreviews.org/doi/pdf/10.1146/annurev.bioch
1775 em.77.060706.093102",
1776 url = "http://arjournals.annualreviews.org/doi/abs/10.1146/annurev.biochem.
1778 abstract = "Although protein-folding studies began several decades ago, it
1779 is only recently that the tools to analyze protein folding at the
1780 single-molecule level have been developed. Advances in single-molecule
1781 fluorescence and force spectroscopy techniques allow investigation of
1782 the folding and dynamics of single protein molecules, both at
1783 equilibrium and as they fold and unfold. The experiments are far from
1784 simple, however, both in execution and in interpretation of the
1785 results. In this review, we discuss some of the highlights of the work
1786 so far and concentrate on cases where comparisons with the classical
1787 experiments can be made. We conclude that, although there have been
1788 relatively few startling insights from single-molecule studies, the
1789 rapid progress that has been made suggests that these experiments have
1790 significant potential to advance our understanding of protein folding.
1791 In particular, new techniques offer the possibility to explore regions
1792 of the energy landscape that are inaccessible to classical ensemble
1793 measurements and, perhaps, to observe rare events undetectable by other
1797 @article { braverman08,
1798 author = EBraverman #" and "# RMamdani,
1799 title = "Continuous versus pulse harvesting for population models in
1800 constant and variable environment",
1804 journal = JMathBiol,
1809 doi = "10.1007/s00285-008-0169-z",
1811 "http://www.springerlink.com/content/a1m23v50201m2401/fulltext.pdf",
1812 url = "http://www.springerlink.com/content/a1m23v50201m2401/",
1813 abstract = "We consider both autonomous and nonautonomous population models
1814 subject to either impulsive or continuous harvesting. It is
1815 demonstrated in the paper that the impulsive strategy can be as good as
1816 the continuous one, but cannot outperform it. We introduce a model,
1817 where certain harm to the population is incorporated in each harvesting
1818 event, and study it for the logistic and the Gompertz laws of growth.
1819 In this case, impulsive harvesting is not only the optimal strategy but
1820 is the only possible one.",
1821 note = "An example of non-exponential Gomperz law."
1824 @article { brochard-wyart99,
1825 author = FBrochard-Wyart #" and "# ABuguin #" and "# PGdeGennes,
1826 title = "Dynamics of taut {DNA} chains",
1833 "http://www.iop.org/EJ/article/0295-5075/47/2/171/epl_47_2_171.pdf",
1834 url = "http://stacks.iop.org/0295-5075/47/171",
1835 abstract = {We discuss the dynamics of stretched DNA chains, subjected to a
1836 tension force f, in a "taut" regime where ph = flp0/kBT $>$ 1 (lp0
1837 being the unperturbed persistence length). We deal with two variables:
1838 the local transverse displacements u, and the longitudinal position of
1839 a monomer u[?]. The variables u and u[?] follow two distinct Rouse
1840 equations, with diffusion coefficients D[?] = f/e (where e is the
1841 solvent viscosity) and D[?] = 4ph1/2D[?]. We apply these ideas to a
1842 discussion of various transient regimes.},
1843 note = "Theory for weakly bending relaxation modes in WLCs and FJCs."
1846 @article { brockwell02,
1847 author = DJBrockwell #" and "# GSBeddard #" and "# JClarkson #" and "#
1848 RCZinober #" and "# AWBlake #" and "# JTrinick #" and "# PDOlmsted #"
1849 and "# DASmith #" and "# SERadford,
1850 title = "The effect of core destabilization on the mechanical resistance of
1859 doi = "10.1016/S0006-3495(02)75182-5",
1860 eprint = "http://www.biophysj.org/cgi/reprint/83/1/458.pdf",
1861 url = "http://www.biophysj.org/cgi/content/abstract/83/1/458",
1862 keywords = "Amino Acid Sequence; Dose-Response Relationship, Drug;
1863 Kinetics; Magnetic Resonance Spectroscopy; Models, Molecular; Molecular
1864 Sequence Data; Monte Carlo Method; Muscle Proteins; Mutation; Peptide
1865 Fragments; Protein Denaturation; Protein Folding; Protein Kinases;
1866 Protein Structure, Secondary; Protein Structure, Tertiary; Proteins;
1868 abstract = "It is still unclear whether mechanical unfolding probes the
1869 same pathways as chemical denaturation. To address this point, we have
1870 constructed a concatamer of five mutant I27 domains (denoted (I27)(5)*)
1871 and used it for mechanical unfolding studies. This protein consists of
1872 four copies of the mutant C47S, C63S I27 and a single copy of C63S I27.
1873 These mutations severely destabilize I27 (DeltaDeltaG(UN) = 8.7 and
1874 17.9 kJ mol(-1) for C63S I27 and C47S, C63S I27, respectively). Both
1875 mutations maintain the hydrogen bond network between the A' and G
1876 strands postulated to be the major region of mechanical resistance for
1877 I27. Measuring the speed dependence of the force required to unfold
1878 (I27)(5)* in triplicate using the atomic force microscope allowed a
1879 reliable assessment of the intrinsic unfolding rate constant of the
1880 protein to be obtained (2.0 x 10(-3) s(-1)). The rate constant of
1881 unfolding measured by chemical denaturation is over fivefold faster
1882 (1.1 x 10(-2) s(-1)), suggesting that these techniques probe different
1883 unfolding pathways. Also, by comparing the parameters obtained from the
1884 mechanical unfolding of a wild-type I27 concatamer with that of
1885 (I27)(5)*, we show that although the observed forces are considerably
1886 lower, core destabilization has little effect on determining the
1887 mechanical sensitivity of this domain."
1890 @article { brockwell03,
1891 author = DJBrockwell #" and "# EPaci #" and "# RCZinober #" and "#
1892 GSBeddard #" and "# PDOlmsted #" and "# DASmith #" and "# RNPerham #"
1894 title = "Pulling geometry defines the mechanical resistance of a beta-sheet
1904 doi = "10.1038/nsb968",
1905 eprint = "http://www.nature.com/nsmb/journal/v10/n9/pdf/nsb968.pdf",
1906 url = "http://www.nature.com/nsmb/journal/v10/n9/abs/nsb968.html",
1907 keywords = "Anisotropy;Escherichia coli;Kinetics;Models, Molecular;Monte
1908 Carlo Method;Protein Folding;Protein Structure, Secondary;Protein
1909 Structure, Tertiary;Proteins;Software;Temperature;Thermodynamics",
1910 abstract = "Proteins show diverse responses when placed under mechanical
1911 stress. The molecular origins of their differing mechanical resistance
1912 are still unclear, although the orientation of secondary structural
1913 elements relative to the applied force vector is thought to have an
1914 important function. Here, by using a method of protein immobilization
1915 that allows force to be applied to the same all-beta protein, E2lip3,
1916 in two different directions, we show that the energy landscape for
1917 mechanical unfolding is markedly anisotropic. These results, in
1918 combination with molecular dynamics (MD) simulations, reveal that the
1919 unfolding pathway depends on the pulling geometry and is associated
1920 with unfolding forces that differ by an order of magnitude. Thus, the
1921 mechanical resistance of a protein is not dictated solely by amino acid
1922 sequence, topology or unfolding rate constant, but depends critically
1923 on the direction of the applied extension.",
1924 note = "Another scaffold effect paper.",
1927 @article { brower-toland02,
1928 author = BDBrowerToland #" and "# CSmith #" and "# RYeh #" and "# JLis #"
1929 and "# CPeterson #" and "# MDWang,
1930 title = "From the Cover: Mechanical disruption of individual nucleosomes
1931 reveals a reversible multistage release of {DNA}",
1936 pages = "1960--1965",
1937 doi = "10.1073/pnas.022638399",
1938 eprint = "http://www.pnas.org/cgi/reprint/99/4/1960.pdf",
1939 url = "http://www.pnas.org/cgi/content/abstract/99/4/1960",
1940 abstract = "The dynamic structure of individual nucleosomes was examined by
1941 stretching nucleosomal arrays with a feedback-enhanced optical trap.
1942 Forced disassembly of each nucleosome occurred in three stages.
1943 Analysis of the data using a simple worm-like chain model yields 76 bp
1944 of DNA released from the histone core at low stretching force.
1945 Subsequently, 80 bp are released at higher forces in two stages: full
1946 extension of DNA with histones bound, followed by detachment of
1947 histones. When arrays were relaxed before the dissociated state was
1948 reached, nucleosomes were able to reassemble and to repeat the
1949 disassembly process. The kinetic parameters for nucleosome disassembly
1950 also have been determined."
1953 @article { bryngelson87,
1954 author = JDBryngelson #" and "# PGWolynes,
1955 title = "Spin glasses and the statistical mechanics of protein folding",
1961 pages = "7524--7528",
1963 keywords = "Kinetics; Mathematics; Models, Theoretical; Protein
1964 Conformation; Proteins; Stochastic Processes",
1965 abstract = "The theory of spin glasses was used to study a simple model of
1966 protein folding. The phase diagram of the model was calculated, and the
1967 results of dynamics calculations are briefly reported. The relation of
1968 these results to folding experiments, the relation of these hypotheses
1969 to previous protein folding theories, and the implication of these
1970 hypotheses for protein folding prediction schemes are discussed.",
1971 note = "Seminal protein folding via energy landscape paper."
1974 @article { bryngelson95,
1975 author = JDBryngelson #" and "# JNOnuchic #" and "# NDSocci #" and "#
1977 title = "Funnels, pathways, and the energy landscape of protein folding: a
1986 doi = "10.1002/prot.340210302",
1987 keywords = "Amino Acid Sequence; Chemistry, Physical; Computer Simulation;
1988 Data Interpretation, Statistical; Kinetics; Models, Chemical; Molecular
1989 Sequence Data; Protein Biosynthesis; Protein Conformation; Protein
1990 Folding; Proteins; Thermodynamics",
1991 abstract = "The understanding, and even the description of protein folding
1992 is impeded by the complexity of the process. Much of this complexity
1993 can be described and understood by taking a statistical approach to the
1994 energetics of protein conformation, that is, to the energy landscape.
1995 The statistical energy landscape approach explains when and why unique
1996 behaviors, such as specific folding pathways, occur in some proteins
1997 and more generally explains the distinction between folding processes
1998 common to all sequences and those peculiar to individual sequences.
1999 This approach also gives new, quantitative insights into the
2000 interpretation of experiments and simulations of protein folding
2001 thermodynamics and kinetics. Specifically, the picture provides simple
2002 explanations for folding as a two-state first-order phase transition,
2003 for the origin of metastable collapsed unfolded states and for the
2004 curved Arrhenius plots observed in both laboratory experiments and
2005 discrete lattice simulations. The relation of these quantitative ideas
2006 to folding pathways, to uniexponential vs. multiexponential behavior in
2007 protein folding experiments and to the effect of mutations on folding
2008 is also discussed. The success of energy landscape ideas in protein
2009 structure prediction is also described. The use of the energy landscape
2010 approach for analyzing data is illustrated with a quantitative analysis
2011 of some recent simulations, and a qualitative analysis of experiments
2012 on the folding of three proteins. The work unifies several previously
2013 proposed ideas concerning the mechanism protein folding and delimits
2014 the regions of validity of these ideas under different thermodynamic
2018 @article { bullard06,
2019 author = BBullard #" and "# TGarcia #" and "# VBenes #" and "# MLeake #"
2020 and "# WALinke #" and "# AOberhauser,
2021 title = "The molecular elasticity of the insect flight muscle proteins
2022 projectin and kettin",
2027 pages = "4451--4456",
2028 doi = "10.1073/pnas.0509016103",
2029 eprint = "http://www.pnas.org/cgi/reprint/103/12/4451.pdf",
2030 url = "http://www.pnas.org/cgi/content/abstract/103/12/4451",
2031 abstract = "Projectin and kettin are titin-like proteins mainly responsible
2032 for the high passive stiffness of insect indirect flight muscles, which
2033 is needed to generate oscillatory work during flight. Here we report
2034 the mechanical properties of kettin and projectin by single-molecule
2035 force spectroscopy. Force-extension and force-clamp curves obtained
2036 from Lethocerus projectin and Drosophila recombinant projectin or
2037 kettin fragments revealed that fibronectin type III domains in
2038 projectin are mechanically weaker (unfolding force, Fu {approx} 50-150
2039 pN) than Ig-domains (Fu {approx} 150-250 pN). Among Ig domains in
2040 Sls/kettin, the domains near the N terminus are less stable than those
2041 near the C terminus. Projectin domains refolded very fast [85% at 15
2042 s-1 (25{degrees}C)] and even under high forces (15-30 pN). Temperature
2043 affected the unfolding forces with a Q10 of 1.3, whereas the refolding
2044 speed had a Q10 of 2-3, probably reflecting the cooperative nature of
2045 the folding mechanism. High bending rigidities of projectin and kettin
2046 indicated that straightening the proteins requires low forces. Our
2047 results suggest that titin-like proteins in indirect flight muscles
2048 could function according to a folding-based-spring mechanism."
2051 @article { bustamante08,
2052 author = CBustamante,
2053 title = "In singulo Biochemistry: When Less Is More",
2059 doi = "10.1146/annurev.biochem.012108.120952",
2060 eprint = "http://arjournals.annualreviews.org/doi/pdf/10.1146/annurev.bioch
2062 url = "http://arjournals.annualreviews.org/doi/abs/10.1146/annurev.biochem.
2064 abstract = "It has been over one-and-a-half decades since methods of
2065 single-molecule detection and manipulation were first introduced in
2066 biochemical research. Since then, the application of these methods to
2067 an expanding variety of problems has grown at a vertiginous pace. While
2068 initially many of these experiments led more to confirmatory results
2069 than to new discoveries, today single-molecule methods are often the
2070 methods of choice to establish new mechanism-based results in
2071 biochemical research. Throughout this process, improvements in the
2072 sensitivity, versatility, and both spatial and temporal resolution of
2073 these techniques has occurred hand in hand with their applications. We
2074 discuss here some of the advantages of single-molecule methods over
2075 their bulk counterparts and argue that these advantages should help
2076 establish them as essential tools in the technical arsenal of the
2080 @article { bustamante94,
2081 author = CBustamante #" and "# JFMarko #" and "# EDSiggia #" and "# SSmith,
2082 title = "Entropic elasticity of lambda-phage {DNA}",
2089 pages = "1599--1600",
2091 doi = "10.1126/science.8079175",
2092 eprint = "http://www.sciencemag.org/cgi/reprint/265/5178/1599.pdf",
2093 url = "http://www.sciencemag.org/cgi/content/abstract/265/5178/1599",
2094 keywords = "Bacteriophage lambda; DNA, Viral; Least-Squares Analysis;
2096 note = "WLC interpolation formula."
2099 @article { bustanji03,
2100 author = YBustanji #" and "# CArciola #" and "# MConti #" and "# EMandello
2101 #" and "# LMontanaro #" and "# BSamori,
2102 title = "Dynamics of the interaction between a fibronectin molecule and a
2103 living bacterium under mechanical force",
2108 pages = "13292--13297",
2109 doi = "10.1073/pnas.1735343100",
2110 eprint = "http://www.pnas.org/cgi/reprint/100/23/13292.pdf",
2111 url = "http://www.pnas.org/cgi/content/abstract/100/23/13292",
2112 abstract = "Fibronectin (Fn) is an important mediator of bacterial
2113 invasions and of persistent infections like that of Staphylococcus
2114 epidermis. Similar to many other types of cell-protein adhesion, the
2115 binding between Fn and S. epidermidis takes place under physiological
2116 shear rates. We investigated the dynamics of the interaction between
2117 individual living S. epidermidis cells and single Fn molecules under
2118 mechanical force by using the scanning force microscope. The mechanical
2119 strength of this interaction and the binding site in the Fn molecule
2120 were determined. The energy landscape of the binding/unbinding process
2121 was mapped, and the force spectrum and the association and dissociation
2122 rate constants of the binding pair were measured. The interaction
2123 between S. epidermidis cells and Fn molecules is compared with those of
2124 two other protein/ligand pairs known to mediate different dynamic
2125 states of adhesion of cells under a hydrodynamic flow: the firm
2126 adhesion mediated by biotin/avidin interactions, and the rolling
2127 adhesion, mediated by L-selectin/P-selectin glycoprotein ligand-1
2128 interactions. The inner barrier in the energy landscape of the Fn case
2129 characterizes a high-energy binding mode that can sustain larger
2130 deformations and for significantly longer times than the correspondent
2131 high-strength L-selectin/P-selectin glycoprotein ligand-1 binding mode.
2132 The association kinetics of the former interaction is much slower to
2133 settle than the latter. On this basis, the observations made at the
2134 macroscopic scale by other authors of a strong lability of the
2135 bacterial adhesions mediated by Fn under high turbulent flow are
2136 rationalized at the molecular level."
2140 author = YMartin #" and "# CCWilliams #" and "# HKWickramasinghe,
2141 title = {Atomic force microscope---force mapping and profiling on a
2149 pages = {4723--4729},
2151 issn_online = "1089-7550",
2152 doi = {10.1063/1.338807},
2153 url = {http://jap.aip.org/resource/1/japiau/v61/i10/p4723_s1},
2155 abstract = {A modified version of the atomic force microscope is
2156 introduced that enables a precise measurement of the force between
2157 a tip and a sample over a tip-sample distance range of 30--150
2158 \AA. As an application, the force signal is used to maintain the
2159 tip-sample spacing constant, so that profiling can be achieved
2160 with a spatial resolution of 50 \AA. A second scheme allows the
2161 simultaneous measurement of force and surface profile; this scheme
2162 has been used to obtain material-dependent information from
2163 surfaces of electronic materials.},
2167 author = HJButt #" and "# MJaschke,
2168 title = "Calculation of thermal noise in atomic force microscopy",
2174 doi = "10.1088/0957-4484/6/1/001",
2175 url = "http://stacks.iop.org/0957-4484/6/1",
2176 abstract = "Thermal fluctuations of the cantilever are a fundamental source
2177 of noise in atomic force microscopy. We calculated thermal noise using
2178 the equipartition theorem and considering all possible vibration modes
2179 of the cantilever. The measurable amplitude of thermal noise depends on
2180 the temperature, the spring constant K of the cantilever and on the
2181 method by which the cantilever defletion is detected. If the deflection
2182 is measured directly, e.g. with an interferometer or a scanning
2183 tunneling microscope, the thermal noise of a cantilever with a free end
2184 can be calculated from square root kT/K. If the end of the cantilever
2185 is supported by a hard surface no thermal fluctuations of the
2186 deflection are possible. If the optical lever technique is applied to
2187 measure the deflection, the thermal noise of a cantilever with a free
2188 end is square root 4kT/3K. When the cantilever is supported thermal
2189 noise decreases to square root kT/3K, but it does not vanish.",
2190 note = "Corrections to basic $kx^2 = kB T$ due to higher order modes in
2191 rectangular cantilevers.",
2192 project = "Cantilever Calibration"
2195 @article{ jaschke95,
2196 author = MJaschke #" and "# HJButt,
2197 title = {Height calibration of optical lever atomic force
2198 microscopes by simple laser interferometry},
2203 pages = {1258--1259},
2205 url = {http://rsi.aip.org/resource/1/rsinak/v66/i2/p1258_s1},
2206 doi = {10.1063/1.1146018},
2208 keywords = {atomic force microscopy;calibration;interferometry;laser
2209 beam applications;mirrors;spatial resolution},
2210 abstract = {A new and simple interferometric method for height
2211 calibration of AFM piezo scanners is presented. Except for a small
2212 mirror no additional equipment is required since the fixed
2213 wavelength of the laser diode is used as a calibration
2214 standard. The calibration is appliable in the range between
2215 several ten nm and several $\mu$m. Besides vertical calibration
2216 many problems of piezo elements like hysteresis, nonlinearity,
2217 creep, derating, etc. and their dependence on scan parameters or
2218 temperature can be investigated.},
2222 author = YCao #" and "# MBalamurali #" and "# DSharma #" and "# HLi,
2223 title = "A functional single-molecule binding assay via force spectroscopy",
2228 pages = "15677--15681",
2229 doi = "10.1073/pnas.0705367104",
2230 eprint = "http://www.pnas.org/cgi/reprint/104/40/15677.pdf",
2231 url = "http://www.pnas.org/cgi/content/abstract/104/40/15677",
2232 abstract = "Protein-ligand interactions, including protein-protein
2233 interactions, are ubiquitously essential in biological processes and
2234 also have important applications in biotechnology. A wide range of
2235 methodologies have been developed for quantitative analysis of protein-
2236 ligand interactions. However, most of them do not report direct
2237 functional/structural consequence of ligand binding. Instead they only
2238 detect the change of physical properties, such as fluorescence and
2239 refractive index, because of the colocalization of protein and ligand,
2240 and are susceptible to false positives. Thus, important information
2241 about the functional state of proteinligand complexes cannot be
2242 obtained directly. Here we report a functional single-molecule binding
2243 assay that uses force spectroscopy to directly probe the functional
2244 consequence of ligand binding and report the functional state of
2245 protein-ligand complexes. As a proof of principle, we used protein G
2246 and the Fc fragment of IgG as a model system in this study. Binding of
2247 Fc to protein G does not induce major structural changes in protein G
2248 but results in significant enhancement of its mechanical stability.
2249 Using mechanical stability of protein G as an intrinsic functional
2250 reporter, we directly distinguished and quantified Fc-bound and Fc-free
2251 forms of protein G on a single-molecule basis and accurately determined
2252 their dissociation constant. This single-molecule functional binding
2253 assay is label-free, nearly background-free, and can detect functional
2254 heterogeneity, if any, among proteinligand interactions. This
2255 methodology opens up avenues for studying protein-ligand interactions
2256 in a functional context, and we anticipate that it will find broad
2257 application in diverse protein-ligand systems."
2261 author = PCarl #" and "# CKwok #" and "# GManderson #" and "# DSpeicher #"
2263 title = "Forced unfolding modulated by disulfide bonds in the Ig domains of
2264 a cell adhesion molecule",
2269 pages = "1565--1570",
2270 doi = "10.1073/pnas.031409698",
2271 eprint = "http://www.pnas.org/cgi/reprint/98/4/1565.pdf",
2272 url = "http://www.pnas.org/cgi/content/abstract/98/4/1565",
2276 @article { carrion-vazquez00,
2277 author = MCarrionVazquez #" and "# AOberhauser #" and "# TEFisher #" and "#
2278 PMarszalek #" and "# HLi #" and "# JFernandez,
2279 title = "Mechanical design of proteins studied by single-molecule force
2280 spectroscopy and protein engineering",
2286 doi = "10.1016/S0079-6107(00)00017-1",
2288 eprint = "http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1302160&blo
2290 url = "http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1302160",
2291 keywords = "Elasticity;Hydrogen Bonding;Microscopy, Atomic Force;Protein
2292 Denaturation;Protein Engineering;Protein Folding;Recombinant
2293 Proteins;Signal Processing, Computer-Assisted",
2294 abstract = "Mechanical unfolding and refolding may regulate the molecular
2295 elasticity of modular proteins with mechanical functions. The
2296 development of the atomic force microscopy (AFM) has recently enabled
2297 the dynamic measurement of these processes at the single-molecule
2298 level. Protein engineering techniques allow the construction of
2299 homomeric polyproteins for the precise analysis of the mechanical
2300 unfolding of single domains. alpha-Helical domains are mechanically
2301 compliant, whereas beta-sandwich domains, particularly those that
2302 resist unfolding with backbone hydrogen bonds between strands
2303 perpendicular to the applied force, are more stable and appear
2304 frequently in proteins subject to mechanical forces. The mechanical
2305 stability of a domain seems to be determined by its hydrogen bonding
2306 pattern and is correlated with its kinetic stability rather than its
2307 thermodynamic stability. Force spectroscopy using AFM promises to
2308 elucidate the dynamic mechanical properties of a wide variety of
2309 proteins at the single molecule level and provide an important
2310 complement to other structural and dynamic techniques (e.g., X-ray
2311 crystallography, NMR spectroscopy, patch-clamp).",
2312 note = {Surface contact \fref{figure}{2} is a modified version of
2313 \xref{baljon96}{figure}{1}. They are both good pictures for
2314 explaining that the tip's radius of curvature ($\sim 20\U{nm}$) is
2315 larger than the I27 domains\citet{improta96} ($\sim 2\U{nm}$).},
2318 @article { carrion-vazquez03,
2319 author = MCarrionVazquez #" and "# HLi #" and "# HLu #" and "# PMarszalek
2320 #" and "# AOberhauser #" and "# JFernandez,
2321 title = "The mechanical stability of ubiquitin is linkage dependent",
2330 doi = "10.1038/nsb965",
2331 eprint = "http://www.nature.com/nsmb/journal/v10/n9/pdf/nsb965.pdf",
2332 url = "http://www.nature.com/nsmb/journal/v10/n9/abs/nsb965.html",
2333 keywords = "Humans;Hydrogen Bonding;Kinetics;Lysine;Microscopy, Atomic
2334 Force;Models, Molecular;Polyubiquitin;Protein Binding;Protein
2335 Folding;Protein Structure, Tertiary;Ubiquitin",
2336 abstract = "Ubiquitin chains are formed through the action of a set of
2337 enzymes that covalently link ubiquitin either through peptide bonds or
2338 through isopeptide bonds between their C terminus and any of four
2339 lysine residues. These naturally occurring polyproteins allow one to
2340 study the mechanical stability of a protein, when force is applied
2341 through different linkages. Here we used single-molecule force
2342 spectroscopy techniques to examine the mechanical stability of
2343 N-C-linked and Lys48-C-linked ubiquitin chains. We combined these
2344 experiments with steered molecular dynamics (SMD) simulations and found
2345 that the mechanical stability and unfolding pathway of ubiquitin
2346 strongly depend on the linkage through which the mechanical force is
2347 applied to the protein. Hence, a protein that is otherwise very stable
2348 may be easily unfolded by a relatively weak mechanical force applied
2349 through the right linkage. This may be a widespread mechanism in
2350 biological systems."
2353 @article { carrion-vazquez99a,
2354 author = MCarrionVazquez #" and "# PMarszalek #" and "# AOberhauser #" and
2356 title = "Atomic force microscopy captures length phenotypes in single
2362 pages = "11288--11292",
2363 doi = "10.1073/pnas.96.20.11288",
2364 eprint = "http://www.pnas.org/cgi/reprint/96/20/11288.pdf",
2365 url = "http://www.pnas.org/cgi/content/abstract/96/20/11288",
2369 @article { carrion-vazquez99b,
2370 author = MCarrionVazquez #" and "# AOberhauser #" and "# SFowler #" and "#
2371 PMarszalek #" and "# SBroedel #" and "# JClarke #" and "# JFernandez,
2372 title = "Mechanical and chemical unfolding of a single protein: A
2378 pages = "3694--3699",
2379 doi = "10.1073/pnas.96.7.3694",
2380 eprint = "http://www.pnas.org/cgi/reprint/96/7/3694.pdf",
2381 url = "http://www.pnas.org/cgi/content/abstract/96/7/3694"
2385 author = CLChyan #" and "# FCLin #" and "# HPeng #" and "# JMYuan #" and "#
2386 CHChang #" and "# SHLin #" and "# GYang,
2387 title = "Reversible mechanical unfolding of single ubiquitin molecules",
2391 address = "Department of Chemistry, National Dong Hwa University,
2396 pages = "3995--4006",
2398 doi = "10.1529/biophysj.104.042754",
2399 eprint = "http://download.cell.com/biophysj/pdf/PIIS0006349504738643.pdf",
2400 url = "http://www.cell.com/biophysj/abstract/S0006-3495(04)73864-3",
2402 keywords = "Computer
2403 Simulation;Elasticity;Mechanics;Micromanipulation;Microscopy, Atomic
2404 Force;Models, Chemical;Models, Molecular;Protein Conformation;Protein
2405 Denaturation;Protein Folding;Stress, Mechanical;Structure-Activity
2406 Relationship;Ubiquitin",
2407 abstract = "Single-molecule manipulation techniques have enabled the
2408 characterization of the unfolding and refolding process of individual
2409 protein molecules, using mechanical forces to initiate the unfolding
2410 transition. Experimental and computational results following this
2411 approach have shed new light on the mechanisms of the mechanical
2412 functions of proteins involved in several cellular processes, as well
2413 as revealed new information on the protein folding/unfolding free-
2414 energy landscapes. To investigate how protein molecules of different
2415 folds respond to a stretching force, and to elucidate the effects of
2416 solution conditions on the mechanical stability of a protein, we
2417 synthesized polymers of the protein ubiquitin and characterized the
2418 force-induced unfolding and refolding of individual ubiquitin molecules
2419 using an atomic-force-microscope-based single-molecule manipulation
2420 technique. The ubiquitin molecule was highly resistant to a stretching
2421 force, and the mechanical unfolding process was reversible. A model
2422 calculation based on the hydrogen-bonding pattern in the native
2423 structure was performed to explain the origin of this high mechanical
2424 stability. Furthermore, pH effects were studied and it was found that
2425 the forces required to unfold the protein remained constant within a pH
2426 range around the neutral value, and forces decreased as the solution pH
2427 was lowered to more acidic values.",
2428 note = "includes pH effects",
2431 @article { ciccotti86,
2432 author = GCiccotti #" and "# JPRyckaert,
2433 title = "Molecular dynamics simulation of rigid molecules",
2440 doi = "10.1016/0167-7977(86)90022-5",
2441 url = "http://dx.doi.org/10.1016/0167-7977(86)90022-5",
2442 note = "I haven't read this, but it looks like a nice review of MD with
2446 @article { claverie01,
2447 author = JMClaverie,
2448 title = "Gene number. What if there are only 30,000 human genes?",
2455 pages = "1255--1257",
2457 url = "http://www.sciencemag.org/cgi/content/full/291/5507/1255",
2458 keywords = "Animals;Computational Biology;Drug Industry;Expressed Sequence
2459 Tags;Gene Expression;Gene Expression Regulation;Genes;Genetic
2460 Techniques;Genome, Human;Genomics;Human Genome Project;Humans;Models,
2461 Genetic;Polymorphism, Single Nucleotide;Proteins;RNA, Messenger"
2464 @misc { codata-boltzmann,
2465 key = "codata-boltzmann",
2466 crossref = "codata06",
2467 url = "http://physics.nist.gov/cgi-bin/cuu/Value?k"
2470 @article { codata06,
2471 author = PJMohr #" and "# BNTaylor #" and "# DBNewell,
2473 title = "{CODATA} recommended values of the fundamental physical constants:
2483 doi = "10.1103/RevModPhys.80.633"
2486 @article { collins03,
2487 author = FSCollins #" and "# MMorgan #" and "# APatrinos,
2488 title = "The Human Genome Project: Lessons from large-scale biology.",
2497 doi = "10.1126/science.1084564",
2498 eprint = "http://www.sciencemag.org/cgi/reprint/300/5617/286.pdf",
2499 url = "http://www.sciencemag.org/cgi/content/summary/300/5617/277",
2500 keywords = "Access to Information;Computational Biology;Databases, Nucleic
2501 Acid;Genome, Human;Genomics;Government Agencies;History, 20th
2502 Century;Human Genome Project;Humans;International Cooperation;National
2503 Institutes of Health (U.S.);Private Sector;Public Policy;Public
2504 Sector;Publishing;Quality Control;Sequence Analysis, DNA;United States",
2505 note = "See also: \href{http://www.ornl.gov/sci/techresources/Human_Genome/
2506 project/journals/journals.shtml}{Landmark HPG Papers}"
2509 @article { cornish07,
2510 author = PVCornish #" and "# THa,
2511 title = "A survey of single-molecule techniques in chemical biology",
2515 journal = ACS:ChemBiol,
2520 doi = "10.1021/cb600342a",
2521 keywords = "Animals;Data Collection;Humans;Microscopy, Atomic
2522 Force;Microscopy, Fluorescence;Molecular Biology",
2523 abstract = "Single-molecule methods have revolutionized scientific research
2524 by rendering the investigation of once-inaccessible biological
2525 processes amenable to scientific inquiry. Several of the more
2526 established techniques will be emphasized in this Review, including
2527 single-molecule fluorescence microscopy, optical tweezers, and atomic
2528 force microscopy, which have been applied to many diverse biological
2529 processes. Serving as a taste of all the exciting research currently
2530 underway, recent examples will be discussed of translocation of RNA
2531 polymerase, myosin VI walking, protein folding, and enzyme activity. We
2532 will end by providing an assessment of what the future holds, including
2533 techniques that are currently in development."
2538 title = "Statistical Data Analysis",
2541 address = "New York",
2542 note = "Noise deconvolution in Chapter 11",
2543 project = "Cantilever Calibration"
2547 author = DCraig #" and "# AKrammer #" and "# KSchulten #" and "# VVogel,
2548 title = "Comparison of the early stages of forced unfolding for fibronectin
2549 type {III} modules",
2554 pages = "5590--5595",
2555 doi = "10.1073/pnas.101582198",
2556 eprint = "http://www.pnas.org/cgi/reprint/98/10/5590.pdf",
2557 url = "http://www.pnas.org/cgi/content/abstract/98/10/5590",
2561 @article { delpech01,
2562 author = BDelpech #" and "# MNCourel #" and "# CMaingonnat #" and "#
2563 CChauzy #" and "# RSesboue #" and "# GPratesi,
2564 title = "Hyaluronan digestion and synthesis in an experimental model of
2567 month = "September/October",
2568 journal = HistochemJ,
2573 keywords = "Animals;Culture Media;Humans;Hyaluronic
2574 Acid;Hyaluronoglucosaminidase;Mice;Mice, Nude;Neoplasm
2575 Metastasis;Neoplasm Transplantation;Neoplasms, Experimental;Tumor
2577 abstract = "To approach the question of hyaluronan catabolism in tumours,
2578 we have selected the cancer cell line H460M, a highly metastatic cell
2579 line in the nude mouse. H460M cells release hyaluronidase in culture
2580 media at a high rate of 57 pU/cell/h, without producing hyaluronan.
2581 Hyaluronidase was measured in the H460M cell culture medium at the
2582 optimum pH 3.8, and was not found above pH 4.5, with the enzyme-linked
2583 sorbent assay technique and zymography. Tritiated hyaluronan was
2584 digested at pH 3.8 by cells or cell membranes as shown by gel
2585 permeation chromatography, but no activity was recorded at pH 7 with
2586 this technique. Hyaluronan was digested in culture medium by tumour
2587 slices, prepared from tumours developed in nude mice grafted with H460M
2588 cells, showing that hyaluronan could be digested in complex tissue at
2589 physiological pH. Culture of tumour slices with tritiated acetate
2590 resulted in the accumulation within 2 days of radioactive
2591 macromolecules in the culture medium. The radioactive macromolecular
2592 material was mostly digested by Streptomyces hyaluronidase, showing
2593 that hyaluronan was its main component and that hyaluronan synthesis
2594 occurred together with its digestion. These results demonstrate that
2595 the membrane-associated hyaluronidase of H460M cells can act in vivo,
2596 and that hyaluronan, which is synthesised by the tumour stroma, can be
2597 made soluble and reduced to a smaller size by tumour cells before being
2598 internalised and further digested."
2601 @article { diCola05,
2602 author = EDCola #" and "# TAWaigh #" and "# JTrinick #" and "#
2603 LTskhovrebova #" and "# AHoumeida #" and "# WPyckhout-Hintzen #" and "#
2606 title = "Persistence length of titin from rabbit skeletal muscles measured
2607 with scattering and microrheology techniques",
2614 pages = "4095--4106",
2616 doi = "10.1529/biophysj.104.054908",
2617 eprint = "http://download.cell.com/biophysj/pdf/PIIS0006349505734603.pdf",
2618 url = "http://www.cell.com/biophysj/retrieve/pii/S0006349505734603",
2619 keywords = "Animals;Biophysics;Elasticity;Light;Muscle Proteins;Muscle,
2620 Skeletal;Neutrons;Protein Conformation;Protein
2621 Kinases;Rabbits;Rheology;Scattering, Radiation;Temperature",
2622 abstract = "The persistence length of titin from rabbit skeletal muscles
2623 was measured using a combination of static and dynamic light
2624 scattering, and neutron small angle scattering. Values of persistence
2625 length in the range 9-16 nm were found for titin-II, which corresponds
2626 to mainly physiologically inelastic A-band part of the protein, and for
2627 a proteolytic fragment with 100-nm contour length from the
2628 physiologically elastic I-band part. The ratio of the hydrodynamic
2629 radius to the static radius of gyration indicates that the proteins
2630 obey Gaussian statistics typical of a flexible polymer in a -solvent.
2631 Furthermore, measurements of the flexibility as a function of
2632 temperature demonstrate that titin-II and the I-band titin fragment
2633 experience a similar denaturation process; unfolding begins at 318 K
2634 and proceeds in two stages: an initial gradual 50\% change in
2635 persistence length is followed by a sharp unwinding transition at 338
2636 K. Complementary microrheology (video particle tracking) measurements
2637 indicate that the viscoelasticity in dilute solution behaves according
2638 to the Flory/Fox model, providing a value of the radius of gyration for
2639 titin-II (63 +/- 1 nm) in agreement with static light scattering and
2640 small angle neutron scattering results."
2644 author = HDietz #" and "# MRief,
2645 title = "Exploring the energy landscape of {GFP} by single-molecule
2646 mechanical experiments",
2651 pages = "16192--16197",
2652 doi = "10.1073/pnas.0404549101",
2653 eprint = "http://www.pnas.org/cgi/reprint/101/46/16192.pdf",
2654 url = "http://www.pnas.org/cgi/content/abstract/101/46/16192",
2655 abstract = "We use single-molecule force spectroscopy to drive
2656 single GFP molecules from the native state through their
2657 complex energy landscape into the completely unfolded
2658 state. Unlike many smaller proteins, mechanical GFP unfolding
2659 proceeds by means of two subsequent intermediate states. The
2660 transition from the native state to the first intermediate
2661 state occurs near thermal equilibrium at $\approx35\U{pN}$ and
2662 is characterized by detachment of a seven-residue N-terminal
2663 $\alpha$-helix from the beta barrel. We measure the
2664 equilibrium free energy cost associated with this transition
2665 as 22 kBT. Detachment of this small $\alpha$-helix completely
2666 destabilizes GFP thermodynamically even though the
2667 $\beta$-barrel is still intact and can bear load. Mechanical
2668 stability of the protein on the millisecond timescale,
2669 however, is determined by the activation barrier of unfolding
2670 the $\beta$-barrel out of this thermodynamically unstable
2671 intermediate state. High bandwidth, time-resolved measurements
2672 of the cantilever relaxation phase upon unfolding of the
2673 $\beta$-barrel revealed a second metastable mechanical
2674 intermediate with one complete $\beta$-strand detached from
2675 the barrel. Quantitative analysis of force distributions and
2676 lifetimes lead to a detailed picture of the complex mechanical
2677 unfolding pathway through a rough energy landscape.",
2678 note = "Towards use of Green Flourescent Protein (GFP) as an
2679 embedded force probe. Nice energy-landscape-to-one-dimension
2680 compression graphic.",
2681 project = "Energy landscape roughness"
2684 @article { dietz06a,
2685 author = HDietz #" and "# MRief,
2686 title = "Protein structure by mechanical triangulation",
2693 pages = "1244--1247",
2694 doi = "10.1073/pnas.0509217103",
2695 eprint = "http://www.pnas.org/cgi/reprint/103/5/1244.pdf",
2696 url = "http://www.pnas.org/cgi/content/abstract/103/5/1244",
2697 abstract = "Knowledge of protein structure is essential to understand
2698 protein function. High-resolution protein structure has so far been the
2699 domain of ensemble methods. Here, we develop a simple single-molecule
2700 technique to measure spatial position of selected residues within a
2701 folded and functional protein structure in solution. Construction and
2702 mechanical unfolding of cysteine-engineered polyproteins with
2703 controlled linkage topology allows measuring intramolecular distance
2704 with angstrom precision. We demonstrate the potential of this technique
2705 by determining the position of three residues in the structure of green
2706 fluorescent protein (GFP). Our results perfectly agree with the GFP
2707 crystal structure. Mechanical triangulation can find many applications
2708 where current bulk structural methods fail."
2711 @article { dietz06b,
2712 author = HDietz #" and "# FBerkemeier #" and "# MBertz #" and "# MRief,
2713 title = "Anisotropic deformation response of single protein molecules",
2720 pages = "12724--12728",
2721 doi = "10.1073/pnas.0602995103",
2722 eprint = "http://www.pnas.org/cgi/reprint/103/34/12724.pdf",
2723 url = "http://www.pnas.org/cgi/content/abstract/103/34/12724",
2724 abstract = "Single-molecule methods have given experimental access to the
2725 mechanical properties of single protein molecules. So far, access has
2726 been limited to mostly one spatial direction of force application.
2727 Here, we report single-molecule experiments that explore the mechanical
2728 properties of a folded protein structure in precisely controlled
2729 directions by applying force to selected amino acid pairs. We
2730 investigated the deformation response of GFP in five selected
2731 directions. We found fracture forces widely varying from 100 pN up to
2732 600 pN. We show that straining the GFP structure in one of the five
2733 directions induces partial fracture of the protein into a half-folded
2734 intermediate structure. From potential widths we estimated directional
2735 spring constants of the GFP structure and found values ranging from 1
2736 N/m up to 17 N/m. Our results show that classical continuum mechanics
2737 and simple mechanistic models fail to describe the complex mechanics of
2738 the GFP protein structure and offer insights into the mechanical design
2739 of protein materials."
2743 author = HDietz #" and "# MRief,
2744 title = "Detecting Molecular Fingerprints in Single Molecule Force
2745 Spectroscopy Using Pattern Recognition",
2750 pages = "5540--5542",
2752 doi = "10.1143/JJAP.46.5540",
2753 url = "http://jjap.ipap.jp/link?JJAP/46/5540/",
2754 keywords = "single molecule, protein mechanics, force spectroscopy, AFM,
2755 pattern recognition, GFP",
2756 abstract = "Single molecule force spectroscopy has given experimental
2757 access to the mechanical properties of protein molecules. Typically,
2758 less than 1% of the experimental recordings reflect true single
2759 molecule events due to abundant surface and multiple-molecule
2760 interactions. A key issue in single molecule force spectroscopy is thus
2761 to identify the characteristic mechanical `fingerprint' of a specific
2762 protein in noisy data sets. Here, we present an objective pattern
2763 recognition algorithm that is able to identify fingerprints in such
2765 note = "Automatic force curve selection. Seems a bit shoddy. Details
2769 @article{ berkemeier11,
2770 author = FBerkemeier #" and "# MBertz #" and "# SXiao #" and "#
2771 NPinotsis #" and "# MWilmanns #" and "# FGrater #" and "# MRief,
2772 title = "Fast-folding $\alpha$-helices as reversible strain absorbers
2773 in the muscle protein myomesin.",
2778 address = "Physik Department E22, Technische Universit{\"a}t
2779 M{\"u}nchen, James-Franck-Stra{\ss}e, 85748 Garching, Germany.",
2782 pages = "14139--14144",
2783 keywords = "Biomechanics",
2784 keywords = "Kinetics",
2785 keywords = "Microscopy, Atomic Force",
2786 keywords = "Molecular Dynamics Simulation",
2787 keywords = "Muscle Proteins",
2788 keywords = "Protein Folding",
2789 keywords = "Protein Multimerization",
2790 keywords = "Protein Stability",
2791 keywords = "Protein Structure, Secondary",
2792 keywords = "Protein Structure, Tertiary",
2793 keywords = "Protein Unfolding",
2794 abstract = "The highly oriented filamentous protein network of
2795 muscle constantly experiences significant mechanical load during
2796 muscle operation. The dimeric protein myomesin has been identified
2797 as an important M-band component supporting the mechanical
2798 integrity of the entire sarcomere. Recent structural studies have
2799 revealed a long $\alpha$-helical linker between the C-terminal
2800 immunoglobulin (Ig) domains My12 and My13 of myomesin. In this
2801 paper, we have used single-molecule force spectroscopy in
2802 combination with molecular dynamics simulations to characterize
2803 the mechanics of the myomesin dimer comprising immunoglobulin
2804 domains My12-My13. We find that at forces of approximately 30?pN
2805 the $\alpha$-helical linker reversibly elongates allowing the
2806 molecule to extend by more than the folded extension of a full
2807 domain. High-resolution measurements directly reveal the
2808 equilibrium folding/unfolding kinetics of the individual helix. We
2809 show that $\alpha$-helix unfolding mechanically protects the
2810 molecule homodimerization from dissociation at physiologically
2811 relevant forces. As fast and reversible molecular springs the
2812 myomesin $\alpha$-helical linkers are an essential component for
2813 the structural integrity of the M band.",
2815 doi = "10.1073/pnas.1105734108",
2816 URL = "http://www.ncbi.nlm.nih.gov/pubmed/21825161",
2821 author = KADill #" and "# HSChan,
2822 title = "From Levinthal to pathways to funnels.",
2830 doi = "10.1038/nsb0197-10",
2831 eprint = "http://www.nature.com/nsmb/journal/v4/n1/pdf/nsb0197-10.pdf",
2832 url = "http://www.nature.com/nsmb/journal/v4/n1/abs/nsb0197-10.html",
2833 keywords = "Kinetics;Models, Chemical;Protein Folding",
2834 abstract = "While the classical view of protein folding kinetics relies on
2835 phenomenological models, and regards folding intermediates in a
2836 structural way, the new view emphasizes the ensemble nature of protein
2837 conformations. Although folding has sometimes been regarded as a linear
2838 sequence of events, the new view sees folding as parallel microscopic
2839 multi-pathway diffusion-like processes. While the classical view
2840 invoked pathways to solve the problem of searching for the needle in
2841 the haystack, the pathway idea was then seen as conflicting with
2842 Anfinsen's experiments showing that folding is pathway-independent
2843 (Levinthal's paradox). In contrast, the new view sees no inherent
2844 paradox because it eliminates the pathway idea: folding can funnel to a
2845 single stable state by multiple routes in conformational space. The
2846 general energy landscape picture provides a conceptual framework for
2847 understanding both two-state and multi-state folding kinetics. Better
2848 tests of these ideas will come when new experiments become available
2849 for measuring not just averages of structural observables, but also
2850 correlations among their fluctuations. At that point we hope to learn
2851 much more about the real shapes of protein folding landscapes.",
2852 note = "Pretty folding funnel figures."
2855 @article { discher06,
2856 author = DDischer #" and "# NBhasin #" and "# CJohnson,
2857 title = "Covalent chemistry on distended proteins",
2862 pages = "7533--7534",
2863 doi = "10.1073/pnas.0602388103",
2864 eprint = "http://www.pnas.org/cgi/reprint/103/20/7533.pdf",
2865 url = "http://www.pnas.org/cgi/content/abstract/103/20/7533.pdf"
2869 author = OKDudko #" and "# AEFilippov #" and "# JKlafter #" and "# MUrbakh,
2870 title = "Beyond the conventional description of dynamic force spectroscopy
2878 pages = "11378--11381",
2880 doi = "10.1073/pnas.1534554100",
2881 eprint = "http://www.pnas.org/content/100/20/11378.full.pdf",
2882 url = "http://www.pnas.org/content/100/20/11378.abstract",
2883 keywords = "Spectrum Analysis;Temperature",
2884 abstract = "Dynamic force spectroscopy of single molecules is described by
2885 a model that predicts a distribution of rupture forces, the
2886 corresponding mean rupture force, and variance, which are all amenable
2887 to experimental tests. The distribution has a pronounced asymmetry,
2888 which has recently been observed experimentally. The mean rupture force
2889 follows a (lnV)2/3 dependence on the pulling velocity, V, and differs
2890 from earlier predictions. Interestingly, at low pulling velocities, a
2891 rebinding process is obtained whose signature is an intermittent
2892 behavior of the spring force, which delays the rupture. An extension to
2893 include conformational changes of the adhesion complex is proposed,
2894 which leads to the possibility of bimodal distributions of rupture
2899 author = OKDudko #" and "# GHummer #" and "# ASzabo,
2900 title = "Intrinsic rates and activation free energies from single-molecule
2901 pulling experiments",
2910 doi = "10.1103/PhysRevLett.96.108101",
2911 keywords = "Biophysics;Computer Simulation;Data Interpretation,
2912 Statistical;Kinetics;Micromanipulation;Models, Chemical;Models,
2913 Molecular;Molecular Conformation;Muscle Proteins;Nucleic Acid
2914 Conformation;Protein Binding;Protein Denaturation;Protein
2915 Folding;Protein Kinases;RNA;Stress, Mechanical;Thermodynamics;Time
2917 abstract = "We present a unified framework for extracting kinetic
2918 information from single-molecule pulling experiments at constant force
2919 or constant pulling speed. Our procedure provides estimates of not only
2920 (i) the intrinsic rate coefficient and (ii) the location of the
2921 transition state but also (iii) the free energy of activation. By
2922 analyzing simulated data, we show that the resulting rates of force-
2923 induced rupture are significantly more reliable than those obtained by
2924 the widely used approach based on Bell's formula. We consider the
2925 uniqueness of the extracted kinetic information and suggest guidelines
2926 to avoid over-interpretation of experiments."
2930 author = OKDudko #" and "# JMathe #" and "# ASzabo #" and "# AMeller #" and
2932 title = "Extracting kinetics from single-molecule force spectroscopy:
2933 Nanopore unzipping of {DNA} hairpins",
2940 pages = "4188--4195",
2942 doi = "10.1529/biophysj.106.102855",
2943 eprint = "http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1877759&blo
2945 keywords = "Computer
2946 Simulation;DNA;Elasticity;Mechanics;Micromanipulation;Microscopy,
2947 Atomic Force;Models, Chemical;Models, Molecular;Nanostructures;Nucleic
2948 Acid Conformation;Porosity;Stress, Mechanical",
2949 abstract = "Single-molecule force experiments provide powerful new tools to
2950 explore biomolecular interactions. Here, we describe a systematic
2951 procedure for extracting kinetic information from force-spectroscopy
2952 experiments, and apply it to nanopore unzipping of individual DNA
2953 hairpins. Two types of measurements are considered: unzipping at
2954 constant voltage, and unzipping at constant voltage-ramp speeds. We
2955 perform a global maximum-likelihood analysis of the experimental data
2956 at low-to-intermediate ramp speeds. To validate the theoretical models,
2957 we compare their predictions with two independent sets of data,
2958 collected at high ramp speeds and at constant voltage, by using a
2959 quantitative relation between the two types of measurements.
2960 Microscopic approaches based on Kramers theory of diffusive barrier
2961 crossing allow us to estimate not only intrinsic rates and transition
2962 state locations, as in the widely used phenomenological approach based
2963 on Bell's formula, but also free energies of activation. The problem of
2964 extracting unique and accurate kinetic parameters of a molecular
2965 transition is discussed in light of the apparent success of the
2966 microscopic theories in reproducing the experimental data."
2970 author = OKDudko #" and "# GHummer #" and "# ASzabo,
2971 title = "Theory, analysis, and interpretation of single-molecule
2972 force spectroscopy experiments.",
2977 address = "Department of Physics and Center for Theoretical
2978 Biological Physics, University of California at San Diego, La
2979 Jolla, CA 92093, USA.
2980 dudko@physics.ucsd.edu",
2983 pages = "15755--15760",
2985 keywords = "Half-Life",
2986 keywords = "Kinetics",
2987 keywords = "Microscopy, Atomic Force",
2988 keywords = "Motion",
2989 keywords = "Nucleic Acid Conformation",
2990 keywords = "Nucleic Acid Denaturation",
2991 keywords = "Protein Folding",
2992 keywords = "Thermodynamics",
2993 abstract = "Dynamic force spectroscopy probes the kinetic and
2994 thermodynamic properties of single molecules and molecular
2995 assemblies. Here, we propose a simple procedure to extract kinetic
2996 information from such experiments. The cornerstone of our method
2997 is a transformation of the rupture-force histograms obtained at
2998 different force-loading rates into the force-dependent lifetimes
2999 measurable in constant-force experiments. To interpret the
3000 force-dependent lifetimes, we derive a generalization of Bell's
3001 formula that is formally exact within the framework of Kramers
3002 theory. This result complements the analytical expression for the
3003 lifetime that we derived previously for a class of model
3004 potentials. We illustrate our procedure by analyzing the nanopore
3005 unzipping of DNA hairpins and the unfolding of a protein attached
3006 by flexible linkers to an atomic force microscope. Our procedure
3007 to transform rupture-force histograms into the force-dependent
3008 lifetimes remains valid even when the molecular extension is a
3009 poor reaction coordinate and higher-dimensional free-energy
3010 surfaces must be considered. In this case the microscopic
3011 interpretation of the lifetimes becomes more challenging because
3012 the lifetimes can reveal richer, and even nonmonotonic, dependence
3015 doi = "10.1073/pnas.0806085105",
3016 URL = "http://www.ncbi.nlm.nih.gov/pubmed/18852468",
3022 title = "Probing the relation between force--lifetime--and chemistry in
3023 single molecular bonds",
3029 doi = "10.1146/annurev.biophys.30.1.105",
3030 url = "http://arjournals.annualreviews.org/doi/abs/10.1146%2Fannurev.biophys.30.1.105",
3031 keywords = "Biophysics;Kinetics;Microscopy, Atomic Force;Models,
3032 Chemical;Protein Binding;Spectrum Analysis;Time Factors",
3033 abstract = "On laboratory time scales, the energy landscape of a weak bond
3034 along a dissociation pathway is fully explored through Brownian-thermal
3035 excitations, and energy barriers become encoded in a dissociation time
3036 that varies with applied force. Probed with ramps of force over an
3037 enormous range of rates (force/time), this kinetic profile is
3038 transformed into a dynamic spectrum of bond rupture force as a function
3039 of loading rate. On a logarithmic scale in loading rate, the force
3040 spectrum provides an easy-to-read map of the prominent energy barriers
3041 traversed along the force-driven pathway and exposes the differences in
3042 energy between barriers. In this way, the method of dynamic force
3043 spectroscopy (DFS) is being used to probe the complex relation between
3044 force-lifetime-and chemistry in single molecular bonds. Most important,
3045 DFS probes the inner world of molecular interactions to reveal barriers
3046 that are difficult or impossible to detect in assays of near
3047 equilibrium dissociation but that determine bond lifetime and strength
3048 under rapid detachment. To use an ultrasensitive force probe as a
3049 spectroscopic tool, we need to understand the physics of bond
3050 dissociation under force, the impact of experimental technique on the
3051 measurement of detachment force (bond strength), the consequences of
3052 complex interactions in macromolecular bonds, and effects of multiply-
3053 bonded attachments."
3056 @article { evans91a,
3057 author = EEvans #" and "# DBerk #" and "# ALeung,
3058 title = "Detachment of agglutinin-bonded red blood cells. {I}. Forces to
3059 rupture molecular-point attachments",
3067 keywords = "ABO Blood-Group System;Animals;Antibodies,
3068 Monoclonal;Erythrocyte Deformability;Erythrocyte
3069 Membrane;Erythrocytes;Glycophorin;Helix
3070 (Snails);Hemagglutinins;Humans;Immune Sera;Lectins;Mathematics;Models,
3072 abstract = "A simple micromechanical method has been developed to measure
3073 the rupture strength of a molecular-point attachment (focal bond)
3074 between two macroscopically smooth membrane capsules. In the procedure,
3075 one capsule is prepared with a low density coverage of adhesion
3076 molecules, formed as a stiff sphere, and held at fixed position by a
3077 micropipette. The second capsule without adhesion molecules is
3078 pressurized into a spherical shape with low suction by another pipette.
3079 This capsule is maneuvered to initiate point contact at the pole
3080 opposite the stiff capsule which leads to formation of a few (or even
3081 one) molecular attachments. Then, the deformable capsule is slowly
3082 withdrawn by displacement of the pipette. Analysis shows that the end-
3083 to-end extension of the capsule provides a direct measure of the force
3084 at the point contact and, therefore, the rupture strength when
3085 detachment occurs. The range for point forces accessible to this
3086 technique depends on the elastic moduli of the membrane, membrane
3087 tension, and the size of the capsule. For biological and synthetic
3088 vesicle membranes, the range of force lies between 10(-7)-10(-5) dyn
3089 (10(-12)-10(-10) N) which is 100-fold less than presently measurable by
3090 Atomic Force Microscopy! Here, the approach was used to study the
3091 forces required to rupture microscopic attachments between red blood
3092 cells formed by a monoclonal antibody to red cell membrane glycophorin,
3093 anti-A serum, and a lectin from the snail-helix pomatia. Failure of the
3094 attachments appeared to be a stochastic function of the magnitude and
3095 duration of the detachment force. We have correlated the statistical
3096 behavior observed for rupture with a random process model for failure
3097 of small numbers of molecular attachments. The surprising outcome of
3098 the measurements and analysis was that the forces deduced for short-
3099 time failure of 1-2 molecular attachments were nearly the same for all
3100 of the agglutinin, i.e., 1-2 x 10(-6) dyn. Hence, microfluorometric
3101 tests were carried out to determine if labeled agglutinins and/or
3102 labeled surface molecules were transferred between surfaces after
3103 separation of large areas of adhesive contact. The results showed that
3104 the attachments failed because receptors were extracted from the
3108 @article { evans91b,
3109 author = EEvans #" and "# DBerk #" and "# ALeung #" and "# NMohandas,
3110 title = "Detachment of agglutinin-bonded red blood cells. {II}. Mechanical
3111 energies to separate large contact areas",
3119 keywords = "Animals;Antibodies, Monoclonal;Cell Adhesion;Erythrocyte
3120 Membrane;Erythrocytes;Helix
3121 (Snails);Hemagglutination;Hemagglutinins;Humans;Immune
3122 Sera;Kinetics;Lectins;Mathematics",
3123 abstract = "As detailed in a companion paper (Berk, D., and E. Evans. 1991.
3124 Biophys. J. 59:861-872), a method was developed to quantitate the
3125 strength of adhesion between agglutinin-bonded membranes without
3126 ambiguity due to mechanical compliance of the cell body. The
3127 experimental method and analysis were formulated around controlled
3128 assembly and detachment of a pair of macroscopically smooth red blood
3129 cell surfaces. The approach provides precise measurement of the
3130 membrane tension applied at the perimeter of an adhesive contact and
3131 the contact angle theta c between membrane surfaces which defines the
3132 mechanical leverage factor (1-cos theta c) important in the definition
3133 of the work to separate a unit area of contact. Here, the method was
3134 applied to adhesion and detachment of red cells bound together by
3135 different monoclonal antibodies to red cell membrane glycophorin and
3136 the snail-helix pomatia-lectin. For these tests, one of the two red
3137 cells was chemically prefixed in the form of a smooth sphere then
3138 equilibrated with the agglutinin before the adhesion-detachment
3139 procedure. The other cell was not exposed to the agglutinin until it
3140 was forced into contact with the rigid cell surface by mechanical
3141 impingement. Large regions of agglutinin bonding were produced by
3142 impingement but no spontaneous spreading was observed beyond the forced
3143 contact. Measurements of suction force to detach the deformable cell
3144 yielded consistent behavior for all of the agglutinins: i.e., the
3145 strength of adhesion increased progressively with reduction in contact
3146 diameter throughout detachment. This tension-contact diameter behavior
3147 was not altered over a ten-fold range of separation rates. In special
3148 cases, contacts separated smoothly after critical tensions were
3149 reached; these were the highest values attained for tension. Based on
3150 measurements reported in another paper (Evans et al. 1991. Biophys. J.
3151 59:838-848) of the forces required to rupture molecular-point
3152 attachments, the density of cross-bridges was estimated with the
3153 assumption that the tension was proportional to the discrete rupture
3154 force x the number of attachments per unit length. These estimates
3155 showed that only a small fraction of agglutinin formed cross-bridges at
3156 initial assembly and increased progressively with separation. When
3157 critical tension levels were reached, it appeared that nearly all local
3158 agglutinin was involved as cross-bridges. Because one cell surface was
3159 chemically fixed, receptor accumulation was unlikely; thus, microscopic
3160 ``roughness'' and steric repulsion probably modulated formation of
3161 cross-bridges on initial contact.(ABSTRACT TRUNCATED AT 400 WORDS)"
3165 author = EEvans #" and "# KRitchie,
3166 title = "Dynamic strength of molecular adhesion bonds",
3172 pages = "1541--1555",
3174 eprint = "http://www.biophysj.org/cgi/reprint/72/4/1541.pdf",
3175 url = "http://www.biophysj.org/cgi/content/abstract/72/4/1541",
3176 keywords = "Avidin; Biotin; Chemistry, Physical; Computer Simulation;
3177 Mathematics; Monte Carlo Method; Protein Binding",
3178 abstract = "In biology, molecular linkages at, within, and beneath cell
3179 interfaces arise mainly from weak noncovalent interactions. These bonds
3180 will fail under any level of pulling force if held for sufficient time.
3181 Thus, when tested with ultrasensitive force probes, we expect cohesive
3182 material strength and strength of adhesion at interfaces to be time-
3183 and loading rate-dependent properties. To examine what can be learned
3184 from measurements of bond strength, we have extended Kramers' theory
3185 for reaction kinetics in liquids to bond dissociation under force and
3186 tested the predictions by smart Monte Carlo (Brownian dynamics)
3187 simulations of bond rupture. By definition, bond strength is the force
3188 that produces the most frequent failure in repeated tests of breakage,
3189 i.e., the peak in the distribution of rupture forces. As verified by
3190 the simulations, theory shows that bond strength progresses through
3191 three dynamic regimes of loading rate. First, bond strength emerges at
3192 a critical rate of loading (> or = 0) at which spontaneous dissociation
3193 is just frequent enough to keep the distribution peak at zero force. In
3194 the slow-loading regime immediately above the critical rate, strength
3195 grows as a weak power of loading rate and reflects initial coupling of
3196 force to the bonding potential. At higher rates, there is crossover to
3197 a fast regime in which strength continues to increase as the logarithm
3198 of the loading rate over many decades independent of the type of
3199 attraction. Finally, at ultrafast loading rates approaching the domain
3200 of molecular dynamics simulations, the bonding potential is quickly
3201 overwhelmed by the rapidly increasing force, so that only naked
3202 frictional drag on the structure remains to retard separation. Hence,
3203 to expose the energy landscape that governs bond strength, molecular
3204 adhesion forces must be examined over an enormous span of time scales.
3205 However, a significant gap exists between the time domain of force
3206 measurements in the laboratory and the extremely fast scale of
3207 molecular motions. Using results from a simulation of biotin-avidin
3208 bonds (Izrailev, S., S. Stepaniants, M. Balsera, Y. Oono, and K.
3209 Schulten. 1997. Molecular dynamics study of unbinding of the avidin-
3210 biotin complex. Biophys. J., this issue), we describe how Brownian
3211 dynamics can help bridge the gap between molecular dynamics and probe
3213 project = "sawtooth simulation"
3217 author = EEvans #" and "# KRitchie,
3218 title = "Strength of a weak bond connecting flexible polymer chains",
3224 pages = "2439--2447",
3226 eprint = "http://www.biophysj.org/cgi/reprint/76/5/2439.pdf",
3227 url = "http://www.biophysj.org/cgi/content/abstract/76/5/2439",
3228 keywords = "Animals; Biophysics; Biopolymers; Microscopy, Atomic Force;
3229 Models, Chemical; Muscle Proteins; Protein Folding; Protein Kinases;
3230 Stochastic Processes; Stress, Mechanical; Thermodynamics",
3231 abstract = "Bond dissociation under steadily rising force occurs most
3232 frequently at a time governed by the rate of loading (Evans and
3233 Ritchie, 1997 Biophys. J. 72:1541-1555). Multiplied by the loading
3234 rate, the breakage time specifies the force for most frequent failure
3235 (called bond strength) that obeys the same dependence on loading rate.
3236 The spectrum of bond strength versus log(loading rate) provides an
3237 image of the energy landscape traversed in the course of unbonding.
3238 However, when a weak bond is connected to very compliant elements like
3239 long polymers, the load applied to the bond does not rise steadily
3240 under constant pulling speed. Because of nonsteady loading, the most
3241 frequent breakage force can differ significantly from that of a bond
3242 loaded at constant rate through stiff linkages. Using generic models
3243 for wormlike and freely jointed chains, we have analyzed the kinetic
3244 process of failure for a bond loaded by pulling the polymer linkages at
3245 constant speed. We find that when linked by either type of polymer
3246 chain, a bond is likely to fail at lower force under steady separation
3247 than through stiff linkages. Quite unexpectedly, a discontinuous jump
3248 can occur in bond strength at slow separation speed in the case of long
3249 polymer linkages. We demonstrate that the predictions of strength
3250 versus log(loading rate) can rationalize conflicting results obtained
3251 recently for unfolding Ig domains along muscle titin with different
3253 note = "Develops Kramers improvement on Bell model for domain unfolding.
3254 Presents unfolding under variable loading rates. Often cited as the
3255 ``Bell--Evans'' model. They derive a unitless treatment, scaling force
3256 by $f_\beta$, time by $\tau_f$, and elasiticity by compliance
3257 $c(f)$. The appendix has relaxation time formulas for WLC and FJC
3259 project = "sawtooth simulation"
3262 @article { fernandez04,
3263 author = JFernandez #" and "# HLi,
3264 title = "Force-clamp spectroscopy monitors the folding trajectory of a
3272 pages = "1674--1678",
3274 doi = "10.1126/science.1092497",
3275 eprint = "http://www.sciencemag.org/cgi/reprint/303/5664/1674.pdf",
3276 url = "http://www.sciencemag.org/cgi/content/abstract/303/5664/1674",
3277 keywords = "Chemistry, Physical;Microscopy, Atomic Force;Physicochemical
3278 Phenomena;Polyubiquitin;Protein Conformation;Protein
3279 Denaturation;Protein Folding;Protein Structure, Secondary;Time
3281 abstract = "We used force-clamp atomic force microscopy to measure the end-
3282 to-end length of the small protein ubiquitin during its folding
3283 reaction at the single-molecule level. Ubiquitin was first unfolded and
3284 extended at a high force, then the stretching force was quenched and
3285 protein folding was observed. The folding trajectories were continuous
3286 and marked by several distinct stages. The time taken to fold was
3287 dependent on the contour length of the unfolded protein and the
3288 stretching force applied during folding. The folding collapse was
3289 marked by large fluctuations in the end-to-end length of the protein,
3290 but these fluctuations vanished upon the final folding contraction.
3291 These direct observations of the complete folding trajectory of a
3292 protein provide a benchmark to determine the physical basis of the
3297 author = JHoward #" and "# AJHudspeth,
3298 title = {Mechanical relaxation of the hair bundle mediates
3299 adaptation in mechanoelectrical transduction by the
3300 bullfrog's saccular hair cell.},
3306 pages = {3064--3068},
3308 url = {http://www.ncbi.nlm.nih.gov/pubmed/3495007},
3309 keywords = {Acclimatization},
3310 keywords = {Animals},
3311 keywords = {Electric Conductivity},
3312 keywords = {Electric Stimulation},
3313 keywords = {Hair Cells, Auditory},
3314 keywords = {Membrane Potentials},
3315 keywords = {Microelectrodes},
3316 keywords = {Physical Stimulation},
3317 keywords = {Rana catesbeiana},
3318 keywords = {Saccule and Utricle},
3319 abstract = {Mechanoelectrical transduction by hair cells of the
3320 frog's internal ear displays adaptation: the electrical response
3321 to a maintained deflection of the hair bundle declines over a
3322 period of tens of milliseconds. We investigated the role of
3323 mechanics in adaptation by measuring changes in hair-bundle
3324 stiffness following the application of force stimuli. Following
3325 step stimulation with a glass fiber, the hair bundle of a saccular
3326 hair cell initially had a stiffness of approximately equal to
3327 $1\U{mN/m}$. The stiffness then declined to a steady-state level
3328 near $0.6\U{mN/m}$ with a time course comparable to that of
3329 adaptation in the receptor current. The hair bundle may be modeled
3330 as the parallel combination of a spring, which represents the
3331 rotational stiffness of the stereocilia, and a series spring and
3332 dashpot, which respectively, represent the elastic element
3333 responsible for channel gating and the apparatus for adaptation.},
3338 author = JHoward #" and "# AJHudspeth,
3339 title = {Compliance of the Hair Bundle Associated with Gating of
3340 Mechanoelectrical Transduction Channels in the Bullfrog's Saccular
3347 doi = {10.1016/0896-6273(88)90139-0},
3348 url = {http://www.cell.com/neuron/retrieve/pii/0896627388901390},
3349 eprint = {http://download.cell.com/neuron/pdf/PII0896627388901390.pdf},
3350 note = {Initial thermal calibration paper as cited by
3351 \citet{florin95}. This is not an AFM paper, but it uses the
3352 equipartition theorem to calculate the spring constant of hair
3353 fibers by measuring their tip displacement variance. The
3354 discussion occurs in the \emph{Manufacture and Calibration of
3355 Fibers} section on pages 197--198. Actual details are scarce, but
3356 I believe this is the original source of the ``Lorentzian'' and
3357 ``10\% accuracy'' ideas that have haunted themal calibration ever
3362 author = ELFlorin #" and "# VMoy #" and "# HEGaub,
3363 title = {Adhesion forces between individual ligand-receptor pairs},
3371 doi = {10.1126/science.8153628},
3372 url = {http://www.sciencemag.org/content/264/5157/415.abstract},
3373 eprint = {http://www.sciencemag.org/content/264/5157/415.full.pdf},
3374 abstract ={The adhesion force between the tip of an atomic force
3375 microscope cantilever derivatized with avidin and agarose beads
3376 functionalized with biotin, desthiobiotin, or iminobiotin was
3377 measured. Under conditions that allowed only a limited number of
3378 molecular pairs to interact, the force required to separate tip
3379 and bead was found to be quantized in integer multiples of
3380 $160\pm20$ piconewtons for biotin and $85\pm15$ piconewtons for
3381 iminobiotin. The measured force quanta are interpreted as the
3382 unbinding forces of individual molecular pairs.},
3385 @article { florin95,
3386 author = ELFlorin #" and "# MRief #" and "# HLehmann #" and "# MLudwig #"
3387 and "# CDornmair #" and "# VMoy #" and "# HEGaub,
3388 title = "Sensing specific molecular interactions with the atomic force
3396 doi = "10.1016/0956-5663(95)99227-C",
3397 url = "http://dx.doi.org/10.1016/0956-5663(95)99227-C",
3398 abstract = "One of the unique features of the atomic force microscope (AFM)
3399 is its capacity to measure interactions between tip and sample with
3400 high sensitivity and unparal leled spatial resolution. Since the
3401 development of methods for the functionaliza tion of the tips, the
3402 versatility of the AFM has been expanded to experiments wh ere specific
3403 molecular interactions are measured. For illustration, we present m
3404 easurements of the interaction between complementary strands of DNA. A
3405 necessary prerequisite for the quantitative analysis of the interaction
3406 force is knowledg e of the spring constant of the cantilevers. Here, we
3407 compare different techniqu es that allow for the in situ measurement of
3408 the absolute value of the spring co nstant of cantilevers.",
3409 note = {Good review of calibration to 1995, with experimental
3410 comparison between resonance-shift, reference-spring, and
3411 thermal methods. They incorrectly cite \citet{hutter93} as
3412 being published in 1994.},
3413 project = "Cantilever Calibration"
3416 @article{ burnham03,
3417 author = NABurnham #" and "# XiChen #" and "# CSHodges #" and "#
3418 GAMatei #" and "# EJThoreson #" and "# CJRoberts #" and "#
3419 MCDavies #" and "# SJBTendler,
3420 title = {Comparison of calibration methods for atomic-force
3421 microscopy cantilevers},
3428 url = {http://stacks.iop.org/0957-4484/14/i=1/a=301},
3429 abstract = {The scientific community needs a rapid and reliable way
3430 of accurately determining the stiffness of atomic-force microscopy
3431 cantilevers. We have compared the experimentally determined values
3432 of stiffness for ten cantilever probes using four different
3433 methods. For rectangular silicon cantilever beams of well defined
3434 geometry, the approaches all yield values within 17\% of the
3435 manufacturer's nominal stiffness. One of the methods is new, based
3436 on the acquisition and analysis of thermal distribution functions
3437 of the oscillator's amplitude fluctuations. We evaluate this
3438 method in comparison to the three others and recommend it for its
3439 ease of use and broad applicability.},
3440 note = {Contains both the overdamped (\fref{equation}{6}) and
3441 general (\fref{equation}{8}) power spectral densities used in
3442 thermal cantilever calibration, but punts to textbooks for the
3447 author = NRForde #" and "# DIzhaky #" and "# GRWoodcock #" and "# GJLWuite
3448 #" and "# CBustamante,
3449 title = "Using mechanical force to probe the mechanism of pausing and
3450 arrest during continuous elongation by Escherichia coli {RNA}
3458 pages = "11682--11687",
3460 doi = "10.1073/pnas.142417799",
3461 eprint = "http://www.pnas.org/cgi/reprint/99/18/11682.pdf",
3462 url = "http://www.pnas.org/content/99/18/11682",
3463 keywords = "DNA-Directed RNA Polymerases;Escherichia
3464 coli;Kinetics;Transcription, Genetic",
3465 abstract = "Escherichia coli RNA polymerase translocates along the DNA
3466 discontinuously during the elongation phase of transcription, spending
3467 proportionally more time at some template positions, known as pause and
3468 arrest sites, than at others. Current models of elongation suggest that
3469 the enzyme backtracks at these locations, but the dynamics are
3470 unresolved. Here, we study the role of lateral displacement in pausing
3471 and arrest by applying force to individually transcribing molecules. We
3472 find that an assisting mechanical force does not alter the
3473 translocation rate of the enzyme, but does reduce the efficiency of
3474 both pausing and arrest. Moreover, arrested molecules cannot be rescued
3475 by force, suggesting that arrest occurs by a bipartite mechanism: the
3476 enzyme backtracks along the DNA followed by a conformational change of
3477 the ternary complex (RNA polymerase, DNA and transcript), which cannot
3478 be reversed mechanically."
3481 @article { freitag97,
3482 author = SFreitag #" and "# ILTrong #" and "# LKlumb #" and "# PSStayton #"
3484 title = "Structural studies of the streptavidin binding loop.",
3490 pages = "1157--1166",
3492 doi = "10.1002/pro.5560060604",
3493 keywords = "Allosteric Regulation;Bacterial Proteins;Binding
3494 Sites;Biotin;Crystallography, X-Ray;Hydrogen Bonding;Ligands;Models,
3495 Molecular;Molecular Conformation;Streptavidin;Tryptophan",
3496 abstract = "The streptavidin-biotin complex provides the basis for many
3497 important biotechnological applications and is an interesting model
3498 system for studying high-affinity protein-ligand interactions. We
3499 report here crystallographic studies elucidating the conformation of
3500 the flexible binding loop of streptavidin (residues 45 to 52) in the
3501 unbound and bound forms. The crystal structures of unbound streptavidin
3502 have been determined in two monoclinic crystal forms. The binding loop
3503 generally adopts an open conformation in the unbound species. In one
3504 subunit of one crystal form, the flexible loop adopts the closed
3505 conformation and an analysis of packing interactions suggests that
3506 protein-protein contacts stabilize the closed loop conformation. In the
3507 other crystal form all loops adopt an open conformation. Co-
3508 crystallization of streptavidin and biotin resulted in two additional,
3509 different crystal forms, with ligand bound in all four binding sites of
3510 the first crystal form and biotin bound in only two subunits in a
3511 second. The major change associated with binding of biotin is the
3512 closure of the surface loop incorporating residues 45 to 52. Residues
3513 49 to 52 display a 3(10) helical conformation in unbound subunits of
3514 our structures as opposed to the disordered loops observed in other
3515 structure determinations of streptavidin. In addition, the open
3516 conformation is stabilized by a beta-sheet hydrogen bond between
3517 residues 45 and 52, which cannot occur in the closed conformation. The
3518 3(10) helix is observed in nearly all unbound subunits of both the co-
3519 crystallized and ligand-free structures. An analysis of the temperature
3520 factors of the binding loop regions suggests that the mobility of the
3521 closed loops in the complexed structures is lower than in the open
3522 loops of the ligand-free structures. The two biotin bound subunits in
3523 the tetramer found in the MONO-b1 crystal form are those that
3524 contribute Trp 120 across their respective binding pockets, suggesting
3525 a structural link between these binding sites in the tetramer. However,
3526 there are no obvious signatures of binding site communication observed
3527 upon ligand binding, such as quaternary structure changes or shifts in
3528 the region of Trp 120. These studies demonstrate that while
3529 crystallographic packing interactions can stabilize both the open and
3530 closed forms of the flexible loop, in their absence the loop is open in
3531 the unbound state and closed in the presence of biotin. If present in
3532 solution, the helical structure in the open loop conformation could
3533 moderate the entropic penalty associated with biotin binding by
3534 contributing an order-to-disorder component to the loop closure.",
3535 note = "\href{http://www.rcsb.org/pdb/explore.do?structureId=1SWE}{PDB ID:
3537 \href{http://dx.doi.org/10.2210/pdb1swe/pdb}{10.2210/pdb1swe/pdb}."
3540 @article { friddle08,
3541 author = RWFriddle #" and "# PPodsiadlo #" and "# ABArtyukhin #" and "#
3543 title = "Near-Equilibrium Chemical Force Microscopy",
3548 pages = "4986--4990",
3549 doi = "10.1021/jp7095967",
3550 eprint = "http://pubs.acs.org/doi/pdf/10.1021/jp7095967",
3551 url = "http://pubs.acs.org/doi/abs/10.1021/jp7095967"
3555 author = TFujii #" and "# YLSun #" and "# KNAn #" and "# ZPLuo,
3556 title = "Mechanical properties of single hyaluronan molecules",
3564 keywords = "Biomechanics;Cross-Linking Reagents;Elasticity;Extracellular
3565 Matrix;Humans;Hyaluronic Acid;Lasers;Microspheres;Nanotechnology",
3566 abstract = "Hyaluronan (HA) is a major component of the extracellular
3567 matrix. It plays an important role in the mechanical functions of the
3568 extracellular matrix and stabilization of cells. Currently, its
3569 mechanical properties have been investigated only at the gross level.
3570 In this study, the mechanical properties of single HA molecules were
3571 directly measured with an optical tweezer technique, yielding a
3572 persistence length of 4.5 +/- 1.2 nm. This information may help us to
3573 understand the mechanical roles in the extracellular matrix
3574 infrastructure, cell attachment, and to design tissue engineering and
3575 drug delivery systems where the mechanical functions of HA are
3579 @article { ganchev08,
3580 author = DNGanchev #" and "# NJCobb #" and "# KSurewicz #" and "#
3582 title = "Nanomechanical properties of human prion protein amyloid as probed
3583 by force spectroscopy",
3590 pages = "2909--2915",
3592 doi = "10.1529/biophysj.108.133108",
3593 abstract = "Amyloids are associated with a number of protein misfolding
3594 disorders, including prion diseases. In this study, we used single-
3595 molecule force spectroscopy to characterize the nanomechanical
3596 properties and molecular structure of amyloid fibrils formed by human
3597 prion protein PrP90-231. Force-extension curves obtained by specific
3598 attachment of a gold-covered atomic force microscope tip to engineered
3599 Cys residues could be described by the worm-like chain model for
3600 entropic elasticity of a polymer chain, with the size of the N-terminal
3601 segment that could be stretched entropically depending on the tip
3602 attachment site. The data presented here provide direct information
3603 about the forces required to extract an individual monomer from the
3604 core of the PrP90-231 amyloid, and indicate that the beta-sheet core of
3605 this amyloid starts at residue approximately 164-169. The latter
3606 finding has important implications for the ongoing debate regarding the
3607 structure of PrP amyloid."
3611 author = MGao #" and "# DCraig #" and "# OLequin #" and "# ICampbell #" and
3612 "# VVogel #" and "# KSchulten,
3613 title = "Structure and functional significance of mechanically unfolded
3614 fibronectin type {III1} intermediates",
3619 pages = "14784--14789",
3620 doi = "10.1073/pnas.2334390100",
3621 eprint = "http://www.pnas.org/cgi/reprint/100/25/14784.pdf",
3622 url = "http://www.pnas.org/cgi/content/abstract/100/25/14784",
3623 abstract = "Fibronectin (FN) forms fibrillar networks coupling cells to the
3624 extracellular matrix. The formation of FN fibrils, fibrillogenesis, is
3625 a tightly regulated process involving the exposure of cryptic binding
3626 sites in individual FN type III (FN-III) repeats presumably exposed by
3627 mechanical tension. The FN-III1 module has been previously proposed to
3628 contain such cryptic sites that promote the assembly of extracellular
3629 matrix FN fibrils. We have combined NMR and steered molecular dynamics
3630 simulations to study the structure and mechanical unfolding pathway of
3631 FN-III1. This study finds that FN-III1 consists of a {beta}-sandwich
3632 structure that unfolds to a mechanically stable intermediate about four
3633 times the length of the native folded state. Considering previous
3634 experimental findings, our studies provide a structural model by which
3635 mechanical stretching of FN-III1 may induce fibrillogenesis through
3636 this partially unfolded intermediate."
3639 @article { gavrilov01,
3640 author = LAGavrilov #" and "# NSGavrilova,
3641 title = "The reliability theory of aging and longevity",
3650 doi = "10.1006/jtbi.2001.2430",
3651 keywords = "Adult;Aged;Aging;Animals;Humans;Longevity;Middle Aged;Models,
3652 Biological;Survival Rate;Systems Theory",
3653 abstract = "Reliability theory is a general theory about systems failure.
3654 It allows researchers to predict the age-related failure kinetics for a
3655 system of given architecture (reliability structure) and given
3656 reliability of its components. Reliability theory predicts that even
3657 those systems that are entirely composed of non-aging elements (with a
3658 constant failure rate) will nevertheless deteriorate (fail more often)
3659 with age, if these systems are redundant in irreplaceable elements.
3660 Aging, therefore, is a direct consequence of systems redundancy.
3661 Reliability theory also predicts the late-life mortality deceleration
3662 with subsequent leveling-off, as well as the late-life mortality
3663 plateaus, as an inevitable consequence of redundancy exhaustion at
3664 extreme old ages. The theory explains why mortality rates increase
3665 exponentially with age (the Gompertz law) in many species, by taking
3666 into account the initial flaws (defects) in newly formed systems. It
3667 also explains why organisms ``prefer'' to die according to the Gompertz
3668 law, while technical devices usually fail according to the Weibull
3669 (power) law. Theoretical conditions are specified when organisms die
3670 according to the Weibull law: organisms should be relatively free of
3671 initial flaws and defects. The theory makes it possible to find a
3672 general failure law applicable to all adult and extreme old ages, where
3673 the Gompertz and the Weibull laws are just special cases of this more
3674 general failure law. The theory explains why relative differences in
3675 mortality rates of compared populations (within a given species) vanish
3676 with age, and mortality convergence is observed due to the exhaustion
3677 of initial differences in redundancy levels. Overall, reliability
3678 theory has an amazing predictive and explanatory power with a few, very
3679 general and realistic assumptions. Therefore, reliability theory seems
3680 to be a promising approach for developing a comprehensive theory of
3681 aging and longevity integrating mathematical methods with specific
3682 biological knowledge.",
3683 note = "An example of exponential (standard) Gomperz law."
3686 @article { gergely00,
3687 author = CGergely #" and "# JCVoegel #" and "# PSchaaf #" and "# BSenger #"
3688 and "# MMaaloum #" and "# JHorber #" and "# JHemmerle,
3689 title = "Unbinding process of adsorbed proteins under external stress
3690 studied by atomic force microscopy spectroscopy",
3695 pages = "10802--10807",
3696 doi = "10.1073/pnas.180293097",
3697 eprint = "http://www.pnas.org/cgi/reprint/97/20/10802.pdf",
3698 url = "http://www.pnas.org/cgi/content/abstract/97/20/10802"
3701 @article { gompertz25,
3703 title = "On the Nature of the Function Expressive of the Law of Human
3704 Mortality, and on a New Mode of Determining the Value of Life
3713 copyright = "Copyright \copy\ 1825 The Royal Society",
3714 url = "http://www.jstor.org/stable/107756",
3716 jstor_articletype = "primary_article",
3717 jstor_formatteddate = 1825,
3718 jstor_issuetitle = ""
3723 title = {The significance of the difference between two means when
3724 the population variances are unequal},
3731 keywords = "Population",
3733 url = "http://www.jstor.org/stable/2332010",
3739 title = {The generalization of {Student's} problems when several
3740 different population variances are involved},
3747 keywords = "Population",
3749 url = "http://www.ncbi.nlm.nih.gov/pubmed/20287819",
3750 jstor_url = "http://www.jstor.org/stable/2332510",
3754 @article { granzier97,
3755 author = HLGranzier #" and "# MSKellermayer #" and "# MHelmes #" and "#
3757 title = "Titin elasticity and mechanism of passive force development in rat
3758 cardiac myocytes probed by thin-filament extraction",
3764 pages = "2043--2053",
3766 doi = "10.1016/S0006-3495(97)78234-1",
3767 url = "http://www.cell.com/biophysj/retrieve/pii/S0006349597782341",
3768 keywords = "Amino Acid Sequence;Animals;Biomechanics;Biophysical
3769 Phenomena;Biophysics;Cell Fractionation;Elasticity;Gelsolin;Microscopy,
3770 Immunoelectron;Models, Cardiovascular;Molecular Structure;Muscle
3771 Proteins;Myocardial Contraction;Myocardium;Protein
3772 Kinases;Rats;Sarcomeres",
3773 abstract = "Titin (also known as connectin) is a giant filamentous protein
3774 whose elastic properties greatly contribute to the passive force in
3775 muscle. In the sarcomere, the elastic I-band segment of titin may
3776 interact with the thin filaments, possibly affecting the molecule's
3777 elastic behavior. Indeed, several studies have indicated that
3778 interactions between titin and actin occur in vitro and may occur in
3779 the sarcomere as well. To explore the properties of titin alone, one
3780 must first eliminate the modulating effect of the thin filaments by
3781 selectively removing them. In the present work, thin filaments were
3782 selectively removed from the cardiac myocyte by using a gelsolin
3783 fragment. Partial extraction left behind approximately 100-nm-long thin
3784 filaments protruding from the Z-line, whereas the rest of the I-band
3785 became devoid of thin filaments, exposing titin. By applying a much
3786 more extensive gelsolin treatment, we also removed the remaining short
3787 thin filaments near the Z-line. After extraction, the extensibility of
3788 titin was studied by using immunoelectron microscopy, and the passive
3789 force-sarcomere length relation was determined by using mechanical
3790 techniques. Titin's regional extensibility was not detectably affected
3791 by partial thin-filament extraction. Passive force, on the other hand,
3792 was reduced at sarcomere lengths longer than approximately 2.1 microm,
3793 with a 33 +/- 9\% reduction at 2.6 microm. After a complete extraction,
3794 the slack sarcomere length was reduced to approximately 1.7 microm. The
3795 segment of titin near the Z-line, which is otherwise inextensible,
3796 collapsed toward the Z-line in sarcomeres shorter than approximately
3797 2.0 microm, but it was extended in sarcomeres longer than approximately
3798 2.3 microm. Passive force became elevated at sarcomere lengths between
3799 approximately 1.7 and approximately 2.1 microm, but was reduced at
3800 sarcomere lengths of >2.3 microm. These changes can be accounted for by
3801 modeling titin as two wormlike chains in series, one of which increases
3802 its contour length by recruitment of the titin segment near the Z-line
3803 into the elastic pool."
3806 @article { grossman05,
3807 author = CGrossman #" and "# AStout,
3808 title = "Optical Tweezers Advanced Lab",
3812 eprint = "http://chirality.swarthmore.edu/PHYS81/OpticalTweezers.pdf",
3813 note = {Fairly complete overdamped PSD derivation in
3814 \fref{section}{4.3}. Cites \citet{tlusty98} and
3815 \citet{bechhoefer02} for further details. However, Tlusty
3816 (listed as reference 8) doesn't contain the thermal response
3817 fn.\ derivation it was cited for. Also, the single sided PSD
3818 definition credited to reference 9 (listed as Bechhoefer)
3819 looks more like Press (listed as reference 10). I imagine
3820 Grossman and Stout mixed up their references, and meant to
3821 refer to \citet{bechhoefer02} and \citet{press92} respectively
3823 project = "Cantilever Calibration"
3826 @article { halvorsen09,
3827 author = KHalvorsen #" and "# WPWong,
3828 title = "Massively parallel single-molecule manipulation using centrifugal
3832 url = "http://arxiv.org/abs/0912.5370",
3833 abstract = {Precise manipulation of single molecules has already led to
3834 remarkable insights in physics, chemistry, biology and medicine.
3835 However, widespread adoption of single-molecule techniques has been
3836 impeded by equipment cost and the laborious nature of making
3837 measurements one molecule at a time. We have solved these issues with a
3838 new approach: massively parallel single-molecule force measurements
3839 using centrifugal force. This approach is realized in a novel
3840 instrument that we call the Centrifuge Force Microscope (CFM), in which
3841 objects in an orbiting sample are subjected to a calibration-free,
3842 macroscopically uniform force-field while their micro-to-nanoscopic
3843 motions are observed. We demonstrate high-throughput single-molecule
3844 force spectroscopy with this technique by performing thousands of
3845 rupture experiments in parallel, characterizing force-dependent
3846 unbinding kinetics of an antibody-antigen pair in minutes rather than
3847 days. Additionally, we verify the force accuracy of the instrument by
3848 measuring the well-established DNA overstretching transition at 66
3849 $\pm$ 3 pN. With significant benefits in efficiency, cost, simplicity,
3850 and versatility, "single-molecule centrifugation" has the potential to
3851 revolutionize single-molecule experimentation, and open access to a
3852 wider range of researchers and experimental systems.}
3855 @article { hanggi90,
3856 author = PHanggi #" and "# PTalkner #" and "# MBorkovec,
3857 title = "Reaction-rate theory: Fifty years after {K}ramers",
3866 doi = "10.1103/RevModPhys.62.251",
3867 eprint = "http://www.physik.uni-augsburg.de/theo1/hanggi/Papers/112.pdf",
3868 url = "http://prola.aps.org/abstract/RMP/v62/i2/p251_1",
3869 note = "\emph{The} Kramers' theory review article. See pages 268--279 for
3870 the Kramers-specific introduction.",
3871 project = "sawtooth simulation"
3874 @article { hatfield99,
3875 author = JWHatfield #" and "# SRQuake,
3876 title = "Dynamic Properties of an Extended Polymer in Solution",
3882 pages = "3548--3551",
3885 doi = "10.1103/PhysRevLett.82.3548",
3886 url = "http://link.aps.org/abstract/PRL/v82/p3548",
3887 note = "Defines WLC and FJC models, citing textbooks.",
3888 project = "sawtooth simulation"
3891 @article { heymann00,
3892 author = BHeymann #" and "# HGrubmuller,
3893 title = "Dynamic force spectroscopy of molecular adhesion bonds",
3900 pages = "6126--6129",
3902 doi = "10.1103/PhysRevLett.84.6126",
3903 eprint = "http://prola.aps.org/pdf/PRL/v84/i26/p6126_1",
3904 url = "http://prola.aps.org/abstract/PRL/v84/p6126",
3905 abstract = "Recent advances in atomic force microscopy, biomembrane force
3906 probe experiments, and optical tweezers allow one to measure the
3907 response of single molecules to mechanical stress with high precision.
3908 Such experiments, due to limited spatial resolution, typically access
3909 only one single force value in a continuous force profile that
3910 characterizes the molecular response along a reaction coordinate. We
3911 develop a theory that allows one to reconstruct force profiles from
3912 force spectra obtained from measurements at varying loading rates,
3913 without requiring increased resolution. We show that spectra obtained
3914 from measurements with different spring constants contain complementary
3918 @article { hummer01,
3919 author = GHummer #" and "# ASzabo,
3920 title = "From the Cover: Free energy reconstruction from nonequilibrium
3921 single-molecule pulling experiments",
3926 pages = "3658--3661",
3927 doi = "10.1073/pnas.071034098",
3928 eprint = "http://www.pnas.org/cgi/reprint/98/7/3658.pdf",
3929 url = "http://www.pnas.org/cgi/content/abstract/98/7/3658",
3933 @article { hummer03,
3934 author = GHummer #" and "# ASzabo,
3935 title = "Kinetics from nonequilibrium single-molecule pulling experiments",
3943 eprint = "http://www.biophysj.org/cgi/reprint/85/1/5.pdf",
3944 url = "http://www.biophysj.org/cgi/content/abstract/85/1/5",
3945 keywords = "Computer Simulation; Crystallography; Energy Transfer;
3946 Kinetics; Lasers; Micromanipulation; Microscopy, Atomic Force; Models,
3947 Molecular; Molecular Conformation; Motion; Muscle Proteins;
3948 Nanotechnology; Physical Stimulation; Protein Conformation; Protein
3949 Denaturation; Protein Folding; Protein Kinases; Stress, Mechanical",
3950 abstract = "Mechanical forces exerted by laser tweezers or atomic force
3951 microscopes can be used to drive rare transitions in single molecules,
3952 such as unfolding of a protein or dissociation of a ligand. The
3953 phenomenological description of pulling experiments based on Bell's
3954 expression for the force-induced rupture rate is found to be inadequate
3955 when tested against computer simulations of a simple microscopic model
3956 of the dynamics. We introduce a new approach of comparable complexity
3957 to extract more accurate kinetic information about the molecular events
3958 from pulling experiments. Our procedure is based on the analysis of a
3959 simple stochastic model of pulling with a harmonic spring and
3960 encompasses the phenomenological approach, reducing to it in the
3961 appropriate limit. Our approach is tested against computer simulations
3962 of a multimodule titin model with anharmonic linkers and then an
3963 illustrative application is made to the forced unfolding of I27
3964 subunits of the protein titin. Our procedure to extract kinetic
3965 information from pulling experiments is simple to implement and should
3966 prove useful in the analysis of experiments on a variety of systems.",
3968 project = "sawtooth simulation"
3971 @article { hutter05,
3973 title = "Comment on tilt of atomic force microscope cantilevers: Effect on
3974 spring constant and adhesion measurements.",
3981 pages = "2630--2632",
3983 doi = "10.1021/la047670t",
3984 note = "Tilted cantilever corrections (not needed? see Ohler/VEECO note)",
3985 project = "Cantilever Calibration"
3988 @article { hutter93,
3989 author = JHutter #" and "# JBechhoefer,
3990 title = "Calibration of atomic-force microscope tips",
3995 pages = "1868--1873",
3997 doi = "10.1063/1.1143970",
3998 url = "http://link.aip.org/link/?RSI/64/1868/1",
3999 keywords = {atomic force microscopy; calibration; quality factor; probes;
4000 resonance; silicon nitrides; mica; van der waals forces},
4001 note = {Original equipartition-based calibration method (thermal
4002 calibration), after the brief mention in \citet{howard88}.
4003 This is the first paper I've found that works out the theory
4004 in detail, although they punt to page 431 of \citet{heer72}
4005 instead of listing a formula for their ``Lorentzian''. The
4006 experimental data uses high-$Q$ cantilevers in air, and their
4007 figure 2 shows clear water-layer snap-off. There is a
4008 published erratum\citep{hutter93-erratum}.},
4009 project = "Cantilever Calibration"
4012 @article{ hutter93-erratum,
4013 author = JHutter #" and "# JBechhoefer,
4014 title = "Erratum: Calibration of atomic-force microscope tips",
4022 doi = "10.1063/1.1144449",
4023 url = "http://rsi.aip.org/resource/1/rsinak/v64/i11/p3342_s1",
4024 note = {V.~Croquette pointed out that they should calibrate the
4025 response of their optical-detection electronics.},
4026 project = "Cantilever Calibration",
4031 title = {Statistical mechanics, kinetic theory, and stochastic processes},
4034 address = {New York},
4036 isbn = {0-123-36550-3},
4037 language = {English},
4038 keywords = {Statistical mechanics.; Kinetic theory of gases.; Stochastic processes.},
4042 author = CHyeon #" and "# DThirumalai,
4043 title = "Can energy landscape roughness of proteins and {RNA} be measured
4044 by using mechanical unfolding experiments?",
4051 pages = "10249--10253",
4053 doi = "10.1073/pnas.1833310100",
4054 eprint = "http://www.pnas.org/cgi/reprint/100/18/10249.pdf",
4055 url = "http://www.pnas.org/cgi/content/abstract/100/18/10249",
4056 keywords = "Protein Folding; Proteins; RNA; Temperature; Thermodynamics",
4057 abstract = "By considering temperature effects on the mechanical unfolding
4058 rates of proteins and RNA, whose energy landscape is rugged, the
4059 question posed in the title is answered in the affirmative. Adopting a
4060 theory by Zwanzig [Zwanzig, R. (1988) Proc. Natl. Acad. Sci. USA 85,
4061 2029-2030], we show that, because of roughness characterized by an
4062 energy scale epsilon, the unfolding rate at constant force is retarded.
4063 Similarly, in nonequilibrium experiments done at constant loading
4064 rates, the most probable unfolding force increases because of energy
4065 landscape roughness. The effects are dramatic at low temperatures. Our
4066 analysis suggests that, by using temperature as a variable in
4067 mechanical unfolding experiments of proteins and RNA, the ruggedness
4068 energy scale epsilon, can be directly measured.",
4069 note = "Derives the major theory behind my thesis. The Kramers rate
4070 equation is \xref{hanggi90}{equation}{4.56c} (page 275).",
4071 project = "Energy Landscape Roughness"
4074 @article { improta96,
4075 author = SImprota #" and "# ASPolitou #" and "# APastore,
4076 title = "Immunoglobulin-like modules from titin {I}-band: Extensible
4077 components of muscle elasticity.",
4086 doi = "10.1016/S0969-2126(96)00036-6",
4087 keywords = "Amino Acid Sequence;Immunoglobulins;Magnetic Resonance
4088 Spectroscopy;Models, Molecular;Molecular Sequence Data;Molecular
4089 Structure;Muscle Proteins;Protein Kinases;Protein Structure,
4090 Secondary;Protein Structure, Tertiary;Sequence Alignment",
4091 abstract = "BACKGROUND. The giant muscle protein titin forms a filament
4092 which spans half of the sarcomere and performs, along its length, quite
4093 diverse functions. The region of titin located in the sarcomere I-band
4094 is believed to play a major role in extensibility and passive
4095 elasticity of muscle. In the I-band, the titin sequence consists mostly
4096 of repetitive motifs of tandem immunoglobulin-like (Ig) modules
4097 intercalated by a potentially non-globular region. The highly
4098 repetitive titin architecture suggests that the molecular basis of its
4099 mechanical properties be approached through the characterization of the
4100 isolated components of the I-band and their interfaces. In the present
4101 paper, we report on the structure determination in solution of a
4102 representative Ig module from the I-band (I27) as solved by NMR
4103 techniques. RESULTS. The structure of I27 consists of a beta sandwich
4104 formed by two four-stranded sheets (named ABED and A'GFC). This fold
4105 belongs to the intermediate frame (I frame) of the immunoglobulin
4106 superfamily. Comparison of I27 with another titin module from the
4107 region located in the M-line (M5) shows that two loops (between the B
4108 and C and the F and G strands) are shorter in I27, conferring a less
4109 elongated appearance to this structure. Such a feature is specific to
4110 the Ig domains in the I-band and might therefore be related to the
4111 functions of the protein in this region. The structure of tandem Ig
4112 domains as modeled from I27 suggests the presence of hinge regions
4113 connecting contiguous modules. CONCLUSIONS. We suggest that titin Ig
4114 domains in the I-band function as extensible components of muscle
4115 elasticity by stretching the hinge regions.",
4116 note = "\href{http://www.rcsb.org/pdb/explore.do?structureId=1TIT}{PDB ID:
4118 \href{http://dx.doi.org/10.2210/pdb1tit/pdb}{10.2210/pdb1tit/pdb}."
4121 @article { irback05,
4122 author = AIrback #" and "# SMitternacht #" and "# SMohanty,
4123 title = "Dissecting the mechanical unfolding of ubiquitin",
4128 pages = "13427--13432",
4129 doi = "10.1073/pnas.0501581102",
4130 eprint = "http://www.pnas.org/cgi/reprint/102/38/13427.pdf",
4131 url = "http://www.pnas.org/cgi/content/abstract/102/38/13427",
4132 abstract = "The unfolding behavior of ubiquitin under the influence of a
4133 stretching force recently was investigated experimentally by single-
4134 molecule constant-force methods. Many observed unfolding traces had a
4135 simple two-state character, whereas others showed clear evidence of
4136 intermediate states. Here, we use Monte Carlo simulations to
4137 investigate the force-induced unfolding of ubiquitin at the atomic
4138 level. In agreement with experimental data, we find that the unfolding
4139 process can occur either in a single step or through intermediate
4140 states. In addition to this randomness, we find that many quantities,
4141 such as the frequency of occurrence of intermediates, show a clear
4142 systematic dependence on the strength of the applied force. Despite
4143 this diversity, one common feature can be identified in the simulated
4144 unfolding events, which is the order in which the secondary-structure
4145 elements break. This order is the same in two- and three-state events
4146 and at the different forces studied. The observed order remains to be
4147 verified experimentally but appears physically reasonable."
4150 @article{ grubmuller96,
4151 author = HGrubmuller #" and "# BHeymann #" and "# PTavan,
4152 title = {Ligand binding: molecular mechanics calculation of the
4153 streptavidin-biotin rupture force.},
4157 address = {Theoretische Biophysik, Institut f{\"u}r Medizinische
4158 Optik, Ludwig- Maximilians-Universit{\"a}t M{\"u}nchen,
4159 Germany. Helmut.Grubmueller@ Physik.uni-muenchen.de},
4165 url = {http://www.ncbi.nlm.nih.gov/pubmed/8584939},
4166 eprint = {http://pubman.mpdl.mpg.de/pubman/item/escidoc:1690312:2/component/escidoc:1690313/1690312.pdf},
4168 keywords = {Bacterial Proteins},
4169 keywords = {Biotin},
4170 keywords = {Chemistry, Physical},
4171 keywords = {Computer Simulation},
4172 keywords = {Hydrogen Bonding},
4173 keywords = {Ligands},
4174 keywords = {Microscopy, Atomic Force},
4175 keywords = {Models, Chemical},
4176 keywords = {Molecular Conformation},
4177 keywords = {Physicochemical Phenomena},
4178 keywords = {Protein Conformation},
4179 keywords = {Streptavidin},
4180 keywords = {Thermodynamics},
4181 abstract = {The force required to rupture the streptavidin-biotin
4182 complex was calculated here by computer simulations.
4183 The computed force agrees well with that obtained by
4184 recent single molecule atomic force microscope
4185 experiments. These simulations suggest a detailed
4186 multiple-pathway rupture mechanism involving five major
4187 unbinding steps. Binding forces and specificity are
4188 attributed to a hydrogen bond network between the
4189 biotin ligand and residues within the binding pocket of
4190 streptavidin. During rupture, additional water bridges
4191 substantially enhance the stability of the complex and
4192 even dominate the binding interactions. In contrast,
4193 steric restraints do not appear to contribute to the
4194 binding forces, although conformational motions were
4199 @article { izrailev97,
4200 author = SIzrailev #" and "# SStepaniants #" and "# MBalsera #" and "#
4201 YOono #" and "# KSchulten,
4202 title = "Molecular dynamics study of unbinding of the avidin-biotin
4209 pages = "1568--1581",
4211 eprint = "http://www.biophysj.org/cgi/reprint/72/4/1568.pdf",
4212 url = "http://www.biophysj.org/cgi/content/abstract/72/4/1568",
4213 keywords = "Avidin;Binding Sites;Biotin;Computer Simulation;Hydrogen
4214 Bonding;Mathematics;Microscopy, Atomic Force;Microspheres;Models,
4215 Molecular;Molecular Structure;Protein Binding;Protein
4216 Conformation;Protein Folding;Sepharose",
4217 abstract = "We report molecular dynamics simulations that induce, over
4218 periods of 40-500 ps, the unbinding of biotin from avidin by means of
4219 external harmonic forces with force constants close to those of AFM
4220 cantilevers. The applied forces are sufficiently large to reduce the
4221 overall binding energy enough to yield unbinding within the measurement
4222 time. Our study complements earlier work on biotin-streptavidin that
4223 employed a much larger harmonic force constant. The simulations reveal
4224 a variety of unbinding pathways, the role of key residues contributing
4225 to adhesion as well as the spatial range over which avidin binds
4226 biotin. In contrast to the previous studies, the calculated rupture
4227 forces exceed by far those observed. We demonstrate, in the framework
4228 of models expressed in terms of one-dimensional Langevin equations with
4229 a schematic binding potential, the associated Smoluchowski equations,
4230 and the theory of first passage times, that picosecond to nanosecond
4231 simulation of ligand unbinding requires such strong forces that the
4232 resulting protein-ligand motion proceeds far from the thermally
4233 activated regime of millisecond AFM experiments, and that simulated
4234 unbinding cannot be readily extrapolated to the experimentally observed
4238 @article { janshoff00,
4239 author = AJanshoff #" and "# MNeitzert #" and "# YOberdorfer #" and "#
4241 title = "Force Spectroscopy of Molecular Systems-Single Molecule
4242 Spectroscopy of Polymers and Biomolecules.",
4249 pages = "3212--3237",
4251 doi = "10.1002/1521-3773(20000915)39:18<3212::AID-ANIE3212>3.0.CO;2-X",
4253 url = "http://dx.doi.org/10.1002/1521-3773(20000915)39:18<3212::AID-ANIE3212>3.0.CO;2-X",
4254 abstract = "How do molecules interact with each other? What happens if a
4255 neurotransmitter binds to a ligand-operated ion channel? How do
4256 antibodies recognize their antigens? Molecular recognition events play
4257 a pivotal role in nature: in enzymatic catalysis and during the
4258 replication and transcription of the genome; it is also important for
4259 the cohesion of cellular structures and in numerous metabolic reactions
4260 that molecules interact with each other in a specific manner.
4261 Conventional methods such as calorimetry provide very precise values of
4262 binding enthalpies; these are, however, average values obtained from a
4263 large ensemble of molecules without knowledge of the dynamics of the
4264 molecular recognition event. Which forces occur when a single molecular
4265 couple meets and forms a bond? Since the development of the scanning
4266 force microscope and force spectroscopy a couple of years ago, tools
4267 have now become available for measuring the forces between interfaces
4268 with high precision-starting from colloidal forces to the interaction
4269 of single molecules. The manipulation of individual molecules using
4270 force spectroscopy is also possible. In this way, the mechanical
4271 properties on a molecular scale are measurable. The study of single
4272 molecules is not an exclusive domain of force spectroscopy; it can also
4273 be performed with a surface force apparatus, laser tweezers, or the
4274 micropipette technique. Regardless of these techniques, force
4275 spectroscopy has been proven as an extraordinary versatile tool. The
4276 intention of this review article is to present a critical evaluation of
4277 the actual development of static force spectroscopy. The article mainly
4278 focuses on experiments dealing with inter- and intramolecular forces-
4279 starting with ``simple'' electrostatic forces, then ligand-receptor
4280 systems, and finally the stretching of individual molecules."
4283 @article { jollymore09,
4284 author = AJollymore #" and "# CLethias #" and "# QPeng #" and "# YCao #"
4286 title = "Nanomechanical properties of tenascin-{X} revealed by single-
4287 molecule force spectroscopy",
4294 pages = "1277--1286",
4296 doi = "10.1016/j.jmb.2008.11.038",
4297 url = "http://dx.doi.org/10.1016/j.jmb.2008.11.038",
4298 keywords = "Animals;Biomechanics;Cattle;Fibronectins;Kinetics;Microscopy,
4299 Atomic Force;Protein Folding;Protein Structure, Tertiary;Spectrum
4301 abstract = "Tenascin-X is an extracellular matrix protein and binds a
4302 variety of molecules in extracellular matrix and on cell membrane.
4303 Tenascin-X plays important roles in regulating the structure and
4304 mechanical properties of connective tissues. Using single-molecule
4305 atomic force microscopy, we have investigated the mechanical properties
4306 of bovine tenascin-X in detail. Our results indicated that tenascin-X
4307 is an elastic protein and the fibronectin type III (FnIII) domains can
4308 unfold under a stretching force and refold to regain their mechanical
4309 stability upon the removal of the stretching force. All the 30 FnIII
4310 domains of tenascin-X show similar mechanical stability, mechanical
4311 unfolding kinetics, and contour length increment upon domain unfolding,
4312 despite their large sequence diversity. In contrast to the homogeneity
4313 in their mechanical unfolding behaviors, FnIII domains fold at
4314 different rates. Using the 10th FnIII domain of tenascin-X (TNXfn10) as
4315 a model system, we constructed a polyprotein chimera composed of
4316 alternating TNXfn10 and GB1 domains and used atomic force microscopy to
4317 confirm that the mechanical properties of TNXfn10 are consistent with
4318 those of the FnIII domains of tenascin-X. These results lay the
4319 foundation to further study the mechanical properties of individual
4320 FnIII domains and establish the relationship between point mutations
4321 and mechanical phenotypic effect on tenascin-X. Moreover, our results
4322 provided the opportunity to compare the mechanical properties and
4323 design of different forms of tenascins. The comparison between
4324 tenascin-X and tenascin-C revealed interesting common as well as
4325 distinguishing features for mechanical unfolding and folding of
4326 tenascin-C and tenascin-X and will open up new avenues to investigate
4327 the mechanical functions and architectural design of different forms of
4332 author = REJones #" and "# DPHart,
4333 title = "Force interactions between substrates and {SPM} cantilevers
4334 immersed in fluids",
4341 doi = "10.1016/j.triboint.2004.08.016",
4342 url = "http://dx.doi.org/10.1016/j.triboint.2004.08.016",
4343 keywords = "AFM;Liquid;Hydrodynamic;Lubrication",
4344 abstract = "With the availability of equipment used in Scanning Probe
4345 Microscopy (SPM), researchers have been able to probe the local fluid-
4346 substrate force interactions with resolutions of pN using a variety of
4347 SPM cantilevers. When using such methods, it is essential to
4348 differentiate between contributions to the net force on the cantilever.
4349 Specifically, the interaction between the cantilever, substrate and
4350 fluid, quantified while generating force curves, are discussed and
4351 compared with theoretical models for squeeze-film effects and drag on
4352 the SPM cantilevers. In addition we have demonstrated a simple method
4353 for utilizing the system as a micro-viscometer, independently measuring
4354 the viscosity of the lubricant for each test."
4357 @article { juckett93,
4358 author = DAJuckett #" and "# BRosenberg,
4359 title = "Comparison of the {G}ompertz and {W}eibull functions as
4360 descriptors for human mortality distributions and their intersections",
4368 doi = "10.1016/0047-6374(93)90068-3",
4369 keywords = "Adolescent;Adult;Aged;Aged, 80 and
4370 over;Aging;Biometry;Child;Child, Preschool;Data Interpretation,
4371 Statistical;Female;Humans;Infant;Infant, Newborn;Longitudinal
4372 Studies;Male;Middle Aged;Models, Biological;Models,
4373 Statistical;Mortality",
4374 abstract = "The Gompertz and Weibull functions are compared with respect to
4375 goodness-of-fit to human mortality distributions; ability to describe
4376 mortality curve intersections; and, parameter interpretation. The
4377 Gompertz function is shown to be a better descriptor for 'all-causes'
4378 of deaths and combined disease categories while the Weibull function is
4379 shown to be a better descriptor of purer, single causes-of-death. A
4380 modified form of the Weibull function maps directly to the inherent
4381 degrees of freedom of human mortality distributions while the Gompertz
4382 function does not. Intersections in the old-age tails of mortality are
4383 explored in the context of both functions and, in particular, the
4384 relationship between distribution intersections, and the Gompertz
4385 ln[R0] versus alpha regression is examined. Evidence is also presented
4386 that mortality intersections are fundamental to the survivorship form
4387 and not the rate (hazard) form. Finally, comparisons are made to the
4388 parameter estimates in recent longitudinal Gompertzian analyses and the
4389 probable errors in those analyses are discussed.",
4390 note = "Nice table of various functions associated with Gompertz and
4394 @article { kaplan58,
4395 author = ELKaplan #" and "# PMeier,
4396 title = "Nonparametric Estimation from Incomplete Observations",
4405 copyright = "Copyright \copy\ 1958 American Statistical Association",
4406 url = "http://www.jstor.org/stable/2281868",
4410 @article { kellermayer03,
4411 author = MSKellermayer #" and "# CBustamante #" and "# HLGranzier,
4412 title = "Mechanics and structure of titin oligomers explored with atomic
4420 doi = "10.1016/S0005-2728(03)00029-X",
4421 url = "http://dx.doi.org/10.1016/S0005-2728(03)00029-X",
4422 keywords = "Titin;Wormlike chain;Unfolding;Elasticity;AFM;Molecular force
4424 abstract = "Titin is a giant polypeptide that spans half of the striated
4425 muscle sarcomere and generates passive force upon stretch. To explore
4426 the elastic response and structure of single molecules and oligomers of
4427 titin, we carried out molecular force spectroscopy and atomic force
4428 microscopy (AFM) on purified full-length skeletal-muscle titin. From
4429 the force data, apparent persistence lengths as long as ~1.5 nm were
4430 obtained for the single, unfolded titin molecule. Furthermore, data
4431 suggest that titin molecules may globally associate into oligomers
4432 which mechanically behave as independent wormlike chains (WLCs).
4433 Consistent with this, AFM of surface-adsorbed titin molecules revealed
4434 the presence of oligomers. Although oligomers may form globally via
4435 head-to-head association of titin, the constituent molecules otherwise
4436 appear independent from each other along their contour. Based on the
4437 global association but local independence of titin molecules, we
4438 discuss a mechanical model of the sarcomere in which titin molecules
4439 with different contour lengths, corresponding to different isoforms,
4440 are held in a lattice. The net force response of aligned titin
4441 molecules is determined by the persistence length of the tandemly
4442 arranged, different WLC components of the individual molecules, the
4443 ratio of their overall contour lengths, and by domain unfolding events.
4444 Biased domain unfolding in mechanically selected constituent molecules
4445 may serve as a compensatory mechanism for contour- and persistence-
4446 length differences. Variation in the ratio and contour length of the
4447 component chains may provide mechanisms for the fine-tuning of the
4448 sarcomeric passive force response.",
4452 @article { kellermayer97,
4453 author = MSKellermayer #" and "# SBSmith #" and "# HLGranzier #" and "#
4455 title = "Folding-unfolding transitions in single titin molecules
4456 characterized with laser tweezers",
4463 pages = "1112--1116",
4465 keywords = "Amino Acid
4466 Sequence;Elasticity;Entropy;Immunoglobulins;Lasers;Models,
4467 Chemical;Muscle Contraction;Muscle Proteins;Muscle Relaxation;Muscle,
4468 Skeletal;Protein Denaturation;Protein Folding;Protein Kinases;Stress,
4470 abstract = "Titin, a giant filamentous polypeptide, is believed to play a
4471 fundamental role in maintaining sarcomeric structural integrity and
4472 developing what is known as passive force in muscle. Measurements of
4473 the force required to stretch a single molecule revealed that titin
4474 behaves as a highly nonlinear entropic spring. The molecule unfolds in
4475 a high-force transition beginning at 20 to 30 piconewtons and refolds
4476 in a low-force transition at approximately 2.5 piconewtons. A fraction
4477 of the molecule (5 to 40 percent) remains permanently unfolded,
4478 behaving as a wormlike chain with a persistence length (a measure of
4479 the chain's bending rigidity) of 20 angstroms. Force hysteresis arises
4480 from a difference between the unfolding and refolding kinetics of the
4481 molecule relative to the stretch and release rates in the experiments,
4482 respectively. Scaling the molecular data up to sarcomeric dimensions
4483 reproduced many features of the passive force versus extension curve of
4488 author = WKing #" and "# MSu #" and "# GYang,
4489 title = "{M}onte {C}arlo simulation of mechanical unfolding of proteins
4490 based on a simple two-state model",
4494 address = "Department of Physics, Drexel University, 3141
4495 Chestnut Street, Philadelphia, PA 19104, USA.",
4501 alternative_issn = "1879-0003",
4502 doi = "10.1016/j.ijbiomac.2009.12.001",
4503 url = "http://dx.doi.org/10.1016/j.ijbiomac.2009.12.001",
4505 keywords = "Atomic force microscopy;Mechanical unfolding;Monte Carlo
4506 simulation;Worm-like chain;Single molecule methods",
4507 abstract = "Single molecule methods are becoming routine biophysical
4508 techniques for studying biological macromolecules. In mechanical
4509 unfolding of proteins, an externally applied force is used to induce
4510 the unfolding of individual protein molecules. Such experiments have
4511 revealed novel information that has significantly enhanced our
4512 understanding of the function and folding mechanisms of several types
4513 of proteins. To obtain information on the unfolding kinetics and the
4514 free energy landscape of the protein molecule from mechanical unfolding
4515 data, a Monte Carlo simulation based on a simple two-state kinetic
4516 model is often used. In this paper, we provide a detailed description
4517 of the procedure to perform such simulations and discuss the
4518 approximations and assumptions involved. We show that the appearance of
4519 the force versus extension curves from mechanical unfolding of proteins
4520 is affected by a variety of experimental parameters, such as the length
4521 of the protein polymer and the force constant of the cantilever. We
4522 also analyze the errors associated with different methods of data
4523 pooling and present a quantitative measure of how well the simulation
4524 results fit experimental data. These findings will be helpful in
4525 experimental design, artifact identification, and data analysis for
4526 single molecule studies of various proteins using the mechanical
4528 note = "Sawsim is available at \url{http://blog.tremily.us/posts/sawsim/}.",
4531 @article { kleiner07,
4532 author = AKleiner #" and "# EShakhnovich,
4533 title = "The mechanical unfolding of ubiquitin through all-atom Monte Carlo
4534 simulation with a Go-type potential",
4541 pages = "2054--2061",
4543 doi = "10.1529/biophysj.106.081257",
4544 eprint = "http://www.biophysj.org/cgi/reprint/92/6/2054",
4545 url = "http://www.biophysj.org/cgi/content/full/92/6/2054",
4546 keywords = "Computer Simulation; Models, Chemical; Models, Molecular;
4547 Models, Statistical; Monte Carlo Method; Motion; Protein Conformation;
4548 Protein Denaturation; Protein Folding; Ubiquitin",
4549 abstract = "The mechanical unfolding of proteins under a stretching force
4550 has an important role in living systems and is a logical extension of
4551 the more general protein folding problem. Recent advances in
4552 experimental methodology have allowed the stretching of single
4553 molecules, thus rendering this process ripe for computational study. We
4554 use all-atom Monte Carlo simulation with a G?-type potential to study
4555 the mechanical unfolding pathway of ubiquitin. A detailed, robust,
4556 well-defined pathway is found, confirming existing results in this vein
4557 though using a different model. Additionally, we identify the protein's
4558 fundamental stabilizing secondary structure interactions in the
4559 presence of a stretching force and show that this fundamental
4560 stabilizing role does not persist in the absence of mechanical stress.
4561 The apparent success of simulation methods in studying ubiquitin's
4562 mechanical unfolding pathway indicates their potential usefulness for
4563 future study of the stretching of other proteins and the relationship
4564 between protein structure and the response to mechanical deformation."
4567 @article { klimov00,
4568 author = DKlimov #" and "# DThirumalai,
4569 title = "Native topology determines force-induced unfolding pathways in
4577 pages = "7254--7259",
4579 doi = "10.1073/pnas.97.13.7254",
4580 eprint = "http://www.pnas.org/cgi/reprint/97/13/7254.pdf",
4581 url = "http://www.pnas.org/cgi/content/abstract/97/13/7254",
4582 keywords = "Animals; Humans; Protein Folding; Proteins; Spectrin",
4583 abstract = "Single-molecule manipulation techniques reveal that stretching
4584 unravels individually folded domains in the muscle protein titin and
4585 the extracellular matrix protein tenascin. These elastic proteins
4586 contain tandem repeats of folded domains with beta-sandwich
4587 architecture. Herein, we propose by stretching two model sequences (S1
4588 and S2) with four-stranded beta-barrel topology that unfolding forces
4589 and pathways in folded domains can be predicted by using only the
4590 structure of the native state. Thermal refolding of S1 and S2 in the
4591 absence of force proceeds in an all-or-none fashion. In contrast, phase
4592 diagrams in the force-temperature (f,T) plane and steered Langevin
4593 dynamics studies of these sequences, which differ in the native
4594 registry of the strands, show that S1 unfolds in an allor-none fashion,
4595 whereas unfolding of S2 occurs via an obligatory intermediate. Force-
4596 induced unfolding is determined by the native topology. After proving
4597 that the simulation results for S1 and S2 can be calculated by using
4598 native topology alone, we predict the order of unfolding events in Ig
4599 domain (Ig27) and two fibronectin III type domains ((9)FnIII and
4600 (10)FnIII). The calculated unfolding pathways for these proteins, the
4601 location of the transition states, and the pulling speed dependence of
4602 the unfolding forces reflect the differences in the way the strands are
4603 arranged in the native states. We also predict the mechanisms of force-
4604 induced unfolding of the coiled-coil spectrin (a three-helix bundle
4605 protein) for all 20 structures deposited in the Protein Data Bank. Our
4606 approach suggests a natural way to measure the phase diagram in the
4607 (f,C) plane, where C is the concentration of denaturants.",
4608 note = {Simulated unfolding time scales for Ig27-like S1 and S2 domains.},
4611 @article { klimov99,
4612 author = DKlimov #" and "# DThirumalai,
4613 title = "Stretching single-domain proteins: Phase diagram and kinetics of
4614 force-induced unfolding",
4621 pages = "6166--6170",
4623 keywords = "Amino Acid Sequence;Kinetics;Models, Chemical;Protein
4624 Denaturation;Protein Folding;Proteins;Thermodynamics;Time Factors",
4625 abstract = "Single-molecule force spectroscopy reveals unfolding of domains
4626 in titin on stretching. We provide a theoretical framework for these
4627 experiments by computing the phase diagrams for force-induced unfolding
4628 of single-domain proteins using lattice models. The results show that
4629 two-state folders (at zero force) unravel cooperatively, whereas
4630 stretching of non-two-state folders occurs through intermediates. The
4631 stretching rates of individual molecules show great variations
4632 reflecting the heterogeneity of force-induced unfolding pathways. The
4633 approach to the stretched state occurs in a stepwise ``quantized''
4634 manner. Unfolding dynamics and forces required to stretch proteins
4635 depend sensitively on topology. The unfolding rates increase
4636 exponentially with force f till an optimum value, which is determined
4637 by the barrier to unfolding when f = 0. A mapping of these results to
4638 proteins shows qualitative agreement with force-induced unfolding of
4639 Ig-like domains in titin. We show that single-molecule force
4640 spectroscopy can be used to map the folding free energy landscape of
4641 proteins in the absence of denaturants."
4644 @article { kosztin06,
4645 author = IKosztin #" and "# BBarz #" and "# LJanosi,
4646 title = "Calculating potentials of mean force and diffusion coefficients
4647 from nonequilibrium processes without Jarzynski's equality",
4655 doi = "10.1063/1.2166379",
4656 url = "http://link.aip.org/link/?JCPSA6/124/064106/1"
4659 @article { kramers40,
4661 title = "Brownian motion in a field of force and the diffusion model of
4662 chemical reactions",
4670 doi = "10.1016/S0031-8914(40)90098-2",
4671 url = "http://dx.doi.org/10.1016/S0031-8914(40)90098-2",
4672 abstract = "A particle which is caught in a potential hole and which,
4673 through the shuttling action of Brownian motion, can escape over a
4674 potential barrier yields a suitable model for elucidating the
4675 applicability of the transition state method for calculating the rate
4676 of chemical reactions.",
4677 note = "Seminal paper on thermally activated barrier crossings."
4680 @article { krammer99,
4681 author = AKrammer #" and "# HLu #" and "# BIsralewitz #" and "# KSchulten
4683 title = "Forced unfolding of the fibronectin type {III} module reveals a
4684 tensile molecular recognition switch",
4691 pages = "1351--1356",
4693 keywords = "Amino Acid Sequence;Binding Sites;Computer
4694 Simulation;Crystallography, X-Ray;Disulfides;Fibronectins;Hydrogen
4695 Bonding;Integrins;Models, Molecular;Oligopeptides;Protein
4696 Conformation;Protein Denaturation;Protein Folding;Protein Structure,
4697 Secondary;Protein Structure, Tertiary;Software;Tensile Strength",
4698 abstract = "The 10th type III module of fibronectin possesses a beta-
4699 sandwich structure consisting of seven beta-strands (A-G) that are
4700 arranged in two antiparallel sheets. It mediates cell adhesion to
4701 surfaces via its integrin binding motif, Arg78, Gly79, and Asp80 (RGD),
4702 which is placed at the apex of the loop connecting beta-strands F and
4703 G. Steered molecular dynamics simulations in which tension is applied
4704 to the protein's terminal ends reveal that the beta-strand G is the
4705 first to break away from the module on forced unfolding whereas the
4706 remaining fold maintains its structural integrity. The separation of
4707 strand G from the remaining fold results in a gradual shortening of the
4708 distance between the apex of the RGD-containing loop and the module
4709 surface, which potentially reduces the loop's accessibility to surface-
4710 bound integrins. The shortening is followed by a straightening of the
4711 RGD-loop from a tight beta-turn into a linear conformation, which
4712 suggests a further decrease of affinity and selectivity to integrins.
4713 The RGD-loop therefore is located strategically to undergo strong
4714 conformational changes in the early stretching stages of the module and
4715 thus constitutes a mechanosensitive control of ligand recognition."
4718 @article { kreuzer01,
4719 author = HJKreuzer #" and "# SHPayne,
4720 title = "Stretching a macromolecule in an atomic force microscope:
4721 statistical mechanical analysis",
4730 eprint = "http://www.biophysj.org/cgi/reprint/80/6/2505.pdf",
4731 url = "http://www.biophysj.org/cgi/content/abstract/80/6/2505",
4732 keywords = "Biophysics;Macromolecular Substances;Microscopy, Atomic
4733 Force;Models, Statistical;Models, Theoretical;Statistics as Topic",
4734 abstract = "We formulate the proper statistical mechanics to describe the
4735 stretching of a macromolecule under a force provided by the cantilever
4736 of an atomic force microscope. In the limit of a soft cantilever the
4737 generalized ensemble of the coupled molecule/cantilever system reduces
4738 to the Gibbs ensemble for an isolated molecule subject to a constant
4739 force in which the extension is fluctuating. For a stiff cantilever we
4740 obtain the Helmholtz ensemble for an isolated molecule held at a fixed
4741 extension with the force fluctuating. Numerical examples are given for
4742 poly (ethylene glycol) chains."
4746 author = KKroy #" and "# JGlaser,
4747 title = "The glassy wormlike chain",
4753 doi = "10.1088/1367-2630/9/11/416",
4754 eprint = "http://www.iop.org/EJ/article/1367-2630/9/11/416/njp7_11_416.pdf",
4755 url = "http://stacks.iop.org/1367-2630/9/416",
4756 abstract = "We introduce a new model for the dynamics of a wormlike chain
4757 (WLC) in an environment that gives rise to a rough free energy
4758 landscape, which we name the glassy WLC. It is obtained from the common
4759 WLC by an exponential stretching of the relaxation spectrum of its
4760 long-wavelength eigenmodes, controlled by a single parameter
4761 \\boldsymbol{\\cal E} . Predictions for pertinent observables such as
4762 the dynamic structure factor and the microrheological susceptibility
4763 exhibit the characteristics of soft glassy rheology and compare
4764 favourably with experimental data for reconstituted cytoskeletal
4765 networks and live cells. We speculate about the possible microscopic
4766 origin of the stretching, implications for the nonlinear rheology, and
4767 the potential physiological significance of our results.",
4768 note = "Has short section on WLC relaxation time in the weakly bending
4772 @article { labeit03,
4773 author = DLabeit #" and "# KWatanabe #" and "# CWitt #" and "# HFujita #"
4774 and "# YWu #" and "# SLahmers #" and "# TFunck #" and "# SLabeit #" and
4776 title = "Calcium-dependent molecular spring elements in the giant protein
4782 pages = "13716--13721",
4783 doi = "10.1073/pnas.2235652100",
4784 eprint = "http://www.pnas.org/cgi/reprint/100/23/13716.pdf",
4785 url = "http://www.pnas.org/cgi/content/abstract/100/23/13716",
4786 abstract = "Titin (also known as connectin) is a giant protein with a wide
4787 range of cellular functions, including providing muscle cells with
4788 elasticity. Its physiological extension is largely derived from the
4789 PEVK segment, rich in proline (P), glutamate (E), valine (V), and
4790 lysine (K) residues. We studied recombinant PEVK molecules containing
4791 the two conserved elements: {approx}28-residue PEVK repeats and E-rich
4792 motifs. Single molecule experiments revealed that calcium-induced
4793 conformational changes reduce the bending rigidity of the PEVK
4794 fragments, and site-directed mutagenesis identified four glutamate
4795 residues in the E-rich motif that was studied (exon 129), as critical
4796 for this process. Experiments with muscle fibers showed that titin-
4797 based tension is calcium responsive. We propose that the PEVK segment
4798 contains E-rich motifs that render titin a calcium-dependent molecular
4799 spring that adapts to the physiological state of the cell."
4803 author = SLabeit #" and "# BKolmerer,
4804 title = "Titins: Giant proteins in charge of muscle ultrastructure
4810 address = "European Molecular Biology Laboratory, Heidelberg, Germany.",
4814 keywords = "Actin Cytoskeleton",
4815 keywords = "Amino Acid Sequence",
4816 keywords = "Animals",
4817 keywords = "DNA, Complementary",
4818 keywords = "Elasticity",
4819 keywords = "Fibronectins",
4820 keywords = "Humans",
4821 keywords = "Immunoglobulins",
4822 keywords = "Molecular Sequence Data",
4823 keywords = "Muscle Contraction",
4824 keywords = "Muscle Proteins",
4825 keywords = "Muscle, Skeletal",
4826 keywords = "Myocardium",
4827 keywords = "Protein Kinases",
4828 keywords = "Rabbits",
4829 keywords = "Repetitive Sequences, Nucleic Acid",
4830 keywords = "Sarcomeres",
4831 abstract = "In addition to thick and thin filaments, vertebrate
4832 striated muscle contains a third filament system formed by the
4833 giant protein titin. Single titin molecules extend from Z discs to
4834 M lines and are longer than 1 micrometer. The titin filament
4835 contributes to muscle assembly and resting tension, but more
4836 details are not known because of the large size of the
4837 protein. The complete complementary DNA sequence of human cardiac
4838 titin was determined. The 82-kilobase complementary DNA predicts a
4839 3-megadalton protein composed of 244 copies of immunoglobulin and
4840 fibronectin type III (FN3) domains. The architecture of sequences
4841 in the A band region of titin suggests why thick filament
4842 structure is conserved among vertebrates. In the I band region,
4843 comparison of titin sequences from muscles of different passive
4844 tension identifies two elements that correlate with tissue
4845 stiffness. This suggests that titin may act as two springs in
4846 series. The differential expression of the springs provides a
4847 molecular explanation for the diversity of sarcomere length and
4848 resting tension in vertebrate striated muscles.",
4850 URL = "http://www.ncbi.nlm.nih.gov/pubmed/7569978",
4855 author = RLaw #" and "# GLiao #" and "# SHarper #" and "# GYang #" and "#
4856 DSpeicher #" and "# DDischer,
4857 title = "Pathway shifts and thermal softening in temperature-coupled forced
4858 unfolding of spectrin domains",
4859 address = "Biophysical Engineering Lab, Institute for Medicine and
4860 Engineering, and School of Engineering and Applied Science,
4861 University of Pennsylvania, Philadelphia, Pennsylvania
4868 pages = "3286--3293",
4870 keywords = "Circular Dichroism;Elasticity;Heat;Microscopy, Atomic
4871 Force;Physical Stimulation;Protein Conformation;Protein
4872 Denaturation;Protein Folding;Protein Structure,
4873 Tertiary;Spectrin;Stress, Mechanical;Temperature",
4874 abstract = "Pathways of unfolding a protein depend in principle on the
4875 perturbation-whether it is temperature, denaturant, or even forced
4876 extension. Widely-shared, helical-bundle spectrin repeats are known to
4877 melt at temperatures as low as 40-45 degrees C and are also known to
4878 unfold via multiple pathways as single molecules in atomic force
4879 microscopy. Given the varied roles of spectrin family proteins in cell
4880 deformability, we sought to determine the coupled effects of
4881 temperature on forced unfolding. Bimodal distributions of unfolding
4882 intervals are seen at all temperatures for the four-repeat beta(1-4)
4883 spectrin-an alpha-actinin homolog. The major unfolding length
4884 corresponds to unfolding of a single repeat, and a minor peak at twice
4885 the length corresponds to tandem repeats. Increasing temperature shows
4886 fewer tandem events but has no effect on unfolding intervals. As T
4887 approaches T(m), however, mean unfolding forces in atomic force
4888 microscopy also decrease; and circular dichroism studies demonstrate a
4889 nearly proportional decrease of helical content in solution. The
4890 results imply a thermal softening of a helical linker between repeats
4891 which otherwise propagates a helix-to-coil transition to adjacent
4892 repeats. In sum, structural changes with temperature correlate with
4893 both single-molecule unfolding forces and shifts in unfolding
4895 doi = "10.1016/S0006-3495(03)74747-X",
4896 URL = "http://www.ncbi.nlm.nih.gov/pubmed/14581229",
4900 @article { levinthal68,
4901 author = CLevinthal,
4902 title = "Are there pathways for protein folding?",
4909 "http://www.biochem.wisc.edu/courses/biochem704/Reading/Levinthal1968.p
4911 note = "\emph{Not} Levinthal's paradox."
4914 @inproceedings { levinthal69,
4915 editor = PDebrunner #" and "# JCMTsibris #" and "# EMunck,
4916 author = CLevinthal,
4917 title = "How to Fold Graciously.",
4918 booktitle = "Mossbauer Spectroscopy in Biological Systems",
4921 publisher = UIP:Urbana,
4922 address = "Allerton House, Monticello, IL",
4923 url = "http://www-miller.ch.cam.ac.uk/levinthal/levinthal.html"
4927 author = RLevy #" and "# MMaaloum,
4928 title = "Measuring the spring constant of atomic force microscope
4929 cantilevers: Thermal fluctuations and other methods",
4935 doi = "10.1088/0957-4484/13/1/307",
4936 url = "http://stacks.iop.org/0957-4484/13/33",
4937 abstract = "Knowledge of the interaction forces between surfaces gained
4938 using an atomic force microscope (AFM) is crucial in a variety of
4939 industrial and scientific applications and necessitates a precise
4940 knowledge of the cantilever spring constant. Many methods have been
4941 devised to experimentally determine the spring constants of AFM
4942 cantilevers. The thermal fluctuation method is elegant but requires a
4943 theoretical model of the bending modes. For a rectangular cantilever,
4944 this model is available (Butt and Jaschke). Detailed thermal
4945 fluctuation measurements of a series of AFM cantilever beams have been
4946 performed in order to test the validity and accuracy of the recent
4947 theoretical models. The spring constant of rectangular cantilevers can
4948 also be determined easily with the method of Sader and White. We found
4949 very good agreement between the two methods. In the case of the
4950 V-shaped cantilever, we have shown that the thermal fluctuation method
4951 is a valid and accurate approach to the evaluation of the spring
4952 constant. A comparison between this method and those of Sader-
4953 Neumeister and of Ducker has been established. In some cases, we found
4954 disagreement between these two methods; the effect of non-conservation
4955 of material properties over all cantilevers from a single chip is
4956 qualitatively invoked.",
4957 note = "Good review of thermal calibration to 2002, but not much on the
4958 derviation of the Lorentzian fit.",
4959 project = "Cantilever Calibration"
4963 author = HLi #" and "# AOberhauser #" and "# SFowler #" and "# JClarke #"
4965 title = "Atomic force microscopy reveals the mechanical design of a modular
4971 pages = "6527--6531",
4972 doi = "10.1073/pnas.120048697",
4973 eprint = "http://www.pnas.org/cgi/reprint/97/12/6527.pdf",
4974 url = "http://www.pnas.org/cgi/content/abstract/97/12/6527",
4976 note = "Unfolding order not from protein-surface interactions. Mechanical
4977 unfolding of a chain of interleaved domains $ABABAB\ldots$ yielded a
4978 run of $A$ unfoldings followed by a run of $B$ unfoldings."
4982 author = HLi #" and "# AOberhauser #" and "# SRedick #" and "#
4983 MCarrionVazquez #" and "# HErickson #" and "# JFernandez,
4984 title = "Multiple conformations of {PEVK} proteins detected by single-
4985 molecule techniques",
4990 pages = "10682--10686",
4991 doi = "10.1073/pnas.191189098",
4992 eprint = "http://www.pnas.org/cgi/reprint/98/19/10682.pdf",
4993 url = "http://www.pnas.org/cgi/content/abstract/98/19/10682",
4994 abstract = "An important component of muscle elasticity is the PEVK region
4995 of titin, so named because of the preponderance of these amino acids.
4996 However, the PEVK region, similar to other elastomeric proteins, is
4997 thought to form a random coil and therefore its structure cannot be
4998 determined by standard techniques. Here we combine single-molecule
4999 electron microscopy and atomic force microscopy to examine the
5000 conformations of the human cardiac titin PEVK region. In contrast to a
5001 simple random coil, we have found that cardiac PEVK shows a wide range
5002 of elastic conformations with end-to-end distances ranging from 9 to 24
5003 nm and persistence lengths from 0.4 to 2.5 nm. Individual PEVK
5004 molecules retained their distinctive elastic conformations through many
5005 stretch-relaxation cycles, consistent with the view that these PEVK
5006 conformers cannot be interconverted by force. The multiple elastic
5007 conformations of cardiac PEVK may result from varying degrees of
5008 proline isomerization. The single-molecule techniques demonstrated here
5009 may help elucidate the conformation of other proteins that lack a well-
5014 author = HLi #" and "# JFernandez,
5015 title = "Mechanical design of the first proximal Ig domain of human cardiac
5016 titin revealed by single molecule force spectroscopy",
5025 doi = "10.1016/j.jmb.2003.09.036",
5026 keywords = "Amino Acid Sequence;Disulfides;Humans;Immunoglobulins;Models,
5027 Molecular;Molecular Sequence Data;Muscle Proteins;Myocardium;Protein
5028 Denaturation;Protein Engineering;Protein Kinases;Protein Structure,
5029 Tertiary;Spectrum Analysis",
5030 abstract = "The elastic I-band part of muscle protein titin contains two
5031 tandem immunoglobulin (Ig) domain regions of distinct mechanical
5032 properties. Until recently, the only known structure was that of the
5033 I27 module of the distal region, whose mechanical properties have been
5034 reported in detail. Recently, the structure of the first proximal
5035 domain, I1, has been resolved at 2.1A. In addition to the
5036 characteristic beta-sandwich structure of all titin Ig domains, the
5037 crystal structure of I1 showed an internal disulfide bridge that was
5038 proposed to modulate its mechanical extensibility in vivo. Here, we use
5039 single molecule force spectroscopy and protein engineering to examine
5040 the mechanical architecture of this domain. In contrast to the
5041 predictions made from the X-ray crystal structure, we find that the
5042 formation of a disulfide bridge in I1 is a relatively rare event in
5043 solution, even under oxidative conditions. Furthermore, our studies of
5044 the mechanical stability of I1 modules engineered with point mutations
5045 reveal significant differences between the mechanical unfolding of the
5046 I1 and I27 modules. Our study illustrates the varying mechanical
5047 architectures of the titin Ig modules."
5051 author = LeLi #" and "# HHuang #" and "# CBadilla #" and "# JFernandez,
5052 title = "Mechanical unfolding intermediates observed by single-molecule
5053 force spectroscopy in a fibronectin type {III} module",
5062 doi = "10.1016/j.jmb.2004.11.021",
5063 keywords = "Fibronectins;Kinetics;Microscopy, Atomic Force;Models,
5064 Molecular;Mutagenesis, Site-Directed;Protein Denaturation;Protein
5065 Folding;Protein Structure, Tertiary;Recombinant Fusion Proteins",
5066 abstract = "Domain 10 of type III fibronectin (10FNIII) is known to play a
5067 pivotal role in the mechanical interactions between cell surface
5068 integrins and the extracellular matrix. Recent molecular dynamics
5069 simulations have predicted that 10FNIII, when exposed to a stretching
5070 force, unfolds along two pathways, each with a distinct, mechanically
5071 stable intermediate. Here, we use single-molecule force spectroscopy
5072 combined with protein engineering to test these predictions by probing
5073 the mechanical unfolding pathway of 10FNIII. Stretching single
5074 polyproteins containing the 10FNIII module resulted in sawtooth
5075 patterns where 10FNIII was seen unfolding in two consecutive steps. The
5076 native state unfolded at 100(+/-20) pN, elongating (10)FNIII by
5077 12(+/-2) nm and reaching a clearly marked intermediate that unfolded at
5078 50(+/-20) pN. Unfolding of the intermediate completed the elongation of
5079 the molecule by extending another 19(+/-2) nm. Site-directed
5080 mutagenesis of residues in the A and B beta-strands (E9P and L19P)
5081 resulted in sawtooth patterns with all-or-none unfolding events that
5082 elongated the molecule by 19(+/-2) nm. In contrast, mutating residues
5083 in the G beta-strand gave results that were dependent on amino acid
5084 position. The mutation I88P in the middle of the G beta-strand resulted
5085 in native like unfolding sawtooth patterns showing an intact
5086 intermediate state. The mutation Y92P, which is near the end of G beta-
5087 strand, produced sawtooth patterns with all-or-none unfolding events
5088 that lengthened the molecule by 17(+/-2) nm. These results are
5089 consistent with the view that 10FNIII can unfold in two different ways.
5090 Along one pathway, the detachment of the A and B beta-strands from the
5091 body of the folded module constitute the first unfolding event,
5092 followed by the unfolding of the remaining beta-sandwich structure.
5093 Along the second pathway, the detachment of the G beta-strands is
5094 involved in the first unfolding event. These results are in excellent
5095 agreement with the sequence of events predicted by molecular dynamics
5096 simulations of the 10FNIII module."
5100 author = MSLi #" and "# CKHu #" and "# DKlimov #" and "# DThirumalai,
5101 title = "Multiple stepwise refolding of immunoglobulin domain {I27} upon
5102 force quench depends on initial conditions",
5108 doi = "10.1073/pnas.0503758103",
5109 eprint = "http://www.pnas.org/cgi/reprint/103/1/93.pdf",
5110 url = "http://www.pnas.org/cgi/content/abstract/103/1/93",
5111 abstract = "Mechanical folding trajectories for polyproteins starting from
5112 initially stretched conformations generated by single-molecule atomic
5113 force microscopy experiments [Fernandez, J. M. & Li, H. (2004) Science
5114 303, 1674-1678] show that refolding, monitored by the end-to-end
5115 distance, occurs in distinct multiple stages. To clarify the molecular
5116 nature of folding starting from stretched conformations, we have probed
5117 the folding dynamics, upon force quench, for the single I27 domain from
5118 the muscle protein titin by using a C{alpha}-Go model. Upon temperature
5119 quench, collapse and folding of I27 are synchronous. In contrast,
5120 refolding from stretched initial structures not only increases the
5121 folding and collapse time scales but also decouples the two kinetic
5122 processes. The increase in the folding times is associated primarily
5123 with the stretched state to compact random coil transition.
5124 Surprisingly, force quench does not alter the nature of the refolding
5125 kinetics, but merely increases the height of the free-energy folding
5126 barrier. Force quench refolding times scale as f1.gif, where {Delta}xf
5127 {approx} 0.6 nm is the location of the average transition state along
5128 the reaction coordinate given by end-to-end distance. We predict that
5129 {tau}F and the folding mechanism can be dramatically altered by the
5130 initial and/or final values of force. The implications of our results
5131 for design and analysis of experiments are discussed."
5136 title = "Divergence measures based on the {S}hannon entropy",
5144 doi = "10.1109/18.61115",
5145 url = "http://ieeexplore.ieee.org/xpl/freeabs_all.jsp?isnumber=2227&arnumbe
5146 r=61115&count=35&index=9",
5147 keywords = "divergence;dissimilarity measure;discrimintation
5148 information;entropy;probability of error bounds",
5149 abstract = "A novel class of information-theoretic divergence measures
5150 based on the Shannon entropy is introduced. Unlike the well-known
5151 Kullback divergences, the new measures do not require the condition of
5152 absolute continuity to be satisfied by the probability distributions
5153 involved. More importantly, their close relationship with the
5154 variational distance and the probability of misclassification error are
5155 established in terms of bounds. These bounds are crucial in many
5156 applications of divergence measures. The measures are also well
5157 characterized by the properties of nonnegativity, finiteness,
5158 semiboundedness, and boundedness."
5162 author = WALinke #" and "# AGrutzner,
5163 title = "Pulling single molecules of titin by {AFM}--recent advances and
5164 physiological implications",
5173 doi = "10.1007/s00424-007-0389-x",
5174 abstract = "Perturbation of a protein away from its native state by
5175 mechanical stress is a physiological process immanent to many cells.
5176 The mechanical stability and conformational diversity of proteins under
5177 force therefore are important parameters in nature. Molecular-level
5178 investigations of ``mechanical proteins'' have enjoyed major
5179 breakthroughs over the last decade, a development to which atomic force
5180 microscopy (AFM) force spectroscopy has been instrumental. The giant
5181 muscle protein titin continues to be a paradigm model in this field. In
5182 this paper, we review how single-molecule mechanical measurements of
5183 titin using AFM have served to elucidate key aspects of protein
5184 unfolding-refolding and mechanisms by which biomolecular elasticity is
5185 attained. We outline recent work combining protein engineering and AFM
5186 force spectroscopy to establish the mechanical behavior of titin
5187 domains using molecular ``fingerprinting.'' Furthermore, we summarize
5188 AFM force-extension data demonstrating different mechanical stabilities
5189 of distinct molecular-spring elements in titin, compare AFM force-
5190 extension to novel force-ramp/force-clamp studies, and elaborate on
5191 exciting new results showing that AFM force clamp captures the
5192 unfolding and refolding trajectory of single mechanical proteins. Along
5193 the way, we discuss the physiological implications of the findings, not
5194 least with respect to muscle mechanics. These studies help us
5195 understand how proteins respond to forces in cells and how
5196 mechanosensing and mechanosignaling events may proceed in vivo."
5199 @article { linke98a,
5200 author = WALinke #" and "# MRStockmeier #" and "# MIvemeyer #" and "#
5201 HHosser #" and "# PMundel,
5202 title = "Characterizing titin's {I}-band {Ig} domain region as an entropic
5207 volume = "111 (Pt 11)",
5208 pages = "1567--1574",
5211 eprint = "http://jcs.biologists.org/cgi/reprint/111/11/1567",
5212 url = "http://jcs.biologists.org/cgi/content/abstract/111/11/1567",
5213 keywords = "Animals;Elasticity;Immunoglobulins;Male;Muscle Proteins;Muscle,
5214 Skeletal;Protein Kinases;Rats;Rats, Wistar;Structure-Activity
5216 abstract = "The poly-immunoglobulin domain region of titin, located within
5217 the elastic section of this giant muscle protein, determines the
5218 extensibility of relaxed myofibrils mainly at shorter physiological
5219 lengths. To elucidate this region's contribution to titin elasticity,
5220 we measured the elastic properties of the N-terminal I-band Ig region
5221 by using immunofluorescence/immunoelectron microscopy and myofibril
5222 mechanics and tried to simulate the results with a model of entropic
5223 polymer elasticity. Rat psoas myofibrils were stained with titin-
5224 specific antibodies flanking the Ig region at the N terminus and C
5225 terminus, respectively, to record the extension behaviour of that titin
5226 segment. The segment's end-to-end length increased mainly at small
5227 stretch, reaching approximately 90\% of the native contour length of
5228 the Ig region at a sarcomere length of 2.8 microm. At this extension,
5229 the average force per single titin molecule, deduced from the steady-
5230 state passive length-tension relation of myofibrils, was approximately
5231 5 or 2.5 pN, depending on whether we assumed a number of 3 or 6 titins
5232 per half thick filament. When the force-extension curve constructed for
5233 the Ig region was simulated by the wormlike chain model, best fits were
5234 obtained for a persistence length, a measure of the chain's bending
5235 rigidity, of 21 or 42 nm (for 3 or 6 titins/half thick filament), which
5236 correctly reproduced the curve for sarcomere lengths up to 3.4 microm.
5237 Systematic deviations between data and fits above that length indicated
5238 that forces of >30 pN per titin strand may induce unfolding of Ig
5239 modules. We conclude that stretches of at least 5-6 Ig domains, perhaps
5240 coinciding with known super repeat patterns of these titin modules in
5241 the I-band, may represent the unitary lengths of the wormlike chain.
5242 The poly-Ig regions might thus act as compliant entropic springs that
5243 determine the minute levels of passive tension at low extensions of a
5247 @article { linke98b,
5248 author = WALinke #" and "# MIvemeyer #" and "# PMundel #" and "#
5249 MRStockmeier #" and "# BKolmerer,
5250 title = "Nature of {PEVK}-titin elasticity in skeletal muscle",
5257 pages = "8052--8057",
5259 keywords = "Animals;Elasticity;Fluorescent Antibody
5260 Technique;Male;Microscopy, Immunoelectron;Muscle Proteins;Muscle,
5261 Skeletal;Protein Kinases;Rats;Rats, Wistar;Stress, Mechanical",
5262 abstract = "A unique sequence within the giant titin molecule, the PEVK
5263 domain, has been suggested to greatly contribute to passive force
5264 development of relaxed skeletal muscle during stretch. To explore the
5265 nature of PEVK elasticity, we used titin-specific antibodies to stain
5266 both ends of the PEVK region in rat psoas myofibrils and determined the
5267 region's force-extension relation by combining immunofluorescence and
5268 immunoelectron microscopy with isolated myofibril mechanics. We then
5269 tried to fit the results with recent models of polymer elasticity. The
5270 PEVK segment elongated substantially at sarcomere lengths above 2.4
5271 micro(m) and reached its estimated contour length at approximately 3.5
5272 micro(m). In immunofluorescently labeled sarcomeres stretched and
5273 released repeatedly above 3 micro(m), reversible PEVK lengthening could
5274 be readily visualized. At extensions near the contour length, the
5275 average force per titin molecule was calculated to be approximately 45
5276 pN. Attempts to fit the force-extension curve of the PEVK segment with
5277 a standard wormlike chain model of entropic elasticity were successful
5278 only for low to moderate extensions. In contrast, the experimental data
5279 also could be correctly fitted at high extensions with a modified
5280 wormlike chain model that incorporates enthalpic elasticity. Enthalpic
5281 contributions are likely to arise from electrostatic stiffening, as
5282 evidenced by the ionic-strength dependency of titin-based myofibril
5283 stiffness; at high stretch, hydrophobic effects also might become
5284 relevant. Thus, at physiological muscle lengths, the PEVK region does
5285 not function as a pure entropic spring. Rather, PEVK elasticity may
5286 have both entropic and enthalpic origins characterizable by a polymer
5287 persistence length and a stretch modulus."
5291 author = WLiu #" and "# VMontana #" and "# EChapman #" and "# UMohideen #"
5293 title = "Botulinum toxin type {B} micromechanosensor",
5298 pages = "13621--13625",
5299 doi = "10.1073/pnas.2233819100",
5300 eprint = "http://www.pnas.org/cgi/reprint/100/23/13621.pdf",
5301 url = "http://www.pnas.org/cgi/content/abstract/100/23/13621",
5302 abstract = "Botulinum neurotoxin (BoNT) types A, B, E, and F are toxic to
5303 humans; early and rapid detection is essential for adequate medical
5304 treatment. Presently available tests for detection of BoNTs, although
5305 sensitive, require hours to days. We report a BoNT-B sensor whose
5306 properties allow detection of BoNT-B within minutes. The technique
5307 relies on the detection of an agarose bead detachment from the tip of a
5308 micromachined cantilever resulting from BoNT-B action on its
5309 substratum, the synaptic protein synaptobrevin 2, attached to the
5310 beads. The mechanical resonance frequency of the cantilever is
5311 monitored for the detection. To suspend the bead off the cantilever we
5312 use synaptobrevin's molecular interaction with another synaptic
5313 protein, syntaxin 1A, that was deposited onto the cantilever tip.
5314 Additionally, this bead detachment technique is general and can be used
5315 in any displacement reaction, such as in receptor-ligand pairs, where
5316 the introduction of one chemical leads to the displacement of another.
5317 The technique is of broad interest and will find uses outside
5322 author = GLois #" and "# JBlawzdziewicz #" and "# CSOHern,
5323 title = "Reliable protein folding on complex energy landscapes: the free
5324 energy reaction path",
5331 pages = "2692--2701",
5333 doi = "10.1529/biophysj.108.133132",
5334 abstract = "A theoretical framework is developed to study the dynamics of
5335 protein folding. The key insight is that the search for the native
5336 protein conformation is influenced by the rate r at which external
5337 parameters, such as temperature, chemical denaturant, or pH, are
5338 adjusted to induce folding. A theory based on this insight predicts
5339 that 1), proteins with complex energy landscapes can fold reliably to
5340 their native state; 2), reliable folding can occur as an equilibrium or
5341 out-of-equilibrium process; and 3), reliable folding only occurs when
5342 the rate r is below a limiting value, which can be calculated from
5343 measurements of the free energy. We test these predictions against
5344 numerical simulations of model proteins with a single energy scale."
5348 author = HLu #" and "# AKrammer #" and "# BIsralewitz #" and "# VVogel #"
5350 title = "Computer modeling of force-induced titin domain unfolding",
5352 journal = AdvExpMedBiol,
5356 url = {http://www.ncbi.nlm.nih.gov/pubmed/10987071},
5357 keywords = "Amino Acid Sequence;Animals;Computer
5358 Simulation;Elasticity;Fibronectins;Humans;Hydrogen
5359 Bonding;Immunoglobulins;Models, Molecular;Muscle Proteins;Muscle,
5360 Skeletal;Myofibrils;Protein Conformation;Protein Denaturation;Protein
5362 abstract = "Titin, a 1 micron long protein found in striated muscle
5363 myofibrils, possesses unique elastic and extensibility properties, and
5364 is largely composed of a PEVK region and beta-sandwich immunoglobulin
5365 (Ig) and fibronectin type III (FnIII) domains. The extensibility
5366 behavior of titin has been shown in atomic force microscope and optical
5367 tweezer experiments to partially depend on the reversible unfolding of
5368 individual Ig and FnIII domains. We performed steered molecular
5369 dynamics simulations to stretch single titin Ig domains in solution
5370 with pulling speeds of 0.1-1.0 A/ps, and FnIII domains with a pulling
5371 speed of 0.5 A/ps. Resulting force-extension profiles exhibit a single
5372 dominant peak for each domain unfolding, consistent with the
5373 experimentally observed sequential, as opposed to concerted, unfolding
5374 of Ig and FnIII domains under external stretching forces. The force
5375 peaks can be attributed to an initial burst of a set of backbone
5376 hydrogen bonds connected to the domains' terminal beta-strands.
5377 Constant force stretching simulations, applying 500-1000 pN of force,
5378 were performed on Ig domains. The resulting domain extensions are
5379 halted at an initial extension of 10 A until the set of all six
5380 hydrogen bonds connecting terminal beta-strands break simultaneously.
5381 This behavior is accounted for by a barrier separating folded and
5382 unfolded states, the shape of which is consistent with AFM and chemical
5383 denaturation data.",
5384 note = "discussion in journal on pages 161--2"
5388 author = HLu #" and "# KSchulten,
5389 title = "The key event in force-induced unfolding of Titin's immunoglobulin
5398 doi = {10.1016/S0006-3495(00)76273-4},
5399 url = {http://www.cell.com/biophysj/abstract/S0006-3495%2800%2976273-4},
5400 eprint = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1300915/pdf/10866937.pdf},
5401 keywords = "Amino Acid Sequence;Computer Simulation;Double Bind
5402 Interaction;Hydrogen Bonding;Immunoglobulins;Microscopy, Atomic
5403 Force;Models, Chemical;Models, Molecular;Molecular Sequence Data;Muscle
5404 Proteins;Protein Folding;Protein Kinases;Protein Structure,
5405 Tertiary;Stress, Mechanical;Water",
5406 abstract = "Steered molecular dynamics simulation of force-induced titin
5407 immunoglobulin domain I27 unfolding led to the discovery of a
5408 significant potential energy barrier at an extension of approximately
5409 14 A on the unfolding pathway that protects the domain against
5410 stretching. Previous simulations showed that this barrier is due to the
5411 concurrent breaking of six interstrand hydrogen bonds (H-bonds) between
5412 beta-strands A' and G that is preceded by the breaking of two to three
5413 hydrogen bonds between strands A and B, the latter leading to an
5414 unfolding intermediate. The simulation results are supported by
5415 Angstrom-resolution atomic force microscopy data. Here we perform a
5416 structural and energetic analysis of the H-bonds breaking. It is
5417 confirmed that H-bonds between strands A and B break rapidly. However,
5418 the breaking of the H-bond between strands A' and G needs to be
5419 assisted by fluctuations of water molecules. In nanosecond simulations,
5420 water molecules are found to repeatedly interact with the protein
5421 backbone atoms, weakening individual interstrand H-bonds until all six
5422 A'-G H-bonds break simultaneously under the influence of external
5423 stretching forces. Only when those bonds are broken can the generic
5424 unfolding take place, which involves hydrophobic interactions of the
5425 protein core and exerts weaker resistance against stretching than the
5430 author = HLu #" and "# BIsralewitz #" and "# AKrammer #" and "# VVogel #"
5432 title = "Unfolding of titin immunoglobulin domains by steered molecular
5433 dynamics simulation",
5441 doi = "10.1016/S0006-3495(98)77556-3",
5442 eprint = "http://download.cell.com/biophysj/pdf/PIIS0006349598775563.pdf",
5443 url = "http://www.cell.com/biophysj/abstract/S0006-3495(98)77556-3",
5444 keywords = "Amino Acid Sequence;Animals;Computer Simulation;Glutamic
5445 Acid;Immunoglobulins;Lysine;Macromolecular Substances;Models,
5446 Molecular;Molecular Sequence Data;Muscle
5447 Proteins;Myocardium;Proline;Protein Denaturation;Protein
5448 Folding;Protein Kinases;Protein Structure, Secondary;Sequence
5449 Alignment;Sequence Homology, Amino Acid;Valine",
5450 abstract = "Titin, a 1-microm-long protein found in striated muscle
5451 myofibrils, possesses unique elastic and extensibility properties in
5452 its I-band region, which is largely composed of a PEVK region (70\%
5453 proline, glutamic acid, valine, and lysine residue) and seven-strand
5454 beta-sandwich immunoglobulin-like (Ig) domains. The behavior of titin
5455 as a multistage entropic spring has been shown in atomic force
5456 microscope and optical tweezer experiments to partially depend on the
5457 reversible unfolding of individual Ig domains. We performed steered
5458 molecular dynamics simulations to stretch single titin Ig domains in
5459 solution with pulling speeds of 0.5 and 1.0 A/ps. Resulting force-
5460 extension profiles exhibit a single dominant peak for each Ig domain
5461 unfolding, consistent with the experimentally observed sequential, as
5462 opposed to concerted, unfolding of Ig domains under external stretching
5463 forces. This force peak can be attributed to an initial burst of
5464 backbone hydrogen bonds, which takes place between antiparallel beta-
5465 strands A and B and between parallel beta-strands A' and G. Additional
5466 features of the simulations, including the position of the force peak
5467 and relative unfolding resistance of different Ig domains, can be
5468 related to experimental observations."
5472 author = HLu #" and "# KSchulten,
5473 title = "Steered molecular dynamics simulations of force-induced protein
5483 doi = "10.1002/(SICI)1097-0134(19990601)35:4<453::AID-PROT9>3.0.CO;2-M",
5484 eprint = "http://www3.interscience.wiley.com/cgi-bin/fulltext/65000328/PDFSTART",
5485 url = "http://www3.interscience.wiley.com/journal/65000328/abstract",
5486 keywords = "Computer Simulation;Fibronectins;Hydrogen Bonding;Microscopy,
5487 Atomic Force;Models, Molecular;Protein Denaturation",
5488 abstract = "Steered molecular dynamics (SMD), a computer simulation method
5489 for studying force-induced reactions in biopolymers, has been applied
5490 to investigate the response of protein domains to stretching apart of
5491 their terminal ends. The simulations mimic atomic force microscopy and
5492 optical tweezer experiments, but proceed on much shorter time scales.
5493 The simulations on different domains for 0.6 nanosecond each reveal two
5494 types of protein responses: the first type, arising in certain beta-
5495 sandwich domains, exhibits nanosecond unfolding only after a force
5496 above 1,500 pN is applied; the second type, arising in a wider class of
5497 protein domain structures, requires significantly weaker forces for
5498 nanosecond unfolding. In the first case, strong forces are needed to
5499 concertedly break a set of interstrand hydrogen bonds which protect the
5500 domains against unfolding through stretching; in the second case,
5501 stretching breaks backbone hydrogen bonds one by one, and does not
5502 require strong forces for this purpose. Stretching of beta-sandwich
5503 (immunoglobulin) domains has been investigated further revealing a
5504 specific relationship between response to mechanical strain and the
5505 architecture of beta-sandwich domains."
5508 @article { makarov01,
5509 author = DEMakarov #" and "# PHansma #" and "# HMetiu,
5510 title = "Kinetic Monte Carlo simulation of titin unfolding",
5516 pages = "9663--9673",
5518 doi = "10.1063/1.1369622",
5519 eprint = "http://hansmalab.physics.ucsb.edu/pdf/297%20-%20Makarov,%20D.E._J
5520 .Chem.Phys._2001.pdf",
5521 url = "http://link.aip.org/link/?JCP/114/9663/1",
5522 keywords = "proteins; hydrogen bonds; digital simulation; Monte Carlo
5523 methods; molecular biophysics; intramolecular mechanics;
5524 macromolecules; atomic force microscopy"
5528 author = JFMarko #" and "# EDSiggia,
5529 title = "Stretching {DNA}",
5535 pages = "8759--8770",
5537 eprint = "http://pubs.acs.org/cgi-
5538 bin/archive.cgi/mamobx/1995/28/i26/pdf/ma00130a008.pdf",
5540 "http://pubs3.acs.org/acs/journals/doilookup?in_doi=10.1021/ma00130a008
5543 note = "Derivation of the Worm-like Chain interpolation function."
5546 @article { marszalek02,
5547 author = PMarszalek #" and "# HLi #" and "# AOberhauser #" and "#
5549 title = "Chair-boat transitions in single polysaccharide molecules observed
5550 with force-ramp {AFM}",
5555 pages = "4278--4283",
5556 doi = "10.1073/pnas.072435699",
5557 eprint = "http://www.pnas.org/cgi/reprint/99/7/4278.pdf",
5558 url = "http://www.pnas.org/cgi/content/abstract/99/7/4278",
5559 abstract = "Under a stretching force, the sugar ring of polysaccharide
5560 molecules switches from the chair to the boat-like or inverted chair
5561 conformation. This conformational change can be observed by stretching
5562 single polysaccharide molecules with an atomic force microscope. In
5563 those early experiments, the molecules were stretched at a constant
5564 rate while the resulting force changed over wide ranges. However,
5565 because the rings undergo force-dependent transitions, an experimental
5566 arrangement where the force is the free variable introduces an
5567 undesirable level of complexity in the results. Here we demonstrate the
5568 use of force-ramp atomic force microscopy to capture the conformational
5569 changes in single polysaccharide molecules. Force-ramp atomic force
5570 microscopy readily captures the ring transitions under conditions where
5571 the entropic elasticity of the molecule is separated from its
5572 conformational transitions, enabling a quantitative analysis of the
5573 data with a simple two-state model. This analysis directly provides the
5574 physico-chemical characteristics of the ring transitions such as the
5575 width of the energy barrier, the relative energy of the conformers, and
5576 their enthalpic elasticity. Our experiments enhance the ability of
5577 single-molecule force spectroscopy to make high-resolution measurements
5578 of the conformations of single polysaccharide molecules under a
5579 stretching force, making an important addition to polysaccharide
5583 @article { marszalek99,
5584 author = PMarszalek #" and "# HLu #" and "# HLi #" and "# MCarrionVazquez
5585 #" and "# AOberhauser #" and "# KSchulten #" and "# JFernandez,
5586 title = "Mechanical unfolding intermediates in titin modules",
5595 doi = "10.1038/47083",
5596 eprint = "http://www.nature.com/nature/journal/v402/n6757/pdf/402100a0.pdf",
5597 url = "http://www.nature.com/nature/journal/v402/n6757/abs/402100a0.html",
5598 keywords = "Biomechanics;Computer Simulation;Humans;Hydrogen
5599 Bonding;Microscopy, Atomic Force;Models, Molecular;Muscle
5600 Proteins;Myocardium;Protein Folding;Protein Kinases;Recombinant
5602 abstract = "The modular protein titin, which is responsible for the passive
5603 elasticity of muscle, is subjected to stretching forces. Previous work
5604 on the experimental elongation of single titin molecules has suggested
5605 that force causes consecutive unfolding of each domain in an all-or-
5606 none fashion. To avoid problems associated with the heterogeneity of
5607 the modular, naturally occurring titin, we engineered single proteins
5608 to have multiple copies of single immunoglobulin domains of human
5609 cardiac titin. Here we report the elongation of these molecules using
5610 the atomic force microscope. We find an abrupt extension of each domain
5611 by approximately 7 A before the first unfolding event. This fast
5612 initial extension before a full unfolding event produces a reversible
5613 'unfolding intermediate' Steered molecular dynamics simulations show
5614 that the rupture of a pair of hydrogen bonds near the amino terminus of
5615 the protein domain causes an extension of about 6 A, which is in good
5616 agreement with our observations. Disruption of these hydrogen bonds by
5617 site-directed mutagenesis eliminates the unfolding intermediate. The
5618 unfolding intermediate extends titin domains by approximately 15\% of
5619 their slack length, and is therefore likely to be an important
5620 previously unrecognized component of titin elasticity."
5623 @article { mcpherson01,
5624 author = JDMcPherson #" and "# MMarra #" and "# LHillier #" and "#
5625 RHWaterston #" and "# AChinwalla #" and "# JWallis #" and "# MSekhon #"
5626 and "# KWylie #" and "# ERMardis #" and "# RKWilson #" and "# RFulton
5627 #" and "# TAKucaba #" and "# CWagner-McPherson #" and "# WBBarbazuk #"
5628 and "# SGGregory #" and "# SJHumphray #" and "# LFrench #" and "#
5629 RSEvans #" and "# GBethel #" and "# AWhittaker #" and "# JLHolden #"
5630 and "# OTMcCann #" and "# ADunham #" and "# CSoderlund #" and "#
5631 CEScott #" and "# DRBentley #" and "# GSchuler #" and "# HCChen #" and
5632 "# WJang #" and "# EDGreen #" and "# JRIdol #" and "# VVMaduro #" and
5633 "# KTMontgomery #" and "# ELee #" and "# AMiller #" and "# SEmerling #"
5634 and "# Kucherlapati #" and "# RGibbs #" and "# SScherer #" and "#
5635 JHGorrell #" and "# ESodergren #" and "# KClerc-Blankenburg #" and "#
5636 PTabor #" and "# SNaylor #" and "# DGarcia #" and "# PJdeJong #" and "#
5637 JJCatanese #" and "# NNowak #" and "# KOsoegawa #" and "# SQin #" and
5638 "# LRowen #" and "# AMadan #" and "# MDors #" and "# LHood #" and "#
5639 BTrask #" and "# CFriedman #" and "# HMassa #" and "# VGCheung #" and
5640 "# IRKirsch #" and "# TReid #" and "# RYonescu #" and "# JWeissenbach
5641 #" and "# TBruls #" and "# RHeilig #" and "# EBranscomb #" and "#
5642 AOlsen #" and "# NDoggett #" and "# JFCheng #" and "# THawkins #" and
5643 "# RMMyers #" and "# JShang #" and "# LRamirez #" and "# JSchmutz #"
5644 and "# OVelasquez #" and "# KDixon #" and "# NEStone #" and "# DRCox #"
5645 and "# DHaussler #" and "# WJKent #" and "# TFurey #" and "# SRogic #"
5646 and "# SKennedy #" and "# SJones #" and "# ARosenthal #" and "# GWen #"
5647 and "# MSchilhabel #" and "# GGloeckner #" and "# GNyakatura #" and "#
5648 RSiebert #" and "# BSchlegelberger #" and "# JKorenberg #" and "#
5649 XNChen #" and "# AFujiyama #" and "# MHattori #" and "# AToyoda #" and
5650 "# TYada #" and "# HSPark #" and "# YSakaki #" and "# NShimizu #" and
5651 "# SAsakawa #" and "# KKawasaki #" and "# TSasaki #" and "# AShintani
5652 #" and "# AShimizu #" and "# KShibuya #" and "# JKudoh #" and "#
5653 SMinoshima #" and "# JRamser #" and "# PSeranski #" and "# CHoff #" and
5654 "# APoustka #" and "# RReinhardt #" and "# HLehrach,
5655 title = "A physical map of the human genome.",
5664 doi = "10.1038/35057157",
5665 eprint = "http://www.nature.com/nature/journal/v409/n6822/pdf/409934a0.pdf",
5666 url = "http://www.nature.com/nature/journal/v409/n6822/full/409934a0.html",
5667 keywords = "Chromosomes, Artificial, Bacterial;Cloning, Molecular;Contig
5668 Mapping;DNA Fingerprinting;Gene Duplication;Genome, Human;Humans;In
5669 Situ Hybridization, Fluorescence;Repetitive Sequences, Nucleic Acid",
5670 abstract = "The human genome is by far the largest genome to be sequenced,
5671 and its size and complexity present many challenges for sequence
5672 assembly. The International Human Genome Sequencing Consortium
5673 constructed a map of the whole genome to enable the selection of clones
5674 for sequencing and for the accurate assembly of the genome sequence.
5675 Here we report the construction of the whole-genome bacterial
5676 artificial chromosome (BAC) map and its integration with previous
5677 landmark maps and information from mapping efforts focused on specific
5678 chromosomal regions. We also describe the integration of sequence data
5683 author = CCMello #" and "# DBarrick,
5684 title = "An experimentally determined protein folding energy landscape",
5691 pages = "14102--14107",
5693 doi = "10.1073/pnas.0403386101",
5694 keywords = "Animals; Ankyrin Repeat; Circular Dichroism; Drosophila
5695 Proteins; Drosophila melanogaster; Gene Deletion; Models, Chemical;
5696 Models, Molecular; Protein Denaturation; Protein Folding; Protein
5697 Structure, Tertiary; Spectrometry, Fluorescence; Thermodynamics; Urea",
5698 abstract = "Energy landscapes have been used to conceptually describe and
5699 model protein folding but have been difficult to measure
5700 experimentally, in large part because of the myriad of partly folded
5701 protein conformations that cannot be isolated and thermodynamically
5702 characterized. Here we experimentally determine a detailed energy
5703 landscape for protein folding. We generated a series of overlapping
5704 constructs containing subsets of the seven ankyrin repeats of the
5705 Drosophila Notch receptor, a protein domain whose linear arrangement of
5706 modular structural units can be fragmented without disrupting
5707 structure. To a good approximation, stabilities of each construct can
5708 be described as a sum of energy terms associated with each repeat. The
5709 magnitude of each energy term indicates that each repeat is
5710 intrinsically unstable but is strongly stabilized by interactions with
5711 its nearest neighbors. These linear energy terms define an equilibrium
5712 free energy landscape, which shows an early free energy barrier and
5713 suggests preferred low-energy routes for folding."
5716 @article { merkel99,
5717 author = RMerkel #" and "# PNassoy #" and "# ALeung #" and "# KRitchie #"
5719 title = "Energy landscapes of receptor-ligand bonds explored with dynamic
5720 force spectroscopy",
5729 doi = "10.1038/16219",
5730 url = "http://www.nature.com/nature/journal/v397/n6714/full/397050a0.html",
5731 keywords = "Biotin;Microscopy, Atomic Force;Protein Binding;Streptavidin",
5732 abstract = "Atomic force microscopy (AFM) has been used to measure the
5733 strength of bonds between biological receptor molecules and their
5734 ligands. But for weak noncovalent bonds, a dynamic spectrum of bond
5735 strengths is predicted as the loading rate is altered, with the
5736 measured strength being governed by the prominent barriers traversed in
5737 the energy landscape along the force-driven bond-dissociation pathway.
5738 In other words, the pioneering early AFM measurements represent only a
5739 single point in a continuous spectrum of bond strengths, because theory
5740 predicts that these will depend on the rate at which the load is
5741 applied. Here we report the strength spectra for the bonds between
5742 streptavidin (or avidin) and biotins-the prototype of receptor-ligand
5743 interactions used in earlier AFM studies, and which have been modelled
5744 by molecular dynamics. We have probed bond formation over six orders of
5745 magnitude in loading rate, and find that the bond survival time
5746 diminished from about 1 min to 0.001 s with increasing loading rate
5747 over this range. The bond strength, meanwhile, increased from about 5
5748 pN to 170 pN. Thus, although they are among the strongest noncovalent
5749 linkages in biology (affinity of 10(13) to 10(15) M(-1)), these bonds
5750 in fact appear strong or weak depending on how fast they are loaded. We
5751 are also able to relate the activation barriers derived from our
5752 strength spectra to the shape of the energy landscape derived from
5753 simulations of the biotin-avidin complex."
5756 @article { metropolis87,
5757 author = NMetropolis,
5758 title = "The Beginning of the {M}onte {C}arlo Method",
5764 url = "http://library.lanl.gov/cgi-bin/getfile?15-12.pdf"
5767 @article { mickler07,
5768 author = MMickler #" and "# RDima #" and "# HDietz #" and "# CHyeon #" and
5769 "# DThirumalai #" and "# MRief,
5770 title = "Revealing the bifurcation in the unfolding pathways of {GFP} by
5771 using single-molecule experiments and simulations",
5776 pages = "20268--20273",
5777 doi = "10.1073/pnas.0705458104",
5778 eprint = "http://www.pnas.org/cgi/reprint/104/51/20268.pdf",
5779 url = "http://www.pnas.org/cgi/content/abstract/104/51/20268",
5780 keywords = "AFM experiments, coarse-grained simulations, cross-link
5781 mutants, pathway bifurcation, plasticity of energy landscape",
5782 abstract = "Nanomanipulation of biomolecules by using single-molecule
5783 methods and computer simulations has made it possible to visualize the
5784 energy landscape of biomolecules and the structures that are sampled
5785 during the folding process. We use simulations and single-molecule
5786 force spectroscopy to map the complex energy landscape of GFP that is
5787 used as a marker in cell biology and biotechnology. By engineering
5788 internal disulfide bonds at selected positions in the GFP structure,
5789 mechanical unfolding routes are precisely controlled, thus allowing us
5790 to infer features of the energy landscape of the wild-type GFP. To
5791 elucidate the structures of the unfolding pathways and reveal the
5792 multiple unfolding routes, the experimental results are complemented
5793 with simulations of a self-organized polymer (SOP) model of GFP. The
5794 SOP representation of proteins, which is a coarse-grained description
5795 of biomolecules, allows us to perform forced-induced simulations at
5796 loading rates and time scales that closely match those used in atomic
5797 force microscopy experiments. By using the combined approach, we show
5798 that forced unfolding of GFP involves a bifurcation in the pathways to
5799 the stretched state. After detachment of an N-terminal {alpha}-helix,
5800 unfolding proceeds along two distinct pathways. In the dominant
5801 pathway, unfolding starts from the detachment of the primary N-terminal
5802 -strand, while in the minor pathway rupture of the last, C-terminal
5803 -strand initiates the unfolding process. The combined approach has
5804 allowed us to map the features of the complex energy landscape of GFP
5805 including a characterization of the structures, albeit at a coarse-
5806 grained level, of the three metastable intermediates.",
5807 note = {Hiccup in unfolding leg corresponds to unfolding
5808 intermediate (\fref{figure}{2}). The unfolding time scale in GFP
5809 is about $6\U{ms}$.},
5813 author = RNevo #" and "# CStroh #" and "# FKienberger #" and "# DKaftan #"
5814 and "# VBrumfeld #" and "# MElbaum #" and "# ZReich #" and "#
5816 title = "A molecular switch between alternative conformational states in
5817 the complex of {Ran} and importin beta1",
5825 doi = "10.1038/nsb940",
5826 eprint = "http://www.nature.com/nsmb/journal/v10/n7/pdf/nsb940.pdf",
5827 url = "http://www.nature.com/nsmb/journal/v10/n7/abs/nsb940.html",
5828 keywords = "Guanosine Diphosphate; Guanosine Triphosphate; Microscopy,
5829 Atomic Force; Protein Binding; Protein Conformation; beta Karyopherins;
5830 ran GTP-Binding Protein",
5831 abstract = "Several million macromolecules are exchanged each minute
5832 between the nucleus and cytoplasm by receptor-mediated transport. Most
5833 of this traffic is controlled by the small GTPase Ran, which regulates
5834 assembly and disassembly of the receptor-cargo complexes in the
5835 appropriate cellular compartment. Here we applied dynamic force
5836 spectroscopy to study the interaction of Ran with the nuclear import
5837 receptor importin beta1 (impbeta) at the single-molecule level. We
5838 found that the complex alternates between two distinct conformational
5839 states of different adhesion strength. The application of an external
5840 mechanical force shifts equilibrium toward one of these states by
5841 decreasing the height of the interstate activation energy barrier. The
5842 other state can be stabilized by a functional Ran mutant that increases
5843 this barrier. These results support a model whereby functional control
5844 of Ran-impbeta is achieved by a population shift between pre-existing
5845 alternative conformations."
5849 author = RNevo #" and "# VBrumfeld #" and "# MElbaum #" and "#
5850 PHinterdorfer #" and "# ZReich,
5851 title = "Direct discrimination between models of protein activation by
5852 single-molecule force measurements",
5858 pages = "2630--2634",
5860 doi = "10.1529/biophysj.104.041889",
5861 eprint = "http://www.biophysj.org/cgi/reprint/87/4/2630.pdf",
5862 url = "http://www.biophysj.org/cgi/content/abstract/87/4/2630",
5863 keywords = "Elasticity; Enzyme Activation; Micromanipulation; Microscopy,
5864 Atomic Force; Models, Chemical; Models, Molecular; Multiprotein
5865 Complexes; Nuclear Proteins; Physical Stimulation; Protein Binding;
5866 Stress, Mechanical; Structure-Activity Relationship; beta Karyopherins;
5867 ran GTP-Binding Protein",
5868 abstract = "The limitations imposed on the analyses of complex chemical and
5869 biological systems by ensemble averaging can be overcome by single-
5870 molecule experiments. Here, we used a single-molecule technique to
5871 discriminate between two generally accepted mechanisms of a key
5872 biological process--the activation of proteins by molecular effectors.
5873 The two mechanisms, namely induced-fit and population-shift, are
5874 normally difficult to discriminate by ensemble approaches. As a model,
5875 we focused on the interaction between the nuclear transport effector,
5876 RanBP1, and two related complexes consisting of the nuclear import
5877 receptor, importin beta, and the GDP- or GppNHp-bound forms of the
5878 small GTPase, Ran. We found that recognition by the effector proceeds
5879 through either an induced-fit or a population-shift mechanism,
5880 depending on the substrate, and that the two mechanisms can be
5881 differentiated by the data."
5885 author = RNevo #" and "# VBrumfeld #" and "# RKapon #" and "# PHinterdorfer
5887 title = "Direct measurement of protein energy landscape roughness",
5895 doi = "10.1038/sj.embor.7400403",
5896 eprint = "http://www.nature.com/embor/journal/v6/n5/pdf/7400403.pdf",
5897 url = "http://www.nature.com/embor/journal/v6/n5/abs/7400403.html",
5898 keywords = "Models, Molecular; Protein Binding; Protein Folding; Spectrum
5899 Analysis; Thermodynamics; beta Karyopherins; ran GTP-Binding Protein",
5900 abstract = "The energy landscape of proteins is thought to have an
5901 intricate, corrugated structure. Such roughness should have important
5902 consequences on the folding and binding kinetics of proteins, as well
5903 as on their equilibrium fluctuations. So far, no direct measurement of
5904 protein energy landscape roughness has been made. Here, we combined a
5905 recent theory with single-molecule dynamic force spectroscopy
5906 experiments to extract the overall energy scale of roughness epsilon
5907 for a complex consisting of the small GTPase Ran and the nuclear
5908 transport receptor importin-beta. The results gave epsilon > 5k(B)T,
5909 indicating a bumpy energy surface, which is consistent with the ability
5910 of importin-beta to accommodate multiple conformations and to interact
5911 with different, structurally distinct ligands.",
5912 note = "Applies \citet{hyeon03} to ligand-receptor binding.",
5913 project = "Energy Landscape Roughness"
5917 author = SNg #" and "# KBillings #" and "# TOhashi #" and "# MAllen #" and
5918 "# RBest #" and "# LRandles #" and "# HErickson #" and "# JClarke,
5919 title = "Designing an extracellular matrix protein with enhanced mechanical
5927 pages = "9633--9637",
5928 doi = "10.1073/pnas.0609901104",
5929 eprint = "http://www.pnas.org/cgi/reprint/104/23/9633.pdf",
5930 url = "http://www.pnas.org/cgi/content/abstract/104/23/9633",
5931 abstract = "The extracellular matrix proteins tenascin and fibronectin
5932 experience significant mechanical forces in vivo. Both contain a number
5933 of tandem repeating homologous fibronectin type III (fnIII) domains,
5934 and atomic force microscopy experiments have demonstrated that the
5935 mechanical strength of these domains can vary significantly. Previous
5936 work has shown that mutations in the core of an fnIII domain from human
5937 tenascin (TNfn3) reduce the unfolding force of that domain
5938 significantly: The composition of the core is apparently crucial to the
5939 mechanical stability of these proteins. Based on these results, we have
5940 used rational redesign to increase the mechanical stability of the 10th
5941 fnIII domain of human fibronectin, FNfn10, which is directly involved
5942 in integrin binding. The hydrophobic core of FNfn10 was replaced with
5943 that of the homologous, mechanically stronger TNfn3 domain. Despite the
5944 extensive substitution, FNoTNc retains both the three-dimensional
5945 structure and the cell adhesion activity of FNfn10. Atomic force
5946 microscopy experiments reveal that the unfolding forces of the
5947 engineered protein FNoTNc increase by {approx}20% to match those of
5948 TNfn3. Thus, we have specifically designed a protein with increased
5949 mechanical stability. Our results demonstrate that core engineering can
5950 be used to change the mechanical strength of proteins while retaining
5951 functional surface interactions."
5955 author = SNg #" and "# JClarke,
5956 title = "Experiments Suggest that Simulations May Overestimate
5957 Electrostatic Contributions to the Mechanical Stability of a
5958 Fibronectin Type {III} Domain",
5962 pages = "851–854",
5967 doi = "10.1016/j.jmb.2007.06.015",
5968 url = "http://dx.doi.org/10.1016/j.jmb.2007.06.015",
5970 keywords = "MD simulations",
5972 keywords = "forced unfolding",
5973 keywords = "extracellular matrix",
5974 abstract = "Steered molecular dynamics simulations have previously
5975 been used to investigate the mechanical properties of the
5976 extracellular matrix protein fibronectin. The simulations
5977 suggest that the mechanical stability of the tenth type III
5978 domain from fibronectin (FNfn10) is largely determined by a
5979 number of critical hydrogen bonds in the peripheral
5980 strands. Interestingly, the simulations predict that lowering
5981 the pH from 7 to ∼4.7 will increase the mechanical stability
5982 of FNfn10 significantly (by ∼33 %) due to the protonation of a
5983 few key acidic residues in the A and B strands. To test this
5984 simulation prediction, we used single-molecule atomic force
5985 microscopy (AFM) to investigate the mechanical stability of
5986 FNfn10 at neutral pH and at lower pH where these key residues
5987 have been shown to be protonated. Our AFM experimental results
5988 show no difference in the mechanical stability of FNfn10 at
5989 these different pH values. These results suggest that some
5990 simulations may overestimate the role played by electrostatic
5991 interactions in determining the mechanical stability of
5996 author = RNome #" and "# JZhao #" and "# WHoff #" and "# NScherer,
5997 title = "Axis-dependent anisotropy in protein unfolding from integrated
5998 nonequilibrium single-molecule experiments, analysis, and simulation",
6005 pages = "20799--20804",
6007 doi = "10.1073/pnas.0701281105",
6008 eprint = "http://www.pnas.org/cgi/reprint/104/52/20799.pdf",
6009 url = "http://www.pnas.org/cgi/content/abstract/104/52/20799",
6010 keywords = "Anisotropy; Bacterial Proteins; Biophysics; Computer
6011 Simulation; Cysteine; Halorhodospira halophila; Hydrogen Bonding;
6012 Kinetics; Luminescent Proteins; Microscopy, Atomic Force; Molecular
6013 Conformation; Protein Binding; Protein Conformation; Protein
6014 Denaturation; Protein Folding; Protein Structure, Secondary",
6015 abstract = "We present a comprehensive study that integrates experimental
6016 and theoretical nonequilibrium techniques to map energy landscapes
6017 along well defined pull-axis specific coordinates to elucidate
6018 mechanisms of protein unfolding. Single-molecule force-extension
6019 experiments along two different axes of photoactive yellow protein
6020 combined with nonequilibrium statistical mechanical analysis and
6021 atomistic simulation reveal energetic and mechanistic anisotropy.
6022 Steered molecular dynamics simulations and free-energy curves
6023 constructed from the experimental results reveal that unfolding along
6024 one axis exhibits a transition-state-like feature where six hydrogen
6025 bonds break simultaneously with weak interactions observed during
6026 further unfolding. The other axis exhibits a constant (unpeaked) force
6027 profile indicative of a noncooperative transition, with enthalpic
6028 (e.g., H-bond) interactions being broken throughout the unfolding
6029 process. Striking qualitative agreement was found between the force-
6030 extension curves derived from steered molecular dynamics calculations
6031 and the equilibrium free-energy curves obtained by JarzynskiHummerSzabo
6032 analysis of the nonequilibrium work data. The anisotropy persists
6033 beyond pulling distances of more than twice the initial dimensions of
6034 the folded protein, indicating a rich energy landscape to the
6035 mechanically fully unfolded state. Our findings challenge the notion
6036 that cooperative unfolding is a universal feature in protein
6042 title = "Handbook of Molecular Force Spectroscopy",
6044 isbn = "978-0-387-49987-1",
6045 publisher = SPRINGER,
6046 note = "The first book about force spectroscopy. Discusses the scaffold
6047 effect in section 8.4.1."
6050 @article { nummela07,
6051 author = JNummela #" and "# IAndricioaei,
6052 title = "{Exact Low-Force Kinetics from High-Force Single-Molecule
6058 pages = "3373--3381",
6059 doi = "10.1529/biophysj.107.111658",
6060 eprint = "http://www.biophysj.org/cgi/reprint/93/10/3373.pdf",
6061 url = "http://www.biophysj.org/cgi/content/abstract/93/10/3373",
6062 abstract = "Mechanical forces play a key role in crucial cellular processes
6063 involving force-bearing biomolecules, as well as in novel single-
6064 molecule pulling experiments. We present an exact method that enables
6065 one to extrapolate, to low (or zero) forces, entire time-correlation
6066 functions and kinetic rate constants from the conformational dynamics
6067 either simulated numerically or measured experimentally at a single,
6068 relatively higher, external force. The method has twofold relevance:
6069 1), to extrapolate the kinetics at physiological force conditions from
6070 molecular dynamics trajectories generated at higher forces that
6071 accelerate conformational transitions; and 2), to extrapolate unfolding
6072 rates from experimental force-extension single-molecule curves. The
6073 theoretical formalism, based on stochastic path integral weights of
6074 Langevin trajectories, is presented for the constant-force, constant
6075 loading rate, and constant-velocity modes of the pulling experiments.
6076 For the first relevance, applications are described for simulating the
6077 conformational isomerization of alanine dipeptide; and for the second
6078 relevance, the single-molecule pulling of RNA is considered. The
6079 ability to assign a weight to each trace in the single-molecule data
6080 also suggests a means to quantitatively compare unfolding pathways
6081 under different conditions."
6084 @article { oberhauser01,
6085 author = AOberhauser #" and "# PHansma #" and "# MCarrionVazquez #" and "#
6087 title = "Stepwise unfolding of titin under force-clamp atomic force
6094 doi = "10.1073/pnas.021321798",
6095 eprint = "http://www.pnas.org/cgi/reprint/98/2/468.pdf",
6096 url = "http://www.pnas.org/cgi/content/abstract/98/2/468",
6102 title = "Cantilever spring constant calibration using laser Doppler
6112 doi = "10.1063/1.2743272",
6113 url = "http://link.aip.org/link/?RSI/78/063701/1",
6114 keywords = "calibration; vibration measurement; measurement by laser beam;
6115 Doppler measurement; measurement uncertainty; atomic force microscopy",
6116 note = "Excellent review of thermal calibration to 2007, but nothing in the
6117 way of derivations. Compares thermal tune and Sader method with laser
6118 Doppler vibrometry.",
6119 project = "Cantilever Calibration"
6122 @article { olshansky97,
6123 author = SJOlshansky #" and "# BACarnes,
6124 title = "Ever since {G}ompertz",
6127 journal = Demography,
6132 url = "http://www.jstor.org/stable/2061656",
6133 keywords = "Aging;Biometry;History, 19th Century;History, 20th
6134 Century;Humans;Life Tables;Mortality;Sexual Maturation",
6135 abstract = "In 1825 British actuary Benjamin Gompertz made a simple but
6136 important observation that a law of geometrical progression pervades
6137 large portions of different tables of mortality for humans. The simple
6138 formula he derived describing the exponential rise in death rates
6139 between sexual maturity and old age is commonly, referred to as the
6140 Gompertz equation-a formula that remains a valuable tool in demography
6141 and in other scientific disciplines. Gompertz's observation of a
6142 mathematical regularity in the life table led him to believe in the
6143 presence of a low of mortality that explained why common age patterns
6144 of death exist. This law of mortality has captured the attention of
6145 scientists for the past 170 years because it was the first among what
6146 are now several reliable empirical tools for describing the dying-out
6147 process of many living organisms during a significant portion of their
6148 life spans. In this paper we review the literature on Gompertz's law of
6149 mortality and discuss the importance of his observations and insights
6150 in light of research on aging that has taken place since then.",
6151 note = "Hardly any actual math, but the references might be interesting.
6152 I'll look into them if I have the time. Available through several
6156 @article { onuchic96,
6157 author = JNOnuchic #" and "# NDSocci #" and "# ZLuthey-Schulten #" and "#
6159 title = "Protein folding funnels: the nature of the transition state
6167 keywords = "Animals; Cytochrome c Group; Humans; Infant; Protein Folding",
6168 abstract = "BACKGROUND: Energy landscape theory predicts that the folding
6169 funnel for a small fast-folding alpha-helical protein will have a
6170 transition state half-way to the native state. Estimates of the
6171 position of the transition state along an appropriate reaction
6172 coordinate can be obtained from linear free energy relationships
6173 observed for folding and unfolding rate constants as a function of
6174 denaturant concentration. The experimental results of Huang and Oas for
6175 lambda repressor, Fersht and collaborators for C12, and Gray and
6176 collaborators for cytochrome c indicate a free energy barrier midway
6177 between the folded and unfolded regions. This barrier arises from an
6178 entropic bottleneck for the folding process. RESULTS: In keeping with
6179 the experimental results, lattice simulations based on the folding
6180 funnel description show that the transition state is not just a single
6181 conformation, but rather an ensemble of a relatively large number of
6182 configurations that can be described by specific values of one or a few
6183 order parameters (e.g. the fraction of native contacts). Analysis of
6184 this transition state or bottleneck region from our lattice simulations
6185 and from atomistic models for small alpha-helical proteins by Boczko
6186 and Brooks indicates a broad distribution for native contact
6187 participation in the transition state ensemble centered around 50\%.
6188 Importantly, however, the lattice-simulated transition state ensemble
6189 does include some particularly hot contacts, as seen in the
6190 experiments, which have been termed by others a folding nucleus.
6191 CONCLUSIONS: Linear free energy relations provide a crude spectroscopy
6192 of the transition state, allowing us to infer the values of a reaction
6193 coordinate based on the fraction of native contacts. This bottleneck
6194 may be thought of as a collection of delocalized nuclei where different
6195 native contacts will have different degrees of participation. The
6196 agreement between the experimental results and the theoretical
6197 predictions provides strong support for the landscape analysis."
6201 author = COpitz #" and "# MKulke #" and "# MLeake #" and "# CNeagoe #" and
6202 "# HHinssen #" and "# RHajjar #" and "# WALinke,
6203 title = "Damped elastic recoil of the titin spring in myofibrils of human
6209 pages = "12688--12693",
6210 doi = "10.1073/pnas.2133733100",
6211 eprint = "http://www.pnas.org/cgi/reprint/100/22/12688.pdf",
6212 url = "http://www.pnas.org/cgi/content/abstract/100/22/12688",
6213 abstract = "The giant protein titin functions as a molecular spring in
6214 muscle and is responsible for most of the passive tension of
6215 myocardium. Because the titin spring is extended during diastolic
6216 stretch, it will recoil elastically during systole and potentially may
6217 influence the overall shortening behavior of cardiac muscle. Here,
6218 titin elastic recoil was quantified in single human heart myofibrils by
6219 using a high-speed charge-coupled device-line camera and a
6220 nanonewtonrange force sensor. Application of a slack-test protocol
6221 revealed that the passive shortening velocity (Vp) of nonactivated
6222 cardiomyofibrils depends on: (i) initial sarcomere length, (ii)
6223 release-step amplitude, and (iii) temperature. Selective digestion of
6224 titin, with low doses of trypsin, decelerated myofibrillar passive
6225 recoil and eventually stopped it. Selective extraction of actin
6226 filaments with a Ca2+-independent gelsolin fragment greatly reduced the
6227 dependency of Vp on release-step size and temperature. These results
6228 are explained by the presence of viscous forces opposing myofibrillar
6229 passive recoil that are caused mainly by weak actin-titin interactions.
6230 Thus, Vp is determined by two distinct factors: titin elastic recoil
6231 and internal viscous drag forces. The recoil could be modeled as that
6232 of a damped entropic spring consisting of independent worm-like chains.
6233 The functional importance of myofibrillar elastic recoil was addressed
6234 by comparing instantaneous Vp to unloaded shortening velocity, which
6235 was measured in demembranated, fully Ca2+-activated, human cardiac
6236 fibers. Titin-driven passive recoil was much faster than active
6237 unloaded shortening velocity in early phases of isotonic contraction.
6238 Damped myofibrillar elastic recoil could help accelerate active
6239 contraction speed of human myocardium during early systolic
6243 @article { oroudjev02,
6244 author = EOroudjev #" and "# JSoares #" and "# SArcidiacono #" and "#
6245 JThompson #" and "# SFossey #" and "# HHansma,
6246 title = "Segmented nanofibers of spider dragline silk: Atomic force
6247 microscopy and single-molecule force spectroscopy",
6252 pages = "6460--6465",
6253 doi = "10.1073/pnas.082526499",
6254 eprint = "http://www.pnas.org/cgi/reprint/99/suppl_2/6460.pdf",
6255 url = "http://www.pnas.org/cgi/content/abstract/99/suppl_2/6460",
6256 abstract = "Despite its remarkable materials properties, the structure of
6257 spider dragline silk has remained unsolved. Results from two probe
6258 microscopy techniques provide new insights into the structure of spider
6259 dragline silk. A soluble synthetic protein from dragline silk
6260 spontaneously forms nanofibers, as observed by atomic force microscopy.
6261 These nanofibers have a segmented substructure. The segment length and
6262 amino acid sequence are consistent with a slab-like shape for
6263 individual silk protein molecules. The height and width of nanofiber
6264 segments suggest a stacking pattern of slab-like molecules in each
6265 nanofiber segment. This stacking pattern produces nano-crystals in an
6266 amorphous matrix, as observed previously by NMR and x-ray diffraction
6267 of spider dragline silk. The possible importance of nanofiber formation
6268 to native silk production is discussed. Force spectra for single
6269 molecules of the silk protein demonstrate that this protein unfolds
6270 through a number of rupture events, indicating a modular substructure
6271 within single silk protein molecules. A minimal unfolding module size
6272 is estimated to be around 14 nm, which corresponds to the extended
6273 length of a single repeated module, 38 amino acids long. The structure
6274 of this spider silk protein is distinctly different from the structures
6275 of other proteins that have been analyzed by single-molecule force
6276 spectroscopy, and the force spectra show correspondingly novel
6281 author = EPaci #" and "# MKarplus,
6282 title = "Unfolding proteins by external forces and temperature: The
6283 importance of topology and energetics",
6288 pages = "6521--6526",
6289 doi = "10.1073/pnas.100124597",
6290 eprint = "http://www.pnas.org/cgi/reprint/97/12/6521.pdf",
6291 url = "http://www.pnas.org/cgi/content/abstract/97/12/6521"
6295 author = EPaci #" and "# MKarplus,
6296 title = "Forced unfolding of fibronectin type 3 modules: an analysis by
6297 biased molecular dynamics simulations",
6306 doi = "10.1006/jmbi.1999.2670",
6307 keywords = "Dimerization;Fibronectins;Humans;Hydrogen Bonding;Microscopy,
6308 Atomic Force;Protein Denaturation;Protein Folding",
6309 abstract = "Titin, an important constituent of vertebrate muscles, is a
6310 protein of the order of a micrometer in length in the folded state.
6311 Atomic force microscopy and laser tweezer experiments have been used to
6312 stretch titin molecules to more than ten times their folded lengths. To
6313 explain the observed relation between force and extension, it has been
6314 suggested that the immunoglobulin and fibronectin domains unfold one at
6315 a time in an all-or-none fashion. We use molecular dynamics simulations
6316 to study the forced unfolding of two different fibronectin type 3
6317 domains (the ninth, 9Fn3, and the tenth, 10Fn3, from human fibronectin)
6318 and of their heterodimer of known structure. An external biasing
6319 potential on the N to C distance is employed and the protein is treated
6320 in the polar hydrogen representation with an implicit solvation model.
6321 The latter provides an adiabatic solvent response, which is important
6322 for the nanosecond unfolding simulation method used here. A series of
6323 simulations is performed for each system to obtain meaningful results.
6324 The two different fibronectin domains are shown to unfold in the same
6325 way along two possible pathways. These involve the partial separation
6326 of the ``beta-sandwich'', an essential structural element, and the
6327 unfolding of the individual sheets in a stepwise fashion. The biasing
6328 potential results are confirmed by constant force unfolding
6329 simulations. For the two connected domains, there is complete unfolding
6330 of one domain (9Fn3) before major unfolding of the second domain
6331 (10Fn3). Comparison of different models for the potential energy
6332 function demonstrates that the dominant cohesive element in both
6333 proteins is due to the attractive van der Waals interactions;
6334 electrostatic interactions play a structural role but appear to make
6335 only a small contribution to the stabilization of the domains, in
6336 agreement with other studies of beta-sheet stability. The unfolding
6337 forces found in the simulations are of the order of those observed
6338 experimentally, even though the speed of the former is more than six
6339 orders of magnitude greater than that used in the latter."
6343 author = QPeng #" and "# HLi,
6344 title = "Atomic force microscopy reveals parallel mechanical unfolding
6345 pathways of T4 lysozyme: Evidence for a kinetic partitioning mechanism",
6350 pages = "1885--1890",
6351 doi = "10.1073/pnas.0706775105",
6352 eprint = "http://www.pnas.org/cgi/reprint/105/6/1885.pdf",
6353 url = "http://www.pnas.org/cgi/content/abstract/105/6/1885",
6354 abstract = "Kinetic partitioning is predicted to be a general mechanism for
6355 proteins to fold into their well defined native three-dimensional
6356 structure from unfolded states following multiple folding pathways.
6357 However, experimental evidence supporting this mechanism is still
6358 limited. By using single-molecule atomic force microscopy, here we
6359 report experimental evidence supporting the kinetic partitioning
6360 mechanism for mechanical unfolding of T4 lysozyme, a small protein
6361 composed of two subdomains. We observed that on stretching from its N
6362 and C termini, T4 lysozyme unfolds by multiple distinct unfolding
6363 pathways: the majority of T4 lysozymes unfold in an all-or-none fashion
6364 by overcoming a dominant unfolding kinetic barrier; and a small
6365 fraction of T4 lysozymes unfold in three-state fashion involving
6366 unfolding intermediate states. The three-state unfolding pathways do
6367 not follow well defined routes, instead they display variability and
6368 diversity in individual unfolding pathways. The unfolding intermediate
6369 states are local energy minima along the mechanical unfolding pathways
6370 and are likely to result from the residual structures present in the
6371 two subdomains after crossing the main unfolding barrier. These results
6372 provide direct evidence for the kinetic partitioning of the mechanical
6373 unfolding pathways of T4 lysozyme, and the complex unfolding behaviors
6374 reflect the stochastic nature of kinetic barrier rupture in mechanical
6375 unfolding processes. Our results demonstrate that single-molecule
6376 atomic force microscopy is an ideal tool to investigate the
6377 folding/unfolding dynamics of complex multimodule proteins that are
6378 otherwise difficult to study using traditional methods."
6382 author = WPress #" and "# STeukolsky #" and "# WVetterling #" and "#
6384 title = "Numerical Recipies in {C}: The Art of Scientific Computing",
6388 address = "New York",
6389 eprint = "http://www.nrbook.com/a/bookcpdf.php",
6390 note = "See Sections 12.0, 12.1, 12.3, and 13.4 for a good introduction to
6391 Fourier transforms and power spectrum estimation.",
6392 project = "Cantilever Calibration"
6395 @article { puchner08,
6396 author = EPuchner #" and "# GFranzen #" and "# MGautel #" and "# HEGaub,
6397 title = "Comparing proteins by their unfolding pattern.",
6405 doi = "10.1529/biophysj.108.129999",
6406 eprint = "http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2426622/pdf/426.pdf",
6407 url = "http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2426622/",
6408 keywords = "Algorithms;Computer Simulation;Microscopy, Atomic Force;Models,
6409 Chemical;Models, Molecular;Protein Denaturation;Protein
6411 abstract = "Single molecule force spectroscopy has evolved into an
6412 important and extremely powerful technique for investigating the
6413 folding potentials of biomolecules. Mechanical tension is applied to
6414 individual molecules, and the subsequent, often stepwise unfolding is
6415 recorded in force extension traces. However, because the energy
6416 barriers of the folding potentials are often close to the thermal
6417 energy, both the extensions and the forces at which these barriers are
6418 overcome are subject to marked fluctuations. Therefore, force extension
6419 traces are an inadequate representation despite widespread use
6420 particularly when large populations of proteins need to be compared and
6421 analyzed. We show in this article that contour length, which is
6422 independent of fluctuations and alterable experimental parameters, is a
6423 more appropriate variable than extension. By transforming force
6424 extension traces into contour length space, histograms are obtained
6425 that directly represent the energy barriers. In contrast to force
6426 extension traces, such barrier position histograms can be averaged to
6427 investigate details of the unfolding potential. The cross-superposition
6428 of barrier position histograms allows us to detect and visualize the
6429 order of unfolding events. We show with this approach that in contrast
6430 to the sequential unfolding of bacteriorhodopsin, two main steps in the
6431 unfolding of the enzyme titin kinase are independent of each other. The
6432 potential of this new method for accurate and automated analysis of
6433 force spectroscopy data and for novel automated screening techniques is
6434 shown with bacteriorhodopsin and with protein constructs containing GFP
6436 note = {Contour length space and barrier position fingerprinting.
6437 There are errors in \fref{equation}{3}, propagated from
6438 \citet{livadaru03}. I contacted Elias Puchner and pointed out the
6439 typos, and he revised his FRC fit parameters from $\gamma=22\dg$
6440 and $b=0.4\U{nm}$ to $\gamma=41\dg$ and $b=0.11\U{nm}$. The
6441 combined effect on \fref{figure}{3} of fixing the equation typos
6442 and adjusting the fit parameters was small, so their conclusions
6446 @article { raible04,
6447 author = MRaible #" and "# MEvstigneev #" and "# PReimann #" and "#
6448 FWBartels #" and "# RRos,
6449 title = "Theoretical analysis of dynamic force spectroscopy experiments on
6450 ligand-receptor complexes",
6459 doi = "10.1016/j.jbiotec.2004.04.017",
6460 keywords = "Binding Sites;Computer Simulation;DNA;DNA-Binding
6461 Proteins;Elasticity;Ligands;Macromolecular
6462 Substances;Micromanipulation;Microscopy, Atomic Force;Models,
6463 Chemical;Molecular Biology;Nucleic Acid Conformation;Physical
6464 Stimulation;Protein Binding;Protein Conformation;Stress, Mechanical",
6465 abstract = "The forced rupture of single chemical bonds in biomolecular
6466 compounds (e.g. ligand-receptor systems) as observed in dynamic force
6467 spectroscopy experiments is addressed. Under the assumption that the
6468 probability of bond rupture depends only on the instantaneously acting
6469 force, a data collapse onto a single master curve is predicted. For
6470 rupture data obtained experimentally by dynamic AFM force spectroscopy
6471 of a ligand-receptor bond between a DNA and a regulatory protein we do
6472 not find such a collapse. We conclude that the above mentioned,
6473 generally accepted assumption is not satisfied and we discuss possible
6477 @article { raible06,
6478 author = MRaible #" and "# MEvstigneev #" and "# FWBartels #" and "# REckel
6479 #" and "# MNguyen-Duong #" and "# RMerkel #" and "# RRos #" and "#
6480 DAnselmetti #" and "# PReimann,
6481 title = "Theoretical analysis of single-molecule force spectroscopy
6482 experiments: heterogeneity of chemical bonds",
6489 pages = "3851--3864",
6491 doi = "10.1529/biophysj.105.077099",
6492 eprint = "http://www.biophysj.org/cgi/reprint/90/11/3851.pdf",
6493 url = "http://www.biophysj.org/cgi/content/abstract/90/11/3851",
6494 keywords = "Biomechanics;Microscopy, Atomic Force;Models,
6495 Molecular;Statistical Distributions;Thermodynamics",
6496 abstract = "We show that the standard theoretical framework in single-
6497 molecule force spectroscopy has to be extended to consistently describe
6498 the experimental findings. The basic amendment is to take into account
6499 heterogeneity of the chemical bonds via random variations of the force-
6500 dependent dissociation rates. This results in a very good agreement
6501 between theory and rupture data from several different experiments."
6504 @article{ bartels03,
6505 author = FWBartels #" and "# BBaumgarth #" and "# DAnselmetti
6506 #" and "# RRos #" and "# ABecker,
6507 title = "Specific binding of the regulatory protein Exp{G} to
6508 promoter regions of the galactoglucan biosynthesis gene cluster of
6509 Sinorhizobium meliloti--a combined molecular biology and force
6510 spectroscopy investigation.",
6511 journal = JStructBiol,
6514 address = "Experimentelle Biophysik, Fakult{\"a}t f{\"u}r Physik,
6515 Universit{\"a}t Bielefeld, 33615 Bielefeld, Germany.",
6519 keywords = "Base Sequence",
6520 keywords = "Binding Sites",
6521 keywords = "Conserved Sequence",
6522 keywords = "Fungal Proteins",
6523 keywords = "Galactans",
6524 keywords = "Glucans",
6525 keywords = "Kinetics",
6526 keywords = "Microscopy, Atomic Force",
6527 keywords = "Multigene Family",
6528 keywords = "Polysaccharides, Bacterial",
6529 keywords = "Promoter Regions, Genetic",
6530 keywords = "Protein Binding",
6531 keywords = "Sinorhizobium meliloti",
6532 keywords = "Trans-Activators",
6533 abstract = "Specific protein-DNA interaction is fundamental for all
6534 aspects of gene transcription. We focus on a regulatory
6535 DNA-binding protein in the Gram-negative soil bacterium
6536 Sinorhizobium meliloti 2011, which is capable of fixing molecular
6537 nitrogen in a symbiotic interaction with alfalfa plants. The ExpG
6538 protein plays a central role in regulation of the biosynthesis of
6539 the exopolysaccharide galactoglucan, which promotes the
6540 establishment of symbiosis. ExpG is a transcriptional activator of
6541 exp gene expression. We investigated the molecular mechanism of
6542 binding of ExpG to three associated target sequences in the exp
6543 gene cluster with standard biochemical methods and single molecule
6544 force spectroscopy based on the atomic force microscope
6545 (AFM). Binding of ExpG to expA1, expG-expD1, and expE1 promoter
6546 fragments in a sequence specific manner was demonstrated, and a 28
6547 bp conserved region was found. AFM force spectroscopy experiments
6548 confirmed the specific binding of ExpG to the promoter regions,
6549 with unbinding forces ranging from 50 to 165 pN in a logarithmic
6550 dependence from the loading rates of 70-79000 pN/s. Two different
6551 regimes of loading rate-dependent behaviour were
6552 identified. Thermal off-rates in the range of k(off)=(1.2+/-1.0) x
6553 10(-3)s(-1) were derived from the lower loading rate regime for
6554 all promoter regions. In the upper loading rate regime, however,
6555 these fragments exhibited distinct differences which are
6556 attributed to the molecular binding mechanism.",
6558 URL = "http://www.ncbi.nlm.nih.gov/pubmed/12972351",
6563 author = MRief #" and "# HGrubmuller,
6564 title = "Force spectroscopy of single biomolecules",
6573 doi = "10.1002/1439-7641(20020315)3:3<255::AID-CPHC255>3.0.CO;2-M",
6574 url = "http://www3.interscience.wiley.com/journal/91016383/abstract",
6575 keywords = "Ligands;Microscopy, Atomic Force;Polysaccharides;Protein
6576 Denaturation;Proteins",
6577 abstract = "Many processes in the body are effected and regulated by highly
6578 specialized protein molecules: These molecules certainly deserve the
6579 name ``biochemical nanomachines''. Recent progress in single-molecule
6580 experiments and corresponding simulations with supercomputers enable us
6581 to watch these ``nanomachines'' at work, revealing a host of astounding
6582 mechanisms. Examples are the fine-tuned movements of the binding pocket
6583 of a receptor protein locking into its ligand molecule and the forced
6584 unfolding of titin, which acts as a molecular shock absorber to protect
6585 muscle cells. At present, we are not capable of designing such high
6586 precision machines, but we are beginning to understand their working
6587 principles and to simulate and predict their function.",
6588 note = "Nice, general review of force spectroscopy to 2002, but not much
6594 title = "Fundamentals of Statistical and Thermal Physics",
6596 publisher = McGraw-Hill,
6597 address = "New York",
6598 note = "Thermal noise for simple harmonic oscillators, in Chapter
6599 15, Sections 6 and 10.",
6600 project = "Cantilever Calibration"
6604 author = MRief #" and "# MGautel #" and "# FOesterhelt #" and "# JFernandez
6606 title = "Reversible Unfolding of Individual Titin Immunoglobulin Domains by
6612 pages = "1109--1112",
6613 doi = "10.1126/science.276.5315.1109",
6614 eprint = "http://www.sciencemag.org/cgi/reprint/276/5315/1109.pdf",
6615 url = "http://www.sciencemag.org/cgi/content/abstract/276/5315/1109",
6616 note = "Seminal paper for force spectroscopy on Titin. Cited by
6617 \citet{dietz04} (ref 9) as an example of how unfolding large proteins
6618 is easily interpreted (vs.\ confusing unfolding in bulk), but Titin is
6619 a rather simple example of that, because of its globular-chain
6621 project = "Energy Landscape Roughness"
6625 author = MRief #" and "# FOesterhelt #" and "# BHeymann #" and "# HEGaub,
6626 title = "Single Molecule Force Spectroscopy on Polysaccharides by Atomic
6634 pages = "1295--1297",
6636 doi = "10.1126/science.275.5304.1295",
6637 eprint = "http://www.sciencemag.org/cgi/reprint/275/5304/1295.pdf",
6638 url = "http://www.sciencemag.org/cgi/content/abstract/275/5304/1295",
6639 abstract = "Recent developments in piconewton instrumentation allow the
6640 manipulation of single molecules and measurements of intermolecular as
6641 well as intramolecular forces. Dextran filaments linked to a gold
6642 surface were probed with the atomic force microscope tip by vertical
6643 stretching. At low forces the deformation of dextran was found to be
6644 dominated by entropic forces and can be described by the Langevin
6645 function with a 6 angstrom Kuhn length. At elevated forces the strand
6646 elongation was governed by a twist of bond angles. At higher forces the
6647 dextran filaments underwent a distinct conformational change. The
6648 polymer stiffened and the segment elasticity was dominated by the
6649 bending of bond angles. The conformational change was found to be
6650 reversible and was corroborated by molecular dynamics calculations."
6654 author = MRief #" and "# JFernandez #" and "# HEGaub,
6655 title = "Elastically Coupled Two-Level Systems as a Model for Biopolymer
6662 pages = "4764--4767",
6665 doi = "10.1103/PhysRevLett.81.4764",
6666 eprint = "http://prola.aps.org/pdf/PRL/v81/i21/p4764_1",
6667 url = "http://prola.aps.org/abstract/PRL/v81/i21/p4764_1",
6668 note = "Original details on mechanical unfolding analysis via Monte Carlo
6673 author = MRief #" and "# HClausen-Schaumann #" and "# HEGaub,
6674 title = "Sequence-dependent mechanics of single {DNA} molecules",
6682 doi = "10.1038/7582",
6683 eprint = "http://www.nature.com/nsmb/journal/v6/n4/pdf/nsb0499_346.pdf",
6684 url = "http://www.nature.com/nsmb/journal/v6/n4/abs/nsb0499_346.html",
6685 keywords = "Bacteriophage lambda;Base Pairing;DNA;DNA, Single-Stranded;DNA,
6686 Viral;Gold;Mechanics;Microscopy, Atomic Force;Nucleotides;Spectrum
6687 Analysis;Thermodynamics",
6688 abstract = "Atomic force microscope-based single-molecule force
6689 spectroscopy was employed to measure sequence-dependent mechanical
6690 properties of DNA by stretching individual DNA double strands attached
6691 between a gold surface and an AFM tip. We discovered that in lambda-
6692 phage DNA the previously reported B-S transition, where 'S' represents
6693 an overstretched conformation, at 65 pN is followed by a nonequilibrium
6694 melting transition at 150 pN. During this transition the DNA is split
6695 into single strands that fully recombine upon relaxation. The sequence
6696 dependence was investigated in comparative studies with poly(dG-dC) and
6697 poly(dA-dT) DNA. Both the B-S and the melting transition occur at
6698 significantly lower forces in poly(dA-dT) compared to poly(dG-dC). We
6699 made use of the melting transition to prepare single poly(dG-dC) and
6700 poly(dA-dT) DNA strands that upon relaxation reannealed into hairpins
6701 as a result of their self-complementary sequence. The unzipping of
6702 these hairpins directly revealed the base pair-unbinding forces for G-C
6703 to be 20 +/- 3 pN and for A-T to be 9 +/- 3 pN."
6706 @article{ schmitt00,
6707 author = LSchmitt #" and "# MLudwig #" and "# HEGaub #" and "# RTampe,
6708 title = "A metal-chelating microscopy tip as a new toolbox for
6709 single-molecule experiments by atomic force microscopy.",
6713 address = "Institut f{\"u}r Physiologische Chemie,
6714 Philipps-Universit{\"a}t Marburg, 35033 Marburg,
6715 Germany. schmittl@mailer.uni-marburg.de",
6718 pages = "3275--3285",
6719 keywords = "Chelating Agents",
6720 keywords = "Edetic Acid",
6721 keywords = "Histidine",
6722 keywords = "Metals",
6723 keywords = "Microscopy, Atomic Force",
6724 keywords = "Nitrilotriacetic Acid",
6725 keywords = "Peptides",
6726 keywords = "Recombinant Fusion Proteins",
6727 abstract = "In recent years, the atomic force microscope (AFM) has
6728 contributed much to our understanding of the molecular forces
6729 involved in various high-affinity receptor-ligand
6730 systems. However, a universal anchor system for such measurements
6731 is still required. This would open up new possibilities for the
6732 study of biological recognition processes and for the
6733 establishment of high-throughput screening applications. One such
6734 candidate is the N-nitrilo-triacetic acid (NTA)/His-tag system,
6735 which is widely used in molecular biology to isolate and purify
6736 histidine-tagged fusion proteins. Here the histidine tag acts as a
6737 high-affinity recognition site for the NTA chelator. Accordingly,
6738 we have investigated the possibility of using this approach in
6739 single-molecule force measurements. Using a histidine-peptide as a
6740 model system, we have determined the binding force for various
6741 metal ions. At a loading rate of 0.5 microm/s, the determined
6742 forces varied from 22 +/- 4 to 58 +/- 5 pN. Most importantly, no
6743 interaction was detected for Ca(2+) and Mg(2+) up to
6744 concentrations of 10 mM. Furthermore, EDTA and a metal ion
6745 reloading step demonstrated the reversibility of the
6746 approach. Here the molecular interactions were turned off (EDTA)
6747 and on (metal reloading) in a switch-like fashion. Our results
6748 show that the NTA/His-tag system will expand the ``molecular
6749 toolboxes'' with which receptor-ligand systems can be investigated
6750 at the single-molecule level.",
6752 doi = "10.1016/S0006-3495(00)76863-9",
6753 URL = "http://www.ncbi.nlm.nih.gov/pubmed/10828003",
6757 @article { roters96,
6758 author = ARoters #" and "# DJohannsmann,
6759 title = "Distance-dependent noise measurements in scanning force
6765 pages = "7561-7577",
6766 doi = "10.1088/0953-8984",
6767 eprint = "http://www.iop.org/EJ/article/0953-8984/8/41/006/c64103.pdf",
6768 url = "http://stacks.iop.org/0953-8984/8/7561",
6769 abstract = "The changes in the thermal noise spectrum of a scanning-force-
6770 microscope cantilever upon approach of the tip to the sample were used
6771 to investigate the interactions between the cantilever and the sample.
6772 The investigation of thermal noise is the natural choice for dynamic
6773 measurements with little disturbance of the sample. In particular, the
6774 small amplitudes involved ensure linear dynamic response. It is
6775 possible to discriminate between viscous coupling, elastic coupling and
6776 changes in the effective mass. The technique is versatile in terms of
6777 substrates and environments. Hydrodynamic long-range interactions
6778 depending on the sample, the geometry and the ambient medium are
6779 observed. The dependence of hydrodynamic interaction on various
6780 parameters such as the viscosity and the density of the medium is
6781 described. For sufficiently soft surfaces, the method is sensitive to
6782 viscoelastic properties of the surface. For example, the viscous
6783 coupling to the surface is strongly increased when the surface is
6784 covered with a swollen `polymer brush'.",
6785 note = "They actually write down a Lagrangian formula and give a decent
6786 derivation of PSD, but don't show or work out the integrals.",
6787 project = "Cantilever Calibration"
6791 author = FGittes #" and "# CFSchmidt,
6792 title = {Thermal noise limitations on micromechanical experiments},
6799 doi = {10.1007/s002490050113},
6800 url = {http://dx.doi.org/10.1007/s002490050113},
6802 publisher = SPRINGER:V,
6803 keywords = {Key words Thermal noise; Optical tweezers; Atomic force
6804 microscopy; Single molecules; Micromechanics},
6805 language = {English},
6808 @article { ryckaert77,
6809 author = JPRyckaert #" and "# GCiccotti #" and "# HJCBerendsen,
6810 title = "Numerical integration of the cartesian equations of motion of a
6811 system with constraints: molecular dynamics of n-alkanes",
6818 doi = "10.1016/0021-9991(77)90098-5",
6819 url = "http://dx.doi.org/10.1016/0021-9991(77)90098-5",
6820 abstract = "A numerical algorithm integrating the 3N Cartesian equations of
6821 motion of a system of N points subject to holonomic constraints is
6822 formulated. The relations of constraint remain perfectly fulfilled at
6823 each step of the trajectory despite the approximate character of
6824 numerical integration. The method is applied to a molecular dynamics
6825 simulation of a liquid of 64 n-butane molecules and compared to a
6826 simulation using generalized coordinates. The method should be useful
6827 for molecular dynamics calculations on large molecules with internal
6828 degrees of freedom.",
6829 note = "Entry-level explaination of MD with rigid constraints. Explicit
6830 Verlet integrator example."
6833 @article { sarkar04,
6834 author = ASarkar #" and "# RRobertson #" and "# JFernandez,
6835 title = "Simultaneous atomic force microscope and fluorescence measurements
6836 of protein unfolding using a calibrated evanescent wave",
6841 pages = "12882--12886",
6842 doi = "10.1073/pnas.0403534101",
6843 eprint = "http://www.pnas.org/cgi/reprint/101/35/12882.pdf",
6844 url = "http://www.pnas.org/cgi/content/abstract/101/35/12882",
6845 abstract = "Fluorescence techniques for monitoring single-molecule dynamics
6846 in the vertical dimension currently do not exist. Here we use an atomic
6847 force microscope to calibrate the distance-dependent intensity decay of
6848 an evanescent wave. The measured evanescent wave transfer function was
6849 then used to convert the vertical motions of a fluorescent particle
6850 into displacement ($SD =< 1$ nm). We demonstrate the use of the
6851 calibrated evanescent wave to resolve the 20.1 {+/-} 0.5-nm step
6852 increases in the length of the small protein ubiquitin during forced
6853 unfolding. The experiments that we report here make an important
6854 contribution to fluorescence microscopy by demonstrating the
6855 unambiguous optical tracking of a single molecule with a resolution
6856 comparable to that of an atomic force microscope."
6860 author = TSato #" and "# MEsaki #" and "# JFernandez #" and "# TEndo,
6861 title = "{Comparison of the protein-unfolding pathways between
6862 mitochondrial protein import and atomic-force microscopy measurements}",
6867 pages = "17999--18004",
6868 doi = "10.1073/pnas.0504495102",
6869 eprint = "http://www.pnas.org/cgi/reprint/102/50/17999.pdf",
6870 url = "http://www.pnas.org/cgi/content/abstract/102/50/17999",
6871 abstract = "Many newly synthesized proteins have to become unfolded during
6872 translocation across biological membranes. We have analyzed the effects
6873 of various stabilization/destabilization mutations in the Ig-like
6874 module of the muscle protein titin upon its import from the N terminus
6875 or C terminus into mitochondria. The effects of mutations on the import
6876 of the titin module from the C terminus correlate well with those on
6877 forced mechanical unfolding in atomic-force microscopy (AFM)
6878 measurements. On the other hand, as long as turnover of the
6879 mitochondrial Hsp70 system is not rate-limiting for the import, import
6880 of the titin module from the N terminus is sensitive to mutations in
6881 the N-terminal region but not the ones in the C-terminal region that
6882 affect resistance to global unfolding in AFM experiments. We propose
6883 that the mitochondrial-import system can catalyze precursor-unfolding
6884 by reducing the stability of unfolding intermediates."
6887 @article { schlierf04,
6888 author = MSchlierf #" and "# HLi #" and "# JFernandez,
6889 title = "The unfolding kinetics of ubiquitin captured with single-molecule
6890 force-clamp techniques",
6897 pages = "7299--7304",
6899 doi = "10.1073/pnas.0400033101",
6900 eprint = "http://www.pnas.org/cgi/reprint/101/19/7299.pdf",
6901 url = "http://www.pnas.org/cgi/content/abstract/101/19/7299",
6902 keywords = "Kinetics;Microscopy, Atomic Force;Probability;Ubiquitin",
6903 abstract = "We use single-molecule force spectroscopy to study the kinetics
6904 of unfolding of the small protein ubiquitin. Upon a step increase in
6905 the stretching force, a ubiquitin polyprotein extends in discrete steps
6906 of 20.3 +/- 0.9 nm marking each unfolding event. An average of the time
6907 course of these unfolding events was well described by a single
6908 exponential, which is a necessary condition for a memoryless Markovian
6909 process. Similar ensemble averages done at different forces showed that
6910 the unfolding rate was exponentially dependent on the stretching force.
6911 Stretching a ubiquitin polyprotein with a force that increased at a
6912 constant rate (force-ramp) directly measured the distribution of
6913 unfolding forces. This distribution was accurately reproduced by the
6914 simple kinetics of an all-or-none unfolding process. Our force-clamp
6915 experiments directly demonstrate that an ensemble average of ubiquitin
6916 unfolding events is well described by a two-state Markovian process
6917 that obeys the Arrhenius equation. However, at the single-molecule
6918 level, deviant behavior that is not well represented in the ensemble
6919 average is readily observed. Our experiments make an important addition
6920 to protein spectroscopy by demonstrating an unambiguous method of
6921 analysis of the kinetics of protein unfolding by a stretching force."
6924 @article { schlierf06,
6925 author = MSchlierf #" and "# MRief,
6926 title = "Single-molecule unfolding force distributions reveal a funnel-
6927 shaped energy landscape",
6936 doi = "10.1529/biophysj.105.077982",
6937 url = "http://www.biophysj.org/cgi/content/abstract/90/4/L33",
6938 keywords = "Models, Molecular; Protein Folding; Proteins; Thermodynamics",
6939 abstract = "The protein folding process is described as diffusion on a
6940 high-dimensional energy landscape. Experimental data showing details of
6941 the underlying energy surface are essential to understanding folding.
6942 So far in single-molecule mechanical unfolding experiments a simplified
6943 model assuming a force-independent transition state has been used to
6944 extract such information. Here we show that this so-called Bell model,
6945 although fitting well to force velocity data, fails to reproduce full
6946 unfolding force distributions. We show that by applying Kramers'
6947 diffusion model, we were able to reconstruct a detailed funnel-like
6948 curvature of the underlying energy landscape and establish full
6949 agreement with the data. We demonstrate that obtaining spatially
6950 resolved details of the unfolding energy landscape from mechanical
6951 single-molecule protein unfolding experiments requires models that go
6952 beyond the Bell model.",
6953 note = {The inspiration behind my sawtooth simulation. Bell model
6954 fit to $f_{unfold}(v)$, but Kramers model fit to unfolding
6955 distribution for a given $v$. \fref{equation}{3} in the
6956 supplement is \xref{evans99}{equation}{2}, but it is just
6957 $[\text{dying percent}] \cdot [\text{surviving population}]
6959 $\nu \equiv k$ is the force/time-dependent off rate. The Kramers'
6960 rate equation (on page L34, the second equation in the paper) is
6961 \xref{hanggi90}{equation}{4.56b} (page 275) and
6962 \xref{socci96}{equation}{2} but \citet{schlierf06} gets the minus
6963 sign wrong in the exponent. $U_F(x=0)\gg 0$ and
6964 $U_F(x_\text{max})\ll 0$ (\cf~\xref{schlierf06}{figure}{1}).
6965 Schlierf's integral (as written) contains
6966 $\exp{-U_F(x_\text{max})}\cdot\exp{U_F(0)}$, which is huge, when
6967 it should contain $\exp{U_F(x_\text{max})}\cdot\exp{-U_F(0)}$,
6968 which is tiny. For more details and a picture of the peak that
6969 forms the bulk of the integrand, see
6970 \cref{eq:kramers,fig:kramers:integrand}. I pointed out this
6971 problem to Michael Schlierf, but he was unconvinced.},
6974 @article { schwaiger04,
6975 author = ISchwaiger #" and "# AKardinal #" and "# MSchleicher #" and "#
6976 AANoegel #" and "# MRief,
6977 title = "A mechanical unfolding intermediate in an actin-crosslinking
6987 doi = "10.1038/nsmb705",
6988 eprint = "http://www.nature.com/nsmb/journal/v11/n1/pdf/nsmb705.pdf",
6989 url = "http://www.nature.com/nsmb/journal/v11/n1/full/nsmb705.html",
6990 keywords = "Actins; Animals; Contractile Proteins; Cross-Linking Reagents;
6991 Dictyostelium; Dimerization; Microfilament Proteins; Microscopy, Atomic
6992 Force; Mutagenesis, Site-Directed; Protein Denaturation; Protein
6993 Folding; Protein Structure, Tertiary; Protozoan Proteins",
6994 abstract = "Many F-actin crosslinking proteins consist of two actin-binding
6995 domains separated by a rod domain that can vary considerably in length
6996 and structure. In this study, we used single-molecule force
6997 spectroscopy to investigate the mechanics of the immunoglobulin (Ig)
6998 rod domains of filamin from Dictyostelium discoideum (ddFLN). We find
6999 that one of the six Ig domains unfolds at lower forces than do those of
7000 all other domains and exhibits a stable unfolding intermediate on its
7001 mechanical unfolding pathway. Amino acid inserts into various loops of
7002 this domain lead to contour length changes in the single-molecule
7003 unfolding pattern. These changes allowed us to map the stable core of
7004 approximately 60 amino acids that constitutes the unfolding
7005 intermediate. Fast refolding in combination with low unfolding forces
7006 suggest a potential in vivo role for this domain as a mechanically
7007 extensible element within the ddFLN rod.",
7008 note = "ddFLN unfolding with WLC params for sacrificial domains. Gives
7009 persistence length $p = 0.5\mbox{ nm}$ in ``high force regime'', $p =
7010 0.9\mbox{ nm}$ in ``low force regime'', with a transition at $F =
7012 project = "sawtooth simulation"
7015 @article { schwaiger05,
7016 author = ISchwaiger #" and "# MSchleicher #" and "# AANoegel #" and "#
7018 title = "The folding pathway of a fast-folding immunoglobulin domain
7019 revealed by single-molecule mechanical experiments",
7027 doi = "10.1038/sj.embor.7400317",
7028 eprint = "http://www.nature.com/embor/journal/v6/n1/pdf/7400317.pdf",
7029 url = "http://www.nature.com/embor/journal/v6/n1/index.html",
7030 keywords = "Animals; Contractile Proteins; Dictyostelium; Immunoglobulins;
7031 Kinetics; Microfilament Proteins; Models, Molecular; Protein Folding;
7032 Protein Structure, Tertiary",
7033 abstract = "The F-actin crosslinker filamin from Dictyostelium discoideum
7034 (ddFLN) has a rod domain consisting of six structurally similar
7035 immunoglobulin domains. When subjected to a stretching force, domain 4
7036 unfolds at a lower force than all the other domains in the chain.
7037 Moreover, this domain shows a stable intermediate along its mechanical
7038 unfolding pathway. We have developed a mechanical single-molecule
7039 analogue to a double-jump stopped-flow experiment to investigate the
7040 folding kinetics and pathway of this domain. We show that an obligatory
7041 and productive intermediate also occurs on the folding pathway of the
7042 domain. Identical mechanical properties suggest that the unfolding and
7043 refolding intermediates are closely related. The folding process can be
7044 divided into two consecutive steps: in the first step 60 C-terminal
7045 amino acids form an intermediate at the rate of 55 s(-1); and in the
7046 second step the remaining 40 amino acids are packed on this core at the
7047 rate of 179 s(-1). This division increases the overall folding rate of
7048 this domain by a factor of ten compared with all other homologous
7049 domains of ddFLN that lack the folding intermediate."
7052 @article { sharma07,
7053 author = DSharma #" and "# OPerisic #" and "# QPeng #" and "# YCao #" and
7054 "# CLam #" and "# HLu #" and "# HLi,
7055 title = "Single-molecule force spectroscopy reveals a mechanically stable
7056 protein fold and the rational tuning of its mechanical stability",
7061 pages = "9278--9283",
7062 doi = "10.1073/pnas.0700351104",
7063 eprint = "http://www.pnas.org/cgi/reprint/104/22/9278.pdf",
7064 url = "http://www.pnas.org/cgi/content/abstract/104/22/9278",
7065 abstract = "It is recognized that shear topology of two directly connected
7066 force-bearing terminal [beta]-strands is a common feature among the
7067 vast majority of mechanically stable proteins known so far. However,
7068 these proteins belong to only two distinct protein folds, Ig-like
7069 [beta] sandwich fold and [beta]-grasp fold, significantly hindering
7070 delineating molecular determinants of mechanical stability and rational
7071 tuning of mechanical properties. Here we combine single-molecule atomic
7072 force microscopy and steered molecular dynamics simulation to reveal
7073 that the de novo designed Top7 fold [Kuhlman B, Dantas G, Ireton GC,
7074 Varani G, Stoddard BL, Baker D (2003) Science 302:13641368] represents
7075 a mechanically stable protein fold that is distinct from Ig-like [beta]
7076 sandwich and [beta]-grasp folds. Although the two force-bearing [beta]
7077 strands of Top7 are not directly connected, Top7 displays significant
7078 mechanical stability, demonstrating that the direct connectivity of
7079 force-bearing [beta] strands in shear topology is not mandatory for
7080 mechanical stability. This finding broadens our understanding of the
7081 design of mechanically stable proteins and expands the protein fold
7082 space where mechanically stable proteins can be screened. Moreover, our
7083 results revealed a substructure-sliding mechanism for the mechanical
7084 unfolding of Top7 and the existence of two possible unfolding pathways
7085 with different height of energy barrier. Such insights enabled us to
7086 rationally tune the mechanical stability of Top7 by redesigning its
7087 mechanical unfolding pathway. Our study demonstrates that computational
7088 biology methods (including de novo design) offer great potential for
7089 designing proteins of defined topology to achieve significant and
7090 tunable mechanical properties in a rational and systematic fashion."
7094 author = YJSheng #" and "# SJiang #" and "# HKTsao,
7095 title = "Forced Kramers escape in single-molecule pulling experiments",
7105 doi = "10.1063/1.2046632",
7106 url = "http://link.aip.org/link/?JCP/123/091102/1",
7107 keywords = "molecular biophysics; bonds (chemical); proteins",
7108 note = "Gives appropriate Einstein-S... relation for diffusion to damping",
7109 project = "sawtooth simulation"
7112 @article { shillcock98,
7113 author = JShillcock #" and "# USeifert,
7114 title = "Escape from a metastable well under a time-ramped force",
7120 pages = "7301--7304",
7123 doi = "10.1103/PhysRevE.57.7301",
7124 eprint = "http://prola.aps.org/pdf/PRE/v57/i6/p7301_1",
7125 url = "http://link.aps.org/abstract/PRE/v57/p7301",
7126 project = "sawtooth simulation"
7130 author = GESims #" and "# SRJun #" and "# GAWu #" and "# SHKim,
7131 title = "Alignment-free genome comparison with feature frequency profiles
7132 ({FFP}) and optimal resolutions",
7139 pages = "2677--2682",
7141 doi = "10.1073/pnas.0813249106",
7142 eprint = "http://www.pnas.org/cgi/reprint/106/31/12826",
7143 url = "http://www.pnas.org/content/106/8/2677",
7144 keywords = "Genome;Introns;Phylogeny",
7145 abstract = "For comparison of whole-genome (genic + nongenic) sequences,
7146 multiple sequence alignment of a few selected genes is not appropriate.
7147 One approach is to use an alignment-free method in which feature (or
7148 l-mer) frequency profiles (FFP) of whole genomes are used for
7149 comparison-a variation of a text or book comparison method, using word
7150 frequency profiles. In this approach it is critical to identify the
7151 optimal resolution range of l-mers for the given set of genomes
7152 compared. The optimum FFP method is applicable for comparing whole
7153 genomes or large genomic regions even when there are no common genes
7154 with high homology. We outline the method in 3 stages: (i) We first
7155 show how the optimal resolution range can be determined with English
7156 books which have been transformed into long character strings by
7157 removing all punctuation and spaces. (ii) Next, we test the robustness
7158 of the optimized FFP method at the nucleotide level, using a mutation
7159 model with a wide range of base substitutions and rearrangements. (iii)
7160 Finally, to illustrate the utility of the method, phylogenies are
7161 reconstructed from concatenated mammalian intronic genomes; the FFP
7162 derived intronic genome topologies for each l within the optimal range
7163 are all very similar. The topology agrees with the established
7164 mammalian phylogeny revealing that intron regions contain a similar
7165 level of phylogenic signal as do coding regions."
7169 author = SBSmith #" and "# LFinzi #" and "# CBustamante,
7170 title = "Direct mechanical measurements of the elasticity of single {DNA}
7171 molecules by using magnetic beads",
7178 pages = "1122--1126",
7180 doi = "10.1126/science.1439819",
7181 eprint = "http://www.sciencemag.org/cgi/reprint/258/5085/1122.pdf",
7182 url = "http://www.sciencemag.org/cgi/content/abstract/258/5085/1122",
7183 keywords = "Chemistry,
7184 Physical;Cisplatin;DNA;Elasticity;Ethidium;Glass;Indoles;Intercalating
7185 Agents;Magnetics;Mathematics;Microspheres",
7186 abstract = "Single DNA molecules were chemically attached by one end to a
7187 glass surface and by their other end to a magnetic bead. Equilibrium
7188 positions of the beads were observed in an optical microscope while the
7189 beads were acted on by known magnetic and hydrodynamic forces.
7190 Extension versus force curves were obtained for individual DNA
7191 molecules at three different salt concentrations with forces between
7192 10(-14) and 10(-11) newtons. Deviations from the force curves predicted
7193 by the freely jointed chain model suggest that DNA has significant
7194 local curvature in solution. Ethidium bromide and
7195 4',6-diamidino-2-phenylindole had little effect on the elastic response
7196 of the molecules, but their extent of intercalation was directly
7197 measured. Conversely, the effect of bend-inducing cis-
7198 diamminedichloroplatinum (II) was large and supports the hypothesis of
7199 natural curvature in DNA."
7203 author = SBSmith #" and "# YCui #" and "# CBustamante,
7204 title = "Overstretching {B}-{DNA}: the elastic response of individual
7205 double-stranded and single-stranded {DNA} molecules",
7214 keywords = "Base Composition;Chemistry, Physical;DNA;DNA, Single-
7215 Stranded;Elasticity;Nucleic Acid Conformation;Osmolar
7216 Concentration;Thermodynamics",
7217 abstract = "Single molecules of double-stranded DNA (dsDNA) were stretched
7218 with force-measuring laser tweezers. Under a longitudinal stress of
7219 approximately 65 piconewtons (pN), dsDNA molecules in aqueous buffer
7220 undergo a highly cooperative transition into a stable form with 5.8
7221 angstroms rise per base pair, that is, 70\% longer than B form dsDNA.
7222 When the stress was relaxed below 65 pN, the molecules rapidly and
7223 reversibly contracted to their normal contour lengths. This transition
7224 was affected by changes in the ionic strength of the medium and the
7225 water activity or by cross-linking of the two strands of dsDNA.
7226 Individual molecules of single-stranded DNA were also stretched giving
7227 a persistence length of 7.5 angstroms and a stretch modulus of 800 pN.
7228 The overstretched form may play a significant role in the energetics of
7233 author = NDSocci #" and "# JNOnuchic #" and "# PGWolynes,
7234 title = "Diffusive dynamics of the reaction coordinate for protein folding
7241 pages = "5860--5868",
7243 doi = "10.1063/1.471317",
7244 eprint = "http://arxiv.org/pdf/cond-mat/9601091",
7245 url = "http://link.aip.org/link/?JCP/104/5860/1",
7246 keywords = "PROTEINS; FOLDS; DIFFUSION; MONTE CARLO METHOD; SIMULATION;
7248 abstract = "The quantitative description of model protein folding kinetics
7249 using a diffusive collective reaction coordinate is examined. Direct
7250 folding kinetics, diffusional coefficients and free energy profiles are
7251 determined from Monte Carlo simulations of a 27-mer, 3 letter code
7252 lattice model, which corresponds roughly to a small helical protein.
7253 Analytic folding calculations, using simple diffusive rate theory,
7254 agree extremely well with the full simulation results. Folding in this
7255 system is best seen as a diffusive, funnel-like process.",
7256 note = "A nice introduction to some quantitative ramifications of the
7257 funnel energy landscape. There's also a bit of Kramers' theory and
7258 graph theory thrown in for good measure."
7262 author = NDSocci #" and "# JNOnuchic #" and "# PGWolynes,
7263 title = "Stretching lattice models of protein folding",
7270 pages = "2031--2035",
7272 keywords = "Amino Acid Sequence;Drug Stability;Kinetics;Models,
7273 Theoretical;Molecular Sequence Data;Peptides;Protein
7274 Denaturation;Protein Folding",
7275 abstract = "A new class of experiments that probe folding of individual
7276 protein domains uses mechanical stretching to cause the transition. We
7277 show how stretching forces can be incorporated in lattice models of
7278 folding. For fast folding proteins, the analysis suggests a complex
7279 relation between the force dependence and the reaction coordinate for
7283 @article { staple08,
7284 author = DBStaple #" and "# SHPayne #" and "# ALCReddin #" and "# HJKreuzer,
7285 title = "Model for stretching and unfolding the giant multidomain muscle
7286 protein using single-molecule force spectroscopy.",
7295 doi = "10.1103/PhysRevLett.101.248301",
7296 url = "http://dx.doi.org/10.1103/PhysRevLett.101.248301",
7297 keywords = "Kinetics;Microscopy, Atomic Force;Models, Chemical;Muscle
7298 Proteins;Protein Conformation;Protein Folding;Protein Kinases;Protein
7299 Structure, Tertiary;Thermodynamics",
7300 abstract = "Single-molecule manipulation has allowed the forced unfolding
7301 of multidomain proteins. Here we outline a theory that not only
7302 explains these experiments but also points out a number of difficulties
7303 in their interpretation and makes suggestions for further experiments.
7304 For titin we reproduce force-extension curves, the dependence of break
7305 force on pulling speed, and break-force distributions and also validate
7306 two common experimental views: Unfolding titin Ig domains can be
7307 explained as stepwise increases in contour length, and increasing force
7308 peaks in native Ig sequences represent a hierarchy of bond strengths.
7309 Our theory is valid for essentially any molecule that can be unfolded
7310 in atomic force microscopy; as a further example, we present force-
7311 extension curves for the unfolding of RNA hairpins."
7315 author = RStark #" and "# TDrobek #" and "# WHeckl,
7316 title = "Thermomechanical noise of a free v-shaped cantilever for atomic-
7325 doi = "http://dx.doi.org/10.1016/S0304-3991(00)00077-2",
7326 abstract = "We have calculated the thermal noise of a v-shaped AFM
7327 cantilever (Microlever, Type E, Thermomicroscopes) by means of a finite
7328 element analysis. The modal shapes of the first 10 eigenmodes are
7329 displayed as well as the numerical constants, which are needed for the
7330 calibration using the thermal noise method. In the first eigenmode,
7331 values for the thermomechanical noise of the z-displacement at 22
7332 degrees C temperature of square root of u2(1) = A/square root of
7333 c(cant) and the photodiode signal (normal-force) of S2(1) = A/square
7334 root of c(cant) were obtained. The results also indicate a systematic
7335 deviation ofthe spectral density of the thermomechanical noise of
7336 v-shaped cantilevers as compared to rectangular beam-shaped
7338 note = "Higher mode adjustments for v-shaped cantilevers from simulation.",
7339 project = "Cantilever Calibration"
7342 @article { strick96,
7343 author = TRStrick #" and "# JFAllemand #" and "# DBensimon #" and "#
7344 ABensimon #" and "# VCroquette,
7345 title = "The elasticity of a single supercoiled {DNA} molecule",
7352 pages = "1835--1837",
7354 keywords = "Bacteriophage lambda;DNA, Superhelical;DNA,
7355 Viral;Elasticity;Magnetics;Nucleic Acid Conformation;Temperature",
7356 abstract = "Single linear DNA molecules were bound at multiple sites at one
7357 extremity to a treated glass cover slip and at the other to a magnetic
7358 bead. The DNA was therefore torsionally constrained. A magnetic field
7359 was used to rotate the beads and thus to coil and pull the DNA. The
7360 stretching force was determined by analysis of the Brownian
7361 fluctuations of the bead. Here the elastic behavior of individual
7362 lambda DNA molecules over- and underwound by up to 500 turns was
7363 studied. A sharp transition was discovered from a low to a high
7364 extension state at a force of approximately 0.45 piconewtons for
7365 underwound molecules and at a force of approximately 3 piconewtons for
7366 overwound ones. These transitions, probably reflecting the formation of
7367 alternative structures in stretched coiled DNA molecules, might be
7368 relevant for DNA transcription and replication."
7371 @article { strunz99,
7372 author = TStrunz #" and "# KOroszlan #" and "# RSchafer #" and "#
7374 title = "Dynamic force spectroscopy of single {DNA} molecules",
7379 pages = "11277--11282",
7380 doi = "10.1073/pnas.96.20.11277",
7381 eprint = "http://www.pnas.org/cgi/reprint/96/20/11277.pdf",
7382 url = "http://www.pnas.org/cgi/content/abstract/96/20/11277"
7386 author = ASzabo #" and "# KSchulten #" and "# ZSchulten,
7387 title = "First passage time approach to diffusion controlled reactions",
7393 pages = "4350--4357",
7395 doi = "10.1063/1.439715",
7396 url = "http://link.aip.org/link/?JCP/72/4350/1",
7397 keywords = "DIFFUSION; CHEMICAL REACTIONS; CHEMICAL REACTION KINETICS;
7398 PROBABILITY; DIFFERENTIAL EQUATIONS"
7401 @article { talaga00,
7402 author = DTalaga #" and "# WLau #" and "# HRoder #" and "# JTang #" and "#
7403 YJia #" and "# WDeGrado #" and "# RHochstrasser,
7404 title = "Dynamics and folding of single two-stranded coiled-coil peptides
7405 studied by fluorescent energy transfer confocal microscopy",
7410 pages = "13021--13026",
7411 doi = "10.1073/pnas.97.24.13021",
7412 eprint = "http://www.pnas.org/cgi/reprint/97/24/13021.pdf",
7413 url = "http://www.pnas.org/cgi/content/abstract/97/24/13021"
7416 @article { thirumalai05,
7417 author = DThirumalai #" and "# CHyeon,
7418 title = "{RNA} and Protein Folding: Common Themes and Variations",
7419 affiliation = "Biophysics Program, and Department of Chemistry and
7420 Biochemistry, Institute for Physical Science and Technology, University
7421 of Maryland, College Park, Maryland 20742",
7426 pages = "4957--4970",
7429 "http://pubs3.acs.org/acs/journals/doilookup?in_doi=10.1021/bi047314+",
7430 abstract = "Visualizing the navigation of an ensemble of unfolded molecules
7431 through the bumpy energy landscape in search of the native state gives
7432 a pictorial view of biomolecular folding. This picture, when combined
7433 with concepts in polymer theory, provides a unified theory of RNA and
7434 protein folding. Just as for proteins, the major folding free energy
7435 barrier for RNA scales sublinearly with the number of nucleotides,
7436 which allows us to extract the elusive prefactor for RNA folding.
7437 Several folding scenarios can be anticipated by considering variations
7438 in the energy landscape that depend on sequence, native topology, and
7439 external conditions. RNA and protein folding mechanism can be described
7440 by the kinetic partitioning mechanism (KPM) according to which a
7441 fraction () of molecules reaches the native state directly, whereas the
7442 remaining fraction gets kinetically trapped in metastable
7443 conformations. For two-state folders 1. Molecular chaperones are
7444 recruited to assist protein folding whenever is small. We show that the
7445 iterative annealing mechanism, introduced to describe chaperonin-
7446 mediated folding, can be generalized to understand protein-assisted RNA
7447 folding. The major differences between the folding of proteins and RNA
7448 arise in the early stages of folding. For RNA, folding can only begin
7449 after the polyelectrolyte problem is solved, whereas protein collapse
7450 requires burial of hydrophobic residues. Cross-fertilization of ideas
7451 between the two fields should lead to an understanding of how RNA and
7452 proteins solve their folding problems.",
7453 note = "unfolding-refolding"
7457 author = SThornton #" and "# JMarion,
7458 title = "Classical Dynamics of Particles and Systems",
7461 isbn = "0-534-40896-6",
7462 publisher = BrooksCole,
7463 address = "Belmont, CA"
7466 @article { tlusty98,
7467 author = TTlusty #" and "# AMeller #" and "# RBar-Ziv,
7468 title = "Optical Gradient Forces of Strongly Localized Fields",
7474 pages = "1738--1741",
7477 doi = "10.1103/PhysRevLett.81.1738",
7478 eprint = "http://prola.aps.org/pdf/PRL/v81/i8/p1738_1",
7480 \url{http://nanoscience.bu.edu/papers/p1738_1_Meller.pdf}.
7481 Cited by \citet{grossman05} for derivation of thermal response
7482 functions. However, I only see a referenced thermal energy when
7483 they list the likelyhood of a small partical (radius $<R_c$)
7484 escaping due to thermal energy, where $R_c$ is roughly $R_c \sim
7485 (k_B T / \alpha I_0)^{1/3}$, $\alpha$ is a dielectric scaling
7486 term, and $I_0$ is the maximum beam energy density. I imagine
7487 Grossman and Stout mixed up this reference.",
7488 project = "Cantilever Calibration"
7491 @article { tshiprut08,
7492 author = ZTshiprut #" and "# JKlafter #" and "# MUrbakh,
7493 title = "Single-molecule pulling experiments: when the stiffness of the
7494 pulling device matters",
7503 doi = "10.1529/biophysj.108.141580",
7504 eprint = "http://www.biophysj.org/cgi/reprint/95/6/L42.pdf",
7505 abstract = "Using Langevin modeling, we investigate the role of the
7506 experimental setup on the unbinding forces measured in single-molecule
7507 pulling experiments. We demonstrate that the stiffness of the pulling
7508 device, K(eff), may influence the unbinding forces through its effect
7509 on the barrier heights for both unbinding and rebinding processes.
7510 Under realistic conditions the effect of K(eff) on the rebinding
7511 barrier is shown to play the most important role. This results in a
7512 significant increase of the mean unbinding force with the stiffness for
7513 a given loading rate. Thus, in contrast to the phenomenological Bell
7514 model, we find that the loading rate (the multiplicative value K(eff)V,
7515 V being the pulling velocity) is not the only control parameter that
7516 determines the mean unbinding force. If interested in intrinsic
7517 properties of a molecular system, we recommend probing the system in
7518 the parameter range corresponding to a weak spring and relatively high
7519 loading rates where rebinding is negligible.",
7520 note = "Cites \citet{dudko03} for Kramers' description of irreversible
7521 rupture, and claims it is required to explain the deviations in
7522 $\avg{F}$ at the same loading rate. Proposes Moese equation as an
7523 example potential. Cites \citet{walton08} for experimental evidence of
7524 $\avg{F}$ increasing with linker stiffness."
7527 @article { uniprot10,
7528 author = UniProtConsort,
7530 title = "The Universal Protein Resource (UniProt) in 2010.",
7536 number = "Database issue",
7537 pages = "D142--D148",
7539 doi = "10.1093/nar/gkp846",
7540 url = "http://nar.oxfordjournals.org/cgi/content/abstract/38/suppl_1/D142",
7541 keywords = "Algorithms;Animals;Computational Biology;Databases, Nucleic
7542 Acid;Databases, Protein;Europe;Genome, Fungal;Genome,
7543 Viral;Humans;Information Storage and Retrieval;Internet;Protein
7544 Isoforms;Proteome;Proteomics;Software",
7545 abstract = "The primary mission of UniProt is to support biological
7546 research by maintaining a stable, comprehensive, fully classified,
7547 richly and accurately annotated protein sequence knowledgebase, with
7548 extensive cross-references and querying interfaces freely accessible to
7549 the scientific community. UniProt is produced by the UniProt Consortium
7550 which consists of groups from the European Bioinformatics Institute
7551 (EBI), the Swiss Institute of Bioinformatics (SIB) and the Protein
7552 Information Resource (PIR). UniProt is comprised of four major
7553 components, each optimized for different uses: the UniProt Archive, the
7554 UniProt Knowledgebase, the UniProt Reference Clusters and the UniProt
7555 Metagenomic and Environmental Sequence Database. UniProt is updated and
7556 distributed every 3 weeks and can be accessed online for searches or
7557 download at http://www.uniprot.org."
7560 @misc { uniprot:STRAV,
7561 key = "uniprot:STRAV",
7562 url = "http://www.uniprot.org/uniprot/P22629"
7565 @book { vanKampen07,
7566 author = NGvanKampen,
7567 title = "Stochastic Processes in Physics and Chemistry",
7571 address = "Amsterdam",
7573 project = "sawtooth simulation"
7576 @article { venter01,
7577 author = JCVenter #" and "# MDAdams #" and "# EWMyers #" and "# PWLi #" and
7578 "# RJMural #" and "# GGSutton #" and "# HOSmith #" and "# MYandell #"
7579 and "# CAEvans #" and "# RAHolt #" and "# JDGocayne #" and "#
7580 PAmanatides #" and "# RMBallew #" and "# DHHuson #" and "# JRWortman #"
7581 and "# QZhang #" and "# CDKodira #" and "# XHZheng #" and "# LChen #"
7582 and "# MSkupski #" and "# GSubramanian #" and "# PDThomas #" and "#
7583 JZhang #" and "# GLGaborMiklos #" and "# CNelson #" and "# SBroder #"
7584 and "# AGClark #" and "# JNadeau #" and "# VAMcKusick #" and "# NZinder
7585 #" and "# AJLevine #" and "# RJRoberts #" and "# MSimon #" and "#
7586 CSlayman #" and "# MHunkapiller #" and "# RBolanos #" and "# ADelcher
7587 #" and "# IDew #" and "# DFasulo #" and "# MFlanigan #" and "# LFlorea
7588 #" and "# AHalpern #" and "# SHannenhalli #" and "# SKravitz #" and "#
7589 SLevy #" and "# CMobarry #" and "# KReinert #" and "# KRemington #" and
7590 "# JAbu-Threideh #" and "# EBeasley #" and "# KBiddick #" and "#
7591 VBonazzi #" and "# RBrandon #" and "# MCargill #" and "#
7592 IChandramouliswaran #" and "# RCharlab #" and "# KChaturvedi #" and "#
7593 ZDeng #" and "# VDiFrancesco #" and "# PDunn #" and "# KEilbeck #" and
7594 "# CEvangelista #" and "# AEGabrielian #" and "# WGan #" and "# WGe #"
7595 and "# FGong #" and "# ZGu #" and "# PGuan #" and "# TJHeiman #" and "#
7596 MEHiggins #" and "# RRJi #" and "# ZKe #" and "# KAKetchum #" and "#
7597 ZLai #" and "# YLei #" and "# ZLi #" and "# JLi #" and "# YLiang #" and
7598 "# XLin #" and "# FLu #" and "# GVMerkulov #" and "# NMilshina #" and
7599 "# HMMoore #" and "# AKNaik #" and "# VANarayan #" and "# BNeelam #"
7600 and "# DNusskern #" and "# DBRusch #" and "# SSalzberg #" and "# WShao
7601 #" and "# BShue #" and "# JSun #" and "# ZWang #" and "# AWang #" and
7602 "# XWang #" and "# JWang #" and "# MWei #" and "# RWides #" and "#
7603 CXiao #" and "# CYan #" and "# AYao #" and "# JYe #" and "# MZhan #"
7604 and "# WZhang #" and "# HZhang #" and "# QZhao #" and "# LZheng #" and
7605 "# FZhong #" and "# WZhong #" and "# SZhu #" and "# SZhao #" and "#
7606 DGilbert #" and "# SBaumhueter #" and "# GSpier #" and "# CCarter #"
7607 and "# ACravchik #" and "# TWoodage #" and "# FAli #" and "# HAn #" and
7608 "# AAwe #" and "# DBaldwin #" and "# HBaden #" and "# MBarnstead #" and
7609 "# IBarrow #" and "# KBeeson #" and "# DBusam #" and "# ACarver #" and
7610 "# ACenter #" and "# MLCheng #" and "# LCurry #" and "# SDanaher #" and
7611 "# LDavenport #" and "# RDesilets #" and "# SDietz #" and "# KDodson #"
7612 and "# LDoup #" and "# SFerriera #" and "# NGarg #" and "# AGluecksmann
7613 #" and "# BHart #" and "# JHaynes #" and "# CHaynes #" and "# CHeiner
7614 #" and "# SHladun #" and "# DHostin #" and "# JHouck #" and "# THowland
7615 #" and "# CIbegwam #" and "# JJohnson #" and "# FKalush #" and "#
7616 LKline #" and "# SKoduru #" and "# ALove #" and "# FMann #" and "# DMay
7617 #" and "# SMcCawley #" and "# TMcIntosh #" and "# IMcMullen #" and "#
7618 MMoy #" and "# LMoy #" and "# BMurphy #" and "# KNelson #" and "#
7619 CPfannkoch #" and "# EPratts #" and "# VPuri #" and "# HQureshi #" and
7620 "# MReardon #" and "# RRodriguez #" and "# YHRogers #" and "# DRomblad
7621 #" and "# BRuhfel #" and "# RScott #" and "# CSitter #" and "#
7622 MSmallwood #" and "# EStewart #" and "# RStrong #" and "# ESuh #" and
7623 "# RThomas #" and "# NNTint #" and "# STse #" and "# CVech #" and "#
7624 GWang #" and "# JWetter #" and "# SWilliams #" and "# MWilliams #" and
7625 "# SWindsor #" and "# EWinn-Deen #" and "# KWolfe #" and "# JZaveri #"
7626 and "# KZaveri #" and "# JFAbril #" and "# RGuigo #" and "# MJCampbell
7627 #" and "# KVSjolander #" and "# BKarlak #" and "# AKejariwal #" and "#
7628 HMi #" and "# BLazareva #" and "# THatton #" and "# ANarechania #" and
7629 "# KDiemer #" and "# AMuruganujan #" and "# NGuo #" and "# SSato #" and
7630 "# VBafna #" and "# SIstrail #" and "# RLippert #" and "# RSchwartz #"
7631 and "# BWalenz #" and "# SYooseph #" and "# DAllen #" and "# ABasu #"
7632 and "# JBaxendale #" and "# LBlick #" and "# MCaminha #" and "#
7633 JCarnes-Stine #" and "# PCaulk #" and "# YHChiang #" and "# MCoyne #"
7634 and "# CDahlke #" and "# AMays #" and "# MDombroski #" and "# MDonnelly
7635 #" and "# DEly #" and "# SEsparham #" and "# CFosler #" and "# HGire #"
7636 and "# SGlanowski #" and "# KGlasser #" and "# AGlodek #" and "#
7637 MGorokhov #" and "# KGraham #" and "# BGropman #" and "# MHarris #" and
7638 "# JHeil #" and "# SHenderson #" and "# JHoover #" and "# DJennings #"
7639 and "# CJordan #" and "# JJordan #" and "# JKasha #" and "# LKagan #"
7640 and "# CKraft #" and "# ALevitsky #" and "# MLewis #" and "# XLiu #"
7641 and "# JLopez #" and "# DMa #" and "# WMajoros #" and "# JMcDaniel #"
7642 and "# SMurphy #" and "# MNewman #" and "# TNguyen #" and "# NNguyen #"
7643 and "# MNodell #" and "# SPan #" and "# JPeck #" and "# MPeterson #"
7644 and "# WRowe #" and "# RSanders #" and "# JScott #" and "# MSimpson #"
7645 and "# TSmith #" and "# ASprague #" and "# TStockwell #" and "# RTurner
7646 #" and "# EVenter #" and "# MWang #" and "# MWen #" and "# DWu #" and
7647 "# MWu #" and "# AXia #" and "# AZandieh #" and "# XZhu,
7648 title = "The sequence of the human genome.",
7655 pages = "1304--1351",
7657 doi = "10.1126/science.1058040",
7658 eprint = "http://www.sciencemag.org/cgi/content/pdf/291/5507/1304",
7659 url = "http://www.sciencemag.org/cgi/content/short/291/5507/1304",
7660 keywords = "Algorithms;Animals;Chromosome Banding;Chromosome
7661 Mapping;Chromosomes, Artificial, Bacterial;Computational
7662 Biology;Consensus Sequence;CpG Islands;DNA, Intergenic;Databases,
7663 Factual;Evolution, Molecular;Exons;Female;Gene
7664 Duplication;Genes;Genetic Variation;Genome, Human;Human Genome
7665 Project;Humans;Introns;Male;Phenotype;Physical Chromosome
7666 Mapping;Polymorphism, Single Nucleotide;Proteins;Pseudogenes;Repetitive
7667 Sequences, Nucleic Acid;Retroelements;Sequence Analysis, DNA;Species
7669 abstract = "A 2.91-billion base pair (bp) consensus sequence of the
7670 euchromatic portion of the human genome was generated by the whole-
7671 genome shotgun sequencing method. The 14.8-billion bp DNA sequence was
7672 generated over 9 months from 27,271,853 high-quality sequence reads
7673 (5.11-fold coverage of the genome) from both ends of plasmid clones
7674 made from the DNA of five individuals. Two assembly strategies-a whole-
7675 genome assembly and a regional chromosome assembly-were used, each
7676 combining sequence data from Celera and the publicly funded genome
7677 effort. The public data were shredded into 550-bp segments to create a
7678 2.9-fold coverage of those genome regions that had been sequenced,
7679 without including biases inherent in the cloning and assembly procedure
7680 used by the publicly funded group. This brought the effective coverage
7681 in the assemblies to eightfold, reducing the number and size of gaps in
7682 the final assembly over what would be obtained with 5.11-fold coverage.
7683 The two assembly strategies yielded very similar results that largely
7684 agree with independent mapping data. The assemblies effectively cover
7685 the euchromatic regions of the human chromosomes. More than 90\% of the
7686 genome is in scaffold assemblies of 100,000 bp or more, and 25\% of the
7687 genome is in scaffolds of 10 million bp or larger. Analysis of the
7688 genome sequence revealed 26,588 protein-encoding transcripts for which
7689 there was strong corroborating evidence and an additional approximately
7690 12,000 computationally derived genes with mouse matches or other weak
7691 supporting evidence. Although gene-dense clusters are obvious, almost
7692 half the genes are dispersed in low G+C sequence separated by large
7693 tracts of apparently noncoding sequence. Only 1.1\% of the genome is
7694 spanned by exons, whereas 24\% is in introns, with 75\% of the genome
7695 being intergenic DNA. Duplications of segmental blocks, ranging in size
7696 up to chromosomal lengths, are abundant throughout the genome and
7697 reveal a complex evolutionary history. Comparative genomic analysis
7698 indicates vertebrate expansions of genes associated with neuronal
7699 function, with tissue-specific developmental regulation, and with the
7700 hemostasis and immune systems. DNA sequence comparisons between the
7701 consensus sequence and publicly funded genome data provided locations
7702 of 2.1 million single-nucleotide polymorphisms (SNPs). A random pair of
7703 human haploid genomes differed at a rate of 1 bp per 1250 on average,
7704 but there was marked heterogeneity in the level of polymorphism across
7705 the genome. Less than 1\% of all SNPs resulted in variation in
7706 proteins, but the task of determining which SNPs have functional
7707 consequences remains an open challenge."
7710 @article { verdier70,
7712 title = "Relaxation Behavior of the Freely Jointed Chain",
7718 pages = "5512--5517",
7720 doi = "10.1063/1.1672818",
7721 url = "http://link.aip.org/link/?JCP/52/5512/1"
7724 @article { walther07,
7725 author = KWalther #" and "# FGrater #" and "# LDougan #" and "# CBadilla #"
7726 and "# BBerne #" and "# JFernandez,
7727 title = "Signatures of hydrophobic collapse in extended proteins captured
7728 with force spectroscopy",
7733 pages = "7916--7921",
7734 doi = "10.1073/pnas.0702179104",
7735 eprint = "http://www.pnas.org/cgi/reprint/104/19/7916.pdf",
7736 url = "http://www.pnas.org/cgi/content/abstract/104/19/7916",
7737 abstract = "We unfold and extend single proteins at a high force and then
7738 linearly relax the force to probe their collapse mechanisms. We observe
7739 a large variability in the extent of their recoil. Although chain
7740 entropy makes a small contribution, we show that the observed
7741 variability results from hydrophobic interactions with randomly varying
7742 magnitude from protein to protein. This collapse mechanism is common to
7743 highly extended proteins, including nonfolding elastomeric proteins
7744 like PEVK from titin. Our observations explain the puzzling differences
7745 between the folding behavior of highly extended proteins, from those
7746 folding after chemical or thermal denaturation. Probing the collapse of
7747 highly extended proteins with force spectroscopy allows separation of
7748 the different driving forces in protein folding."
7751 @mastersthesis{ lee05,
7753 title = {Chemical Functionalization of AFM Cantilevers},
7757 url = {http://dspace.mit.edu/handle/1721.1/34205},
7758 abstract = {Atomic force microscopy (AFM) has been a powerful
7759 instrument that provides nanoscale imaging of surface features,
7760 mainly of rigid metal or ceramic surfaces that can be insulators
7761 as well as conductors. Since it has been demonstrated that AFM
7762 could be used in aqueous environment such as in water or various
7763 buffers from which physiological condition can be maintained, the
7764 scope of the application of this imaging technique has been
7765 expanded to soft biological materials. In addition, the main usage
7766 of AFM has been to image the material and provide the shape of
7767 surface, which has also been diversified to molecular-recognition
7768 imaging - functional force imaging through force spectroscopy and
7769 modification of AFM cantilevers. By immobilizing of certain
7770 molecules at the end of AFM cantilever, specific molecules or
7771 functionalities can be detected by the combination of intrinsic
7772 feature of AFM and chemical modification technique of AFM
7773 cantilever. The surface molecule that is complementary to the
7774 molecule at the end of AFM probe can be investigated via
7775 specificity of molecule-molecule interaction.(cont.) Thus, this
7776 AFM cantilever chemistry, or chemical functionalization of AFM
7777 cantilever for the purpose of chemomechanical surface
7778 characterization, can be considered as an infinite source of
7779 applications important to understanding biological materials and
7780 material interactions. This thesis is mainly focused on three
7781 parts: (1) AFM cantilever chemistry that introduces specific
7782 protocols in details such as adsorption method, gold chemistry,
7783 and silicon nitride cantilever modification; (2) validation of
7784 cantilever chemistry such as X-ray photoelectron spectroscopy
7785 (XPS), AFM blocking experiment, and fluorescence microscopy,
7786 through which various AFM cantilever chemistry is verified; and
7787 (3) application of cantilever chemistry, especially toward the
7788 potential of force spectroscopy and the imaging of biological
7789 material surfaces.},
7791 note = {Binding proteins to gold-coated cantilevers via EDC (among
7792 other things in this thesis.},
7795 @article { walton08,
7796 author = EBWalton #" and "# SLee #" and "# KJVanVliet,
7797 title = "Extending {B}ell's model: How force transducer stiffness alters
7798 measured unbinding forces and kinetics of molecular complexes",
7805 pages = "2621--2630",
7807 doi = "10.1529/biophysj.107.114454",
7808 keywords = "Biotin;Computer
7809 Simulation;Elasticity;Kinetics;Mechanotransduction, Cellular;Models,
7810 Chemical;Models, Molecular;Molecular Motor
7811 Proteins;Motion;Streptavidin;Stress, Mechanical;Transducers",
7812 abstract = "Forced unbinding of complementary macromolecules such as
7813 ligand-receptor complexes can reveal energetic and kinetic details
7814 governing physiological processes ranging from cellular adhesion to
7815 drug metabolism. Although molecular-level experiments have enabled
7816 sampling of individual ligand-receptor complex dissociation events,
7817 disparities in measured unbinding force F(R) among these methods lead
7818 to marked variation in inferred binding energetics and kinetics at
7819 equilibrium. These discrepancies are documented for even the ubiquitous
7820 ligand-receptor pair, biotin-streptavidin. We investigated these
7821 disparities and examined atomic-level unbinding trajectories via
7822 steered molecular dynamics simulations, as well as via molecular force
7823 spectroscopy experiments on biotin-streptavidin. In addition to the
7824 well-known loading rate dependence of F(R) predicted by Bell's model,
7825 we find that experimentally accessible parameters such as the effective
7826 stiffness of the force transducer k can significantly perturb the
7827 energy landscape and the apparent unbinding force of the complex for
7828 sufficiently stiff force transducers. Additionally, at least 20\%
7829 variation in unbinding force can be attributed to minute differences in
7830 initial atomic positions among energetically and structurally
7831 comparable complexes. For force transducers typical of molecular force
7832 spectroscopy experiments and atomistic simulations, this energy barrier
7833 perturbation results in extrapolated energetic and kinetic parameters
7834 of the complex that depend strongly on k. We present a model that
7835 explicitly includes the effect of k on apparent unbinding force of the
7836 ligand-receptor complex, and demonstrate that this correction enables
7837 prediction of unbinding distances and dissociation rates that are
7838 decoupled from the stiffness of actual or simulated molecular linkers.",
7839 note = "Some detailed estimates at U(x)."
7842 @article { walton86,
7844 title = "The Abbe theory of imaging: an alternative derivation of the
7851 url = "http://stacks.iop.org/0143-0807/7/62"
7854 @article { watanabe05,
7855 author = HWatanabe #" and "# TInoue,
7856 title = "Conformational dynamics of Rouse chains during creep/recovery
7857 processes: a review",
7862 pages = "R607--R636",
7863 doi = "10.1088/0953-8984/17/19/R01",
7864 eprint = "http://www.iop.org/EJ/article/0953-8984/17/19/R01/cm5_19_R01.pdf",
7865 url = "http://stacks.iop.org/0953-8984/17/R607",
7866 abstract = "The Rouse model is a well-established model for non-entangled
7867 polymer chains and also serves as a fundamental model for entangled
7868 chains. The dynamic behaviour of this model under strain-controlled
7869 conditions has been fully analysed in the literature. However, despite
7870 the importance of the Rouse model, no analysis has been made so far of
7871 the orientational anisotropy of the Rouse eigenmodes during the stress-
7872 controlled, creep and recovery processes. For completeness of the
7873 analysis of the model, the Rouse equation of motion is solved to
7874 calculate this anisotropy for monodisperse chains and their binary
7875 blends during the creep/recovery processes. The calculation is simple
7876 and straightforward, but the result is intriguing in the sense that
7877 each Rouse eigenmode during these processes has a distribution in the
7878 retardation times. This behaviour, reflecting the interplay/correlation
7879 among the Rouse eigenmodes of different orders (and for different
7880 chains in the blends) under the constant stress condition, is quite
7881 different from the behaviour under rate-controlled flow (where each
7882 eigenmode exhibits retardation/relaxation associated with a single
7883 characteristic time). Furthermore, the calculation indicates that the
7884 Rouse chains exhibit affine deformation on sudden imposition/removal of
7885 the stress and the magnitude of this deformation is inversely
7886 proportional to the number of bond vectors per chain. In relation to
7887 these results, a difference between the creep and relaxation properties
7888 is also discussed for chains obeying multiple relaxation mechanisms
7889 (Rouse and reptation mechanisms).",
7890 note = "Middly-detailed Rouse model review."
7894 author = AWiita #" and "# SAinavarapu #" and "# HHuang #" and "# JFernandez,
7895 title = "From the Cover: Force-dependent chemical kinetics of disulfide
7896 bond reduction observed with single-molecule techniques",
7901 pages = "7222--7227",
7902 doi = "10.1073/pnas.0511035103",
7903 eprint = "http://www.pnas.org/cgi/reprint/103/19/7222.pdf",
7904 url = "http://www.pnas.org/cgi/content/abstract/103/19/7222",
7905 abstract = "The mechanism by which mechanical force regulates the kinetics
7906 of a chemical reaction is unknown. Here, we use single-molecule force-
7907 clamp spectroscopy and protein engineering to study the effect of force
7908 on the kinetics of thiol/disulfide exchange. Reduction of disulfide
7909 bonds through the thiol/disulfide exchange chemical reaction is crucial
7910 in regulating protein function and is known to occur in mechanically
7911 stressed proteins. We apply a constant stretching force to single
7912 engineered disulfide bonds and measure their rate of reduction by DTT.
7913 Although the reduction rate is linearly dependent on the concentration
7914 of DTT, it is exponentially dependent on the applied force, increasing
7915 10-fold over a 300-pN range. This result predicts that the disulfide
7916 bond lengthens by 0.34 A at the transition state of the thiol/disulfide
7917 exchange reaction. Our work at the single bond level directly
7918 demonstrates that thiol/disulfide exchange in proteins is a force-
7919 dependent chemical reaction. Our findings suggest that mechanical force
7920 plays a role in disulfide reduction in vivo, a property that has never
7921 been explored by traditional biochemistry. Furthermore, our work also
7922 indicates that the kinetics of any chemical reaction that results in
7923 bond lengthening will be force-dependent."
7926 @article { wilcox05,
7927 author = AWilcox #" and "# JChoy #" and "# CBustamante #" and "#
7929 title = "Effect of protein structure on mitochondrial import",
7934 pages = "15435--15440",
7935 doi = "10.1073/pnas.0507324102",
7936 eprint = "http://www.pnas.org/cgi/reprint/102/43/15435.pdf",
7937 url = "http://www.pnas.org/cgi/content/abstract/102/43/15435",
7938 abstract = "Most proteins that are to be imported into the mitochondrial
7939 matrix are synthesized as precursors, each composed of an N-terminal
7940 targeting sequence followed by a mature domain. Precursors are
7941 recognized through their targeting sequences by receptors at the
7942 mitochondrial surface and are then threaded through import channels
7943 into the matrix. Both the targeting sequence and the mature domain
7944 contribute to the efficiency with which proteins are imported into
7945 mitochondria. Precursors must be in an unfolded conformation during
7946 translocation. Mitochondria can unfold some proteins by changing their
7947 unfolding pathways. The effectiveness of this unfolding mechanism
7948 depends on the local structure of the mature domain adjacent to the
7949 targeting sequence. This local structure determines the extent to which
7950 the unfolding pathway can be changed and, therefore, the unfolding rate
7951 increased. Atomic force microscopy studies find that the local
7952 structures of proteins near their N and C termini also influence their
7953 resistance to mechanical unfolding. Thus, protein unfolding during
7954 import resembles mechanical unfolding, and the specificity of import is
7955 determined by the resistance of the mature domain to unfolding as well
7956 as by the properties of the targeting sequence."
7959 @article { wolfsberg01,
7960 author = TGWolfsberg #" and "# JMcEntyre #" and "# GDSchuler,
7961 title = "Guide to the draft human genome.",
7970 doi = "10.1038/35057000",
7971 eprint = "http://www.nature.com/nature/journal/v409/n6822/pdf/409824a0.pdf",
7972 url = "http://www.nature.com/nature/journal/v409/n6822/full/409824a0.html",
7973 keywords = "Amino Acid Sequence;Chromosome Mapping;Computational
7974 Biology;Genes;Genetic Variation;Genome, Human;Human Genome
7975 Project;Humans;Internet;Molecular Sequence Data;Sequence Analysis, DNA",
7976 abstract = "There are a number of ways to investigate the structure,
7977 function and evolution of the human genome. These include examining the
7978 morphology of normal and abnormal chromosomes, constructing maps of
7979 genomic landmarks, following the genetic transmission of phenotypes and
7980 DNA sequence variations, and characterizing thousands of individual
7981 genes. To this list we can now add the elucidation of the genomic DNA
7982 sequence, albeit at 'working draft' accuracy. The current challenge is
7983 to weave together these disparate types of data to produce the
7984 information infrastructure needed to support the next generation of
7985 biomedical research. Here we provide an overview of the different
7986 sources of information about the human genome and how modern
7987 information technology, in particular the internet, allows us to link
7992 author = JWWu #" and "# WLHung #" and "# CHTsai,
7993 title = "Estimation of parameters of the {G}ompertz distribution using the
7994 least squares method",
8003 doi = "10.1016/j.amc.2003.08.086",
8004 url = "http://dx.doi.org/10.1016/j.amc.2003.08.086",
8005 keywords = "Gompertz distribution; Least squares estimate; Maximum
8006 likelihood estimate; First failure-censored; Series system",
8007 abstract = "The Gompertz distribution has been used to describe human
8008 mortality and establish actuarial tables. Recently, this distribution
8009 has been again studied by some authors. The maximum likelihood
8010 estimates for the parameters of the Gompertz distribution has been
8011 discussed by Garg et al. [J. R. Statist. Soc. C 19 (1970) 152]. The
8012 purpose of this paper is to propose unweighted and weighted least
8013 squares estimates for parameters of the Gompertz distribution under the
8014 complete data and the first failure-censored data (series systems; see
8015 [J. Statist. Comput. Simulat. 52 (1995) 337]). A simulation study is
8016 carried out to compare the proposed estimators and the maximum
8017 likelihood estimators. Results of the simulation studies show that the
8018 performance of the weighted least squares estimators is acceptable."
8022 author = GYang #" and "# CCecconi #" and "# WBaase #" and "# IVetter #" and
8023 "# WBreyer #" and "# JHaack #" and "# BMatthews #" and "# FDahlquist #"
8025 title = "Solid-state synthesis and mechanical unfolding of polymers of {T4}
8032 doi = "10.1073/pnas.97.1.139",
8033 eprint = "http://www.pnas.org/cgi/reprint/97/1/139.pdf",
8034 url = "http://www.pnas.org/cgi/content/abstract/97/1/139"
8038 author = YYang #" and "# FCLin #" and "# GYang,
8039 title = "Temperature control device for single molecule measurements using
8040 the atomic force microscope",
8050 doi = "10.1063/1.2204580",
8051 url = "http://link.aip.org/link/?RSI/77/063701/1",
8052 keywords = "temperature control; atomic force microscopy; thermocouples;
8054 note = "Introduces our temperature control system",
8055 project = "Energy Landscape Roughness"
8059 author = WYu #" and "# JLamb #" and "# FHan #" and "# JBirchler,
8060 title = "Telomere-mediated chromosomal truncation in maize",
8065 pages = "17331--17336",
8066 doi = "10.1073/pnas.0605750103",
8067 eprint = "http://www.pnas.org/cgi/reprint/103/46/17331.pdf",
8068 url = "http://www.pnas.org/cgi/content/abstract/103/46/17331",
8069 abstract = "Direct repeats of Arabidopsis telomeric sequence were
8070 constructed to test telomere-mediated chromosomal truncation in maize.
8071 Two constructs with 2.6 kb of telomeric sequence were used to transform
8072 maize immature embryos by Agrobacterium-mediated transformation. One
8073 hundred seventy-six transgenic lines were recovered in which 231
8074 transgene loci were revealed by a FISH analysis. To analyze chromosomal
8075 truncations that result in transgenes located near chromosomal termini,
8076 Southern hybridization analyses were performed. A pattern of smear in
8077 truncated lines was seen as compared with discrete bands for internal
8078 integrations, because telomeres in different cells are elongated
8079 differently by telomerase. When multiple restriction enzymes were used
8080 to map the transgene positions, the size of the smears shifted in
8081 accordance with the locations of restriction sites on the construct.
8082 This result demonstrated that the transgene was present at the end of
8083 the chromosome immediately before the integrated telomere sequence.
8084 Direct evidence for chromosomal truncation came from the results of
8085 FISH karyotyping, which revealed broken chromosomes with transgene
8086 signals at the ends. These results demonstrate that telomere-mediated
8087 chromosomal truncation operates in plant species. This technology will
8088 be useful for chromosomal engineering in maize as well as other plant
8093 author = JZhao #" and "# HLee #" and "# RNome #" and "# SMajid #" and "#
8094 NScherer #" and "# WHoff,
8095 title = "Single-molecule detection of structural changes during
8096 {P}er-{A}rnt-{S}im ({PAS}) domain activation",
8101 pages = "11561--11566",
8102 doi = "10.1073/pnas.0601567103",
8103 eprint = "http://www.pnas.org/cgi/reprint/103/31/11561.pdf",
8104 url = "http://www.pnas.org/cgi/content/abstract/103/31/11561",
8105 abstract = "The Per-Arnt-Sim (PAS) domain is a ubiquitous protein module
8106 with a common three-dimensional fold involved in a wide range of
8107 regulatory and sensory functions in all domains of life. The activation
8108 of these functions is thought to involve partial unfolding of N- or
8109 C-terminal helices attached to the PAS domain. Here we use atomic force
8110 microscopy to probe receptor activation in single molecules of
8111 photoactive yellow protein (PYP), a prototype of the PAS domain family.
8112 Mechanical unfolding of Cys-linked PYP multimers in the presence and
8113 absence of illumination reveals that, in contrast to previous studies,
8114 the PAS domain itself is extended by {approx}3 nm (at the 10-pN
8115 detection limit of the measurement) and destabilized by {approx}30% in
8116 the light-activated state of PYP. Comparative measurements and steered
8117 molecular dynamics simulations of two double-Cys PYP mutants that probe
8118 different regions of the PAS domain quantify the anisotropy in
8119 stability and changes in local structure, thereby demonstrating the
8120 partial unfolding of their PAS domain upon activation. These results
8121 establish a generally applicable single-molecule approach for mapping
8122 functional conformational changes to selected regions of a protein. In
8123 addition, the results have profound implications for the molecular
8124 mechanism of PAS domain activation and indicate that stimulus-induced
8125 partial protein unfolding can be used as a signaling mechanism."
8128 @article { zhuang06,
8129 author = WZhuang #" and "# DAbramavicius #" and "# SMukamel,
8130 title = "Two-dimensional vibrational optical probes for peptide fast
8131 folding investigation",
8136 pages = "18934--18938",
8137 doi = "10.1073/pnas.0606912103",
8138 eprint = "http://www.pnas.org/cgi/reprint/103/50/18934.pdf",
8139 url = "http://www.pnas.org/cgi/content/abstract/103/50/18934",
8140 abstract = "A simulation study shows that early protein folding events may
8141 be investigated by using a recently developed family of nonlinear
8142 infrared techniques that combine the high temporal and spatial
8143 resolution of multidimensional spectroscopy with the chirality-specific
8144 sensitivity of amide vibrations to structure. We demonstrate how the
8145 structural sensitivity of cross-peaks in two-dimensional correlation
8146 plots of chiral signals of an {alpha} helix and a [beta] hairpin may be
8147 used to clearly resolve structural and dynamical details undetectable
8148 by one-dimensional techniques (e.g. circular dichroism) and identify
8149 structures indistinguishable by NMR."
8152 @article { zinober02,
8153 author = RCZinober #" and "# DJBrockwell #" and "# GSBeddard #" and "#
8154 AWBlake #" and "# PDOlmsted #" and "# SERadford #" and "# DASmith,
8155 title = "Mechanically unfolding proteins: the effect of unfolding history
8156 and the supramolecular scaffold",
8162 pages = "2759--2765",
8164 doi = "10.1110/ps.0224602",
8165 eprint = "http://www.proteinscience.org/cgi/reprint/11/12/2759.pdf",
8166 url = "http://www.proteinscience.org/cgi/content/abstract/11/12/2759",
8167 keywords = "Computer Simulation; Models, Molecular; Monte Carlo Method;
8168 Protein Folding; Protein Structure, Tertiary; Proteins",
8169 abstract = "The mechanical resistance of a folded domain in a polyprotein
8170 of five mutant I27 domains (C47S, C63S I27)(5)is shown to depend on the
8171 unfolding history of the protein. This observation can be understood on
8172 the basis of competition between two effects, that of the changing
8173 number of domains attempting to unfold, and the progressive increase in
8174 the compliance of the polyprotein as domains unfold. We present Monte
8175 Carlo simulations that show the effect and experimental data that
8176 verify these observations. The results are confirmed using an
8177 analytical model based on transition state theory. The model and
8178 simulations also predict that the mechanical resistance of a domain
8179 depends on the stiffness of the surrounding scaffold that holds the
8180 domain in vivo, and on the length of the unfolded domain. Together,
8181 these additional factors that influence the mechanical resistance of
8182 proteins have important consequences for our understanding of natural
8183 proteins that have evolved to withstand force.",
8184 note = "Introduces unfolding-order \emph{scaffold effect} on average
8186 project = "sawtooth simulation"
8189 @article { zwanzig92,
8190 author = RZwanzig #" and "# ASzabo #" and "# BBagchi,
8191 title = "Levinthal's paradox.",
8201 "http://www.ncbi.nlm.nih.gov/pmc/articles/PMC48166/pdf/pnas01075-0036.p
8203 url = "http://www.ncbi.nlm.nih.gov/pmc/articles/PMC48166/",
8204 keywords = "Mathematics;Models, Theoretical;Protein Conformation;Proteins",
8205 abstract = "Levinthal's paradox is that finding the native folded state of
8206 a protein by a random search among all possible configurations can take
8207 an enormously long time. Yet proteins can fold in seconds or less.
8208 Mathematical analysis of a simple model shows that a small and
8209 physically reasonable energy bias against locally unfavorable
8210 configurations, of the order of a few kT, can reduce Levinthal's time
8211 to a biologically significant size."
8215 author = XHong #" and "# XChu #" and "# PZou #" and "# YLiu
8217 title = "Magnetic-field-assisted rapid ultrasensitive
8218 immunoassays using Fe3{O4}/Zn{O}/Au nanorices as Raman
8224 address = "Centre for Advanced Optoelectronic Functional
8225 Materials Research, Key Laboratory for UV
8226 Light-Emitting Materials and Technology of Ministry of
8227 Education, Northeast Normal University, Changchun
8232 keywords = "Biosensing Techniques",
8233 keywords = "Electromagnetic Fields",
8234 keywords = "Equipment Design",
8235 keywords = "Equipment Failure Analysis",
8236 keywords = "Immunoassay",
8237 keywords = "Magnetite Nanoparticles",
8238 keywords = "Spectrum Analysis, Raman",
8239 keywords = "Zinc Oxide",
8240 abstract = "Rapid and ultrasensitive immunoassays were developed
8241 by using biofunctional Fe3O4/ZnO/Au nanorices as Raman
8242 probes. Taking advantage of the superparamagnetic
8243 property of the nanorices, the labeled proteins can
8244 rapidly be separated and purified with a commercial
8245 permanent magnet. The unsusceptible multiphonon
8246 resonant Raman scattering of the nanorices provided a
8247 characteristic spectroscopic fingerprint function,
8248 which allowed an accurate detection of the analyte.
8249 High specificity and selectivity of the assay were
8250 demonstrated. It was found that the diffusion barriers
8251 and the boundary layer effects had a great influence on
8252 the detection limit. Manipulation of the nanorice
8253 probes using an external magnetic field can enhance the
8254 assay sensitivity by several orders of magnitude, and
8255 reduce the detection time from 1 h to 3 min. This
8256 magnetic-field-assisted rapid and ultrasensitive
8257 immunoassay based on the resonant Raman scatting of
8258 semiconductor shows significant value for potential
8259 applications in biomedicine, food safety, and
8260 environmental defence.",
8262 doi = "10.1016/j.bios.2010.06.066",
8263 URL = "http://www.ncbi.nlm.nih.gov/pubmed/20667438",
8268 author = LZhao #" and "# ABulhassan #" and "# GYang #" and "#
8270 title = "Real-time detection of the morphological change in
8271 cellulose by a nanomechanical sensor.",
8276 address = "Department of Physics, Drexel University,
8277 Philadelphia, Pennsylvania, USA.",
8281 keywords = "Cellulose",
8282 keywords = "Computer Systems",
8283 keywords = "Equipment Design",
8284 keywords = "Equipment Failure Analysis",
8285 keywords = "Micro-Electrical-Mechanical Systems",
8286 keywords = "Molecular Conformation",
8287 keywords = "Nanotechnology",
8288 keywords = "Transducers",
8289 abstract = "Up to now, experimental limitations have prevented
8290 researchers from achieving the molecular-level
8291 understanding for the initial steps of the enzymatic
8292 hydrolysis of cellulose, where cellulase breaks down
8293 the crystal structure on the surface region of
8294 cellulose and exposes cellulose chains for the
8295 subsequent hydrolysis by cellulase. Because one of
8296 these non-hydrolytic enzymatic steps could be the
8297 rate-limiting step for the entire enzymatic hydrolysis
8298 of crystalline cellulose by cellulase, being able to
8299 analyze and understand these steps is instrumental in
8300 uncovering novel leads for improving the efficiency of
8301 cellulase. In this communication, we report an
8302 innovative application of the microcantilever technique
8303 for a real-time assessment of the morphological change
8304 of cellulose induced by a treatment of sodium chloride.
8305 This sensitive nanomechanical approach to define
8306 changes in surface structure of cellulose has the
8307 potential to permit a real-time assessment of the
8308 effect of the non-hydrolytic activities of cellulase on
8309 cellulose and thereby to provide a comprehensive
8310 understanding of the initial steps of the enzymatic
8311 hydrolysis of cellulose.",
8313 doi = "10.1002/bit.22754",
8314 URL = "http://www.ncbi.nlm.nih.gov/pubmed/20653025",
8319 author = RLiu #" and "# MRoman #" and "# GYang,
8320 title = "Correction of the viscous drag induced errors in
8321 macromolecular manipulation experiments using atomic
8326 address = "Department of Physics, Drexel University,
8327 Philadelphia, Pennsylvania 19104, USA.",
8331 keywords = "Algorithms",
8332 keywords = "Artifacts",
8333 keywords = "Macromolecular Substances",
8334 keywords = "Mechanical Processes",
8335 keywords = "Microscopy, Atomic Force",
8336 keywords = "Models, Theoretical",
8337 keywords = "Motion",
8338 keywords = "Protein Folding",
8339 keywords = "Signal Processing, Computer-Assisted",
8340 keywords = "Viscosity",
8341 abstract = "We describe a method to correct the errors induced by
8342 viscous drag on the cantilever in macromolecular
8343 manipulation experiments using the atomic force
8344 microscope. The cantilever experiences a viscous drag
8345 force in these experiments because of its motion
8346 relative to the surrounding liquid. This viscous force
8347 superimposes onto the force generated by the
8348 macromolecule under study, causing ambiguity in the
8349 experimental data. To remove this artifact, we analyzed
8350 the motions of the cantilever and the liquid in
8351 macromolecular manipulation experiments, and developed
8352 a novel model to treat the viscous drag on the
8353 cantilever as the superposition of the viscous force on
8354 a static cantilever in a moving liquid and that on a
8355 bending cantilever in a static liquid. The viscous
8356 force was measured under both conditions and the
8357 results were used to correct the viscous drag induced
8358 errors from the experimental data. The method will be
8359 useful for many other cantilever based techniques,
8360 especially when high viscosity and high cantilever
8361 speed are involved.",
8363 doi = "10.1063/1.3436646",
8364 URL = "http://www.ncbi.nlm.nih.gov/pubmed/20590242",
8368 @phdthesis { roman12,
8370 title = "Macromolecular crowding effects in the mechanical unfolding
8371 forces of proteins",
8375 url = "http://hdl.handle.net/1860/3854",
8376 eprint = "http://idea.library.drexel.edu/bitstream/1860/3854/1/Roman_Marisa.pdf",
8377 keywords = "Physics",
8378 keywords = "Biophysics",
8379 keywords = "Protein folding",
8380 abstract = "Macromolecules can occupy a large fraction of the volume
8381 of a cell and this crowded environment influences the behavior and
8382 properties of the proteins, such as mechanical unfolding forces,
8383 thermal stability and rates of folding and diffusion. Although
8384 much is already known about molecular crowding, it is not well
8385 understood how it affects a protein’s resistance to mechanical
8386 stress in a crowded environment and how the size of the crowders
8387 affect those changes. An atomic force microscope-based single
8388 molecule method was used to measure the effects of the crowding on
8389 the mechanical stability of a model protein, in this case I-27. As
8390 proteins tend to aggregate, single molecule methods provided a way
8391 to prevent aggregation because of the very low concentration of
8392 proteins in the solution under study. Dextran was used as the
8393 crowding agent with three different molecular weights 6kDa, 10 kDa
8394 and 40 kDa, with concentrations varying from zero to 300 grams per
8395 liter in a pH neutral buffer solution at room temperature. Results
8396 showed that the forces required to unfold biomolecules were
8397 increased when a high concentration of crowder molecules were
8398 added to the buffer solution and that the maximum force required
8399 to unfold a domain was when the crowder size was 10 kDa, which is
8400 comparable to the protein size. Unfolding rates obtained from
8401 Monte Carlo simulations showed that they were also affected in the
8402 presence of crowders. As a consequence, the energy barrier was
8403 also affected. These effects were most notable when the size of
8404 the crowder was 10 kDa, comparable to the size of the protein. On
8405 the other hand, distances to the transition state did not seem to
8406 change when crowders were added to the solution. The effect of
8407 Dextran on the energy barrier was modeled by using established
8408 theories such as Ogston’s and scaled particle theory, neither of
8409 which was completely convincing at describing the results. It can
8410 be hypothesized that the composition of Dextran plays a role in
8411 the deviation of the predicted behavior with respect to the
8412 experimental data.",
8416 @article { measey09,
8417 author = TMeasey #" and "# KBSmith #" and "# SDecatur #" and "#
8418 LZhao #" and "# GYang #" and "# RSchweitzerStenner,
8419 title = "Self-aggregation of a polyalanine octamer promoted by
8420 its {C}-terminal tyrosine and probed by a strongly
8421 enhanced vibrational circular dichroism signal.",
8426 address = "Department of Chemistry, Drexel University, 3141
8427 Chestnut Street, Philadelphia, Pennsylvania 19104,
8431 pages = "18218--18219",
8432 keywords = "Amyloid",
8433 keywords = "Circular Dichroism",
8434 keywords = "Dimerization",
8435 keywords = "Oligopeptides",
8436 keywords = "Peptides",
8437 keywords = "Protein Conformation",
8438 keywords = "Tyrosine",
8439 abstract = "The eight-residue alanine oligopeptide
8440 Ac-A(4)KA(2)Y-NH(2) (AKY8) was found to form
8441 amyloid-like fibrils upon incubation at room
8442 temperature in acidified aqueous solution at peptide
8443 concentrations >10 mM. The fibril solution exhibits an
8444 enhanced vibrational circular dichroism (VCD) couplet
8445 in the amide I' band region that is nearly 2 orders of
8446 magnitude larger than typical polypeptide/protein
8447 signals in this region. The UV-CD spectrum of the
8448 fibril solution shows CD in the region associated with
8449 the tyrosine side chain absorption. A similar peptide,
8450 Ac-A(4)KA(2)-NH(2) (AK7), which lacks a terminal
8451 tyrosine residue, does not aggregate. These results
8452 suggest a pivotal role for the C-terminal tyrosine
8453 residue in stabilizing the aggregation state of this
8454 peptide. It is speculated that interactions between the
8455 lysine and tyrosine side chains of consecutive strands
8456 in an antiparallel arrangement (e.g., cation-pi
8457 interactions) are responsible for the stabilization of
8458 the resulting fibrils. These results offer
8459 considerations and insight regarding the de novo design
8460 of self-assembling oligopeptides for biomedical and
8461 biotechnological applications and highlight the
8462 usefulness of VCD as a tool for probing amyloid fibril
8465 doi = "10.1021/ja908324m",
8466 URL = "http://www.ncbi.nlm.nih.gov/pubmed/19958029",
8471 author = GShan #" and "# SWang #" and "# XFei #" and "# YLiu
8473 title = "Heterostructured Zn{O}/Au nanoparticles-based resonant
8474 Raman scattering for protein detection.",
8479 address = "Center for Advanced Optoelectronic Functional
8480 Materials Research, Northeast Normal University,
8481 Changchun 130024, P. R. China.",
8484 pages = "1468--1472",
8485 keywords = "Animals",
8487 keywords = "Humans",
8488 keywords = "Immunoglobulin G",
8489 keywords = "Metal Nanoparticles",
8490 keywords = "Microscopy, Electron, Transmission",
8491 keywords = "Spectrum Analysis, Raman",
8492 keywords = "Zinc Oxide",
8493 abstract = "A new method of protein detection was explored on the
8494 resonant Raman scattering signal of ZnO nanoparticles.
8495 A probe for the target protein was constructed by
8496 binding the ZnO/Au nanoparticles to secondary protein
8497 by eletrostatic interaction. The detection of proteins
8498 was achieved by an antibody-based sandwich assay. A
8499 first antibody, which could be specifically recognized
8500 by target protein, was attached to a solid silicon
8501 surface. The ZnO/Au protein probe could specifically
8502 recognize and bind to the complex of the target protein
8503 and first antibody. This method on the resonant Raman
8504 scattering signal of ZnO nanoparticles showed good
8505 selectivity and sensitivity for the target protein.",
8507 doi = "10.1021/jp8046032",
8508 URL = "http://www.ncbi.nlm.nih.gov/pubmed/19138135",
8513 author = JMYuan #" and "# CLChyan #" and "# HXZhou #" and "#
8514 TYChung #" and "# HPeng #" and "# GPing #" and "#
8516 title = "The effects of macromolecular crowding on the
8517 mechanical stability of protein molecules.",
8522 address = "Department of Physics, Drexel University,
8523 Philadelphia, Pennsylvania 19104, USA.",
8526 pages = "2156--2166",
8527 keywords = "Circular Dichroism",
8528 keywords = "Dextrans",
8529 keywords = "Kinetics",
8530 keywords = "Microscopy, Atomic Force",
8531 keywords = "Microscopy, Scanning Probe",
8532 keywords = "Protein Folding",
8533 keywords = "Protein Stability",
8534 keywords = "Protein Structure, Secondary",
8535 keywords = "Thermodynamics",
8536 keywords = "Ubiquitin",
8537 abstract = "Macromolecular crowding, a common phenomenon in the
8538 cellular environments, can significantly affect the
8539 thermodynamic and kinetic properties of proteins. A
8540 single-molecule method based on atomic force microscopy
8541 (AFM) was used to investigate the effects of
8542 macromolecular crowding on the forces required to
8543 unfold individual protein molecules. It was found that
8544 the mechanical stability of ubiquitin molecules was
8545 enhanced by macromolecular crowding from added dextran
8546 molecules. The average unfolding force increased from
8547 210 pN in the absence of dextran to 234 pN in the
8548 presence of 300 g/L dextran at a pulling speed of 0.25
8549 microm/sec. A theoretical model, accounting for the
8550 effects of macromolecular crowding on the native and
8551 transition states of the protein molecule by applying
8552 the scaled-particle theory, was used to quantitatively
8553 explain the crowding-induced increase in the unfolding
8554 force. The experimental results and interpretation
8555 presented could have wide implications for the many
8556 proteins that experience mechanical stresses and
8557 perform mechanical functions in the crowded environment
8560 doi = "10.1110/ps.037325.108",
8561 URL = "http://www.ncbi.nlm.nih.gov/pubmed/18780817",
8566 author = YLiu #" and "# MZhong #" and "# GShan #" and "# YLi
8567 #" and "# BHuang #" and "# GYang,
8568 title = "Biocompatible Zn{O}/Au nanocomposites for
8569 ultrasensitive {DNA} detection using resonance Raman
8575 address = "Centre for Advanced Optoelectronic Functional
8576 Materials Research, Institute of Genetics and Cytology,
8577 Northeast Normal University, Changchun, People's
8578 Republic of China. ycliu@nenu.edu.cn",
8581 pages = "6484--6489",
8582 keywords = "Base Sequence",
8585 keywords = "Microscopy, Electron, Transmission",
8586 keywords = "Nanocomposites",
8587 keywords = "Sensitivity and Specificity",
8588 keywords = "Spectrum Analysis, Raman",
8589 keywords = "Zinc Oxide",
8590 abstract = "A novel method for identifying DNA microarrays based
8591 on ZnO/Au nanocomposites functionalized with
8592 thiol-oligonucleotide as probes is descried here. DNA
8593 labeled with ZnO/Au nanocomposites has a strong Raman
8594 signal even without silver acting as a surface-enhanced
8595 Raman scattering promoter. X-ray photoelectron spectra
8596 confirmed the formation of a three-component sandwich
8597 assay, i.e., constituted DNA and ZnO/Au nanocomposites.
8598 The resonance multiple-phonon Raman signal of the
8599 ZnO/Au nanocomposites as a spectroscopic fingerprint is
8600 used to detect a target sequence of oligonucleotide.
8601 This method exhibits extraordinary sensitivity and the
8602 detection limit is at least 1 fM.",
8604 doi = "10.1021/jp710399d",
8605 URL = "http://www.ncbi.nlm.nih.gov/pubmed/18444675",
8610 author = YGuo #" and "# AMylonakis #" and "# ZZhang #" and "#
8611 GYang #" and "# PLelkes #" and "# SChe #" and "#
8613 title = "Templated synthesis of electroactive periodic
8614 mesoporous organosilica bridged with oligoaniline.",
8617 address = "Department of Chemistry, Drexel University,
8618 Philadelphia, Pennsylvania 19104, USA.",
8621 pages = "2909--2917",
8622 keywords = "Aniline Compounds",
8623 keywords = "Cetrimonium Compounds",
8624 keywords = "Electrochemistry",
8625 keywords = "Hydrolysis",
8626 keywords = "Microscopy, Electron, Transmission",
8627 keywords = "Molecular Structure",
8628 keywords = "Organosilicon Compounds",
8629 keywords = "Particle Size",
8630 keywords = "Porosity",
8631 keywords = "Spectroscopy, Fourier Transform Infrared",
8632 keywords = "Surface Properties",
8633 keywords = "Thermogravimetry",
8634 keywords = "X-Ray Diffraction",
8635 abstract = "The synthesis and characterization of novel
8636 electroactive periodic mesoporous organosilica (PMO)
8637 are reported. The silsesquioxane precursor,
8638 N,N'-bis(4'-(3-triethoxysilylpropylureido)phenyl)-1,4-quinonene-diimine
8639 (TSUPQD), was prepared from the emeraldine base of
8640 amino-capped aniline trimer (EBAT) using a one-step
8641 coupling reaction and was used as an organic silicon
8642 source in the co-condensation with tetraethyl
8643 orthosilicate (TEOS) in proper ratios. By means of a
8644 hydrothermal sol-gel approach with the cationic
8645 surfactant cetyltrimethyl-ammonium bromide (CTAB) as
8646 the structure-directing template and acetone as the
8647 co-solvent for the dissolution of TSUPQD, a series of
8648 novel MCM-41 type siliceous materials (TSU-PMOs) were
8649 successfully prepared under mild alkaline conditions.
8650 The resultant mesoporous organosilica were
8651 characterized by Fourier transform infrared (FT-IR)
8652 spectroscopy, thermogravimetry, X-ray diffraction,
8653 nitrogen sorption, and transmission electron microscopy
8654 (TEM) and showed that this series of TSU-PMOs exhibited
8655 hexagonally patterned mesostructures with pore
8656 diameters of 2.1-2.8 nm. Although the structural
8657 regularity and pore parameters gradually deteriorated
8658 with increasing loading of organic bridges, the
8659 electrochemical behavior of TSU-PMOs monitored by
8660 cyclic voltammetry demonstrated greater
8661 electroactivities for samples with higher concentration
8662 of the incorporated TSU units.",
8664 doi = "10.1002/chem.200701605",
8665 URL = "http://www.ncbi.nlm.nih.gov/pubmed/18224650",
8670 author = LiLi #" and "# BLi #" and "# GYang #" and "# CYLi,
8671 title = "Polymer decoration on carbon nanotubes via physical
8677 address = "A. J. Drexel Nanotechnology Institute and Department
8678 of Materials Science and Engineering, Drexel
8679 University, Philadelphia, Pennsylvania 19104, USA.",
8682 pages = "8522--8525",
8683 keywords = "Microscopy, Atomic Force",
8684 keywords = "Microscopy, Electron, Transmission",
8685 keywords = "Nanotubes, Carbon",
8686 keywords = "Polymers",
8687 keywords = "Surface Properties",
8688 keywords = "Volatilization",
8689 abstract = "The polymer decoration technique has been widely used
8690 to study the chain folding behavior of polymer single
8691 crystals. In this article, we demonstrate that this
8692 method can be successfully adopted to pattern a variety
8693 of polymers on carbon nanotubes (CNTs). The resulting
8694 structure is a two-dimensional nanohybrid shish kebab
8695 (2D NHSK), wherein the CNT forms the shish and the
8696 polymer crystals form the kebabs. 2D NHSKs consisting
8697 of CNTs and polymers such as polyethylene, nylon 66,
8698 polyvinylidene fluoride and poly(L-lysine) have been
8699 achieved. Transmission electron microscopy and atomic
8700 force microscopy were used to study the nanoscale
8701 morphology of these hybrid materials. Relatively
8702 periodic decoration of polymers on both single-walled
8703 and multi-walled CNTs was observed. It is envisaged
8704 that this unique method offers a facile means to
8705 achieve patterned CNTs for nanodevice applications.",
8707 doi = "10.1021/la700480z",
8708 URL = "http://www.ncbi.nlm.nih.gov/pubmed/17602575",
8713 author = MSu #" and "# YYang #" and "# GYang,
8714 title = "Quantitative measurement of hydroxyl radical induced
8715 {DNA} double-strand breaks and the effect of
8716 {N}-acetyl-{L}-cysteine.",
8721 address = "Department of Physics, Drexel University,
8722 Philadelphia, PA 19104, USA.",
8725 pages = "4136--4142",
8726 keywords = "Acetylcysteine",
8727 keywords = "Animals",
8728 keywords = "DNA Damage",
8729 keywords = "Humans",
8730 keywords = "Hydroxyl Radical",
8731 keywords = "Microscopy, Atomic Force",
8732 keywords = "Nucleic Acid Conformation",
8733 keywords = "Plasmids",
8734 abstract = "Reactive oxygen species, such as hydroxyl or
8735 superoxide radicals, can be generated by exogenous
8736 agents as well as from normal cellular metabolism.
8737 Those radicals are known to induce various lesions in
8738 DNA, including strand breaks and base modifications.
8739 These lesions have been implicated in a variety of
8740 diseases such as cancer, arteriosclerosis, arthritis,
8741 neurodegenerative disorders and others. To assess these
8742 oxidative DNA damages and to evaluate the effects of
8743 the antioxidant N-acetyl-L-cysteine (NAC), atomic force
8744 microscopy (AFM) was used to image DNA molecules
8745 exposed to hydroxyl radicals generated via Fenton
8746 chemistry. AFM images showed that the circular DNA
8747 molecules became linear after incubation with hydroxyl
8748 radicals, indicating the development of double-strand
8749 breaks. The occurrence of the double-strand breaks was
8750 found to depend on the concentration of the hydroxyl
8751 radicals and the duration of the reaction. Under the
8752 conditions of the experiments, NAC was found to
8753 exacerbate the free radical-induced DNA damage.",
8755 doi = "10.1016/j.febslet.2006.06.060",
8756 URL = "http://www.ncbi.nlm.nih.gov/pubmed/16828758",
8761 author = LiLi #" and "# YYang #" and "# GYang #" and "# XuChen
8762 #" and "# BHsiao #" and "# BChu #" and "#
8763 JSpanier #" and "# CYLi,
8764 title = "Patterning polyethylene oligomers on carbon nanotubes
8765 using physical vapor deposition.",
8769 address = "A. J. Drexel Nanotechnology Institute and Department
8770 of Materials Science and Engineering, Drexel
8771 University, Philadelphia, Pennsylvania 19104, USA.",
8774 pages = "1007--1012",
8775 keywords = "Microscopy, Atomic Force",
8776 keywords = "Nanotechnology",
8777 keywords = "Nanotubes, Carbon",
8778 keywords = "Polyethylenes",
8779 keywords = "Volatilization",
8780 abstract = "Periodic patterning on one-dimensional (1D) carbon
8781 nanotubes (CNTs) is of great interest from both
8782 scientific and technological points of view. In this
8783 letter, we report using a facile physical vapor
8784 deposition method to achieve periodic polyethylene (PE)
8785 oligomer patterning on individual CNTs. Upon heating
8786 under vacuum, PE degraded into oligomers and
8787 crystallized into rod-shaped single crystals. These PE
8788 rods periodically decorate on CNTs with their long axes
8789 perpendicular to the CNT axes. The formation mechanism
8790 was attributed to ``soft epitaxy'' growth of PE
8791 oligomer crystals on CNTs. Both SWNTs and MWNTs were
8792 decorated successfully with PE rods. The intermediate
8793 state of this hybrid structure, MWNTs absorbed with a
8794 thin layer of PE, was captured successfully by
8795 depositing PE vapor on MWNTs detached from the solid
8796 substrate, and was observed using high-resolution
8797 transmission electron microscopy. Furthermore, this
8798 hybrid structure formation depends critically on CNT
8799 surface chemistry: alkane-modification of the MWNT
8800 surface prohibited the PE single-crystal growth on the
8801 CNTs. We anticipate that this work could open a gateway
8802 for creating complex CNT-based nanoarchitectures for
8803 nanodevice applications.",
8805 doi = "10.1021/nl060276q",
8806 URL = "http://www.ncbi.nlm.nih.gov/pubmed/16683841",
8811 author = MKuhn #" and "# HJanovjak #" and "# MHubain #" and "# DJMuller,
8812 title = {Automated alignment and pattern recognition of
8813 single-molecule force spectroscopy data.},
8816 address = {Division of Computer Science, California Institute of
8817 Technology, Pasadena, California 91125, USA.},
8823 doi = {10.1111/j.1365-2818.2005.01478.x},
8824 URL = {http://www.ncbi.nlm.nih.gov/pubmed/15857374},
8826 keywords = {Algorithms},
8827 keywords = {Bacteriorhodopsins},
8828 keywords = {Data Interpretation, Statistical},
8829 keywords = {Escherichia coli Proteins},
8830 keywords = {Microscopy, Atomic Force},
8831 keywords = {Protein Folding},
8832 keywords = {Sodium-Hydrogen Antiporter},
8833 keywords = {Software},
8834 abstract = {Recently, direct measurements of forces stabilizing
8835 single proteins or individual receptor-ligand bonds became
8836 possible with ultra-sensitive force probe methods like the atomic
8837 force microscope (AFM). In force spectroscopy experiments using
8838 AFM, a single molecule or receptor-ligand pair is tethered between
8839 the tip of a micromachined cantilever and a supporting
8840 surface. While the molecule is stretched, forces are measured by
8841 the deflection of the cantilever and plotted against extension,
8842 yielding a force spectrum characteristic for each biomolecular
8843 system. In order to obtain statistically relevant results, several
8844 hundred to thousand single-molecule experiments have to be
8845 performed, each resulting in a unique force spectrum. We developed
8846 software and algorithms to analyse large numbers of force
8847 spectra. Our algorithms include the fitting polymer extension
8848 models to force peaks as well as the automatic alignment of
8849 spectra. The aligned spectra allowed recognition of patterns of
8850 peaks across different spectra. We demonstrate the capabilities of
8851 our software by analysing force spectra that were recorded by
8852 unfolding single transmembrane proteins such as bacteriorhodopsin
8853 and NhaA. Different unfolding pathways were detected by
8854 classifying peak patterns. Deviant spectra, e.g. those with no
8855 attachment or erratic peaks, can be easily identified. The
8856 software is based on the programming language C++, the GNU
8857 Scientific Library (GSL), the software WaveMetrics IGOR Pro and
8858 available open-source at http://bioinformatics.org/fskit/.},
8859 note = {Development stalled in 2005 after Michael graduated.},
8862 @article{ janovjak05,
8863 author = HJanovjak #" and "# JStruckmeier #" and "# DJMuller,
8864 title = {Hydrodynamic effects in fast {AFM} single-molecule
8865 force measurements.},
8869 address = {BioTechnological Center, University of Technology
8870 Dresden, 01307 Dresden, Germany.},
8876 doi = {10.1007/s00249-004-0430-3},
8877 url = {http://www.ncbi.nlm.nih.gov/pubmed/15257425},
8879 keywords = {Algorithms},
8880 keywords = {Computer Simulation},
8881 keywords = {Elasticity},
8882 keywords = {Microfluidics},
8883 keywords = {Microscopy, Atomic Force},
8884 keywords = {Models, Chemical},
8885 keywords = {Models, Molecular},
8886 keywords = {Physical Stimulation},
8887 keywords = {Protein Binding},
8888 keywords = {Proteins},
8889 keywords = {Stress, Mechanical},
8890 keywords = {Viscosity},
8891 abstract = {Atomic force microscopy (AFM) allows the critical forces
8892 that unfold single proteins and rupture individual receptor-ligand
8893 bonds to be measured. To derive the shape of the energy landscape,
8894 the dynamic strength of the system is probed at different force
8895 loading rates. This is usually achieved by varying the pulling
8896 speed between a few nm/s and a few $\mu$m/s, although for a more
8897 complete investigation of the kinetic properties higher speeds are
8898 desirable. Above 10 $\mu$m/s, the hydrodynamic drag force acting
8899 on the AFM cantilever reaches the same order of magnitude as the
8900 molecular forces. This has limited the maximum pulling speed in
8901 AFM single-molecule force spectroscopy experiments. Here, we
8902 present an approach for considering these hydrodynamic effects,
8903 thereby allowing a correct evaluation of AFM force measurements
8904 recorded over an extended range of pulling speeds (and thus
8905 loading rates). To support and illustrate our theoretical
8906 considerations, we experimentally evaluated the mechanical
8907 unfolding of a multi-domain protein recorded at $30\U{$mu$m/s}$
8912 author = MSandal #" and "# FValle #" and "# ITessari #" and "#
8913 SMammi #" and "# EBergantino #" and "# FMusiani #" and "#
8914 MBrucale #" and "# LBubacco #" and "# BSamori,
8915 title = {Conformational Equilibria in Monomeric $\alpha$-Synuclein
8916 at the Single-Molecule Level},
8919 address = {Department of Biochemistry G. Moruzzi,
8920 University of Bologna, Bologna, Italy.},
8926 doi = {10.1371/journal.pbio.0060006},
8927 url = {http://www.ncbi.nlm.nih.gov/pubmed/18198943},
8929 keywords = {Buffers},
8930 keywords = {Circular Dichroism},
8931 keywords = {Copper},
8932 keywords = {Entropy},
8933 keywords = {Models, Molecular},
8934 keywords = {Molecular Sequence Data},
8935 keywords = {Mutation},
8936 keywords = {Protein Structure, Secondary},
8937 keywords = {Protein Structure, Tertiary},
8938 keywords = {alpha-Synuclein},
8939 abstract = {Human $\alpha$-Synuclein ($\alpha$Syn) is a natively
8940 unfolded protein whose aggregation into amyloid fibrils is
8941 involved in the pathology of Parkinson disease. A full
8942 comprehension of the structure and dynamics of early intermediates
8943 leading to the aggregated states is an unsolved problem of
8944 essential importance to researchers attempting to decipher the
8945 molecular mechanisms of $\alpha$Syn aggregation and formation of
8946 fibrils. Traditional bulk techniques used so far to solve this
8947 problem point to a direct correlation between $\alpha$Syn's unique
8948 conformational properties and its propensity to aggregate, but
8949 these techniques can only provide ensemble-averaged information
8950 for monomers and oligomers alike. They therefore cannot
8951 characterize the full complexity of the conformational equilibria
8952 that trigger the aggregation process. We applied atomic force
8953 microscopy-based single-molecule mechanical unfolding methodology
8954 to study the conformational equilibrium of human wild-type and
8955 mutant $\alpha$Syn. The conformational heterogeneity of monomeric
8956 $\alpha$Syn was characterized at the single-molecule level. Three
8957 main classes of conformations, including disordered and
8958 ``$\beta$-like'' structures, were directly observed and quantified
8959 without any interference from oligomeric soluble forms. The
8960 relative abundance of the ``$\beta$-like'' structures
8961 significantly increased in different conditions promoting the
8962 aggregation of $\alpha$Syn: the presence of \Cu, the pathogenic
8963 A30P mutation, and high ionic strength. This methodology can
8964 explore the full conformational space of a protein at the
8965 single-molecule level, detecting even poorly populated conformers
8966 and measuring their distribution in a variety of biologically
8967 important conditions. To the best of our knowledge, we present
8968 for the first time evidence of a conformational equilibrium that
8969 controls the population of a specific class of monomeric
8970 $\alpha$Syn conformers, positively correlated with conditions
8971 known to promote the formation of aggregates. A new tool is thus
8972 made available to test directly the influence of mutations and
8973 pharmacological strategies on the conformational equilibrium of
8974 monomeric $\alpha$Syn.},
8978 author = MSandal #" and "# FBenedetti #" and "# MBrucale #" and "#
8979 AGomezCasado #" and "# BSamori,
8980 title = "Hooke: An open software platform for force spectroscopy.",
8985 address = "Department of Biochemistry, University of Bologna,
8986 Bologna, Italy. massimo.sandal@unibo.it",
8989 pages = "1428--1430",
8990 keywords = "Algorithms",
8991 keywords = "Computational Biology",
8992 keywords = "Internet",
8993 keywords = "Microscopy, Atomic Force",
8994 keywords = "Proteome",
8995 keywords = "Proteomics",
8996 keywords = "Software",
8997 abstract = "SUMMARY: Hooke is an open source, extensible software
8998 intended for analysis of atomic force microscope (AFM)-based
8999 single molecule force spectroscopy (SMFS) data. We propose it as a
9000 platform on which published and new algorithms for SMFS analysis
9001 can be integrated in a standard, open fashion, as a general
9002 solution to the current lack of a standard software for SMFS data
9003 analysis. Specific features and support for file formats are coded
9004 as independent plugins. Any user can code new plugins, extending
9005 the software capabilities. Basic automated dataset filtering and
9006 semi-automatic analysis facilities are included. AVAILABILITY:
9007 Software and documentation are available at
9008 (http://code.google.com/p/hooke). Hooke is a free software under
9009 the GNU Lesser General Public License.",
9011 doi = "10.1093/bioinformatics/btp180",
9012 URL = "http://www.ncbi.nlm.nih.gov/pubmed/19336443",
9016 @article{ materassi09,
9017 author = DMaterassi #" and "# PBaschieri #" and "# BTiribilli #" and "#
9018 GZuccheri #" and "# BSamori,
9019 title = {An open source/real-time atomic force microscope
9020 architecture to perform customizable force spectroscopy
9024 address = {Department of Electrical and Computer Engineering,
9025 University of Minnesota, 200 Union St. SE, Minneapolis,
9026 Minnesota 55455, USA. mater013@umn.edu},
9032 doi = "10.1063/1.3194046",
9033 url = "http://www.ncbi.nlm.nih.gov/pubmed/19725671",
9035 keywords = {Algorithms},
9036 keywords = {Animals},
9037 keywords = {Calibration},
9039 keywords = {Microscopy, Atomic Force},
9040 keywords = {Muscle Proteins},
9041 keywords = {Myocardium},
9042 keywords = {Optics and Photonics},
9043 keywords = {Ownership},
9044 keywords = {Protein Kinases},
9045 keywords = {Software},
9046 keywords = {Spectrum Analysis},
9047 keywords = {Time Factors},
9048 abstract = {We describe the realization of an atomic force
9049 microscope architecture designed to perform customizable
9050 experiments in a flexible and automatic way. Novel technological
9051 contributions are given by the software implementation platform
9052 (RTAI-LINUX), which is free and open source, and from a functional
9053 point of view, by the implementation of hard real-time control
9054 algorithms. Some other technical solutions such as a new way to
9055 estimate the optical lever constant are described as well. The
9056 adoption of this architecture provides many degrees of freedom in
9057 the device behavior and, furthermore, allows one to obtain a
9058 flexible experimental instrument at a relatively low cost. In
9059 particular, we show how such a system has been employed to obtain
9060 measures in sophisticated single-molecule force spectroscopy
9061 experiments\citep{fernandez04}. Experimental results on proteins
9062 already studied using the same methodologies are provided in order
9063 to show the reliability of the measure system.},
9064 note = {Although this paper claims to present an open source
9065 experiment control framework (on Linux!), it doesn't actually link
9066 to any source code. This is puzzling and frusterating.},
9069 @article{ aioanei11,
9070 author = DAioanei #" and "# MBrucale #" and "# BSamori,
9071 title = {Open source platform for the execution and analysis of
9072 mechanical refolding experiments.},
9076 address = {Department of Biochemistry G.~Moruzzi,
9077 University of Bologna, Via Irnerio 48, 40126 Bologna, Italy.
9078 aioaneid@gmail.com},
9084 doi = {10.1093/bioinformatics/btq663},
9085 url = {http://www.ncbi.nlm.nih.gov/pubmed/21123222},
9087 keywords = {Computational Biology},
9088 keywords = {Kinetics},
9089 keywords = {Protein Denaturation},
9090 keywords = {Protein Refolding},
9091 keywords = {Software},
9092 abstract = {Single-molecule force spectroscopy has facilitated the
9093 experimental investigation of biomolecular force-coupled kinetics,
9094 from which the kinetics at zero force can be extrapolated via
9095 explicit theoretical models. The atomic force microscope (AFM) in
9096 particular is routinely used to study protein unfolding kinetics,
9097 but only rarely protein folding kinetics. The discrepancy arises
9098 because mechanical protein refolding studies are more technically
9100 note = {\href{http://code.google.com/p/refolding/}{Refolding} is a
9101 suite for performing and analyzing double-pulse refolding
9102 experiments. The experiment-driver is mostly written in Java with
9103 the analysis code in Python. The driver is curious; it uses the
9104 NanoScope scripting interface to drive the experiment through the
9105 NanoScope software by impersonating a mouse-wielding user (like
9106 Selenium does for web browsers). See the
9107 \imint{sh}|RobotNanoDriver.java| code for details. There is also
9108 support for automatic velocity clamp analysis.},
9111 @article{ benedetti11,
9112 author = FBenedetti #" and "# CMicheletti #" and "# GBussi #" and "#
9113 SKSekatskii #" and "# GDietler,
9114 title = {Nonkinetic modeling of the mechanical unfolding of
9115 multimodular proteins: theory and experiments.},
9119 address = {Laboratory of Physics of Living Matter,
9120 Ecole Polytechnique F{\'e}d{\'e}rale de Lausanne,
9121 Lausanne, Switzerland.},
9125 pages = {1504--1512},
9127 doi = {10.1016/j.bpj.2011.07.047},
9128 url = {http://www.ncbi.nlm.nih.gov/pubmed/21943432},
9130 keywords = {Kinetics},
9131 keywords = {Microscopy, Atomic Force},
9132 keywords = {Models, Molecular},
9133 keywords = {Monte Carlo Method},
9134 keywords = {Protein Unfolding},
9135 keywords = {Stochastic Processes},
9136 abstract = {We introduce and discuss a novel approach called
9137 back-calculation for analyzing force spectroscopy experiments on
9138 multimodular proteins. The relationship between the histograms of
9139 the unfolding forces for different peaks, corresponding to a
9140 different number of not-yet-unfolded protein modules, is exploited
9141 in such a manner that the sole distribution of the forces for one
9142 unfolding peak can be used to predict the unfolding forces for
9143 other peaks. The scheme is based on a bootstrap prediction method
9144 and does not rely on any specific kinetic model for multimodular
9145 unfolding. It is tested and validated in both
9146 theoretical/computational contexts (based on stochastic
9147 simulations) and atomic force microscopy experiments on (GB1)(8)
9148 multimodular protein constructs. The prediction accuracy is so
9149 high that the predicted average unfolding forces corresponding to
9150 each peak for the GB1 construct are within only 5 pN of the
9151 averaged directly-measured values. Experimental data are also used
9152 to illustrate how the limitations of standard kinetic models can
9153 be aptly circumvented by the proposed approach.},
9156 @phdthesis{ benedetti12,
9157 author = FBenedetti,
9158 title = {Statistical Study of the Unfolding of Multimodular Proteins
9159 and their Energy Landscape by Atomic Force Microscopy},
9161 address = {Lausanne},
9162 affiliation = {EPFL},
9165 doi = {10.5075/epfl-thesis-5440},
9166 url = {http://infoscience.epfl.ch/record/181215},
9167 eprint = {http://infoscience.epfl.ch/record/181215/files/EPFL_TH5440.pdf},
9168 keywords = {atomic force microscope (AFM); single molecule force
9169 spectrosopy; velocity clamp AFM; Monte carlo simulations; force
9170 modulation spectroscopy; energy barrier model; non kinetic methods
9171 for force spectroscopy},
9172 abstract = {The aim of the present thesis is to investigate several
9173 aspects of: the proteins mechanics, interprotein interactions and
9174 to study also new techniques, theoretical and technical, to obtain
9175 and analyze the force spectroscopy experiments. The first section
9176 is dedicated to the statistical properties of the unfolding forces
9177 in a chain of homomeric multimodular proteins. The basic idea of
9178 this kind of statistic is to divide the peaks observed in a force
9179 extension curve in separate groups and then analyze these groups
9180 considering their position in the force curves. In fact in a
9181 multimodular homomeric protein the unfolding force is related to
9182 the number of not yet unfolded modules (we call it "N"). Such
9183 effect yields to a linear dependence of the most probable
9184 unfolding force of a peak on ln(N). We demonstrate how such
9185 dependence can be used to extract the kinetic parameters and how,
9186 ignoring it, could lead to significant errors. Following this
9187 topic we continue with non kinetic methods that, using the
9188 resampling from the rupture forces of any peak, could reconstruct
9189 the rupture forces for all the other peaks in a chain. Then a
9190 discussion about the Monte Carlo simulation for protein pulling is
9191 present. In fact a theoretical framework for such methodology has
9192 to be introduced to understand the various simulations done. In
9193 this chapter we also introduce a methodology to study the ligand
9194 receptor interactions when we directly functionalize the AFM tip
9195 and the substrate. In fact, in many of our experiments, we see a
9196 "cloud of points" in the force vs loading rate graph. We have
9197 modeled a system composed by "N" parallel springs, and studying
9198 the distribution of forces obtained in the force vs loading rate
9199 graph we have establish a procedure to restore the kinetic
9200 parameters used. Such procedure has then been used to discuss real
9201 experiments similar to biotin-avidin interaction. In the following
9202 chapter we discuss a first order approximation of the Bell-Evans
9203 model where a more explicit form of the potential is
9204 considered. In particular the dependence of the curvature of the
9205 potential on the applied force at the minimum and at the
9206 metastable state is considered. In the well known Bell-Evans model
9207 the prefactors of the transition rate are fixed at any force,
9208 however this is not what happen in nature, where the prefactors
9209 (that are the second local derivative of the interacting energy
9210 with respect to the reaction coordinate in its minimum and
9211 maximum) depend on the force applied. The results obtained with
9212 the force spectroscopy of the Laminin-binding-protein are
9213 discussed, in particular this protein showed a phase transition
9214 when the pH was changed. The behavior of this protein changes,
9215 from a normal WLC behavior to a plateau behavior. The analysis of
9216 the force spectroscopy curves shows a distribution of length where
9217 the maximum of the first prominent peak correspond to the full
9218 length of the protein. However, length that could be associated
9219 with dimers and trymers are also present in this
9220 distribution. Later a new approach to study the lock and key
9221 mechanism, using "handles" with a specific force extension
9222 pattern, is introduced. In particular handles of (I27)3 and
9223 (I27–SNase)3 were biochemically attached to: strept-actin
9224 molecules, biotin molecules, RNase and Angiogenin. The main idea
9225 is to have a system composed by "handle-(molecule A)-(molecule
9226 B)-handle" where the handles are covalently attached to the
9227 respective molecules and the two molecules "A and B" are attached
9228 by secondary bonds. This approach allows a better recognition of
9229 the protein-protein interaction enabling us to filter out spurious
9230 events. Doing a statistic on the rupture forces and comparing this
9231 with the statistic of the detachments of the system of the bare
9232 handles, we are able to extract the information of the interaction
9233 between the molecule A and B. The two last chapters are of more
9234 preliminary character that the previous part of the thesis. A
9235 section is dedicated to the estimation of effective mass and
9236 viscous drag of the cantilevers studied by autocorrelation and
9237 noise power spectrum. Usually the noise power spectrum method is
9238 the most used, however the autocorrelation should give
9239 approximately the same information. The parameters obtained are
9240 important in high frequency modulation techniques. In fact, they
9241 are needed to interpret the results. The results of these two
9242 methods show a good agreement in the estimation of the mass and
9243 the viscous drag of the various cantilever used. Afterwards a
9244 chapter is dedicated to the discussion of the force spectroscopy
9245 experiments using a low frequency modulation of the cantilever
9246 base. Such experiments allow us to record the phase and the
9247 amplitude shift of the modulation signal used. Using the amplitude
9248 channel we managed to restore the static force signal with a lower
9249 level of noise. Moreover these signals give us direct information
9250 about the dynamic stiffness and the lose of energy in the system,
9251 information that, using the standard technique would be difficult
9252 (or even impossible) to obtain.},
9256 author = TKempe #" and "# SBHKent #" and "# FChow #" and "# SMPeterson
9257 #" and "# WSundquist #" and "# JLItalien #" and "# DHarbrecht
9258 #" and "# DPlunkett #" and "# WDeLorbe,
9259 title = "Multiple-copy genes: Production and modification of
9260 monomeric peptides from large multimeric fusion proteins.",
9266 keywords = "Cloning, Molecular",
9267 keywords = "Cyanogen Bromide",
9268 keywords = "DNA, Recombinant",
9269 keywords = "Escherichia coli",
9270 keywords = "Gene Expression Regulation",
9271 keywords = "Genetic Vectors",
9272 keywords = "Humans",
9273 keywords = "Molecular Weight",
9274 keywords = "Peptide Fragments",
9275 keywords = "Plasmids",
9276 keywords = "Substance P",
9277 keywords = "beta-Galactosidase",
9278 abstract = "A vector system has been designed for obtaining high
9279 yields of polypeptides synthesized in Escherichia coli. Multiple
9280 copies of a synthetic gene encoding the neuropeptide substance P
9281 (SP) (Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2) have been
9282 linked and fused to the lacZ gene. Each copy of the SP gene was
9283 flanked by codons for methionine to create sites for cleavage by
9284 cyanogen bromide (CNBr). The isolated multimeric SP fusion
9285 protein was converted to monomers of SP analog, each containing a
9286 carboxyl-terminal homoserine lactone (Hse-lactone) residue
9287 (Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Hse-lactone), upon
9288 treatment with CNBr in formic acid. The Hse-lactone moiety was
9289 subjected to chemical modifications to produce an SP Hse
9290 amide. This method permits synthesis of peptide amide analogs and
9291 other peptide derivatives by combining recombinant DNA techniques
9292 and chemical methods.",
9294 URL = "http://www.ncbi.nlm.nih.gov/pubmed/2419204",
9299 author = MHonda #" and "# YBaba #" and "# NHiaro #" and "# TSekiguchi,
9300 title = "Metal-molecular interface of sulfur-containing amino acid
9301 and thiophene on gold surface",
9306 url = "http://dx.doi.org/10.1088/1742-6596/100/5/052071",
9308 abstract = "Chemical-bonding states of metal-molecular interface
9309 have been investigated for L-cysteine and thiophene on gold by
9310 x-ray photoelectron spectroscopy (XPS) and near edge x-ray
9311 adsorption fine structure (NEXAFS). A remarkable difference in
9312 Au-S bonding states was found between L-cysteine and
9313 thiophene. For mono-layered L-cysteine on gold, the binding energy
9314 of S 1s in XPS and the resonance energy at the S K-edge in NEXAFS
9315 are higher by 8–9 eV than those for multi-layered film (molecular
9316 L-cysteine). In contrast, the S K-edge resonance energy for
9317 mono-layered thiophene on gold was 2475.0 eV, which is the same as
9318 that for molecular L-cysteine. In S 1s XPS for mono-layered
9319 thiophene, two peaks were observed. The higher binging-energy and
9320 more intense peak at 2473.4 eV are identified as gold sulfide. The
9321 binding energy of smaller peak, whose intensity is less than 1/3
9322 of the higher binding energy peak, is 2472.2 eV, which is the same
9323 as that for molecular thiophene. These observations indicate that
9324 Au-S interface behavior shows characteristic chemical bond only
9325 for the Au-S interface of L-cysteine monolayer on gold
9331 title = "Formation and Structure of Self-Assembled Monolayers.",
9336 address = "Department of Chemical Engineering, Chemistry and
9337 Materials Science, and the Herman F. Mark Polymer Research
9338 Institute, Polytechnic University, Six MetroTech Center, Brooklyn,
9342 pages = "1533--1554",
9344 URL = "http://www.ncbi.nlm.nih.gov/pubmed/11848802",
9349 author = GHager #" and "# ABrolo,
9350 title = "Adsorption/desorption behaviour of cysteine and cystine in
9351 neutral and basic media: electrochemical evidence for differing
9352 thiol and disulfide adsorption to a {Au(111)} single crystal
9355 volume = "550--551",
9360 doi = "10.1016/S0022-0728(03)00052-4",
9361 url = "http://dx.doi.org/10.1016/S0022-0728(03)00052-4",
9363 keywords = "Disulfide",
9364 keywords = "Thiol adsorption",
9365 keywords = "Self-assembled monolayers",
9366 keywords = "Au(111) single crystal electrode",
9367 keywords = "Cysteine",
9368 keywords = "Cystine",
9369 abstract = "The adsorption/desorption behaviour of the
9370 thiol/disulfide redox couple, cysteine/cystine, was monitored at a
9371 Au(111) single crystal electrode. The monolayers were formed
9372 electrochemically from 0.1 M KClO4 and 0.1 M NaOH solutions
9373 containing either the thiol or the disulfide. Distinct features in
9374 the adsorption potential were noted. An adsorption peak was
9375 observed in the cyclic voltammograms (CVs) from Au(111) in 0.1 M
9376 KClO4 solutions containing cystine at $-0.57$ V vs. saturated
9377 calomel electrode. Under the same conditions, the CVs from
9378 solutions containing cysteine showed an adsorption peak at $-0.43$
9379 V (0.14 V more positive than the corresponding peak from disulfide
9380 solutions). This showed that the thiol and disulfide species have
9381 different adsorption properties. Similar behaviour was observed in
9382 0.1 M NaOH. Cyclic voltammetric and chronocoulometric data were
9383 employed to determine the surface coverage of the different
9384 monolayers. Cysteine solutions prepared in 0.1 M KClO4 provided
9385 coverages of $3.0\times10^{-10}$ and $2.5\times10^{-10}$
9386 mol~cm$^{-2}$ for the L and the D--L species, respectively as
9387 evaluated from the desorption peaks. Desorption of cystine in the
9388 same medium yielded coverages of $1.2\times10^{-10}$ mol~cm$^{-2}$
9389 for both L and D--L solutions (or $2.4\times10^{-10}$
9390 mol~cm$^{-2}$ in cysteine equivalents). Surface coverages obtained
9391 from Au(111) in 0.1 M NaOH corresponded to $3.9\times10^{10}$
9392 mol~cm$^{-2}$ for L-cysteine, and $1.2\times10^{-10}$
9393 mol~cm$^{-2}$ (or $2.4\times10^{-10}$ mol~cm$^{-2}$ cysteine
9394 equivalents) for L and D--L cystine.",
9399 title = "The Nanomechanics of Polycystin-1: A Kidney Mechanosensor",
9403 url = "http://etd.utmb.edu/theses/available/etd-07072010-132038/",
9405 keywords = "Polycystin-1",
9406 keywords = "Missense mutations",
9407 keywords = "Atomic Force Microscopy",
9408 keywords = "Osmolyte",
9409 keywords = "Mechanosensor",
9410 abstract = "Mutations in polycystin-1 (PC1) can cause Autosomal
9411 Dominant Polycystic Kidney Disease (ADPKD), which is a leading
9412 cause of renal failure. The available evidence suggests that PC1
9413 acts as a mechanosensor, receiving signals from the primary cilia,
9414 neighboring cells, and extracellular matrix. PC1 is a large
9415 membrane protein that has a long N-terminal extracellular region
9416 (about 3000 aa) with a multimodular structure including sixteen
9417 Ig-like PKD domains, which are targeted by many naturally
9418 occurring missense mutations. Nothing is known about the effects
9419 of these mutations on the biophysical properties of PKD
9420 domains. In addition, PC1 is expressed along the renal tubule,
9421 where it is exposed to a wide range of concentration of urea. Urea
9422 is known to destabilize proteins. Other osmolytes found in the
9423 kidney such as sorbitol, betaine and TMAO are known to counteract
9424 urea's negative effects on proteins. Nothing is known about how
9425 the mechanical properties of PC1 are affected by these
9426 osmolytes. Here I use nano-mechanical techniques to study the
9427 effects of missense mutations and effects of denaturants and
9428 various osmolytes on the mechanical properties of PKD
9429 domains. Several missense mutations were found to alter the
9430 mechanical stability of PKD domains resulting in distinct
9431 mechanical phenotypes. Based on these findings, I hypothesize that
9432 missense mutations may cause ADPKD by altering the stability of
9433 the PC1 ectodomain, thereby perturbing its ability to sense
9434 mechanical signals. I also found that urea has a significant
9435 impact on both the mechanical stability and refolding rate of PKD
9436 domains. It not only lowers their mechanical stability, but also
9437 slows down their refolding rate. Moreover, several osmolytes were
9438 found to effectively counteract the effects of urea. Our data
9439 provide the evidence that naturally occurring osmolytes can help
9440 to maintain Polycystin-1 mechanical stability and folding
9441 kinetics. This study has the potential to provide new therapeutic
9442 approaches (e.g. through the use of osmolytes or chemical
9443 chaperones) for rescuing destabilized and misfolded PKD domains.",
9447 @article{ sundberg03,
9448 author = MSundberg #" and "# JRosengren #" and "# RBunk
9449 #" and "# JLindahl #" and "# INicholls #" and "# STagerud
9450 #" and "# POmling #" and "# LMontelius #" and "# AMansson,
9451 title = "Silanized surfaces for in vitro studies of actomyosin
9452 function and nanotechnology applications.",
9457 address = "Department of Chemistry and Biomedical Sciences,
9458 University of Kalmar, SE-391 82 Kalmar, Sweden.",
9462 keywords = "Actomyosin",
9463 keywords = "Adsorption",
9464 keywords = "Animals",
9465 keywords = "Collodion",
9466 keywords = "Kinetics",
9467 keywords = "Methods",
9468 keywords = "Movement",
9469 keywords = "Nanotechnology",
9470 keywords = "Rabbits",
9471 keywords = "Silicon",
9472 keywords = "Surface Properties",
9473 keywords = "Trimethylsilyl Compounds",
9474 abstract = "We have previously shown that selective heavy meromyosin
9475 (HMM) adsorption to predefined regions of nanostructured polymer
9476 resist surfaces may be used to produce a nanostructured in vitro
9477 motility assay. However, actomyosin function was of lower quality
9478 than on conventional nitrocellulose films. We have therefore
9479 studied actomyosin function on differently derivatized glass
9480 surfaces with the aim to find a substitute for the polymer
9481 resists. We have found that surfaces derivatized with
9482 trimethylchlorosilane (TMCS) were superior to all other surfaces
9483 tested, including nitrocellulose. High-quality actin filament
9484 motility was observed up to 6 days after incubation with HMM and
9485 the fraction of motile actin filaments and the velocity of smooth
9486 sliding were generally higher on TMCS than on nitrocellulose. The
9487 actomyosin function on TMCS-derivatized glass and nitrocellulose
9488 is considered in relation to roughness and hydrophobicity of these
9489 surfaces. The results suggest that TMCS is an ideal substitute for
9490 polymer resists in the nanostructured in vitro motility
9491 assay. Furthermore, TMCS derivatized glass also seems to offer
9492 several advantages over nitrocellulose for HMM adsorption in the
9493 ordinary in /vitro motility assay.",
9495 URL = "http://www.ncbi.nlm.nih.gov/pubmed/14622967",
9496 doi = "10.1016/j.ab.2003.07.022",
9501 author = HItoh #" and "# ATakahashi #" and "# KAdachi #" and "#
9502 HNoji #" and "# RYasuda #" and "# MYoshida #" and "#
9504 title = "Mechanically driven {ATP} synthesis by {F1}-{ATP}ase.",
9509 address = "Tsukuba Research Laboratory, Hamamatsu Photonics KK,
9510 Joko, Hamamatsu 431-3103, Japan.
9511 hiritoh@hpk.trc-net.co.jp",
9515 keywords = "Adenosine Diphosphate",
9516 keywords = "Adenosine Triphosphate",
9517 keywords = "Bacillus",
9518 keywords = "Catalysis",
9520 keywords = "Magnetics",
9521 keywords = "Microchemistry",
9522 keywords = "Microspheres",
9523 keywords = "Molecular Motor Proteins",
9524 keywords = "Proton-Translocating ATPases",
9525 keywords = "Rotation",
9526 keywords = "Torque",
9527 abstract = "ATP, the main biological energy currency, is synthesized
9528 from ADP and inorganic phosphate by ATP synthase in an
9529 energy-requiring reaction. The F1 portion of ATP synthase, also
9530 known as F1-ATPase, functions as a rotary molecular motor: in
9531 vitro its gamma-subunit rotates against the surrounding
9532 alpha3beta3 subunits, hydrolysing ATP in three separate catalytic
9533 sites on the beta-subunits. It is widely believed that reverse
9534 rotation of the gamma-subunit, driven by proton flow through the
9535 associated F(o) portion of ATP synthase, leads to ATP synthesis in
9536 biological systems. Here we present direct evidence for the
9537 chemical synthesis of ATP driven by mechanical energy. We attached
9538 a magnetic bead to the gamma-subunit of isolated F1 on a glass
9539 surface, and rotated the bead using electrical magnets. Rotation
9540 in the appropriate direction resulted in the appearance of ATP in
9541 the medium as detected by the luciferase-luciferin reaction. This
9542 shows that a vectorial force (torque) working at one particular
9543 point on a protein machine can influence a chemical reaction
9544 occurring in physically remote catalytic sites, driving the
9545 reaction far from equilibrium.",
9547 doi = "10.1038/nature02212",
9548 URL = "http://www.ncbi.nlm.nih.gov/pubmed/14749837",
9553 author = NSakaki #" and "# RShimoKon #" and "# KAdachi
9554 #" and "# HItoh #" and "# SFuruike #" and "# EMuneyuki
9555 #" and "# MYoshida #" and "# KKinosita,
9556 title = "One rotary mechanism for {F1}-{ATP}ase over {ATP}
9557 concentrations from millimolar down to nanomolar.",
9562 address = "Department of Functional Molecular Science, The Graduate
9563 University for Advanced Studies, Nishigonaka 38, Myodaiji, Okazaki
9567 pages = "2047--2056",
9568 keywords = "Adenosine Triphosphate",
9569 keywords = "Hydrolysis",
9570 keywords = "Kinetics",
9571 keywords = "Microchemistry",
9572 keywords = "Molecular Motor Proteins",
9573 keywords = "Nanostructures",
9574 keywords = "Protein Binding",
9575 keywords = "Protein Conformation",
9576 keywords = "Proton-Translocating ATPases",
9577 keywords = "Rotation",
9578 keywords = "Torque",
9579 abstract = "F(1)-ATPase is a rotary molecular motor in which the
9580 central gamma-subunit rotates inside a cylinder made of
9581 alpha(3)beta(3)-subunits. The rotation is driven by ATP hydrolysis
9582 in three catalytic sites on the beta-subunits. How many of the
9583 three catalytic sites are filled with a nucleotide during the
9584 course of rotation is an important yet unsettled question. Here we
9585 inquire whether F(1) rotates at extremely low ATP concentrations
9586 where the site occupancy is expected to be low. We observed under
9587 an optical microscope rotation of individual F(1) molecules that
9588 carried a bead duplex on the gamma-subunit. Time-averaged rotation
9589 rate was proportional to the ATP concentration down to 200 pM,
9590 giving an apparent rate constant for ATP binding of 2 x 10(7)
9591 M(-1)s(-1). A similar rate constant characterized bulk ATP
9592 hydrolysis in solution, which obeyed a simple Michaelis-Menten
9593 scheme between 6 mM and 60 nM ATP. F(1) produced the same torque
9594 of approximately 40 pN.nm at 2 mM, 60 nM, and 2 nM ATP. These
9595 results point to one rotary mechanism governing the entire range
9596 of nanomolar to millimolar ATP, although a switchover between two
9597 mechanisms cannot be dismissed. Below 1 nM ATP, we observed less
9598 regular rotations, indicative of the appearance of another
9601 doi = "10.1529/biophysj.104.054668",
9602 URL = "http://www.ncbi.nlm.nih.gov/pubmed/15626703",
9606 @article{ schmidt02,
9607 author = JSchmidt #" and "# XJiang #" and "# CMontemagno,
9608 title = "Force Tolerances of Hybrid Nanodevices",
9612 pages = "1229--1233",
9614 doi = "10.1021/nl025773v",
9615 URL = "http://pubs.acs.org/doi/abs/10.1021/nl025773v",
9616 eprint = "http://pubs.acs.org/doi/pdf/10.1021/nl025773v",
9617 abstract = "We have created hybrid devices consisting of nanoscale
9618 fabricated inorganic components integrated with and powered by a
9619 genetically engineered motor protein. We wish to increase the
9620 assembly yield and lifetime of these devices through
9621 identification, measurement, and improvement of weak internal
9622 bonds. Using dynamic force spectroscopy, we have measured the bond
9623 rupture force of (histidine)\textsubscript{6} on a number of
9624 different surfaces as a function of loading rate. The bond sizes,
9625 lifetimes, and energy barrier heights were derived from these
9626 measurements. We compare the (His)\textsubscript{6}--nickel bonds
9627 to other bonds composing the hybrid device and describe
9628 preliminary measurements of the force tolerances of the protein
9629 itself. Pathways for improvement of device longevity and
9630 robustness are discussed.",
9634 author = YSLo #" and "# YJZhu #" and "# TBeebe,
9635 title = "Loading-Rate Dependence of Individual Ligand−Receptor
9636 Bond-Rupture Forces Studied by Atomic Force Microscopy",
9640 pages = "3741--3748",
9642 doi = "10.1021/la001569g",
9643 URL = "http://pubs.acs.org/doi/abs/10.1021/la001569g",
9644 eprint = "http://pubs.acs.org/doi/pdf/10.1021/la001569g",
9645 abstract = "It is known that bond strength is a dynamic property
9646 that is dependent upon the force loading rate applied during the
9647 rupturing of a bond. For biotin--avidin and biotin--streptavidin
9648 systems, dynamic force spectra, which are plots of bond strength
9649 vs loge(loading rate), have been acquired in a recent biomembrane
9650 force probe (BFP) study at force loading rates in the range
9651 0.05--60 000 pN/s. In the present study, the dynamic force spectrum
9652 of the biotin--streptavidin bond strength in solution was extended
9653 from loading rates of ∼104 to ∼107 pN/s with the atomic force
9654 microscope (AFM). A Poisson statistical analysis method was
9655 applied to extract the magnitude of individual bond-rupture forces
9656 and nonspecific interactions from the AFM force--distance curve
9657 measurements. The bond strengths were found to scale linearly with
9658 the logarithm of the loading rate. The nonspecific interactions
9659 also exhibited a linear dependence on the logarithm of loading
9660 rate, although not increasing as rapidly as the specific
9661 interactions. The dynamic force spectra acquired here with the AFM
9662 combined well with BFP measurements by Merkel et al. The combined
9663 spectrum exhibited two linear regimes, consistent with the view
9664 that multiple energy barriers are present along the unbinding
9665 coordinate of the biotin--streptavidin complex. This study
9666 demonstrated that unbinding forces measured by different
9667 techniques are in agreement and can be used together to obtain a
9668 dynamic force spectrum covering 9 orders of magnitude in loading
9670 note = "These guys seem to be pretty thorough, give this one another read.",
9674 author = ABaljon #" and "# MRobbins,
9675 title = "Energy Dissipation During Rupture of Adhesive Bonds",
9682 doi = "10.1126/science.271.5248.482",
9683 URL = "http://www.sciencemag.org/content/271/5248/482.abstract",
9684 eprint = "http://www.sciencemag.org/content/271/5248/482.full.pdf",
9685 abstract = "Molecular dynamics simulations were used to study
9686 energy-dissipation mechanisms during the rupture of a thin
9687 adhesive bond formed by short chain molecules. The degree of
9688 dissipation and its velocity dependence varied with the state of
9689 the film. When the adhesive was in a liquid phase, dissipation was
9690 caused by viscous loss. In glassy films, dissipation occurred
9691 during a sequence of rapid structural rearrangements. Roughly
9692 equal amounts of energy were dissipated in each of three types of
9693 rapid motion: cavitation, plastic yield, and bridge rupture. These
9694 mechanisms have similarities to nucleation, plastic flow, and
9695 crazing in commercial polymeric adhesives.",
9698 @article{ fisher99a,
9699 author = TEFisher #" and "# PMarszalek #" and "# AOberhauser
9700 #" and "# MCarrionVazquez #" and "# JFernandez,
9701 title = "The micro-mechanics of single molecules studied with
9702 atomic force microscopy.",
9707 address = "Department of Physiology and Biophysics, Mayo Foundation,
9708 1-117 Medical Sciences Building, Rochester, MN 55905, USA.",
9709 volume = "520 Pt 1",
9711 keywords = "Animals",
9712 keywords = "Extracellular Matrix",
9713 keywords = "Extracellular Matrix Proteins",
9714 keywords = "Humans",
9715 keywords = "Microscopy, Atomic Force",
9716 keywords = "Polysaccharides",
9717 abstract = "The atomic force microscope (AFM) in its force-measuring
9718 mode is capable of effecting displacements on an angstrom scale
9719 (10 A = 1 nm) and measuring forces of a few piconewtons. Recent
9720 experiments have applied AFM techniques to study the mechanical
9721 properties of single biological polymers. These properties
9722 contribute to the function of many proteins exposed to mechanical
9723 strain, including components of the extracellular matrix
9724 (ECM). The force-bearing proteins of the ECM typically contain
9725 multiple tandem repeats of independently folded domains, a common
9726 feature of proteins with structural and mechanical
9727 roles. Polysaccharide moieties of adhesion glycoproteins such as
9728 the selectins are also subject to strain. Force-induced extension
9729 of both types of molecules with the AFM results in conformational
9730 changes that could contribute to their mechanical function. The
9731 force-extension curve for amylose exhibits a transition in
9732 elasticity caused by the conversion of its glucopyranose rings
9733 from the chair to the boat conformation. Extension of multi-domain
9734 proteins causes sequential unraveling of domains, resulting in a
9735 force-extension curve displaying a saw tooth pattern of peaks. The
9736 engineering of multimeric proteins consisting of repeats of
9737 identical domains has allowed detailed analysis of the mechanical
9738 properties of single protein domains. Repetitive extension and
9739 relaxation has enabled direct measurement of rates of domain
9740 unfolding and refolding. The combination of site-directed
9741 mutagenesis with AFM can be used to elucidate the amino acid
9742 sequences that determine mechanical stability. The AFM thus offers
9743 a novel way to explore the mechanical functions of proteins and
9744 will be a useful tool for studying the micro-mechanics of
9747 URL = "http://www.ncbi.nlm.nih.gov/pubmed/10517795",
9751 @article{ fisher99b,
9752 author = TEFisher #" and "# AOberhauser #" and "# MCarrionVazquez
9753 #" and "# PMarszalek #" and "# JFernandez,
9754 title = "The study of protein mechanics with the atomic force microscope.",
9755 journal = "Trends in biochemical sciences",
9758 address = "Dept of Physiology and Biophysics, Mayo Foundation, 1-117
9759 Medical Sciences Building, Rochester, MN 55905, USA.",
9763 keywords = "Entropy",
9764 keywords = "Kinetics",
9765 keywords = "Microscopy, Atomic Force",
9766 keywords = "Protein Binding",
9767 keywords = "Protein Folding",
9768 keywords = "Proteins",
9769 abstract = "The unfolding and folding of single protein molecules
9770 can be studied with an atomic force microscope (AFM). Many
9771 proteins with mechanical functions contain multiple, individually
9772 folded domains with similar structures. Protein engineering
9773 techniques have enabled the construction and expression of
9774 recombinant proteins that contain multiple copies of identical
9775 domains. Thus, the AFM in combination with protein engineering
9776 has enabled the kinetic analysis of the force-induced unfolding
9777 and refolding of individual domains as well as the study of the
9778 determinants of mechanical stability.",
9780 URL = "http://www.ncbi.nlm.nih.gov/pubmed/10500301",
9784 @article{ zlatanova00,
9785 author = JZlatanova #" and "# SLindsay #" and "# SLeuba,
9786 title = "Single molecule force spectroscopy in biology using the
9787 atomic force microscope.",
9790 address = "Biochip Technology Center, Argonne National Laboratory,
9791 9700 South Cass Avenue, Bldg. 202-A253, Argonne, IL 60439,
9792 USA. jzlatano@duke.poly.edu",
9796 keywords = "Biophysics",
9797 keywords = "Cell Adhesion",
9799 keywords = "Elasticity",
9800 keywords = "Microscopy, Atomic Force",
9801 keywords = "Polysaccharides",
9802 keywords = "Proteins",
9803 keywords = "Signal Processing, Computer-Assisted",
9804 keywords = "Viscosity",
9805 abstract = "The importance of forces in biology has been recognized
9806 for quite a while but only in the past decade have we acquired
9807 instrumentation and methodology to directly measure interactive
9808 forces at the level of single biological macromolecules and/or
9809 their complexes. This review focuses on force measurements
9810 performed with the atomic force microscope. A general introduction
9811 to the principle of action is followed by review of the types of
9812 interactions being studied, describing the main results and
9813 discussing the biological implications.",
9815 URL = "http://www.ncbi.nlm.nih.gov/pubmed/11106806",
9817 note = "Lots of great force-clamp cartoons explaining different
9818 approach/retract features.",
9822 author = MViani #" and "# TESchafer #" and "# AChand #" and "# MRief
9823 #" and "# HEGaub #" and "# HHansma,
9824 title = "Small cantilevers for force spectroscopy of single molecules",
9829 pages = "2258--2262",
9830 abstract = "We have used a simple process to fabricate small
9831 rectangular cantilevers out of silicon nitride. They have lengths
9832 of 9--50 $\mu$m, widths of 3--5 $\mu$m, and thicknesses of 86 and
9833 102 nm. We have added metallic reflector pads to some of the
9834 cantilever ends to maximize reflectivity while minimizing
9835 sensitivity to temperature changes. We have characterized small
9836 cantilevers through their thermal spectra and show that they can
9837 measure smaller forces than larger cantilevers with the same
9838 spring constant because they have lower coefficients of viscous
9839 damping. Finally, we show that small cantilevers can be used for
9840 experiments requiring large measurement bandwidths, and have used
9841 them to unfold single titin molecules over an order of magnitude
9842 faster than previously reported with conventional cantilevers.",
9844 issn_online = "1089-7550",
9845 doi = "10.1063/1.371039",
9846 URL = "http://jap.aip.org/resource/1/japiau/v86/i4/p2258_s1",
9850 @article{ capitanio02,
9851 author = MCapitanio #" and "# GRomano #" and "# RBallerini #" and "#
9852 MGiuntini #" and "# FPavone #" and "# DDunlap #" and "# LFinzi,
9853 title = "Calibration of optical tweezers with differential
9854 interference contrast signals",
9859 pages = "1687--1696",
9860 abstract = "A comparison of different calibration methods for
9861 optical tweezers with the differential interference contrast (DIC)
9862 technique was performed to establish the uses and the advantages
9863 of each method. A detailed experimental and theoretical analysis
9864 of each method was performed with emphasis on the anisotropy
9865 involved in the DIC technique and the noise components in the
9866 detection. Finally, a time of flight method that permits the
9867 reconstruction of the optical potential well was demonstrated.",
9869 issn_online = "1089-7623",
9870 doi = "10.1063/1.1460929",
9871 URL = "http://rsi.aip.org/resource/1/rsinak/v73/i4/p1687_s1",
9876 author = GBinnig #" and "# CQuate #" and "# CGerber,
9877 title = "Atomic force microscope",
9885 abstract = "The scanning tunneling microscope is proposed as a
9886 method to measure forces as small as $10^{-18}$ N. As one
9887 application for this concept, we introduce a new type of
9888 microscope capable of investigating surfaces of insulators on an
9889 atomic scale. The atomic force microscope is a combination of the
9890 principles of the scanning tunneling microscope and the stylus
9891 profilometer. It incorporates a probe that does not damage the
9892 surface. Our preliminary results in air demonstrate a lateral
9893 resolution of 30 \AA and a vertical resolution less than 1 \AA.",
9895 doi = "10.1103/PhysRevLett.56.930",
9896 URL = "http://www.ncbi.nlm.nih.gov/pubmed/10033323",
9897 eprint = {http://prl.aps.org/pdf/PRL/v56/i9/p930_1},
9899 note = "Original AFM paper.",
9903 author = BDrake #" and "# CBPrater #" and "# ALWeisenhorn #" and "#
9904 SAGould #" and "# TRAlbrecht #" and "# CQuate #" and "#
9905 DSCannell #" and "# HHansma #" and "# PHansma,
9906 title = {Imaging crystals, polymers, and processes in water with the
9907 atomic force microscope},
9914 pages = {1586--1589},
9915 doi = {10.1126/science.2928794},
9916 url = {http://www.sciencemag.org/content/243/4898/1586.abstract},
9917 eprint = {http://www.sciencemag.org/content/243/4898/1586.full.pdf},
9918 abstract ={The atomic force microscope (AFM) can be used to image
9919 the surface of both conductors and nonconductors even if they are
9920 covered with water or aqueous solutions. An AFM was used that
9921 combines microfabricated cantilevers with a previously described
9922 optical lever system to monitor deflection. Images of mica
9923 demonstrate that atomic resolution is possible on rigid materials,
9924 thus opening the possibility of atomic-scale corrosion experiments
9925 on nonconductors. Images of polyalanine, an amino acid polymer,
9926 show the potential of the AFM for revealing the structure of
9927 molecules important in biology and medicine. Finally, a series of
9928 ten images of the polymerization of fibrin, the basic component of
9929 blood clots, illustrate the potential of the AFM for revealing
9930 subtle details of biological processes as they occur in real
9934 @article{ radmacher92,
9935 author = MRadmacher #" and "# RWTillmann #" and "# MFritz #" and "# HEGaub,
9936 title = {From molecules to cells: imaging soft samples with the
9937 atomic force microscope},
9944 pages = {1900--1905},
9945 doi = {10.1126/science.1411505},
9946 url = {http://www.sciencemag.org/content/257/5078/1900.abstract},
9947 eprint = {http://www.sciencemag.org/content/257/5078/1900.full.pdf},
9948 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.},
9951 @article{ williams86,
9952 author = CCWilliams #" and "# HKWickramasinghe,
9953 title = "Scanning thermal profiler",
9960 pages = "1587--1589",
9961 abstract = "A new high-resolution profilometer has been demonstrated
9962 based upon a noncontacting near-field thermal probe. The thermal
9963 probe consists of a thermocouple sensor with dimensions
9964 approaching 100 nm. Profiling is achieved by scanning the heated
9965 sensor above but close to the surface of a solid. The conduction
9966 of heat between tip and sample via the air provides a means for
9967 maintaining the sample spacing constant during the lateral
9968 scan. The large difference in thermal properties between air and
9969 solids makes the profiling technique essentially independent of
9970 the material properties of the solid. Noncontact profiling of
9971 resist and metal films has shown a lateral resolution of 100 nm
9972 and a depth solution of 3 nm. The basic theory of the new probe is
9973 described and the results presented.",
9975 issn_online = "1077-3118",
9976 doi = "10.1063/1.97288",
9977 URL = "http://apl.aip.org/resource/1/applab/v49/i23/p1587_s1",
9982 author = GMeyer #" and "# NMAmer,
9983 title = "Novel optical approach to atomic force microscopy",
9990 pages = "1045--1047",
9991 abstract = "A sensitive and simple optical method for detecting the
9992 cantilever deflection in atomic force microscopy is described. The
9993 method was incorporated in an atomic force microscope, and imaging
9994 and force measurements, in ultrahigh vacuum, were successfully
9997 issn_online = "1077-3118",
9998 doi = "10.1063/1.100061",
9999 URL = "http://apl.aip.org/resource/1/applab/v53/i12/p1045_s1",
10004 author = EDijkstra,
10005 title = {Notes on Structured Programming},
10008 url = {http://www.cs.utexas.edu/users/EWD/ewd02xx/EWD249.PDF},
10009 publisher = THEMath,
10010 note = {T.H. Report 70-WSK-03},
10015 title = {On the Composition of Well-Structured Programs},
10016 journal = ACM:CSur,
10021 pages = {247--259},
10023 issn = {0360-0300},
10024 doi = {10.1145/356635.356639},
10025 url = {http://doi.acm.org/10.1145/356635.356639},
10027 address = {New York, NY, USA},
10030 @article{ shneiderman79,
10031 author = BShneiderman #" and "# RMayer,
10032 title = {Syntactic/semantic interactions in programmer behavior: A
10033 model and experimental results},
10038 pages = {219--238},
10039 issn = {0091-7036},
10040 doi = {10.1007/BF00977789},
10041 url = {http://dx.doi.org/10.1007/BF00977789},
10043 keywords = {Programming; programming languages; cognitive models;
10044 program composition; program comprehension; debugging;
10045 modification; learning; education; information processing},
10046 language = {English},
10049 @article{ hughes89,
10051 title = {Why Functional Programming Matters},
10057 doi = {10.1093/comjnl/32.2.98},
10058 URL = {http://comjnl.oxfordjournals.org/content/32/2/98.abstract},
10059 eprint = {http://comjnl.oxfordjournals.org/content/32/2/98.full.pdf+html},
10060 abstract ={As software becomes more and more complex, it is more and
10061 more important to structure it well. Well-structured software is
10062 easy to write, easy to debug, and provides a collection of modules
10063 that can be re-used to reduce future programming
10064 costs. Conventional languages place conceptual limits on the way
10065 problems can be modularised. Functional languages push those
10066 limits back. In this paper we show that two features of functional
10067 languages in particular, higher-order functions and lazy
10068 evaluation, can contribute greatly to modularity. As examples, we
10069 manipulate lists and trees, program several numerical algorithms,
10070 and implement the alpha-beta heuristics (an Artificial
10071 Intelligence algorithm used in game-playing programs). Since
10072 modularity is the key to successful programming, functional
10073 languages are vitally important to the real world.},
10076 @article{ hilburn93,
10078 title = {A top-down approach to teaching an introductory computer science course},
10079 journal = ACM:SIGCSE,
10084 issn = {0097-8418},
10087 doi = {10.1145/169073.169349},
10088 url = {http://doi.acm.org/10.1145/169073.169349},
10091 address = {New York, NY, USA},
10096 title = {The mythical man-month},
10097 edition = {20$^\text{th}$ anniversary},
10099 isbn = {0-201-83595-9},
10101 address = {Boston, MA, USA},
10102 url = {http://dl.acm.org/citation.cfm?id=207583},
10103 note = {First published in 1975},
10106 @inproceedings{ claerbout92,
10107 author = JClaerbout #" and "# MKarrenbach,
10108 title = {Electronic documents give reproducible research a new meaning},
10109 booktitle = {SEG Technical Program Expanded Abstracts 1992},
10112 pages = {601--604},
10113 doi = {10.1190/1.1822162},
10114 issn = {1052-3812},
10116 url = {http://library.seg.org/doi/abs/10.1190/1.1822162},
10117 eprint = {http://sepwww.stanford.edu/doku.php?id=sep:research:reproducible:seg92},
10120 @incollection{ buckheit95,
10121 author = JBuckheit #" and "# DDonoho,
10122 title = {WaveLab and Reproducible Research},
10123 booktitle = {Wavelets and Statistics},
10124 series = {Lecture Notes in Statistics},
10125 editor = AAntoniadis #" and "# GOppenheim,
10129 isbn = {978-0-387-94564-4},
10130 doi = {10.1007/978-1-4612-2544-7_5},
10131 url = {http://dx.doi.org/10.1007/978-1-4612-2544-7_5},
10132 eprint = {http://www-stat.stanford.edu/~wavelab/Wavelab_850/wavelab.pdf},
10133 publisher = SPRINGER,
10134 language = {English},
10137 @article{ schwab00,
10138 author = MSchwab #" and "# MKarrenbach #" and "# JClaerbout,
10139 title = {Making scientific computations reproducible},
10142 month = {November--December},
10146 doi = {10.1109/5992.881708},
10147 ISSN = {1521-9615},
10148 keywords = {document handling;file organisation;natural sciences
10149 computing;research and development
10150 management;ReDoc;authors;computational results;reproducible
10151 scientific computations;research paper;software filing
10152 system;standardized rules;Computer
10153 interfaces;Documentation;Electronic
10154 publishing;Laboratories;Organizing;Reproducibility of
10155 results;Software maintenance;Software systems;Software
10156 testing;Technological innovation},
10157 abstract = {To verify a research paper's computational results,
10158 readers typically have to recreate them from scratch. ReDoc is a
10159 simple software filing system for authors that lets readers easily
10160 reproduce computational results using standardized rules and
10164 @article{ wilson06a,
10166 title = {Where's the Real Bottleneck in Scientific Computing?},
10169 month = {January--February},
10172 @article{ wilson06b,
10174 title = {Software Carpentry: Getting Scientists to Write Better
10175 Code by Making Them More Productive},
10178 month = {November--December},
10181 @article{ vandewalle09,
10182 author = PVandewalle #" and "# JKovacevic #" and "# MVetterli ,
10183 title = {Reproducible Research in Signal Processing - What, why, and how},
10184 journal = IEEE:SPM,
10190 doi = {10.1109/MSP.2009.932122},
10191 issn = {1053-5888},
10192 url = {http://rr.epfl.ch/17/},
10193 eprint = {http://rr.epfl.ch/17/1/VandewalleKV09.pdf},
10194 keywords={research and development;signal processing;high-quality
10195 reviewing process;large data set;reproducible research;signal
10196 processing;win-win situation;Advertising;Digital signal
10197 processing;Education;Programming;Reproducibility of
10198 results;Scholarships;Signal processing;Signal processing
10199 algorithms;Testing;Wikipedia},
10200 abstract = {Have you ever tried to reproduce the results presented
10201 in a research paper? For many of our current publications, this
10202 would unfortunately be a challenging task. For a computational
10203 algorithm, details such as the exact data set, initialization or
10204 termination procedures, and precise parameter values are often
10205 omitted in the publication for various reasons, such as a lack of
10206 space, a lack of self-discipline, or an apparent lack of interest
10207 to the readers, to name a few. This makes it difficult, if not
10208 impossible, for someone else to obtain the same results. In our
10209 experience, it is often even worse as even we are not always able
10210 to reproduce our own experiments, making it difficult to answer
10211 questions from colleagues about details. Following are some
10212 examples of e-mails we have received: ``I just read your paper
10213 X. It is very completely described, however I am confused by
10214 Y. Could you provide the implementation code to me for reference
10215 if possible?'' ``Hi! I am also working on a project related to
10216 X. I have implemented your algorithm but cannot get the same
10217 results as described in your paper. Which values should I use for
10218 parameters Y and Z?''},
10221 @article{ aruliah12,
10222 author = DAruliah #" and "# CTBrown #" and "# NPCHong #" and "#
10223 MDavis #" and "# RTGuy #" and "# SHaddock #" and "# KHuff #" and "#
10224 IMitchell #" and "# MPlumbley #" and "# BWaugh #" and "#
10225 EPWhite #" and "# GWilson #" and "# PWilson,
10226 title = {Best Practices for Scientific Computing},
10228 volume = {abs/1210.0530},
10233 url = {http://arxiv.org/abs/1210.0530},
10234 eprint = {http://arxiv.org/pdf/1210.0530v3},
10235 note = {v3: Thu, 29 Nov 2012 19:28:27 GMT},
10238 @article{ ziegler42,
10239 author = JZiegler #" and "# NNichols,
10240 title = {Optimum Settings for Automatic Controllers},
10245 pages = {759--765},
10246 url = {http://www.driedger.ca/Z-N/Z-N.html},
10247 eprint = {http://www.driedger.ca/Z-N/Z-n.pdf},
10251 author = GHCohen #" and "# GACoon,
10252 title = {Theoretical considerations of retarded control},
10256 pages = {827--834},
10260 author = FSWang #" and "# WSJuang #" and "# CTChan,
10261 title = {Optimal tuning of {PID} controllers for single and
10262 cascade control loops},
10268 publisher = GordonBreach,
10269 issn = {0098-6445},
10270 doi = {10.1080/00986449508936294},
10271 url = {http://www.tandfonline.com/doi/abs/10.1080/00986449508936294},
10272 keywords = {process control; cascade control; controller tuning},
10273 abstract = {Design of one parameter tuning of three-mode PID
10274 controller was developed in this present study. The integral time
10275 and the derivative time of the controller were expressed in terms
10276 of the time constant and dead time of the process. Only the
10277 proportional gain was observed to be dependent on the implemented
10278 tunable parameter in which the stable region could be
10279 predetermined by the Routh test. Extension of the concept towards
10280 designing cascade PID controllers was straightforward such that
10281 only two parameters for the inner and outer PID controllers
10282 required to be tuned, respectively. The optimal tuning correlative
10283 formulas of the proportional gain for single and cascade control
10284 systems were obtained by the least square regression method.},
10287 @article{ astrom93,
10288 author = KAstrom #" and "# THagglund #" and "# CCHang #" and "# WKHo,
10289 title = {Automatic tuning and adaptation for {PID} controllers---a survey},
10294 pages = {699--714},
10295 issn = "0967-0661",
10296 doi = "10.1016/0967-0661(93)91394-C",
10297 url = "http://dx.doi.org/10.1016/0967-0661(93)91394-C",
10298 keywords = {Adaptive control},
10299 keywords = {automatic tuning},
10300 keywords = {gain scheduling},
10301 keywords = {{PID} control},
10302 abstract = {Adaptive techniques such as gain scheduling, automatic
10303 tuning and continuous adaptation have been used in industrial
10304 single-loop controllers for about ten years. This paper gives a
10305 survey of the different adaptive techniques, the underlying
10306 process models and control designs. An overview of industrial
10307 products is also presented, which includes a fairly detailed
10308 investigation of four different adaptive single-loop
10314 title = {Notes on the use of propagation of error formulas},
10320 pages = {263--273},
10322 issn = {0022-4316},
10323 url = {http://nistdigitalarchives.contentdm.oclc.org/cdm/compoundobject/collection/p13011coll6/id/78003/rec/5},
10324 eprint = {http://nistdigitalarchives.contentdm.oclc.org/utils/getfile/collection/p13011coll6/id/78003/filename/print/page/download},
10325 keywords = {Approximation; error; formula; imprecision; law of
10326 error; products; propagation of error; random; ratio; systematic;
10328 abstract = {The ``law of propagation of error'' is a tool that
10329 physical scientists have conveniently and frequently used in their
10330 work for many years, yet an adequate reference is difficult to
10331 find. In this paper an expository review of this topic is
10332 presented, particularly in the light of current practices and
10333 interpretations. Examples on the accuracy of the approximations
10334 are given. The reporting of the uncertainties of final results is
10338 @article{ livadaru03,
10339 author = LLivadaru #" and "# RRNetz #" and "# HJKreuzer,
10340 title = {Stretching Response of Discrete Semiflexible Polymers},
10344 journal = Macromol,
10347 pages = {3732--3744},
10348 doi = {10.1021/ma020751g},
10349 URL = {http://pubs.acs.org/doi/abs/10.1021/ma020751g},
10350 eprint = {http://pubs.acs.org/doi/pdf/10.1021/ma020751g},
10351 abstract = {We demonstrate that semiflexible polymer chains
10352 (characterized by a persistence length $l$) made up of discrete
10353 segments or bonds of length $b$ show at large stretching forces a
10354 crossover from the standard wormlike chain (WLC) behavior to a
10355 discrete-chain (DC) behavior. In the DC regime, the stretching
10356 response is independent of the persistence length and shows a
10357 different force dependence than in the WLC regime. We perform
10358 extensive transfer-matrix calculations for the force-response of a
10359 freely rotating chain (FRC) model as a function of varying bond
10360 angle $\gamma$ (and thus varying persistence length) and chain
10361 length. The FRC model is a first step toward the understanding of
10362 the stretching behavior of synthetic polymers, denatured proteins,
10363 and single-stranded DNA under large tensile forces. We also
10364 present scaling results for the force response of the elastically
10365 jointed chain (EJC) model, that is, a chain made up of freely
10366 jointed bonds that are connected by joints with some bending
10367 stiffness; this is the discretized version of the continuum WLC
10368 model. The EJC model might be applicable to stiff biopolymers such
10369 as double-stranded DNA or Actin. Both models show a similar
10370 crossover from the WLC to the DC behavior, which occurs at a force
10371 $f/k_BT\sim l/b^2$ and is thus (for polymers with a moderately
10372 large persistence length) in the piconewton range probed in many
10373 AFM experiments. We also give a heuristic simple function for the
10374 force--distance relation of a FRC, valid in the global force
10375 range, which can be used to fit experimental data. Our findings
10376 might help to resolve the discrepancies encountered when trying to
10377 fit experimental data for the stretching response of polymers in a
10378 broad force range with a single effective persistence length.},
10379 note = {There are two typos in \fref{equation}{46}.
10380 \citet{livadaru03} have
10382 \frac{R_z}{L} = \begin{cases}
10383 \frac{fa}{3k_BT} & \frac{fb}{k_BT} < \frac{b}{l} \\
10384 1 - \p({\frac{fl}{4k_BT}})^{-0.5}
10385 & \frac{b}{l} < \frac{fb}{k_BT} < \frac{l}{b} \\
10386 1 - \p({\frac{fb}{ck_BT}})^{-1} & \frac{1}{b} < \frac{fb}{k_BT} \;,
10389 but the correct formula is
10391 \frac{R_z}{L} = \begin{cases}
10392 \frac{fa}{3k_BT} & \frac{fb}{k_BT} < \frac{b}{l} \\
10393 1 - \p({\frac{4fl}{k_BT}})^{-0.5}
10394 & \frac{b}{l} < \frac{fb}{k_BT} < \frac{l}{b} \\
10395 1 - \p({\frac{cfb}{k_BT}})^{-1} & \frac{1}{b} < \frac{fb}{k_BT} \;,
10398 with both the $4$ and the $c$ moved into their respective
10399 numerators. I pointed these errors out to Roland Netz in 2012,
10400 along with the fact that even with the corrected formula there is
10401 a discontinuity between the low- and moderate-force regimes. Netz
10402 confirmed the errors, and pointed out that the discontinuity is
10403 because \fref{equation}{46} only accounts for the scaling (without
10404 prefactors). Unfortunately, there does not seem to be a published
10405 erratum pointing out the error and at least \citet{puchner08} have
10406 quoted the incorrect form.},
10410 author = PCarl #" and "# PDalhaimer,
10411 title = {{PUNIAS}: Protein Unfolding and Nano-indentation Analysis
10416 note = {4 Int. Workshop, Scanning Probe Microscopy in Life Sciences},
10417 address = {Berlin},
10418 url = {http://punias.voila.net/},
10422 author = PCarl #" and "# HSchillers,
10423 title = {Elasticity measurement of living cells with an atomic force
10424 microscope: data acquisition and processing.},
10428 address = {Institute of Physiology II, University of M{\"u}nster,
10429 Robert-Koch-Str. 27b, 48149, M{\"u}nster, Germany.},
10433 pages = {551--559},
10434 issn = {0031-6768},
10435 doi = {10.1007/s00424-008-0524-3},
10436 url = {http://www.ncbi.nlm.nih.gov/pubmed/18481081},
10438 keywords = {Animals},
10439 keywords = {Biomechanics},
10440 keywords = {CHO Cells},
10441 keywords = {Cricetinae},
10442 keywords = {Cricetulus},
10443 keywords = {Cystic Fibrosis Transmembrane Conductance Regulator},
10444 keywords = {Elastic Modulus},
10445 keywords = {Equipment Design},
10446 keywords = {Microscopy, Atomic Force},
10447 keywords = {Models, Biological},
10448 keywords = {Reproducibility of Results},
10449 keywords = {Signal Processing, Computer-Assisted},
10450 keywords = {Transfection},
10451 abstract = {Elasticity of living cells is a parameter of increasing
10452 importance in cellular physiology, and the atomic force microscope
10453 is a suitable instrument to quantitatively measure it. The
10454 principle of an elasticity measurement is to physically indent a
10455 cell with a probe, to measure the applied force, and to process
10456 this force-indentation data using an appropriate model. It is
10457 crucial to know what extent the geometry of the indenting probe
10458 influences the result. Therefore, we indented living Chinese
10459 hamster ovary cells at 37 degrees C with sharp tips and colloidal
10460 probes (spherical particle tips) of different sizes and
10461 materials. We furthermore developed an implementation of the Hertz
10462 model, which simplifies the data processing. Our results show (a)
10463 that the size of the colloidal probe does not influence the result
10464 over a wide range (radii $0.5$-$26\U{$\mu$m}$) and (b) indenting
10465 cells with sharp tips results in higher Young's moduli
10466 (approximately $1,300\U{Pa}$) than using colloidal probes
10467 (approximately $400\U{Pa}$).},
10468 note = {Mentions \citetalias{punias} as if it was in-house software,
10469 which makes sense because Philippe Carl seems to be a major author.},
10472 @article{ struckmeier08,
10473 author = JStruckmeier #" and "# RWahl #" and "# MLeuschner #" and "#
10474 JNunes #" and "# HJanovjak #" and "# UGeisler #" and "#
10475 GHofmann #" and "# TJahnke #" and "# DJMuller,
10476 title = {Fully automated single-molecule force spectroscopy for
10477 screening applications},
10481 address = {Cellular Machines, Biotechnology Center,
10482 Technische Universit{\"a}t Dresden, Tatzberg 47, D-01307
10488 issn = {0957-4484},
10489 doi = {10.1088/0957-4484/19/38/384020},
10490 url = {http://www.ncbi.nlm.nih.gov/pubmed/21832579},
10492 abstract = {With the introduction of single-molecule force
10493 spectroscopy (SMFS) it has become possible to directly access the
10494 interactions of various molecular systems. A bottleneck in
10495 conventional SMFS is collecting the large amount of data required
10496 for statistically meaningful analysis. Currently, atomic force
10497 microscopy (AFM)-based SMFS requires the user to tediously `fish'
10498 for single molecules. In addition, most experimental and
10499 environmental conditions must be manually adjusted. Here, we
10500 developed a fully automated single-molecule force
10501 spectroscope. The instrument is able to perform SMFS while
10502 monitoring and regulating experimental conditions such as buffer
10503 composition and temperature. Cantilever alignment and calibration
10504 can also be automatically performed during experiments. This,
10505 combined with in-line data analysis, enables the instrument, once
10506 set up, to perform complete SMFS experiments autonomously.},
10507 note = {An advertisement for JPK's \citetalias{force-robot}.},
10510 @article{ andreopoulos11,
10511 author = BAndreopoulos #" and "# DLabudde,
10512 title = {Efficient unfolding pattern recognition in single molecule
10513 force spectroscopy data},
10517 address = {Department of Bioinformatics, Biotechnological Center,
10518 University of Technology Dresden, Dresden, Germany.
10519 williama@biotec.tu-dresden.de},
10524 issn = {1748-7188},
10525 doi = {10.1186/1748-7188-6-16},
10526 url = {http://www.ncbi.nlm.nih.gov/pubmed/21645400},
10528 abstract = {Single-molecule force spectroscopy (SMFS) is a technique
10529 that measures the force necessary to unfold a protein. SMFS
10530 experiments generate Force-Distance (F-D) curves. A statistical
10531 analysis of a set of F-D curves reveals different unfolding
10532 pathways. Information on protein structure, conformation,
10533 functional states, and inter- and intra-molecular interactions can
10538 editor = HWTurnbull,
10540 title = {The correspondence of Isaac Newton},
10545 url = {http://books.google.com/books?id=pr8WAQAAMAAJ},
10546 note = {The ``Giants'' quote is on page 416, in a letter to Robert
10547 Hooke dated February 5, 1676.},
10550 @book{ whitehead11,
10551 author = ANWhitehead,
10552 title = {An introduction to mathematics},
10556 address = {London},
10557 url = {http://archive.org/details/introductiontoma00whitiala},
10558 note = {The ``civilization'' quote is on page 61.},
10562 author = NJMlot #" and "# CATovey #" and "# DLHu,
10563 title = {Fire ants self-assemble into waterproof rafts to survive floods},
10567 address = {Schools of Mechanical Engineering, Industrial and
10568 Systems Engineering, and Biology,
10569 Georgia Institute of Technology, Atlanta, GA 30318, USA.},
10573 pages = {7669--7673},
10574 issn = {1091-6490},
10575 doi = {10.1073/pnas.1016658108},
10576 url = {http://www.ncbi.nlm.nih.gov/pubmed/21518911},
10578 keywords = {Animals},
10580 keywords = {Behavior, Animal},
10581 keywords = {Biophysical Phenomena},
10582 keywords = {Floods},
10583 keywords = {Hydrophobic and Hydrophilic Interactions},
10584 keywords = {Microscopy, Electron, Scanning},
10585 keywords = {Models, Biological},
10586 keywords = {Social Behavior},
10587 keywords = {Surface Properties},
10588 keywords = {Time-Lapse Imaging},
10589 keywords = {Video Recording},
10590 keywords = {Water},
10591 abstract = {Why does a single fire ant \species{Solenopsis invicta}
10592 struggle in water, whereas a group can float effortlessly for
10593 days? We use time-lapse photography to investigate how fire ants
10594 \species{S.~invicta} link their bodies together to build
10595 waterproof rafts. Although water repellency in nature has been
10596 previously viewed as a static material property of plant leaves
10597 and insect cuticles, we here demonstrate a self-assembled
10598 hydrophobic surface. We find that ants can considerably enhance
10599 their water repellency by linking their bodies together, a process
10600 analogous to the weaving of a waterproof fabric. We present a
10601 model for the rate of raft construction based on observations of
10602 ant trajectories atop the raft. Central to the construction
10603 process is the trapping of ants at the raft edge by their
10604 neighbors, suggesting that some ``cooperative'' behaviors may rely
10606 note = {Higher resolution pictures are available at
10607 \url{http://antlab.gatech.edu/antlab/The_Ant_Raft.html}.},
10610 @article{ chauhan97,
10611 author = VPChauhan #" and "# IRay #" and "# AChauhan #" and "#
10612 JWegiel #" and "# HMWisniewski,
10613 title = {Metal cations defibrillize the amyloid beta-protein fibrils.},
10616 address = {New York State Institute for Basic Research in
10617 Developmental Disabilities, Staten Island 10314-6399,
10622 pages = {805--809},
10623 issn = {0364-3190},
10624 url = {http://www.ncbi.nlm.nih.gov/pubmed/9232632},
10625 doi = {10.1023/A:1022079709085},
10627 keywords = {Alzheimer Disease},
10628 keywords = {Amyloid beta-Peptides},
10629 keywords = {Drug Evaluation, Preclinical},
10630 keywords = {Humans},
10631 keywords = {Metals},
10632 keywords = {Peptide Fragments},
10633 keywords = {Solubility},
10634 abstract = {Amyloid beta-protein (A beta) is the major constituent
10635 of amyloid fibrils composing beta-amyloid plaques and
10636 cerebrovascular amyloid in Alzheimer's disease (AD). We studied
10637 the effect of metal cations on preformed fibrils of synthetic A
10638 beta by Thioflavin T (ThT) fluorescence spectroscopy and
10639 electronmicroscopy (EM) in negative staining. The amount of cross
10640 beta-pleated sheet structure of A beta 1-40 fibrils was found to
10641 decrease by metal cations in a concentration-dependent manner as
10642 measured by ThT fluorescence spectroscopy. The order of
10643 defibrillization of A beta 1-40 fibrils by metal cations was: Ca2+
10644 and Zn2+ (IC50 = 100 microM) > Mg3+ (IC50 = 300 microM) > Al3+
10645 (IC50 = 1.1 mM). EM analysis in negative staining showed that A
10646 beta 1-40 fibrils in the absence of cations were organized in a
10647 fine network with a little or no amorphous material. The addition
10648 of Ca2+, Mg2+, and Zn2+ to preformed A beta 1-40 fibrils
10649 defibrillized the fibrils or converted them into short rods or to
10650 amorphous material. Al3+ was less effective, and reduced the
10651 fibril network by about 80\% of that in the absence of any metal
10652 cation. Studies with A beta 1-42 showed that this peptide forms
10653 more dense network of fibrils as compared to A beta 1-40. Both ThT
10654 fluorescence spectroscopy and EM showed that similar to A beta
10655 1-40, A beta 1-42 fibrils are also defibrillized in the presence
10656 of millimolar concentrations of Ca2+. These studies suggest that
10657 metal cations can defibrillize the fibrils of synthetic A beta.},
10658 note = {From page 806, ``The exact mechanism by which these metal
10659 ions affect the fibrillization of A$\beta$ is not known.''},
10662 @article{ friedman05,
10663 author = RFriedman #" and "# ENachliel #" and "# MGutman,
10664 title = {Molecular dynamics of a protein surface: ion-residues
10669 address = {Laser Laboratory for Fast Reactions in Biology,
10670 Department of Biochemistry, The George S. Wise Faculty
10671 for Life Sciences, Tel Aviv University, Israel.},
10675 pages = {768--781},
10676 issn = {0006-3495},
10677 doi = {10.1529/biophysj.105.058917},
10678 url = {http://www.ncbi.nlm.nih.gov/pubmed/15894639},
10680 keywords = {Amino Acids},
10681 keywords = {Binding Sites},
10682 keywords = {Chlorine},
10683 keywords = {Computer Simulation},
10685 keywords = {Models, Chemical},
10686 keywords = {Models, Molecular},
10687 keywords = {Motion},
10688 keywords = {Protein Binding},
10689 keywords = {Protein Conformation},
10690 keywords = {Ribosomal Protein S6},
10691 keywords = {Sodium},
10692 keywords = {Solutions},
10693 keywords = {Static Electricity},
10694 keywords = {Surface Properties},
10695 keywords = {Water},
10696 abstract = {Time-resolved measurements indicated that protons could
10697 propagate on the surface of a protein or a membrane by a special
10698 mechanism that enhanced the shuttle of the proton toward a
10699 specific site. It was proposed that a suitable location of
10700 residues on the surface contributes to the proton shuttling
10701 function. In this study, this notion was further investigated by
10702 the use of molecular dynamics simulations, where Na(+) and Cl(-)
10703 are the ions under study, thus avoiding the necessity for quantum
10704 mechanical calculations. Molecular dynamics simulations were
10705 carried out using as a model a few Na(+) and Cl(-) ions enclosed
10706 in a fully hydrated simulation box with a small globular protein
10707 (the S6 of the bacterial ribosome). Three independent 10-ns-long
10708 simulations indicated that the ions and the protein's surface were
10709 in equilibrium, with rapid passage of the ions between the
10710 protein's surface and the bulk. However, it was noted that close
10711 to some domains the ions extended their duration near the surface,
10712 thus suggesting that the local electrostatic potential hindered
10713 their diffusion to the bulk. During the time frame in which the
10714 ions were detained next to the surface, they could rapidly shuttle
10715 between various attractor sites located under the electrostatic
10716 umbrella. Statistical analysis of the molecular dynamics and
10717 electrostatic potential/entropy consideration indicated that the
10718 detainment state is an energetic compromise between attractive
10719 forces and entropy of dilution. The similarity between the motion
10720 of free ions next to a protein and the proton transfer on the
10721 protein's surface are discussed.},
10724 @article{ friedman11,
10725 author = RFriedman,
10726 title = {Ions and the protein surface revisited: extensive molecular
10727 dynamics simulations and analysis of protein structures in
10728 alkali-chloride solutions.},
10732 address = {School of Natural Sciences, Linn{\ae}us University,
10733 391 82 Kalmar, Sweden. ran.friedman@lnu.se},
10737 pages = {9213--9223},
10738 issn = {1520-5207},
10739 doi = {10.1021/jp112155m},
10740 URL = {http://www.ncbi.nlm.nih.gov/pubmed/21688775},
10742 keywords = {Alkalies},
10743 keywords = {Amyloid},
10744 keywords = {Chlorides},
10745 keywords = {Databases, Protein},
10746 keywords = {Fungal Proteins},
10747 keywords = {HIV Protease},
10748 keywords = {Humans},
10749 keywords = {Molecular Dynamics Simulation},
10750 keywords = {Protein Multimerization},
10751 keywords = {Protein Structure, Secondary},
10752 keywords = {Proteins},
10753 keywords = {Ribosomal Protein S6},
10754 keywords = {Solutions},
10755 keywords = {Solvents},
10756 keywords = {Surface Properties},
10757 abstract = {Proteins interact with ions in various ways. The surface
10758 of proteins has an innate capability to bind ions, and it is also
10759 influenced by the screening of the electrostatic potential owing
10760 to the presence of salts in the bulk solution. Alkali metal ions
10761 and chlorides interact with the protein surface, but such
10762 interactions are relatively weak and often transient. In this
10763 paper, computer simulations and analysis of protein structures are
10764 used to characterize the interactions between ions and the protein
10765 surface. The results show that the ion-binding properties of
10766 protein residues are highly variable. For example, alkali metal
10767 ions are more often associated with aspartate residues than with
10768 glutamates, whereas chlorides are most likely to be located near
10769 arginines. When comparing NaCl and KCl solutions, it was found
10770 that certain surface residues attract the anion more strongly in
10771 NaCl. This study demonstrates that protein-salt interactions
10772 should be accounted for in the planning and execution of
10773 experiments and simulations involving proteins, particularly if
10774 subtle structural details are sought after.},
10778 author = YZhang #" and "# PSCremer,
10779 title = {Interactions between macromolecules and ions: The
10780 {H}ofmeister series.},
10784 address = {Department of Chemistry, Texas A\&M University,
10785 College Station, TX 77843, USA.},
10789 pages = {658--663},
10790 issn = {1367-5931},
10791 doi = {10.1016/j.cbpa.2006.09.020},
10792 url = {http://www.ncbi.nlm.nih.gov/pubmed/17035073},
10794 keywords = {Acrylamides},
10795 keywords = {Biopolymers},
10796 keywords = {Solubility},
10797 keywords = {Thermodynamics},
10798 keywords = {Water},
10799 abstract = {The Hofmeister series, first noted in 1888, ranks the
10800 relative influence of ions on the physical behavior of a wide
10801 variety of aqueous processes ranging from colloidal assembly to
10802 protein folding. Originally, it was thought that an ion's
10803 influence on macromolecular properties was caused at least in part
10804 by `making' or `breaking' bulk water structure. Recent
10805 time-resolved and thermodynamic studies of water molecules in salt
10806 solutions, however, demonstrate that bulk water structure is not
10807 central to the Hofmeister effect. Instead, models are being
10808 developed that depend upon direct ion-macromolecule interactions
10809 as well as interactions with water molecules in the first
10810 hydration shell of the macromolecule.},
10811 note = {A quick pass through Hofmeister history, but no discussion
10812 of cations (``A complete picture will inevitably involve an
10813 integrated understanding of the role of cations (including
10814 guanidinium ions) and osmolytes (such as urea and tri-methylamine
10815 N-oxide) as well. There has been some progress in these fields,
10816 although such subjects are generally beyond the scope of this
10817 short review.'').},
10820 @article{ isaacs06,
10821 author = AMIsaacs #" and "# DBSenn #" and "# MYuan #" and "#
10822 JPShine #" and "# BAYankner,
10823 title = {Acceleration of Amyloid $\beta$-Peptide Aggregation by
10824 Physiological Concentrations of Calcium.},
10828 address = {Department of Neurology and Division of Neuroscience,
10829 The Children's Hospital, Harvard Medical School,
10830 Boston, Massachusetts 02115, USA.},
10834 pages = {27916--27923},
10835 issn = {0021-9258},
10836 doi = {10.1074/jbc.M602061200},
10837 url = {http://www.ncbi.nlm.nih.gov/pubmed/16870617},
10839 keywords = {Alzheimer Disease},
10840 keywords = {Amyloid},
10841 keywords = {Amyloid beta-Peptides},
10842 keywords = {Animals},
10843 keywords = {Calcium},
10844 keywords = {Cells, Cultured},
10845 keywords = {Copper},
10846 keywords = {Neurons},
10849 abstract = {Alzheimer disease is characterized by the accumulation
10850 of aggregated amyloid beta-peptide (Abeta) in the brain. The
10851 physiological mechanisms and factors that predispose to Abeta
10852 aggregation and deposition are not well understood. In this
10853 report, we show that calcium can predispose to Abeta aggregation
10854 and fibril formation. Calcium increased the aggregation of early
10855 forming protofibrillar structures and markedly increased
10856 conversion of protofibrils to mature amyloid fibrils. This
10857 occurred at levels 20-fold below the calcium concentration in the
10858 extracellular space of the brain, the site at which amyloid plaque
10859 deposition occurs. In the absence of calcium, protofibrils can
10860 remain stable in vitro for several days. Using this approach, we
10861 directly compared the neurotoxicity of protofibrils and mature
10862 amyloid fibrils and demonstrate that both species are inherently
10863 toxic to neurons in culture. Thus, calcium may be an important
10864 predisposing factor for Abeta aggregation and toxicity. The high
10865 extracellular concentration of calcium in the brain, together with
10866 impaired intraneuronal calcium regulation in the aging brain and
10867 Alzheimer disease, may play an important role in the onset of
10868 amyloid-related pathology.},
10869 note = {Physiological levels of \NaCl\ are $\sim 150\U{mM}$. \Ca\
10870 is $\sim 2\U{mM}$.},
10874 author = AItkin #" and "# VDupres #" and "# YFDufrene #" and "#
10875 BBechinger #" and "# JMRuysschaert #" and "# VRaussens,
10876 title = {Calcium ions promote formation of amyloid $\beta$-peptide
10877 (1-40) oligomers causally implicated in neuronal toxicity of
10878 {A}lzheimer's disease.},
10882 address = {Laboratory of Structure and Function of Biological
10883 Membranes, Center for Structural Biology and
10884 Bioinformatics, Universit{\'e} Libre de Bruxelles,
10885 Brussels, Belgium.},
10886 journal = PLOS:ONE,
10890 keywords = {Alzheimer Disease},
10891 keywords = {Amyloid beta-Peptides},
10892 keywords = {Blotting, Western},
10893 keywords = {Calcium},
10894 keywords = {Fluorescence},
10895 keywords = {Humans},
10897 keywords = {Models, Biological},
10898 keywords = {Mutant Proteins},
10899 keywords = {Neurons},
10900 keywords = {Protein Structure, Quaternary},
10901 keywords = {Protein Structure, Secondary},
10902 keywords = {Spectroscopy, Fourier Transform Infrared},
10903 keywords = {Thiazoles},
10904 ISSN = {1932-6203},
10905 doi = {10.1371/journal.pone.0018250},
10906 URL = {http://www.ncbi.nlm.nih.gov/pubmed/21464905},
10908 abstract = {Amyloid $\beta$-peptide (A$\beta$) is directly linked to
10909 Alzheimer's disease (AD). In its monomeric form, A$\beta$
10910 aggregates to produce fibrils and a range of oligomers, the latter
10911 being the most neurotoxic. Dysregulation of Ca(2+) homeostasis in
10912 aging brains and in neurodegenerative disorders plays a crucial
10913 role in numerous processes and contributes to cell dysfunction and
10914 death. Here we postulated that calcium may enable or accelerate
10915 the aggregation of A$\beta$. We compared the aggregation pattern
10916 of A$\beta$(1-40) and that of A$\beta$(1-40)E22G, an amyloid
10917 peptide carrying the Arctic mutation that causes early onset of
10918 the disease. We found that in the presence of Ca(2+),
10919 A$\beta$(1-40) preferentially formed oligomers similar to those
10920 formed by A$\beta$(1-40)E22G with or without added Ca(2+), whereas
10921 in the absence of added Ca(2+) the A$\beta$(1-40) aggregated to
10922 form fibrils. Morphological similarities of the oligomers were
10923 confirmed by contact mode atomic force microscopy imaging. The
10924 distribution of oligomeric and fibrillar species in different
10925 samples was detected by gel electrophoresis and Western blot
10926 analysis, the results of which were further supported by
10927 thioflavin T fluorescence experiments. In the samples without
10928 Ca(2+), Fourier transform infrared spectroscopy revealed
10929 conversion of oligomers from an anti-parallel $\beta$-sheet to the
10930 parallel $\beta$-sheet conformation characteristic of
10931 fibrils. Overall, these results led us to conclude that calcium
10932 ions stimulate the formation of oligomers of A$\beta$(1-40), that
10933 have been implicated in the pathogenesis of AD.},
10934 note = {$2\U{mM}$ of \Ca\ is the \emph{extracellular} concentration.
10935 Cytosol concetrations are in the $\mu$M range.},
10939 author = JZidar #" and "# FMerzel,
10940 title = {Probing amyloid-beta fibril stability by increasing ionic
10945 address = {National Institute of Chemistry, Hajdrihova 19,
10946 SI-1000 Ljubljana, Slovenia.},
10950 pages = {2075--2081},
10951 issn = {1520-5207},
10952 doi = {10.1021/jp109025b},
10953 URL = {http://www.ncbi.nlm.nih.gov/pubmed/21329333},
10955 keywords = {Amyloid beta-Peptides},
10956 keywords = {Entropy},
10957 keywords = {Hydrogen Bonding},
10958 keywords = {Molecular Dynamics Simulation},
10959 keywords = {Osmolar Concentration},
10960 keywords = {Protein Multimerization},
10961 keywords = {Protein Stability},
10962 keywords = {Protein Structure, Secondary},
10963 keywords = {Solvents},
10964 keywords = {Vibration},
10965 abstract = {Previous experimental studies have demonstrated changing
10966 the ionic strength of the solvent to have a great impact on the
10967 mechanism of aggregation of amyloid-beta (A$\beta$) protein
10968 leading to distinct fibril morphology at high and low ionic
10969 strength. Here, we use molecular dynamics simulations to elucidate
10970 the ionic strength-dependent effects on the structure and dynamics
10971 of the model A$\beta$ fibril. The change in ionic strength was
10972 brought forth by varying the NaCl concentration in the environment
10973 surrounding the A$\beta$ fibril. Comparison of the calculated
10974 vibrational spectra of A$\beta$ derived from 40 ns all-atom
10975 molecular dynamics simulations at different ionic strength reveals
10976 the fibril structure to be stiffer with increasing ionic
10977 strength. This finding is further corroborated by the calculation
10978 of the stretching force constants. Decomposition of binding and
10979 dynamical properties into contributions from different structural
10980 segments indicates the elongation of the fibril at low ionic
10981 strength is most likely promoted by hydrogen bonding between
10982 N-terminal parts of the fibril, whereas aggregation at higher
10983 ionic strength is suggested to be driven by the hydrophobic
10985 note = {Only study \NaCl\ over the range to $308\U{mM}$, but show a
10986 general decreased hydrogen bonding as concentration increases.},
10990 author = LMiao #" and "# HQin #" and "# PKoehl #" and "# JSong,
10991 title = {Selective and specific ion binding on proteins at
10992 physiologically-relevant concentrations.},
10996 address = {Department of Biological Sciences, Faculty of Science,
10997 National University of Singapore, Singapore.},
11001 pages = {3126--3132},
11002 issn = {1873-3468},
11003 doi = {10.1016/j.febslet.2011.08.048},
11004 url = {http://www.ncbi.nlm.nih.gov/pubmed/21907714},
11006 keywords = {Amino Acid Sequence},
11007 keywords = {Ephrin-B2},
11009 keywords = {Models, Molecular},
11010 keywords = {Molecular Sequence Data},
11011 keywords = {Nuclear Magnetic Resonance, Biomolecular},
11012 keywords = {Protein Binding},
11013 keywords = {Protein Folding},
11014 keywords = {Protein Structure, Tertiary},
11015 keywords = {Salts},
11016 keywords = {Solutions},
11017 keywords = {Thermodynamics},
11018 keywords = {Water},
11019 abstract = {Insoluble proteins dissolved in unsalted water appear to
11020 have no well-folded tertiary structures. This raises a fundamental
11021 question as to whether being unstructured is due to the absence of
11022 salt ions. To address this issue, we solubilized the insoluble
11023 ephrin-B2 cytoplasmic domain in unsalted water and first confirmed
11024 using NMR spectroscopy that it is only partially folded. Using NMR
11025 HSQC titrations with 14 different salts, we further demonstrate
11026 that the addition of salt triggers no significant folding of the
11027 protein within physiologically relevant ion concentrations. We
11028 reveal however that their 8 anions bind to the ephrin-B2 protein
11029 with high affinity and specificity at biologically-relevant
11030 concentrations. Interestingly, the binding is found to be both
11031 salt- and residue-specific.},
11032 note = {They suggest that for low concentrations ($<100\U{mM}$),
11033 protein-ion interactions are mostly electrostatic. The Hofmeister
11034 effects only kick in at higher consentrations.},
11038 author = HJDyson #" and "# PEWright,
11039 title = {Intrinsically unstructured proteins and their functions.},
11043 address = {Department of Molecular Biology and Skaggs Institute
11044 for Chemical Biology, The Scripps Research Institute,
11045 10550 North Torrey Pines Road, La Jolla, California
11046 92037, USA. dyson@scripps.edu},
11049 pages = {197--208},
11050 issn = {1471-0072},
11051 doi = {10.1038/nrm1589},
11052 url = {http://www.ncbi.nlm.nih.gov/pubmed/15738986},
11054 keywords = {CREB-Binding Protein},
11055 keywords = {Humans},
11056 keywords = {Nuclear Proteins},
11057 keywords = {Nucleic Acids},
11058 keywords = {Protein Binding},
11059 keywords = {Protein Processing, Post-Translational},
11060 keywords = {Protein Structure, Tertiary},
11061 keywords = {Proteins},
11062 keywords = {Trans-Activators},
11063 keywords = {Tumor Suppressor Protein p53},
11064 abstract = {Many gene sequences in eukaryotic genomes encode entire
11065 proteins or large segments of proteins that lack a well-structured
11066 three-dimensional fold. Disordered regions can be highly conserved
11067 between species in both composition and sequence and, contrary to
11068 the traditional view that protein function equates with a stable
11069 three-dimensional structure, disordered regions are often
11070 functional, in ways that we are only beginning to discover. Many
11071 disordered segments fold on binding to their biological targets
11072 (coupled folding and binding), whereas others constitute flexible
11073 linkers that have a role in the assembly of macromolecular
11077 @article{ cleland64,
11078 author = WWCleland,
11079 title = {Dithiothreitol, a New Protective Reagent for SH Groups},
11085 pages = {480--482},
11086 keywords = {Alcohols},
11087 keywords = {Chromatography},
11088 keywords = {Coenzyme A},
11089 keywords = {Oxidation-Reduction},
11090 keywords = {Research},
11091 keywords = {Sulfhydryl Compounds},
11092 keywords = {Sulfides},
11093 keywords = {Ultraviolet Rays},
11094 issn = {0006-2960},
11095 doi = {10.1021/bi00892a002},
11096 url = {http://www.ncbi.nlm.nih.gov/pubmed/14192894},
11097 eprint = {http://pubs.acs.org/doi/pdf/10.1021/bi00892a002},