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{AEPP = "Archive f{\"u}r experimentelle Pathologie und Pharmakologie"}
45 @string{SArcidiacono = "Arcidiacono, S"}
46 @string{CArciola = "Arciola, Carla Renata"}
47 @string{ABArtyukhin = "Artyukhin, Alexander B."}
48 @string{DAruliah = "Aruliah, Dhavide A."}
49 @string{SAsakawa = "Asakawa, S."}
50 @string{AAwe = "Awe, A."}
51 @string{SBedard = "B\'edard, Sabrina"}
52 @string{WBaase = "Baase, Walter A."}
53 @string{YBaba = "Baba, Y."}
54 @string{HBaden = "Baden, H."}
55 @string{CBadilla = "Badilla, Carmen L."}
56 @string{VBafna = "Bafna, V."}
57 @string{BBagchi = "Bagchi, B."}
58 @string{MBalamurali = "Balamurali, M. M."}
59 @string{DBaldwin = "Baldwin, D."}
60 @string{ABaljon = "Baljon, Arlette R. C."}
61 @string{RBallerini = "Ballerini, R."}
62 @string{RMBallew = "Ballew, R. M."}
63 @string{MBalsera = "Balsera, M."}
64 @string{GBaneyx = "Baneyx, Gretchen"}
65 @string{RBar-Ziv = "Bar-Ziv, Roy"}
66 @string{WBBarbazuk = "Barbazuk, W. B."}
67 @string{MBarnstead = "Barnstead, M."}
68 @string{DBarrick = "Barrick, Doug"}
69 @string{IBarrow = "Barrow, I."}
70 @string{FWBartels = "Bartels, Frank Wilco"}
71 @string{BBarz = "Barz, Bogdan"}
72 @string{TBasche = "Basche, Th."}
73 @string{PBaschieri = "Baschieri, Paolo"}
74 @string{ABasu = "Basu, A."}
75 @string{LBaugh = "Baugh, Loren"}
76 @string{BBaumgarth = "Baumgarth, Birgit"}
77 @string{SBaumhueter = "Baumhueter, S."}
78 @string{JBaxendale = "Baxendale, J."}
79 @string{EABayer = "Bayer, Edward A."}
80 @string{EBeasley = "Beasley, E."}
81 @string{JBechhoefer = "Bechhoefer, John"}
82 @string{BBechinger = "Bechinger, Burkhard"}
83 @string{ABecker = "Becker, Anke"}
84 @string{GSBeddard = "Beddard, Godfrey S."}
85 @string{TBeebe = "Beebe, Thomas P."}
86 @string{KBeeson = "Beeson, K."}
87 @string{GIBell = "Bell, G. I."}
88 @string{FBenedetti = "Benedetti, Fabrizio"}
89 @string{VBenes = "Benes, Vladimir"}
90 @string{ABensimon = "Bensimon, A."}
91 @string{DBensimon = "Bensimon, David"}
92 @string{DRBentley = "Bentley, D. R."}
93 @string{HJCBerendsen = "Berendsen, Herman J. C."}
94 @string{KBergSorensen = "Berg-S{\o}rensen, Kirstine"}
95 @string{EBergantino = "Bergantino, Elisabetta"}
96 @string{DBerk = "Berk, D."}
97 @string{FBerkemeier = "Berkemeier, Felix"}
98 @string{BBerne = "Berne, Bruce J."}
99 @string{MBertz = "Bertz, Morten"}
100 @string{RBest = "Best, Robert B."}
101 @string{GBethel = "Bethel, G."}
102 @string{NBhasin = "Bhasin, Nishant"}
103 @string{KBiddick = "Biddick, K."}
104 @string{KBillings = "Billings, Kate S."}
105 @string{GBinnig = "Binnig, Gerd"}
106 @string{BCBPRC = "Biochemical and Biophysical Research Communications"}
107 @string{Biochem = "Biochemistry"}
108 @string{BBABE = "Biochimica et Biophysica Acta (BBA) - Bioenergetics"}
109 @string{BIOINFO = "Bioinformatics (Oxford, England)"}
110 @string{Biomet = "Biometrika"}
111 @string{BPJ = "Biophysical Journal"}
112 %string{BPJ = "Biophys. J."}
113 @string{BIOSENSE = "Biosensors and Bioelectronics"}
114 @string{BIOTECH = "Biotechnology and Bioengineering"}
115 @string{JBirchler = "Birchler, James A."}
116 @string{AWBlake = "Blake, Anthony W."}
117 @string{JBlawzdziewicz = "Blawzdziewicz, Jerzy"}
118 @string{LBlick = "Blick, L."}
119 @string{RBolanos = "Bolanos, R."}
120 @string{VBonazzi = "Bonazzi, V."}
121 @string{Borgia = "Borgia"}
122 @string{MBorkovec = "Borkovec, Michal"}
123 @string{RBrandon = "Brandon, R."}
124 @string{EBranscomb = "Branscomb, E."}
125 @string{EBraverman = "Braverman, Elena"}
126 @string{WBreyer = "Breyer, Wendy A."}
127 @string{FBrochard-Wyart = "Brochard-Wyart, F."}
128 @string{DJBrockwell = "Brockwell, David J."}
129 @string{SBroder = "Broder, S."}
130 @string{SBroedel = "Broedel, Sheldon E."}
131 @string{ABrolo = "Brolo, Alexandre G."}
132 @string{FBrooks = "Brooks, Jr., Frederick P."}
133 @string{BrooksCole = "Brooks/Cole"}
134 @string{BDBrowerToland = "Brower-Toland, Brent D."}
135 @string{CTBrown = "Brown, C. Titus"}
136 @string{MBrucale = "Brucale, Marco"}
137 @string{TBruls = "Bruls, T."}
138 @string{VBrumfeld = "Brumfeld, Vlad"}
139 @string{JDBryngelson = "Bryngelson, J. D."}
140 @string{LBubacco = "Bubacco, Luigi"}
141 @string{JBuckheit = "Buckheit, Jonathan B."}
142 @string{ABuguin = "Buguin, A."}
143 @string{ABulhassan = "Bulhassan, Ahmed"}
144 @string{BBullard = "Bullard, Belinda"}
145 @string{RBunk = "Bunk, Richard"}
146 @string{NABurnham = "Burnham, N.~A."}
147 @string{DBusam = "Busam, D."}
148 @string{GBussi = "Bussi, Giovanni"}
149 @string{CBustamante = "Bustamante, Carlos"}
150 @string{YBustanji = "Bustanji, Yasser"}
151 @string{HJButt = {Butt, Hans-J\"urgen}}
152 @string{CUP = "Cambridge University Press"}
153 @string{MCaminha = "Caminha, M."}
154 @string{ICampbell = "Campbell, Iain D."}
155 @string{MJCampbell = "Campbell, M. J."}
156 @string{DSCannell = "Cannell, D.~S."}
157 @string{YCao = "Cao, Yi"}
158 @string{MCapitanio = "Capitanio, M."}
159 @string{MCargill = "Cargill, M."}
160 @string{PCarl = "Carl, Philippe"}
161 @string{BACarnes = "Carnes, B. A."}
162 @string{JCarnes-Stine = "Carnes-Stine, J."}
163 @string{MCarrionVazquez = "Carrion-Vazquez, Mariano"}
164 @string{CCarter = "Carter, C."}
165 @string{ACarver = "Carver, A."}
166 @string{JJCatanese = "Catanese, J.~J."}
167 @string{PCaulk = "Caulk, P."}
168 @string{CCecconi = "Cecconi, Ciro"}
169 @string{ACenter = "Center, A."}
170 @string{CTChan = "Chan, C.~T."}
171 @string{HSChan = "Chan, H.~S."}
172 @string{AChand = "Chand, Ami"}
173 @string{IChandramouliswaran = "Chandramouliswaran, I."}
174 @string{CHChang = "Chang, Chung-Hung"}
175 @string{EChapman = "Chapman, Edwin R."}
176 @string{RCharlab = "Charlab, R."}
177 @string{KChaturvedi = "Chaturvedi, K."}
178 @string{AChauhan = "Chauhan, A."}
179 @string{VPChauhan = "Chauhan, V.~P."}
180 @string{CChauzy = "Chauzy, C."}
181 @string{SChe = "Che, Shunai"}
182 @string{CEC = "Chemical Engineering Communications"}
183 @string{CHEMREV = "Chemical reviews"}
184 @string{CHEM = "Chemistry (Weinheim an der Bergstrasse, Germany)"}
185 @string{CPC = "Chemphyschem"}
186 @string{HCChen = "Chen, H. C."}
187 @string{LChen = "Chen, L."}
188 @string{XNChen = "Chen, X. N."}
189 @string{XiChen = "Chen, Xinyong"}
190 @string{XuChen = "Chen, Xuming"}
191 @string{JFCheng = "Cheng, J. F."}
192 @string{MLCheng = "Cheng, M. L."}
193 @string{VGCheung = "Cheung, V. G."}
194 @string{YHChiang = "Chiang, Y. H."}
195 @string{AChinwalla = "Chinwalla, A."}
196 @string{FChow = "Chow, Flora"}
197 @string{JChoy = "Choy, Jason"}
198 @string{BChu = "Chu, Benjamin"}
199 @string{XChu = "Chu, Xueying"}
200 @string{TYChung = "Chung, Tse-Yu"}
201 @string{CLChyan = "Chyan, Chia-Lin"}
202 @string{GCiccotti = "Ciccotti, Giovanni"}
203 @string{JClaerbout = "Claerbout, Jon F."}
204 @string{AGClark = "Clark, A. G."}
205 @string{Clarke = "Clarke"}
206 @string{JClarke = "Clarke, Jane"}
207 @string{JClarkson = "Clarkson, John"}
208 @string{HClausen-Schaumann = "Clausen-Schaumann, H."}
209 @string{JMClaverie = "Claverie, J. M."}
210 @string{WWCleland = "Cleland, W.~W."}
211 @string{KClerc-Blankenburg = "Clerc-Blankenburg, K."}
212 @string{NJCobb = "Cobb, Nathan J."}
213 @string{GHCohen = "Cohen, G.~H."}
214 @string{FSCollins = "Collins, Francis S."}
215 @string{CUP = "Columbia University Press"}
216 @string{CPR = "Computer Physics Reports"}
217 @string{CSE = "Computing in Science \& Engineering"}
218 @string{UniProtConsort = "Consortium, The UniProt"}
219 @string{MConti = "Conti, Matteo"}
220 @string{CEP = "Control Engineering Practice"}
221 @string{GACoon = "Coon, G.~A."}
222 @string{PVCornish = "Cornish, Peter V."}
223 @string{MNCourel = "Courel, M. N."}
224 @string{GCowan = "Cowan, Glen"}
225 @string{DRCox = "Cox, D. R."}
226 @string{MCoyne = "Coyne, M."}
227 @string{DCraig = "Craig, David"}
228 @string{ACravchik = "Cravchik, A."}
229 @string{PSCremer = "Cremer, Paul S."}
230 @string{CCroarkin = "Croarkin, Carroll"}
231 @string{VCroquette = "Croquette, Vincent"}
232 @string{LCCruz = "Cruz, Luis Cruz"}
233 @string{YCui = "Cui, Y."}
234 @string{COSB = "Current Opinion in Structural Biology"}
235 @string{COCB = "Current Opinion in Chemical Biology"}
236 @string{LCurry = "Curry, L."}
237 @string{CDahlke = "Dahlke, C."}
238 @string{FDahlquist = "Dahlquist, Frederick W."}
239 @string{PDalhaimer = "Dalhaimer, Paul"}
240 @string{SDanaher = "Danaher, S."}
241 @string{LDavenport = "Davenport, L."}
242 @string{MCDavies = "Davies, M.~C."}
243 @string{MDavis = "Davis, Matt"}
244 @string{SDecatur = "Decatur, Sean M."}
245 @string{WDeGrado = "DeGrado, William F."}
246 @string{PDebrunner = "Debrunner, P."}
247 @string{ADelcher = "Delcher, A."}
248 @string{WDeLorbe = "DeLorbe, William J."}
249 @string{BDelpech = "Delpech, B."}
250 @string{Demography = "Demography"}
251 @string{ZDeng = "Deng, Z."}
252 @string{RDesilets = "Desilets, R."}
253 @string{IDew = "Dew, I."}
254 @string{CDewhurst = "Dewhurst, Charles"}
255 @string{VDiFrancesco = "Di Francesco, V."}
256 @string{KDiemer = "Diemer, K."}
257 @string{GDietler = "Dietler, Giovanni"}
258 @string{HDietz = "Dietz, Hendrik"}
259 @string{SDietz = "Dietz, S."}
260 @string{EDijkstra = "Dijkstra, Edsger Wybe"}
261 @string{KADill = "Dill, K. A."}
262 @string{RDima = "Dima, Ruxandra I."}
263 @string{DDischer = "Discher, Dennis E."}
264 @string{KDixon = "Dixon, K."}
265 @string{KDodson = "Dodson, K."}
266 @string{NDoggett = "Doggett, N."}
267 @string{MDombroski = "Dombroski, M."}
268 @string{MDonnelly = "Donnelly, M."}
269 @string{DDonoho = "Donoho, David L."}
270 @string{CDornmair = "Dornmair, C."}
271 @string{MDors = "Dors, M."}
272 @string{LDougan = "Dougan, Lorna"}
273 @string{LDoup = "Doup, L."}
274 @string{BDrake = "Drake, B."}
275 @string{TDrobek = "Drobek, T."}
276 @string{Drexel = "Drexel University"}
277 @string{OKDudko = "Dudko, Olga K."}
278 @string{YFDufrene = "Dufr{\^e}ne, Yves F."}
279 @string{ADunham = "Dunham, A."}
280 @string{DDunlap = "Dunlap, D."}
281 @string{PDunn = "Dunn, P."}
282 @string{VDupres = "Dupres, Vincent"}
283 @string{HJDyson = "Dyson, H.~Jane"}
284 @string{EMBORep = "EMBO Rep"}
285 @string{EMBO = "EMBO Rep."}
286 @string{REckel = "Eckel, R."}
287 @string{KEilbeck = "Eilbeck, K."}
288 @string{MElbaum = "Elbaum, Michael"}
289 @string{E:NHPL = "Elsevier, North-Holland Personal Library"}
290 @string{DEly = "Ely, D."}
291 @string{SEmerling = "Emerling, S."}
292 @string{TEndo = "Endo, Toshiya"}
293 @string{SWEnglander = "Englander, S. Walter"}
294 @string{HErickson = "Erickson, Harold P."}
295 @string{MEsaki = "Esaki, Masatoshi"}
296 @string{SEsparham = "Esparham, S."}
297 @string{EBJ = "European Biophysics Journal"}
298 @string{EJP = "European Journal of Physics"}
299 @string{EPL = "Europhysics Letters"}
300 @string{CEvangelista = "Evangelista, C."}
301 @string{CAEvans = "Evans, C. A."}
302 @string{EEvans = "Evans, E."}
303 @string{RSEvans = "Evans, R. S."}
304 @string{MEvstigneev = "Evstigneev, M."}
305 @string{DFasulo = "Fasulo, D."}
306 @string{FEBS = "FEBS letters"}
307 @string{XFei = "Fei, Xiaofang"}
308 @string{JFernandez = "Fernandez, Julio M."}
309 @string{SFerriera = "Ferriera, S."}
310 @string{AEFilippov = "Filippov, A. E."}
311 @string{LFinzi = "Finzi, L."}
312 @string{TEFisher = "Fisher, T. E."}
313 @string{MFlanigan = "Flanigan, M."}
314 @string{BFlannery = "Flannery, B."}
315 @string{LFlorea = "Florea, L."}
316 @string{ELFlorin = "Florin, Ernst-Ludwig"}
317 @string{HFlyvbjerg = "Flyvbjerg, Henrik"}
318 @string{FoldDes = "Fold Des"}
319 @string{NRForde = "Forde, Nancy R."}
320 @string{CFosler = "Fosler, C."}
321 @string{SFossey = "Fossey, S. A."}
322 @string{SFowler = "Fowler, Susan B."}
323 @string{GFranzen = "Franzen, Gereon"}
324 @string{SFreitag = "Freitag, S."}
325 @string{LFrench = "French, L."}
326 @string{RWFriddle = "Friddle, Raymond W."}
327 @string{CFriedman = "Friedman, C."}
328 @string{RFriedman = "Friedman, Ran"}
329 @string{MFritz = "Fritz, M."}
330 @string{HFuchs = "Fuchs, Harald"}
331 @string{TFujii = "Fujii, Tadashi"}
332 @string{HFujita = "Fujita, Hideaki"}
333 @string{AFujiyama = "Fujiyama, A."}
334 @string{RFulton = "Fulton, R."}
335 @string{TFunck = "Funck, Theodor"}
336 @string{TFurey = "Furey, T."}
337 @string{SFuruike = "Furuike, Shou"}
338 @string{GLGaborMiklos = "Gabor Miklos, G. L."}
339 @string{AEGabrielian = "Gabrielian, A. E."}
340 @string{WGan = "Gan, W."}
341 @string{DNGanchev = "Ganchev, Dragomir N."}
342 @string{MGao = "Gao, Mu"}
343 @string{DGarcia = "Garcia, D."}
344 @string{TGarcia = "Garcia, Tzintzuni"}
345 @string{NGarg = "Garg, N."}
346 @string{HEGaub = "Gaub, Hermann E."}
347 @string{MGautel = "Gautel, Mathias"}
348 @string{LAGavrilov = "Gavrilov, L. A."}
349 @string{NSGavrilova = "Gavrilova, N. S."}
350 @string{WGe = "Ge, W."}
351 @string{UGeisler = "Geisler, Ulrich"}
352 @string{GENE = "Gene"}
353 @string{CGerber = "Gerber, Christoph"}
354 @string{CGergely = "Gergely, C."}
355 @string{RGibbs = "Gibbs, R."}
356 @string{DGilbert = "Gilbert, D."}
357 @string{HGire = "Gire, H."}
358 @string{MGiuntini = "Giuntini, M."}
359 @string{FGittes = "Gittes, Frederick"}
360 @string{SGlanowski = "Glanowski, S."}
361 @string{JGlaser = "Glaser, Jens"}
362 @string{KGlasser = "Glasser, K."}
363 @string{AGlodek = "Glodek, A."}
364 @string{GGloeckner = "Gloeckner, G."}
365 @string{AGluecksmann = "Gluecksmann, A."}
366 @string{JDGocayne = "Gocayne, J. D."}
367 @string{AGomezCasado = "Gomez-Casado, Alberto"}
368 @string{BGompertz = "Gompertz, Benjamin"}
369 @string{FGong = "Gong, F."}
370 @string{GordonBreach = "Gordon Breach Scientific Publishing Ltd."}
371 @string{MGorokhov = "Gorokhov, M."}
372 @string{JHGorrell = "Gorrell, J. H."}
373 @string{SAGould = "Gould, S.~A."}
374 @string{KGraham = "Graham, K."}
375 @string{HLGranzier = "Granzier, Henk L."}
376 @string{FGrater = "Gr{\"a}ter, Frauke"}
377 @string{EDGreen = "Green, E. D."}
378 @string{SGGregory = "Gregory, S. G."}
379 @string{BGropman = "Gropman, B."}
380 @string{CGrossman = "Grossman, C."}
381 @string{HGrubmuller = {Grubm\"uller, Helmut}}
382 @string{AGrutzner = {Gr\"utzner, Anika}}
383 @string{ZGu = "Gu, Z."}
384 @string{PGuan = "Guan, P."}
385 @string{RGuigo = "Guig\'o, R."}
386 @string{EJGumbel = "Gumbel, Emil Julius"}
387 @string{HJGuntherodt = "Guntherodt, Hans-Joachim"}
388 @string{NGuo = "Guo, N."}
389 @string{YGuo = "Guo, Yi"}
390 @string{MGutman = "Gutman, Menachem"}
391 @string{RTGuy = "Guy, Richard T."}
392 @string{PHanggi = {H\"anggi, Peter}}
393 @string{THa = "Ha, Taekjip"}
394 @string{JHaack = "Haack, Julie A."}
395 @string{SHaddock = "Haddock, Steven H.~D."}
396 @string{GHager = "Hager, Gabriele"}
397 @string{THagglund = "H{\"a}gglund, T."}
398 @string{RHajjar = "Hajjar, Roger J."}
399 @string{AHalpern = "Halpern, A."}
400 @string{KHalvorsen = "Halvorsen, Ken"}
401 @string{FHan = "Han, Fangpu"}
402 @string{CCHang = "Hang, C.~C."}
403 @string{SHannenhalli = "Hannenhalli, S."}
404 @string{HHansma = "Hansma, H. G."}
405 @string{PHansma = "Hansma, Paul K."}
406 @string{DHarbrecht = "Harbrecht, Douglas"}
407 @string{SHarper = "Harper, Sandy"}
408 @string{MHarris = "Harris, M."}
409 @string{BHart = "Hart, B."}
410 @string{DPHart = "Hart, D.P."}
411 @string{JWHatfield = "Hatfield, John William"}
412 @string{THatton = "Hatton, T."}
413 @string{MHattori = "Hattori, M."}
414 @string{DHaussler = "Haussler, D."}
415 @string{THawkins = "Hawkins, T."}
416 @string{CHaynes = "Haynes, C."}
417 @string{JHaynes = "Haynes, J."}
418 @string{WHeckl = "Heckl, W. M."}
419 @string{CVHeer = "Heer, C.~V."}
420 @string{JHeil = "Heil, J."}
421 @string{RHeilig = "Heilig, R."}
422 @string{TJHeiman = "Heiman, T. J."}
423 @string{CHeiner = "Heiner, C."}
424 @string{MHelmes = "Helmes, M."}
425 @string{JHemmerle = "Hemmerle, J."}
426 @string{SHenderson = "Henderson, S."}
427 @string{BHeymann = "Heymann, Berthold"}
428 @string{NHiaro = "Hiaro, N."}
429 @string{MEHiggins = "Higgins, M. E."}
430 @string{THilburn = "Hilburn, Thomas B."}
431 @string{LHillier = "Hillier, L."}
432 @string{HHinssen = "Hinssen, Horst"}
433 @string{PHinterdorfer = "Hinterdorfer, Peter"}
434 @string{HistochemJ = "Histochem J"}
435 @string{SHladun = "Hladun, S."}
436 @string{WKHo = "Ho, W.~K."}
437 @string{RHochstrasser = "Hochstrasser, Robin M."}
438 @string{CSHodges = "Hodges, C.~S."}
439 @string{CHoff = "Hoff, C."}
440 @string{WHoff = "Hoff, Wouter D."}
441 @string{JLHolden = "Holden, J. L."}
442 @string{RAHolt = "Holt, R. A."}
443 @string{GHofmann = "Hofmann, Gerd"}
444 @string{FHofmeister = "Hofmeister, Franz"}
445 @string{MHonda = "Honda, M."}
446 @string{NPCHong = "Hong, Neil P. Chue"}
447 @string{XHong = "Hong, Xia"}
448 @string{LHood = "Hood, L."}
449 @string{JHoover = "Hoover, J."}
450 @string{JHorber = "Horber, J. K. H."}
451 @string{HHosser = "Hosser, H."}
452 @string{DHostin = "Hostin, D."}
453 @string{JHouck = "Houck, J."}
454 @string{AHoumeida = "Houmeida, Ahmed"}
455 @string{JHoward = "Howard, J."}
456 @string{THowland = "Howland, T."}
457 @string{BHsiao = "Hsiao, Benjamin S."}
458 @string{CKHu = "Hu, Chin-Kun"}
459 @string{DLHu = "Hu, David L."}
460 @string{BHuang = "Huang, Baiqu"}
461 @string{HHuang = "Huang, Hector Han-Li"}
462 @string{MHubain = "Hubain, Maurice"}
463 @string{AJHudspeth = "Hudspeth, A.~J."}
464 @string{KHuff = "Huff, Katy"}
465 @string{JHughes = "Hughes, John"}
466 @string{GHummer = "Hummer, Gerhard"}
467 @string{SJHumphray = "Humphray, S. J."}
468 @string{WLHung = "Hung, Wen-Liang"}
469 @string{MHunkapiller = "Hunkapiller, M."}
470 @string{DHHuson = "Huson, D. H."}
471 @string{JHutter = "Hutter, Jeffrey L."}
472 @string{CHyeon = "Hyeon, Changbong"}
473 @string{IEEE:TIT = "IEEE Transactions on Information Theory"}
474 @string{IEEE:SPM = "IEEE Signal Processing Magazine"}
475 @string{CIbegwam = "Ibegwam, C."}
476 @string{JRIdol = "Idol, J. R."}
477 @string{SImprota = "Improta, S."}
478 @string{TInoue = "Inoue, Tadashi"}
479 @string{IJBMM = "International Journal of Biological Macromolecules"}
480 @string{IJCIS = "International Journal of Computer \& Information Sciences"}
481 @string{AItkin = "Itkin, Anna"}
482 @string{HItoh = "Itoh, Hiroyasu"}
483 @string{AIrback = "Irback, Anders"}
484 @string{AMIsaacs = "Isaacs, Adrian M."}
485 @string{BIsralewitz = "Isralewitz, B."}
486 @string{SIstrail = "Istrail, S."}
487 @string{MIvemeyer = "Ivemeyer, M."}
488 @string{DIzhaky = "Izhaky, David"}
489 @string{SIzrailev = "Izrailev, S."}
490 @string{TJahnke = "J{\"a}hnke, Torsten"}
491 @string{WJang = "Jang, W."}
492 @string{HJanovjak = "Janovjak, Harald"}
493 @string{LJanosi = "Janosi, Lorant"}
494 @string{AJanshoff = "Janshoff, Andreas"}
495 @string{JJAP = "Japanese Journal of Applied Physics"}
496 @string{MJaschke = "Jaschke, Manfred"}
497 @string{DJennings = "Jennings, D."}
498 @string{HFJi = "Ji, Hai-Feng"}
499 @string{RRJi = "Ji, R. R."}
500 @string{YJia = "Jia, Yiwei"}
501 @string{SJiang = "Jiang, Shaoyi"}
502 @string{XJiang = "Jiang, Xingqun"}
503 @string{DJohannsmann = "Johannsmann, Diethelm"}
504 @string{CJohnson = "Johnson, Colin P."}
505 @string{JJohnson = "Johnson, J."}
506 @string{AJollymore = "Jollymore, Ashlee"}
507 @string{REJones = "Jones, R.E."}
508 @string{SJones = "Jones, S."}
509 @string{CJordan = "Jordan, C."}
510 @string{JJordan = "Jordan, J."}
511 %string{JACS = "J Am Chem Soc"}
512 @string{JACS = "Journal of the American Chemical Society"}
513 @string{JASA = "Journal of the American Statistical Association"}
514 @string{JAP = "Journal of Applied Physics"}
515 @string{JBM = "J Biomech"}
516 @string{JBT = "J Biotechnol"}
517 @string{JCPPCB = "Journal de Chimie Physique et de Physico-Chimie Biologique"}
518 @string{JCS = "Journal of Cell Science"}
519 @string{JCompP = "Journal of Computational Physics"}
520 @string{JEChem = "Journal of Electroanalytical Chemistry"}
521 @string{JMathBiol = "J Math Biol"}
522 @string{JMicro = "Journal of Microscopy"}
523 @string{JPhysio = "Journal of Physiology"}
524 @string{JStructBiol = "Journal of Structural Biology"}
525 @string{JTB = "J Theor Biol"}
526 @string{JMB = "Journal of Molecular Biology"}
527 @string{JP:CM = "Journal of Physics: Condensed Matter"}
528 @string{JP:CON = "Journal of Physics: Conference Series"}
529 @string{JRNBS:C = "Journal of Research of the National Bureau of Standards. Section C: Engineering and Instrumentation"}
530 @string{WSJuang = "Juang, F.~S."}
531 @string{DAJuckett = "Juckett, D. A."}
532 @string{SRJun = "Jun, Se-Ran"}
533 @string{DKaftan = "Kaftan, David"}
534 @string{LKagan = "Kagan, L."}
535 @string{FKalush = "Kalush, F."}
536 @string{ELKaplan = "Kaplan, E. L."}
537 @string{RKapon = "Kapon, Ruti"}
538 @string{AKardinal = "Kardinal, Angelika"}
539 @string{BKarlak = "Karlak, B."}
540 @string{MKarplus = "Karplus, Martin"}
541 @string{MKarrenbach = "Karrenbach, Martin"}
542 @string{JKasha = "Kasha, J."}
543 @string{KKawasaki = "Kawasaki, K."}
544 @string{ZKe = "Ke, Z."}
545 @string{AKejariwal = "Kejariwal, A."}
546 @string{MSKellermayer = "Kellermayer, Mikl\'os S. Z."}
547 @string{TKempe = "Kempe, Thomas"}
548 @string{SKennedy = "Kennedy, S."}
549 @string{SBHKent = "Kent, Stephen B. H."}
550 @string{WJKent = "Kent, W. J."}
551 @string{KAKetchum = "Ketchum, K. A."}
552 @string{FKienberger = "Kienberger, Ferry"}
553 @string{SHKim = "Kim, Sung-Hou"}
554 @string{WKing = "King, William Trevor"}
555 @string{KKinosita = "{Kinosita Jr.}, Kazuhiko"}
556 @string{IRKirsch = "Kirsch, I. R."}
557 @string{JKlafter = "Klafter, J."}
558 @string{AKleiner = "Kleiner, Ariel"}
559 @string{DKlimov = "Klimov, Dmitri K."}
560 @string{LKline = "Kline, L."}
561 @string{LKlumb = "Klumb, L."}
562 @string{KAPPP = "Kluwer Academic Publishers--Plenum Publishers"}
563 @string{CDKodira = "Kodira, C. D."}
564 @string{SKoduru = "Koduru, S."}
565 @string{PKoehl = "Koehl, Patrice"}
566 @string{BKolmerer = "Kolmerer, B."}
567 @string{JKorenberg = "Korenberg, J."}
568 @string{IKosztin = "Kosztin, Ioan"}
569 @string{JKovacevic = "Kovacevic, Jelena"}
570 @string{CKraft = "Kraft, C."}
571 @string{HAKramers = "Kramers, H. A."}
572 @string{AKrammer = "Krammer, Andre"}
573 @string{SKravitz = "Kravitz, S."}
574 @string{HJKreuzer = {Kreuzer, Hans J\"urgen}}
575 @string{MMGKrishna = "Krishna, Mallela M. G."}
576 @string{KKroy = "Kroy, Klaus"}
577 @string{HHKu = "Ku, H.~H."}
578 @string{TAKucaba = "Kucaba, T. A."}
579 @string{Kucherlapati = "Kucherlapati"}
580 @string{JKudoh = "Kudoh, J."}
581 @string{MKuhn = "Kuhn, Michael"}
582 @string{MKulke = "Kulke, Michael"}
583 @string{CKwok = "Kwok, Carol H."}
584 @string{RLevy = "L\'evy, R"}
585 @string{DLabeit = "Labeit, Dietmar"}
586 @string{SLabeit = "Labeit, Siegfried"}
587 @string{DLabudde = "Labudde, Dirk"}
588 @string{SLahmers = "Lahmers, Sunshine"}
589 @string{ZLai = "Lai, Z."}
590 @string{CLam = "Lam, Canaan"}
591 @string{JLamb = "Lamb, Jonathan C."}
592 @string{LANG = "Langmuir"}
593 % "Langmuir : the ACS journal of surfaces and colloids",
594 @string{WLau = "Lau, Wai Leung"}
595 @string{RLaw = "Law, Richard"}
596 @string{BLazareva = "Lazareva, B."}
597 @string{MLeake = "Leake, Mark C."}
598 @string{ELee = "Lee, E."}
599 @string{HLee = "Lee, Haeshin"}
600 @string{SLee = "Lee, Sunyoung"}
601 @string{HLehmann = "Lehmann, H."}
602 @string{HLehrach = "Lehrach, H."}
603 @string{YLei = "Lei, Y."}
604 @string{PLelkes = "Lelkes, Peter I."}
605 @string{OLequin = "Lequin, Olivier"}
606 @string{CLethias = "Lethias, Claire"}
607 @string{SLeuba = "Leuba, Sanford H."}
608 @string{ALeung = "Leung, A."}
609 @string{MLeuschner = "Leuschner, Mirko"}
610 @string{AJLevine = "Levine, A. J."}
611 @string{CLevinthal = "Levinthal, Cyrus"}
612 @string{ALevitsky = "Levitsky, A."}
613 @string{SLevy = "Levy, S."}
614 @string{MLewis = "Lewis, M."}
615 @string{JLItalien = "L'Italien, James J."}
616 @string{BLi = "Li, Bing"}
617 @string{CYLi = "Li, Christopher Y."}
618 @string{HLi = "Li, Hongbin"}
619 @string{JLi = "Li, J."}
620 @string{LeLi = "Li, Lewyn"}
621 @string{LiLi = "Li, Lingyu"}
622 @string{MSLi = "Li, Mai Suan"}
623 @string{PWLi = "Li, P. W."}
624 @string{YLi = "Li, Yajun"}
625 @string{ZLi = "Li, Z."}
626 @string{YLiang = "Liang, Y."}
627 @string{GLiao = "Liao, George"}
628 @string{FCLin = "Lin, Fan-Chi"}
629 @string{JLin = "Lin, Jianhua"}
630 @string{SHLin = "Lin, Sheng-Hsien"}
631 @string{XLin = "Lin, X."}
632 @string{JLindahl = "Lindahl, Joakim"}
633 @string{SLindsay = "Lindsay, Stuart M."}
634 @string{WALinke = "Linke, Wolfgang A."}
635 @string{RLippert = "Lippert, R."}
636 @string{JLis = "Lis, John T."}
637 @string{RLiu = "Liu, Runcong"}
638 @string{WLiu = "Liu, W."}
639 @string{XLiu = "Liu, X."}
640 @string{YLiu = "Liu, Yichun"}
641 @string{LLivadaru = "Livadaru, L."}
642 @string{YSLo = "Lo, Yu-Shiu"}
643 @string{GLois = "Lois, Gregg"}
644 @string{JLopez = "Lopez, J."}
645 @string{LANL = "Los Alamos National Laboratory"}
646 @string{LAS = "Los Alamos Science"}
647 @string{ALove = "Love, A."}
648 @string{FLu = "Lu, F."}
649 @string{HLu = "Lu, Hui"}
650 @string{QLu = "Lu, Qinghua"}
651 @string{MLudwig = "Ludwig, Markus"}
652 @string{ZPLuo = "Luo, Zong-Ping"}
653 @string{ZLuthey-Schulten = "Luthey-Schulten, Z."}
654 @string{EMunck = {M\"unck, E.}}
655 @string{DMa = "Ma, D."}
656 @string{LMa = "Ma, Liang"}
657 @string{MMaaloum = "Maaloum, Mounir"}
658 @string{Macromol = "Macromolecules"}
659 @string{AMadan = "Madan, A."}
660 @string{VVMaduro = "Maduro, V. V."}
661 @string{CMaingonnat = "Maingonnat, C."}
662 @string{SMajid = "Majid, Sophia"}
663 @string{WMajoros = "Majoros, W."}
664 @string{DEMakarov = "Makarov, Dmitrii E."}
665 @string{RMamdani = "Mamdani, Reneeta"}
666 @string{SMammi = "Mammi, Stefano"}
667 @string{EMandello = "Mandello, Enrico"}
668 @string{GManderson = "Manderson, Gavin"}
669 @string{FMann = "Mann, F."}
670 @string{AMansson = "M{\aa}nsson, Alf"}
671 @string{ERMardis = "Mardis, E. R."}
672 @string{JMarion = "Marion, J."}
673 @string{JFMarko = "Marko, John F."}
674 @string{MMarra = "Marra, M."}
675 @string{PMarszalek = "Marszalek, Piotr E."}
676 @string{MMartin = "Martin, M. J."}
677 @string{YMartin = "Martin, Y."}
678 @string{HMassa = "Massa, H."}
679 @string{MIT = "Massachusetts Institute of Technology"}
680 @string{GAMatei = "Matei, G.~A."}
681 @string{DMaterassi = "Materassi, Donatello"}
682 @string{JMathe = "Math\'e, J\'er\^ome"}
683 @string{AMatouschek = "Matouschek, Andreas"}
684 @string{BMatthews = "Matthews, Brian W."}
685 @string{DMay = "May, D."}
686 @string{RMayer = "Mayer, Richard"}
687 @string{LMayne = "Mayne, Leland"}
688 @string{AMays = "Mays, A."}
689 @string{OTMcCann = "McCann, O. T."}
690 @string{SMcCawley = "McCawley, S."}
691 @string{JMcDaniel = "McDaniel, J."}
692 @string{JMcEntyre = "McEntyre, J."}
693 @string{McGraw-Hill = "McGraw-Hill"}
694 @string{TMcIntosh = "McIntosh, T."}
695 @string{VAMcKusick = "McKusick, V. A."}
696 @string{IMcMullen = "McMullen, I."}
697 @string{JDMcPherson = "McPherson, J. D."}
698 @string{TMeasey = "Measey, Thomas J."}
699 @string{MAD = "Mech Ageing Dev"}
700 @string{PMeier = "Meier, Paul"}
701 @string{AMeller = "Meller, Amit"}
702 @string{CCMello = "Mello, Cecilia C."}
703 @string{RMerkel = "Merkel, R."}
704 @string{GVMerkulov = "Merkulov, G. V."}
705 @string{FMerzel = "Merzel, Franci"}
706 @string{HMetiu = "Metiu, Horia"}
707 @string{NMetropolis = "Metropolis, Nicholas"}
708 @string{GMeyer = "Meyer, Gerhard"}
709 @string{HMi = "Mi, H."}
710 @string{LMiao = "Miao, Linlin"}
711 @string{CMicheletti = "Micheletti, Cristian"}
712 @string{MMickler = "Mickler, Moritz"}
713 @string{AMiller = "Miller, A."}
714 @string{NMilshina = "Milshina, N."}
715 @string{SMinoshima = "Minoshima, S."}
716 @string{IMitchell = "Mitchell, Ian"}
717 @string{SMitternacht = "Mitternacht, Simon"}
718 @string{NJMlot = "Mlot, Nathan J."}
719 @string{CMobarry = "Mobarry, C."}
720 @string{NMohandas = "Mohandas, N."}
721 @string{SMohanty = "Mohanty, Sandipan"}
722 @string{UMohideen = "Mohideen, U."}
723 @string{PJMohr = "Mohr, Peter J."}
724 @string{VMontana = "Montana, Vedrana"}
725 @string{LMontanaro = "Montanaro, Lucio"}
726 @string{LMontelius = "Montelius, Lars"}
727 @string{CMontemagno = "Montemagno, Carlo D."}
728 @string{KTMontgomery = "Montgomery, K. T."}
729 @string{HMMoore = "Moore, H. M."}
730 @string{MMorgan = "Morgan, Michael"}
731 @string{LMoy = "Moy, L."}
732 @string{MMoy = "Moy, M."}
733 @string{VMoy = "Moy, Vincent T."}
734 @string{SMukamel = "Mukamel, Shaul"}
735 @string{DJMuller = "M{\"u}ller, Daniel J."}
736 @string{PMundel = "Mundeol, P."}
737 @string{EMuneyuki = "Muneyuki, Eiro"}
738 @string{RJMural = "Mural, R. J."}
739 @string{BMurphy = "Murphy, B."}
740 @string{SMurphy = "Murphy, S."}
741 @string{AMuruganujan = "Muruganujan, A."}
742 @string{FMusiani = "Musiani, Francesco"}
743 @string{EWMyers = "Myers, E. W."}
744 @string{RMMyers = "Myers, R. M."}
745 @string{AMylonakis = "Mylonakis, Andreas"}
746 @string{ENachliel = "Nachliel, Esther"}
747 @string{JNadeau = "Nadeau, J."}
748 @string{AKNaik = "Naik, A. K."}
749 @string{NANO = "Nano letters"}
750 @string{NT = "Nanotechnology"}
751 @string{VANarayan = "Narayan, V. A."}
752 @string{ANarechania = "Narechania, A."}
753 @string{PNassoy = "Nassoy, P."}
754 @string{NBS = "National Bureau of Standards"}
755 @string{NAT = "Nature"}
756 @string{NSB = "Nature Structural Biology"}
757 @string{NSMB = "Nature Structural Molecular Biology"}
758 @string{NRMCB = "Nature Reviews Molecular Cell Biology"}
759 @string{SNaylor = "Naylor, S."}
760 @string{CNeagoe = "Neagoe, Ciprian"}
761 @string{BNeelam = "Neelam, B."}
762 @string{MNeitzert = "Neitzert, Marcus"}
763 @string{CNelson = "Nelson, C."}
764 @string{KNelson = "Nelson, K."}
765 @string{RRNetz = "Netz, R.~R."}
766 @string{NR = "Neurochemical research"}
767 @string{NEURON = "Neuron"}
768 @string{RNevo = "Nevo, Reinat"}
769 @string{NJP = "New Journal of Physics"}
770 @string{DBNewell = "Newell, David B."}
771 @string{MNewman = "Newman, M."}
772 @string{INewton = "Newton, Isaac"}
773 @string{SNg = "Ng, Sean P."}
774 @string{NNguyen = "Nguyen, N."}
775 @string{TNguyen = "Nguyen, T."}
776 @string{MNguyen-Duong = "Nguyen-Duong, M."}
777 @string{INicholls = "Nicholls, Ian A."}
778 @string{NNichols = "Nichols, N.~B."}
779 @string{SNie = "Nie, S."}
780 @string{MNodell = "Nodell, M."}
781 @string{AANoegel = "Noegel, Angelika A."}
782 @string{HNoji = "Noji, Hiroyuki"}
783 @string{RNome = "Nome, Rene A."}
784 @string{NNowak = "Nowak, N."}
785 @string{ANoy = "Noy, Aleksandr"}
786 @string{NAR = "Nucleic Acids Research"}
787 @string{JNummela = "Nummela, Jeremiah"}
788 @string{JNunes = "Nunes, Joao"}
789 @string{DNusskern = "Nusskern, D."}
790 @string{GNyakatura = "Nyakatura, G."}
791 @string{CSOHern = "O'Hern, Corey S."}
792 @string{YOberdorfer = {Oberd\"orfer, York}}
793 @string{AOberhauser = "Oberhauser, Andres F."}
794 @string{FOesterhelt = "Oesterhelt, Filipp"}
795 @string{TOhashi = "Ohashi, Tomoo"}
796 @string{BOhler = "Ohler, Benjamin"}
797 @string{PDOlmsted = "Olmsted, Peter D."}
798 @string{AOlsen = "Olsen, A."}
799 @string{SJOlshansky = "Olshansky, S. J."}
800 @string{POmling = {Omlink, P{\"a}r}}
801 @string{JNOnuchic = "Onuchic, J. N."}
802 @string{YOono = "Oono, Y."}
803 @string{GOppenheim = "Oppenheim, Georges"}
804 @string{COpitz = "Optiz, Christiane A."}
805 @string{KOroszlan = "Oroszlan, Krisztina"}
806 @string{EOroudjev = "Oroudjev, E."}
807 @string{KOsoegawa = "Osoegawa, K."}
808 @string{OUP = "Oxford University Press"}
809 @string{EPaci = "Paci, Emanuele"}
810 @string{SPan = "Pan, S."}
811 @string{HSPark = "Park, H. S."}
812 @string{VParpura = "Parpura, Vladimir"}
813 @string{APastore = "Pastore, A."}
814 @string{APatrinos = "Patrinos, Aristides"}
815 @string{FPavone = "Pavone, F. S."}
816 @string{SHPayne = "Payne, Stephen H."}
817 @string{JPeck = "Peck, J."}
818 @string{HPeng = "Peng, Haibo"}
819 @string{QPeng = "Peng, Qing"}
820 @string{RNPerham = "Perham, Richard N."}
821 @string{OPerisic = "Perisic, Ognjen"}
822 @string{CPeterson = "Peterson, Craig L."}
823 @string{MPeterson = "Peterson, M."}
824 @string{SMPeterson = "Peterson, Susan M."}
825 @string{CPfannkoch = "Pfannkoch, C."}
826 @string{PA = "Pfl{\"u}gers Archiv: European journal of physiology"}
827 @string{PTRSL = "Philosophical Transactions of the Royal Society of London"}
828 @string{PR:E = "Phys Rev E Stat Nonlin Soft Matter Phys"}
829 @string{PRL = "Physical Review Letters"}
830 %string{PRL = "Phys Rev Lett"}
831 @string{Physica = "Physica"}
832 @string{GPing = "Ping, Guanghui"}
833 @string{NPinotsis = "Pinotsis, Nikos"}
834 @string{MPlumbley = "Plumbley, Mark"}
835 @string{PLOS:ONE = "PLOS ONE"}
836 %string{PLOS:ONE = "Public Library of Science ONE"}
837 @string{PLOS:BIO = "PLOS Biology"}
838 @string{DPlunkett = "Plunkett, David"}
839 @string{PPodsiadlo = "Podsiadlo, Paul"}
840 @string{ASPolitou = "Politou, A. S."}
841 @string{APoustka = "Poustka, A."}
842 @string{CBPrater = "Prater, C.~B."}
843 @string{GPratesi = "Pratesi, G."}
844 @string{EPratts = "Pratts, E."}
845 @string{WPress = "Press, W."}
846 @string{PNAS = "Proceedings of the National Academy of Sciences of the
847 United States of America"}
848 @string{PBPMB = "Progress in Biophysics and Molecular Biology"}
849 @string{PS = "Protein Science"}
850 @string{PROT = "Proteins"}
851 @string{RSUP = "Published for the Royal Society at the University Press"}
852 @string{EPuchner = "Puchner, Elias M."}
853 @string{VPuri = "Puri, V."}
854 @string{WPyckhout-Hintzen = "Pyckhout-Hintzen, Wim"}
855 @string{HQin = "Qin, Haina"}
856 @string{SQin = "Qin, S."}
857 @string{SRQuake = "Quake, Stephen R."}
858 @string{CQuate = "Quate, Calvin F."}
859 @string{HQureshi = "Qureshi, H."}
860 @string{SERadford = "Radford, Sheena E."}
861 @string{MRadmacher = "Radmacher, M."}
862 @string{MRaible = "Raible, M."}
863 @string{LRamirez = "Ramirez, L."}
864 @string{JRamser = "Ramser, J."}
865 @string{LRandles = "Randles, Lucy G."}
866 @string{VRaussens = "Raussens, Vincent"}
867 @string{IRay = "Ray, I."}
868 @string{MReardon = "Reardon, M."}
869 @string{ALCReddin = "Reddin, Andrew L. C."}
870 @string{SRedick = "Redick, Sambra D."}
871 @string{ZReich = "Reich, Ziv"}
872 @string{TReid = "Reid, T."}
873 @string{PReimann = "Reimann, P."}
874 @string{KReinert = "Reinert, K."}
875 @string{RReinhardt = "Reinhardt, R."}
876 @string{KRemington = "Remington, K."}
877 @string{RMP = "Rev. Mod. Phys."}
878 @string{RSI = "Review of Scientific Instruments"}
879 @string{FRief = "Rief, Frederick"}
880 @string{MRief = "Rief, Matthias"}
881 @string{KRitchie = "Ritchie, K."}
882 @string{MRobbins = "Robbins, Mark O."}
883 @string{CJRoberts = "Roberts, C.~J."}
884 @string{RJRoberts = "Roberts, R. J."}
885 @string{RRobertson = "Robertson, Ragan B."}
886 @string{HRoder = "Roder, Heinrich"}
887 @string{RRodriguez = "Rodriguez, R."}
888 @string{YHRogers = "Rogers, Y. H."}
889 @string{SRogic = "Rogic, S."}
890 @string{MRoman = "Roman, Marisa B."}
891 @string{GRomano = "Romano, G."}
892 @string{DRomblad = "Romblad, D."}
893 @string{RRos = "Ros, Robert"}
894 @string{BRosenberg = "Rosenberg, B."}
895 @string{JRosengren = "Rosengren, Jenny P."}
896 @string{ARosenthal = "Rosenthal, A."}
897 @string{ARoters = "Roters, Andreas"}
898 @string{WRowe = "Rowe, W."}
899 @string{LRowen = "Rowen, L."}
900 @string{BRuhfel = "Ruhfel, B."}
901 @string{DBRusch = "Rusch, D. B."}
902 @string{JMRuysschaert = "Ruysschaert, Jean-Marie"}
903 @string{JPRyckaert = "Ryckaert, Jean-Paul"}
904 @string{NSakaki = "Sakaki, Naoyoshi"}
905 @string{YSakaki = "Sakaki, Y."}
906 @string{SSalzberg = "Salzberg, S."}
907 @string{BSamori = "Samor{\`i}, Bruno"}
908 @string{MSandal = "Sandal, Massimo"}
909 @string{RSanders = "Sanders, R."}
910 @string{ASarkar = "Sarkar, Atom"}
911 @string{TSasaki = "Sasaki, T."}
912 @string{SSato = "Sato, S."}
913 @string{TSato = "Sato, Takehiro"}
914 @string{PSchaaf = "Schaaf, P."}
915 @string{RSchafer = "Schafer, Rolf"}
916 @string{TESchafer = "Sch{\"a}fer, Tilman E."}
917 @string{NScherer = "Scherer, Norbert F."}
918 @string{SScherer = "Scherer, S."}
919 @string{MSchilhabel = "Schilhabel, M."}
920 @string{HSchillers = "Schillers, Hermann"}
921 @string{BSchlegelberger = "Schlegelberger, B."}
922 @string{MSchleicher = "Schleicher, Michael"}
923 @string{MSchlierf = "Schlierf, Michael"}
924 @string{CFSchmidt = "Schmidt, Christoph F."}
925 @string{JSchmidt = "Schmidt, Jacob J."}
926 @string{LSchmitt = "Schmitt, Lutz"}
927 @string{JSchmutz = "Schmutz, J."}
928 @string{GSchuler = "Schuler, G."}
929 @string{GDSchuler = "Schuler, G. D."}
930 @string{KSchulten = "Schulten, Klaus"}
931 @string{ZSchulten = "Schulten, Zan"}
932 @string{MSchwab = "Schwab, M."}
933 @string{ISchwaiger = "Schwaiger, Ingo"}
934 @string{RSchwartz = "Schwartz, R."}
935 @string{RSchweitzerStenner = "Scheitzer-Stenner, Reinhard"}
936 @string{SCI = "Science"}
937 @string{CEScott = "Scott, C. E."}
938 @string{JScott = "Scott, J."}
939 @string{RScott = "Scott, R."}
940 @string{USeifert = "Seifert, Udo"}
941 @string{SKSekatskii = "Sekatskii, Sergey K."}
942 @string{MSekhon = "Sekhon, M."}
943 @string{TSekiguchi = "Sekiguchi, T."}
944 @string{BSenger = "Senger, B."}
945 @string{DBSenn = "Senn, David B."}
946 @string{PSeranski = "Seranski, P."}
947 @string{RSesboue = {Sesbo\"u\'e, R.}}
948 @string{EShakhnovich = "Shakhnovich, Eugene"}
949 @string{GShan = "Shan, Guiye"}
950 @string{JShang = "Shang, J."}
951 @string{WShao = "Shao, W."}
952 @string{DSharma = "Sharma, Deepak"}
953 @string{YJSheng = "Sheng, Yu-Jane"}
954 @string{KShibuya = "Shibuya, K."}
955 @string{JShillcock = "Shillcock, Julian"}
956 @string{AShimizu = "Shimizu, A."}
957 @string{NShimizu = "Shimizu, N."}
958 @string{RShimoKon = "Shimo-Kon, Rieko"}
959 @string{JPShine = "Shine, James P."}
960 @string{AShintani = "Shintani, A."}
961 @string{BShneiderman = "Shneiderman, Ben"}
962 @string{BShue = "Shue, B."}
963 @string{RSiebert = "Siebert, R."}
964 @string{EDSiggia = "Siggia, Eric D."}
965 @string{MSimon = "Simon, M."}
966 @string{MSimpson = "Simpson, M."}
967 @string{GESims = "Sims, Gregory E."}
968 @string{CSitter = "Sitter, C."}
969 @string{KVSjolander = "Sjolander, K. V."}
970 @string{MSkupski = "Skupski, M."}
971 @string{CSlayman = "Slayman, C."}
972 @string{MSmallwood = "Smallwood, M."}
973 @string{CSmith = "Smith, Corey L."}
974 @string{DASmith = "Smith, D. Alastair"}
975 @string{HOSmith = "Smith, H. O."}
976 @string{KBSmith = "Smith, Kathryn B."}
977 @string{MDSmith = "Smith, Micholas Dean"}
978 @string{SSmith = "Smith, S."}
979 @string{SBSmith = "Smith, S. B."}
980 @string{TSmith = "Smith, T."}
981 @string{JSoares = "Soares, J."}
982 @string{NDSocci = "Socci, N. D."}
983 @string{SEG = "Society of Exploration Geophysicists"}
984 @string{ESodergren = "Sodergren, E."}
985 @string{CSoderlund = "Soderlund, C."}
986 @string{JSong = "Song, Jianxing"}
987 @string{JSpanier = "Spanier, Jonathan E."}
988 @string{DSpeicher = "Speicher, David W."}
989 @string{GSpier = "Spier, G."}
990 @string{ASprague = "Sprague, A."}
991 @string{SPRINGER = "Springer Science + Business Media, LLC"}
992 @string{SPRINGER:V = "Springer-Verlag"}
993 @string{DBStaple = "Staple, Douglas B."}
994 @string{RStark = "Stark, R. W."}
995 @string{PSStayton = "Stayton, P. S."}
996 @string{REStenkamp = "Stenkamp, R. E."}
997 @string{SStepaniants = "Stepaniants, S."}
998 @string{EStewart = "Stewart, E."}
999 @string{MRStockmeier = "Stockmeier, M. R."}
1000 @string{TStockwell = "Stockwell, T."}
1001 @string{NEStone = "Stone, N. E."}
1002 @string{AStout = "Stout, A."}
1003 @string{TRStrick = "Strick, T. R."}
1004 @string{CStroh = "Stroh, Cordula"}
1005 @string{RStrong = "Strong, R."}
1006 @string{JStruckmeier = "Struckmeier, Jens"}
1007 @string{STR = "Structure"}
1008 @string{TStrunz = "Strunz, Torsten"}
1009 @string{MSu = "Su, Meihong"}
1010 @string{GSubramanian = "Subramanian, G."}
1011 @string{ESuh = "Suh, E."}
1012 @string{JSun = "Sun, J."}
1013 @string{YLSun = "Sun, Yu-Long"}
1014 @string{MSundberg = "Sundberg, Mark"}
1015 @string{WSundquist = "Sundquist, Wesley I."}
1016 @string{KSurewicz = "Surewicz, Krystyna"}
1017 @string{WKSurewicz = "Surewicz, Witold K."}
1018 @string{GGSutton = "Sutton, G. G."}
1019 @string{ASzabo = "Szabo, Attila"}
1020 @string{STagerud = "T{\aa}gerud, Sven"}
1021 @string{PTabor = "Tabor, P."}
1022 @string{ATakahashi = "Takahashi, Akiri"}
1023 @string{DTalaga = "Talaga, David S."}
1024 @string{PTalkner = "Talkner, Peter"}
1025 @string{RTampe = "Tamp{\'e}, Robert"}
1026 @string{JTang = "Tang, Jianyong"}
1027 @string{PTavan = "Tavan, P."}
1028 @string{BNTaylor = "Taylor, Barry N."}
1029 @string{THEMath = "Technische Hogeschool Eindhoven, Nederland,
1030 Onderafdeling der Wiskunde"}
1031 @string{SJBTendler = "Tendler, S.~J.~B."}
1032 @string{ITessari = "Tessari, Isabella"}
1033 @string{STeukolsky = "Teukolsky, S."}
1034 @string{CJ = "The Computer Journal"}
1035 @string{JBC = "The Journal of Biological Chemistry"}
1036 @string{JCP = "The Journal of Chemical Physics"}
1037 @string{JPC:B = "The Journal of Physical Chemistry B"}
1038 @string{JPC:C = "The Journal of Physical Chemistry C"}
1039 @string{RS = "The Royal Society"}
1040 @string{DThirumalai = "Thirumalai, Devarajan"}
1041 @string{PDThomas = "Thomas, P. D."}
1042 @string{RThomas = "Thomas, R."}
1043 @string{JThompson = "Thompson, J. B."}
1044 @string{EJThoreson = "Thoreson, E.~J."}
1045 @string{SThornton = "Thornton, S."}
1046 @string{RWTillmann = "Tillmann, R.~W."}
1047 @string{NNTint = "Tint, N. N."}
1048 @string{BTiribilli = "Tiribilli, Bruno"}
1049 @string{TTlusty = "Tlusty, Tsvi"}
1050 @string{PTobias = "Tobias, Paul"}
1051 @string{JTocaHerrera = "Toca-Herrera, Jose L."}
1052 @string{CATovey = "Tovey, Craig A."}
1053 @string{AToyoda = "Toyoda, A."}
1054 @string{TASME = "Transactions of the American Society of Mechanical Engineers"}
1055 @string{BTrask = "Trask, B."}
1056 @string{TBI = "Tribology International"}
1057 @string{JTrinick = "Trinick, John"}
1058 @string{KTrombitas = "Trombit\'as, K."}
1059 @string{ILTrong = "Trong, I. Le"}
1060 @string{CHTsai = "Tsai, Chih-Hui"}
1061 @string{HKTsao = "Tsao, Heng-Kwong"}
1062 @string{STse = "Tse, S."}
1063 @string{ZTshiprut = "Tshiprut, Z."}
1064 @string{JCMTsibris = "Tsibris, J.C.M."}
1065 @string{LTskhovrebova = "Tskhovrebova, Larissa"}
1066 @string{HWTurnbull = "Turnbull, Herbert Westren"}
1067 @string{RTurner = "Turner, R."}
1068 @string{AUlman = "Ulman, Abraham"}
1069 @string{UltraMic = "Ultramicroscopy"}
1070 @string{UIP:Urbana = "University of Illinois Press, Urbana"}
1071 @string{UTMB = "University of Texas Medical Branch"}
1072 @string{MUrbakh = "Urbakh, M."}
1073 @string{FValle = "Valle, Francesco"}
1074 @string{KJVanVliet = "Van Vliet, Krystyn J."}
1075 @string{PVandewalle = "Vandewalle, Patrick"}
1076 @string{CVech = "Vech, C."}
1077 @string{OVelasquez = "Velasquez, O."}
1078 @string{EVenter = "Venter, E."}
1079 @string{JCVenter = "Venter, J. C."}
1080 @string{PHVerdier = "Verdier, Peter H."}
1081 @string{IVetter = "Vetter, Ingrid R."}
1082 @string{MVetterli = "Vetterli, Martin"}
1083 @string{WVetterling = "Vetterling, W."}
1084 @string{MViani = "Viani, Mario B."}
1085 @string{JCVoegel = "Voegel, J.-C."}
1086 @string{VVogel = "Vogel, Viola"}
1087 @string{CWagner-McPherson = "Wagner-McPherson, C."}
1088 @string{RWahl = "Wahl, Reiner"}
1089 @string{TAWaigh = "Waigh, Thomas A."}
1090 @string{BWalenz = "Walenz, B."}
1091 @string{JWallis = "Wallis, J."}
1092 @string{KWalther = "Walther, Kirstin A."}
1093 @string{AJWalton = "Walton, Alan J"}
1094 @string{EBWalton = "Walton, Emily B."}
1095 @string{AWang = "Wang, A."}
1096 @string{FSWang = "Wang, F.~S."}
1097 @string{GWang = "Wang, G."}
1098 @string{JWang = "Wang, J."}
1099 @string{MWang = "Wang, M."}
1100 @string{MDWang = "Wang, Michelle D."}
1101 @string{SWang = "Wang, Shuang"}
1102 @string{XWang = "Wang, X."}
1103 @string{ZWang = "Wang, Z."}
1104 @string{HWatanabe = "Watanabe, Hiroshi"}
1105 @string{KWatanabe = "Watanabe, Kaori"}
1106 @string{RHWaterston = "Waterston, R. H."}
1107 @string{BWaugh = "Waugh, Ben"}
1108 @string{JWegiel = "Wegiel, J."}
1109 @string{MWei = "Wei, M."}
1110 @string{YWei = "Wei, Yen"}
1111 @string{ALWeisenhorn = "Weisenhorn, A.~L."}
1112 @string{JWeissenbach = "Weissenbach, J."}
1113 @string{BLWelch = "Welch, Bernard Lewis"}
1114 @string{GWen = "Wen, G."}
1115 @string{MWen = "Wen, M."}
1116 @string{JWetter = "Wetter, J."}
1117 @string{EPWhite = "White, Ethan P."}
1118 @string{ANWhitehead = "Whitehead, Alfred North"}
1119 @string{AWhittaker = "Whittaker, A."}
1120 @string{HKWickramasinghe = "Wickramasinghe, H. K."}
1121 @string{RWides = "Wides, R."}
1122 @string{AWiita = "Wiita, Arun P."}
1123 @string{MWilchek = "Wilchek, Meir"}
1124 @string{AWilcox = "Wilcox, Alexander J."}
1125 @string{Williams = "Williams"}
1126 @string{CCWilliams = "Williams, C. C."}
1127 @string{MWilliams = "Williams, M."}
1128 @string{SWilliams = "Williams, S."}
1129 @string{WN = "Williams \& Norgate"}
1130 @string{MWilmanns = "Wilmanns, Matthias"}
1131 @string{GWilson = "Wilson, Greg"}
1132 @string{PWilson = "Wilson, Paul"}
1133 @string{RKWilson = "Wilson, R. K."}
1134 @string{SWilson = "Wilson, Scott"}
1135 @string{SWindsor = "Windsor, S."}
1136 @string{EWinn-Deen = "Winn-Deen, E."}
1137 @string{NWirth = "Wirth, Niklaus"}
1138 @string{HMWisniewski = "Wisniewski, H.~M."}
1139 @string{CWitt = "Witt, Christian"}
1140 @string{KWolfe = "Wolfe, K."}
1141 @string{TGWolfsberg = "Wolfsberg, T. G."}
1142 @string{PGWolynes = "Wolynes, P. G."}
1143 @string{WPWong = "Wong, Wesley P."}
1144 @string{TWoodage = "Woodage, T."}
1145 @string{GRWoodcock = "Woodcock, Glenna R."}
1146 @string{JRWortman = "Wortman, J. R."}
1147 @string{PEWright = "Wright, Peter E."}
1148 @string{DWu = "Wu, D."}
1149 @string{GAWu = "Wu, Guohong A."}
1150 @string{JWWu = "Wu, Jong-Wuu"}
1151 @string{MWu = "Wu, M."}
1152 @string{YWu = "Wu, Yiming"}
1153 @string{GJLWuite = "Wuite, Gijs J. L."}
1154 @string{KWylie = "Wylie, K."}
1155 @string{JXi = "Xi, Jun"}
1156 @string{AXia = "Xia, A."}
1157 @string{CXiao = "Xiao, C."}
1158 @string{SXiao = "Xiao, Senbo"}
1159 @string{TYada = "Yada, T."}
1160 @string{CYan = "Yan, C."}
1161 @string{MYandell = "Yandell, M."}
1162 @string{GYang = "Yang, Guoliang"}
1163 @string{YYang = "Yang, Yao"}
1164 @string{BAYankner = "Yankner, Bruce A."}
1165 @string{AYao = "Yao, A."}
1166 @string{RYasuda = "Yaduso, Ryohei"}
1167 @string{JYe = "Ye, J."}
1168 @string{RYeh = "Yeh, Richard C."}
1169 @string{RYonescu = "Yonescu, R."}
1170 @string{SYooseph = "Yooseph, S."}
1171 @string{MYoshida = "Yoshida, Masasuke"}
1172 @string{WYu = "Yu, Weichang"}
1173 @string{JMYuan = "Yuan, Jian-Min"}
1174 @string{MYuan = "Yuan, Menglan"}
1175 @string{AZandieh = "Zandieh, A."}
1176 @string{JZaveri = "Zaveri, J."}
1177 @string{KZaveri = "Zaveri, K."}
1178 @string{MZhan = "Zhan, M."}
1179 @string{HZhang = "Zhang, H."}
1180 @string{JZhang = "Zhang, J."}
1181 @string{QZhang = "Zhang, Q."}
1182 @string{WZhang = "Zhang, W."}
1183 @string{YZhang = "Zhang, Yanjie"}
1184 @string{ZZhang = "Zhang, Zongtao"}
1185 @string{JZhao = "Zhao, Jason Ming"}
1186 @string{LZhao = "Zhao, Liming"}
1187 @string{QZhao = "Zhao, Q."}
1188 @string{SZhao = "Zhao, S."}
1189 @string{LZheng = "Zheng, L."}
1190 @string{XHZheng = "Zheng, X. H."}
1191 @string{FZhong = "Zhong, F."}
1192 @string{MZhong = "Zhong, Mingya"}
1193 @string{WZhong = "Zhong, W."}
1194 @string{HXZhou = "Zhou, Huan-Xiang"}
1195 @string{SZhu = "Zhu, S."}
1196 @string{XZhu = "Zhu, X."}
1197 @string{YJZhu = "Zhu, Ying-Jie"}
1198 @string{WZhuang = "Zhuang, Wei"}
1199 @string{JZidar = "Zidar, Jernej"}
1200 @string{JZiegler = "Ziegler, J.G."}
1201 @string{NZinder = "Zinder, N."}
1202 @string{RCZinober = "Zinober, Rebecca C."}
1203 @string{JZlatanova = "Zlatanova, Jordanka"}
1204 @string{PZou = "Zou, Peng"}
1205 @string{GZuccheri = "Zuccheri, Giampaolo"}
1206 @string{RZwanzig = "Zwanzig, R."}
1207 @string{arXiv = "arXiv"}
1208 @string{PGdeGennes = "de Gennes, P. G."}
1209 @string{PJdeJong = "de Jong, P. J."}
1210 @string{NGvanKampen = "van Kampen, N.G."}
1211 @string{NIST:SEMATECH = "{NIST/SEMATECH}"}
1212 @string{EDCola = "{\uppercase{d}}i Cola, Emanuela"}
1214 @inbook{ NIST:chi-square,
1215 crossref = {NIST:ESH},
1216 chapter = {1.3.5.15: Chi-Square Goodness-of-Fit Test},
1220 url = {http://www.itl.nist.gov/div898/handbook/eda/section3/eda35f.htm},
1223 @inbook{ NIST:gumbel,
1224 crossref = {NIST:ESH},
1225 chapter = {1.3.6.6.16: Extreme Value Type {I} Distribution},
1229 url = {http://www.itl.nist.gov/div898/handbook/eda/section3/eda366g.htm},
1233 editor = CCroarkin #" and "# PTobias,
1234 author = NIST:SEMATECH,
1235 title = {e-{H}andbook of Statistical Methods},
1238 publisher = NIST:SEMATECH,
1239 address = {Boulder, Colorado},
1240 url = {http://www.itl.nist.gov/div898/handbook/},
1241 note = {This manual was developed from seed material produced by
1245 @misc{ wikipedia:gumbel,
1246 author = "Wikipedia",
1247 title = "Gumbel distribution --- {W}ikipedia{,} The Free Encyclopedia",
1249 url = "http://en.wikipedia.org/wiki/Gumbel_distribution",
1254 title = "Statistics of Extremes",
1257 address = "New York",
1258 wtk_note = "Find and read",
1261 @misc{ wikipedia:GEV,
1262 author = "Wikipedia",
1263 title = "Generalized extreme value distribution --- {W}ikipedia{,}
1264 The Free Encyclopedia",
1266 url = "http://en.wikipedia.org/wiki/Generalized_extreme_value_distribution",
1269 @misc{ wikipedia:gompertz,
1270 author = "Wikipedia",
1271 title = "Gompertz distribution --- {W}ikipedia{,} The Free Encyclopedia",
1273 url = "http://en.wikipedia.org/wiki/Gompertz_distribution",
1276 @misc{ wikipedia:gumbel-t1,
1277 author = "Wikipedia",
1278 title = "Type-1 Gumbel distribution --- {W}ikipedia{,} The Free
1281 url = "http://en.wikipedia.org/wiki/Type-1_Gumbel_distribution",
1284 @misc{ wikipedia:gumbel-t2,
1285 author = "Wikipedia",
1286 title = "Type-2 Gumbel distribution --- {W}ikipedia{,} The Free
1289 url = "http://en.wikipedia.org/wiki/Type-2_Gumbel_distribution",
1292 @article { allemand03,
1293 author = JFAllemand #" and "# DBensimon #" and "# VCroquette,
1294 title = "Stretching {DNA} and {RNA} to probe their interactions with
1303 keywords = "DNA;DNA-Binding
1304 Proteins;Isomerases;Micromanipulation;Microscopy, Atomic Force;Nucleic
1305 Acid Conformation;Nucleotidyltransferases",
1306 abstract = "When interacting with a single stretched DNA, many proteins
1307 modify its end-to-end distance. This distance can be monitored in real
1308 time using various micromanipulation techniques that were initially
1309 used to determine the elastic properties of bare nucleic acids and
1310 their mechanically induced structural transitions. These methods are
1311 currently being applied to the study of DNA enzymes such as DNA and RNA
1312 polymerases, topoisomerases and structural proteins such as RecA. They
1313 permit the measurement of the probability distributions of the rate,
1314 processivity, on-time, affinity and efficiency for a large variety of
1315 DNA-based molecular motors."
1319 author = RAlon #" and "# EABayer #" and "# MWilchek,
1320 title = "Streptavidin contains an {RYD} sequence which mimics the {RGD}
1321 receptor domain of fibronectin",
1328 pages = "1236--1241",
1330 doi = "10.1016/0006-291X(90)90526-S",
1331 url = "http://dx.doi.org/10.1016/0006-291X(90)90526-S",
1332 keywords = "Amino Acid Sequence;Animals;Bacterial Proteins;Binding
1333 Sites;Cell Line;Cell Membrane;Cricetinae;Fibronectins;Molecular
1334 Sequence Data;Streptavidin",
1335 abstract = "Streptavidin binds at low levels and high affinity to cell
1336 surfaces, the cause of which can be traced to the occurrence of a
1337 sequence containing RYD (Arg-Tyr-Asp) in the protein molecule. This
1338 binding is enhanced in the presence of biotin. Cell-bound streptavidin
1339 can be displaced by fibronectin, as well as by RGD- and RYD-containing
1340 peptides. In addition, streptavidin can displace fibronectin from cell
1341 surfaces. The RYD sequence of streptavidin thus mimics RGD (Arg-Gly-
1342 Asp), the universal recognition domain present in fibronectin and other
1343 adhesion-related molecules. The observed adhesion to cells has no
1344 relevance to biotin-binding since the RYD sequence is not part of the
1345 biotin-binding site of streptavidin. Since the use of streptavidin in
1346 avidin-biotin technology is based on its biotin-binding properties,
1347 researchers are hereby warned against its indiscriminate use in
1348 histochemical and cytochemical studies.",
1349 note = "Biological role of streptavidin."
1352 @article { balsera97,
1353 author = MBalsera #" and "# SStepaniants #" and "# SIzrailev #" and "#
1354 YOono #" and "# KSchulten,
1355 title = "Reconstructing potential energy functions from simulated force-
1356 induced unbinding processes",
1362 pages = "1281--1287",
1364 eprint = "http://www.biophysj.org/cgi/reprint/73/3/1281.pdf",
1365 url = "http://www.biophysj.org/cgi/content/abstract/73/3/1281",
1366 keywords = "Binding Sites;Biopolymers;Kinetics;Ligands;Microscopy, Atomic
1367 Force;Models, Chemical;Molecular Conformation;Protein
1368 Conformation;Proteins;Reproducibility of Results;Stochastic
1369 Processes;Thermodynamics",
1370 abstract = "One-dimensional stochastic models demonstrate that molecular
1371 dynamics simulations of a few nanoseconds can be used to reconstruct
1372 the essential features of the binding potential of macromolecules. This
1373 can be accomplished by inducing the unbinding with the help of external
1374 forces applied to the molecules, and discounting the irreversible work
1375 performed on the system by these forces. The fluctuation-dissipation
1376 theorem sets a fundamental limit on the precision with which the
1377 binding potential can be reconstructed by this method. The uncertainty
1378 in the resulting potential is linearly proportional to the irreversible
1379 component of work performed on the system during the simulation. These
1380 results provide an a priori estimate of the energy barriers observable
1381 in molecular dynamics simulations."
1384 @article { baneyx02,
1385 author = GBaneyx #" and "# LBaugh #" and "# VVogel,
1386 title = "Supramolecular Chemistry And Self-assembly Special Feature:
1387 Fibronectin extension and unfolding within cell matrix fibrils
1388 controlled by cytoskeletal tension",
1393 pages = "5139--5143",
1394 doi = "10.1073/pnas.072650799",
1395 eprint = "http://www.pnas.org/cgi/reprint/99/8/5139.pdf",
1396 url = "http://www.pnas.org/cgi/content/abstract/99/8/5139",
1397 abstract = "Evidence is emerging that mechanical stretching can alter the
1398 functional states of proteins. Fibronectin (Fn) is a large,
1399 extracellular matrix protein that is assembled by cells into elastic
1400 fibrils and subjected to contractile forces. Assembly into fibrils
1401 coincides with expression of biological recognition sites that are
1402 buried in Fn's soluble state. To investigate how supramolecular
1403 assembly of Fn into fibrillar matrix enables cells to mechanically
1404 regulate its structure, we used fluorescence resonance energy transfer
1405 (FRET) as an indicator of Fn conformation in the fibrillar matrix of
1406 NIH 3T3 fibroblasts. Fn was randomly labeled on amine residues with
1407 donor fluorophores and site-specifically labeled on cysteine residues
1408 in modules FnIII7 and FnIII15 with acceptor fluorophores.
1409 Intramolecular FRET was correlated with known structural changes of Fn
1410 in denaturing solution, then applied in cell culture as an indicator of
1411 Fn conformation within the matrix fibrils of NIH 3T3 fibroblasts. Based
1412 on the level of FRET, Fn in many fibrils was stretched by cells so that
1413 its dimer arms were extended and at least one FnIII module unfolded.
1414 When cytoskeletal tension was disrupted using cytochalasin D, FRET
1415 increased, indicating refolding of Fn within fibrils. These results
1416 suggest that cell-generated force is required to maintain Fn in
1417 partially unfolded conformations. The results support a model of Fn
1418 fibril elasticity based on unraveling and refolding of FnIII modules.
1419 We also observed variation of FRET between and along single fibrils,
1420 indicating variation in the degree of unfolding of Fn in fibrils.
1421 Molecular mechanisms by which mechanical force can alter the structure
1422 of Fn, converting tensile forces into biochemical cues, are discussed."
1425 @article { basche01,
1426 author = TBasche #" and "# SNie #" and "# JFernandez,
1427 title = "Single molecules",
1432 pages = "10527--10528",
1433 doi = "10.1073/pnas.191365898",
1434 eprint = "http://www.pnas.org/cgi/reprint/98/19/10527.pdf",
1435 url = "http://www.pnas.org/cgi/content/abstract/98/19/10527",
1436 note = "Mini summary of single-molecule techniques and look to future.
1437 Focuses on AFM, but mentions others."
1440 @article { bechhoefer02,
1441 author = JBechhoefer #" and "# SWilson,
1442 title = "Faster, cheaper, safer optical tweezers for the undergraduate
1451 doi = "10.1119/1.1445403",
1452 url = "http://link.aip.org/link/?AJP/70/393/1",
1453 keywords = "student experiments; safety; radiation pressure; laser beam
1455 note = {Good discussion of the effect of correlation time on
1456 calibration. References work on deconvolving thermal noise from
1457 other noise\citep{cowan98}. Excellent detail on power spectrum
1458 derivation and thermal noise for extremely overdamped
1459 oscillators in Appendix A (references \citet{rief65}), except
1460 that their equation A12 is missing a factor of $1/\pi$. I
1461 pointed this out to John Bechhoefer and he confirmed the
1463 project = "Cantilever Calibration"
1466 @article{ berg-sorensen04,
1467 author = KBergSorensen #" and "# HFlyvbjerg,
1468 title = {Power spectrum analysis for optical tweezers},
1475 url = {http://rsi.aip.org/resource/1/rsinak/v75/i3/p594_s1},
1476 doi = {10.1063/1.1645654},
1478 keywords = {radiation pressure, Brownian motion, spectral analysis,
1479 dielectric bodies, measurement by laser beam, flow measurement},
1480 abstract = {The force exerted by an optical trap on a dielectric
1481 bead in a fluid is often found by fitting a Lorentzian to the
1482 power spectrum of Brownian motion of the bead in the trap. We
1483 present explicit functions of the experimental power spectrum that
1484 give the values of the parameters fitted, including error bars and
1485 correlations, for the best such $\chi^2$ fit in a given frequency
1486 range. We use these functions to determine the information
1487 content of various parts of the power spectrum, and find, at odds
1488 with lore, much information at relatively high frequencies.
1489 Applying the method to real data, we obtain perfect fits and
1490 calibrate tweezers with less than 1\% error when the trapping
1491 force is not too strong. Relatively strong traps have power
1492 spectra that cannot be fitted properly with any Lorentzian, we
1493 find. This underscores the need for better understanding of the
1494 power spectrum than the Lorentzian provides. This is achieved
1495 using old and new theory for Brownian motion in an incompressible
1496 fluid, and new results for a popular photodetection system. The
1497 trap and photodetection system are then calibrated simultaneously
1498 in a manner that makes optical tweezers a tool of precision for
1499 force spectroscopy, local viscometry, and probably other
1503 @article{ berg-sorensen05,
1504 author = KBergSorensen #" and "# HFlyvbjerg,
1505 title = {The colour of thermal noise in classical Brownian motion: a
1506 feasibility study of direct experimental observation},
1514 doi = {10.1088/1367-2630/7/1/038},
1515 url = {http://stacks.iop.org/1367-2630/7/i=1/a=038},
1516 eprint = {http://iopscience.iop.org/1367-2630/7/1/038/pdf/1367-2630_7_1_038.pdf},
1517 abstract = {One hundred years after Einstein modelled Brownian
1518 motion, a central aspect of this motion in incompressible fluids
1519 has not been verified experimentally: the thermal noise that
1520 drives the Brownian particle, is not white, as in Einstein's
1521 simple theory. It is slightly coloured, due to hydrodynamics and
1522 the fluctuation--dissipation theorem. This theoretical result from
1523 the 1970s was prompted by computer simulation results in apparent
1524 violation of Einstein's theory. We discuss how a direct
1525 experimental observation of this colour might be carried out by
1526 using optical tweezers to separate the thermal noise from the
1527 particle's dynamic response to it. Since the thermal noise is
1528 almost white, very good statistics is necessary to resolve its
1529 colour. That requires stable equipment and long recording times,
1530 possibly making this experiment one for the future only. We give
1531 results for experimental requirements and for stochastic errors as
1532 functions of experimental window and measurement time, and discuss
1533 some potential sources of systematic errors.},
1536 @article { bedard08,
1537 author = SBedard #" and "# MMGKrishna #" and "# LMayne #" and "#
1539 title = "Protein folding: Independent unrelated pathways or predetermined
1540 pathway with optional errors.",
1547 pages = "7182--7187",
1549 doi = "10.1073/pnas.0801864105",
1550 eprint = "http://www.pnas.org/content/105/20/7182.full.pdf",
1551 url = "http://www.pnas.org/content/105/20/7182.full",
1552 keywords = "Biochemistry;Guanidine;Kinetics;Micrococcal Nuclease;Models,
1553 Biological;Models, Chemical;Models, Theoretical;Protein
1554 Conformation;Protein Denaturation;Protein Folding;Protein Structure,
1555 Secondary;Proteins;Proteomics;Reproducibility of
1556 Results;Thermodynamics",
1557 abstract = "The observation of heterogeneous protein folding kinetics has
1558 been widely interpreted in terms of multiple independent unrelated
1559 pathways (IUP model), both experimentally and in theoretical
1560 calculations. However, direct structural information on folding
1561 intermediates and their properties now indicates that all of a protein
1562 population folds through essentially the same stepwise pathway,
1563 determined by cooperative native-like foldon units and the way that the
1564 foldons fit together in the native protein. It is essential to decide
1565 between these fundamentally different folding mechanisms. This article
1566 shows, contrary to previous supposition, that the heterogeneous folding
1567 kinetics observed for the staphylococcal nuclease protein (SNase) does
1568 not require alternative parallel pathways. SNase folding kinetics can
1569 be fit equally well by a single predetermined pathway that allows for
1570 optional misfolding errors, which are known to occur ubiquitously in
1571 protein folding. Structural, kinetic, and thermodynamic information for
1572 the folding intermediates and pathways of many proteins is consistent
1573 with the predetermined pathway-optional error (PPOE) model but contrary
1574 to the properties implied in IUP models."
1579 title = "Models for the specific adhesion of cells to cells",
1588 url = "http://www.jstor.org/stable/1746930",
1589 keywords = "Antigen-Antibody Reactions; Cell Adhesion; Cell Membrane;
1590 Chemistry, Physical; Electrophysiology; Enzymes; Glycoproteins;
1591 Kinetics; Ligands; Membrane Proteins; Models, Biological; Receptors,
1593 abstract = "A theoretical framework is proposed for the analysis of
1594 adhesion between cells or of cells to surfaces when the adhesion is
1595 mediated by reversible bonds between specific molecules such as antigen
1596 and antibody, lectin and carbohydrate, or enzyme and substrate. From a
1597 knowledge of the reaction rates for reactants in solution and of their
1598 diffusion constants both in solution and on membranes, it is possible
1599 to estimate reaction rates for membrane-bound reactants. Two models are
1600 developed for predicting the rate of bond formation between cells and
1601 are compared with experiments. The force required to separate two cells
1602 is shown to be greater than the expected electrical forces between
1603 cells, and of the same order of magnitude as the forces required to
1604 pull gangliosides and perhaps some integral membrane proteins out of
1605 the cell membrane.",
1606 note = "The Bell model and a fair bit of cell bonding background.",
1607 project = "sawtooth simulation"
1611 author = DBerk #" and "# EEvans,
1612 title = "Detachment of agglutinin-bonded red blood cells. {III}. Mechanical
1613 analysis for large contact areas",
1621 keywords = "Cell Adhesion;Erythrocyte Membrane;Erythrocytes;Hemagglutinatio
1622 n;Hemagglutinins;Humans;Kinetics;Mathematics;Models,
1623 Biological;Pressure",
1624 abstract = "An experimental method and analysis are introduced which
1625 provide direct quantitation of the strength of adhesive contact for
1626 large agglutinin-bonded regions between macroscopically smooth membrane
1627 capsules (e.g., red blood cells). The approach yields intrinsic
1628 properties for separation of adherent regions independent of mechanical
1629 deformation of the membrane capsules during detachment. Conceptually,
1630 the micromechanical method involves one rigid test-capsule surface (in
1631 the form of a perfect sphere) held fixed by a micropipette and a second
1632 deformable capsule maneuvered with another micropipette to force
1633 contact with the test capsule. Only the test capsule is bound with
1634 agglutinin so that the maximum number of cross-bridges can be formed
1635 without steric interference. Following formation of a large adhesion
1636 region by mechanical impingement, the deformable capsule is detached
1637 from the rigid capsule surface by progressive aspiration into the
1638 micropipette. For the particular case modeled here, the deformable
1639 capsule is assumed to be a red blood cell which is preswollen by slight
1640 osmotic hydration before the test. The caliber of the detachment
1641 pipette is chosen so that the capsule will form a smooth cylindrical
1642 ``piston'' inside the pipette as it is aspirated. Because of the high
1643 flexibility of the membrane, the capsule naturally seals against the
1644 tube wall by pressurization even though it does not adhere to the
1645 glass. This arrangement maintains perfect axial symmetry and prevents
1646 the membrane from folding or buckling. Hence, it is possible to
1647 rigorously analyze the mechanics of deformation of the cell body to
1648 obtain the crucial ``transducer'' relation between pipette suction
1649 force and the membrane tension applied directly at the perimeter of the
1650 adhesive contact. Further, the geometry of the cell throughout the
1651 detachment process is predicted which provides accurate specification
1652 of the contact angle theta c between surfaces at the perimeter of the
1653 contact. A full analysis of red cell capsules during detachment has
1654 been carried out; however, it is shown that the shear rigidity of the
1655 red cell membrane can often be neglected so that the red cell can be
1656 treated as if it were an underfilled lipid bilayer vesicle. From the
1657 analysis, the mechanical leverage factor (1-cos theta c) and the
1658 membrane tension at the contact perimeter are determined to provide a
1659 complete description of the local mechanics of membrane separation as
1660 functions of large-scale experimental variables (e.g., suction force,
1661 contact diameter, overall cell length).(ABSTRACT TRUNCATED AT 400
1666 author = RBest #" and "# SFowler #" and "# JTocaHerrera #" and "# JClarke,
1667 title = "A simple method for probing the mechanical unfolding pathway of
1668 proteins in detail",
1673 pages = "12143--12148",
1674 doi = "10.1073/pnas.192351899",
1675 eprint = "http://www.pnas.org/cgi/reprint/99/19/12143.pdf",
1676 url = "http://www.pnas.org/cgi/content/abstract/99/19/12143",
1677 abstract = "Atomic force microscopy is an exciting new single-molecule
1678 technique to add to the toolbox of protein (un)folding methods.
1679 However, detailed analysis of the unfolding of proteins on application
1680 of force has, to date, relied on protein molecular dynamics simulations
1681 or a qualitative interpretation of mutant data. Here we describe how
1682 protein engineering {Phi} value analysis can be adapted to characterize
1683 the transition states for mechanical unfolding of proteins. Single-
1684 molecule studies also have an advantage over bulk experiments, in that
1685 partial {Phi} values arising from partial structure in the transition
1686 state can be clearly distinguished from those averaged over alternate
1687 pathways. We show that unfolding rate constants derived in the standard
1688 way by using Monte Carlo simulations are not reliable because of the
1689 errors involved. However, it is possible to circumvent these problems,
1690 providing the unfolding mechanism is not changed by mutation, either by
1691 a modification of the Monte Carlo procedure or by comparing mutant and
1692 wild-type data directly. The applicability of the method is tested on
1693 simulated data sets and experimental data for mutants of titin I27.",
1694 note = "Points out order-of-magnitude errors in $k_{u0}$ estimation from
1695 fitting Monte Carlo simulations."
1699 author = RBest #" and "# GHummer,
1700 title = "Protein folding kinetics under force from molecular simulation.",
1707 pages = "3706--3707",
1709 doi = "10.1021/ja0762691",
1710 keywords = "Computer Simulation;Kinetics;Models, Chemical;Protein
1711 Folding;Stress, Mechanical;Ubiquitin",
1712 abstract = "Despite a large number of studies on the mechanical unfolding
1713 of proteins, there are still relatively few successful attempts to
1714 refold proteins in the presence of a stretching force. We explore
1715 refolding kinetics under force using simulations of a coarse-grained
1716 model of ubiquitin. The effects of force on the folding kinetics can be
1717 fitted by a one-dimensional Kramers theory of diffusive barrier
1718 crossing, resulting in physically meaningful parameters for the height
1719 and location of the folding activation barrier. By comparing parameters
1720 obtained from pulling in different directions, we find that the
1721 unfolded state plays a dominant role in the refolding kinetics. Our
1722 findings explain why refolding becomes very slow at even moderate
1723 pulling forces and suggest how it could be practically observed in
1724 experiments at higher forces."
1728 author = RBest #" and "# EPaci #" and "# GHummer #" and "# OKDudko,
1729 title = "Pulling direction as a reaction coordinate for the mechanical
1730 unfolding of single molecules.",
1737 pages = "5968--5976",
1739 doi = "10.1021/jp075955j",
1740 keywords = "Computer Simulation;Kinetics;Models, Molecular;Protein
1741 Folding;Protein Structure, Tertiary;Time Factors;Ubiquitin",
1742 abstract = "The folding and unfolding kinetics of single molecules, such as
1743 proteins or nucleic acids, can be explored by mechanical pulling
1744 experiments. Determining intrinsic kinetic information, at zero
1745 stretching force, usually requires an extrapolation by fitting a
1746 theoretical model. Here, we apply a recent theoretical approach
1747 describing molecular rupture in the presence of force to unfolding
1748 kinetic data obtained from coarse-grained simulations of ubiquitin.
1749 Unfolding rates calculated from simulations over a broad range of
1750 stretching forces, for different pulling directions, reveal a
1751 remarkable ``turnover'' from a force-independent process at low force
1752 to a force-dependent process at high force, akin to the ``roll-over''
1753 in unfolding rates sometimes seen in studies using chemical denaturant.
1754 While such a turnover in rates is unexpected in one dimension, we
1755 demonstrate that it can occur for dynamics in just two dimensions. We
1756 relate the turnover to the quality of the pulling direction as a
1757 reaction coordinate for the intrinsic folding mechanism. A novel
1758 pulling direction, designed to be the most relevant to the intrinsic
1759 folding pathway, results in the smallest turnover. Our results are in
1760 accord with protein engineering experiments and simulations which
1761 indicate that the unfolding mechanism at high force can differ from the
1762 intrinsic mechanism. The apparent similarity between extrapolated and
1763 intrinsic rates in experiments, unexpected for different unfolding
1764 barriers, can be explained if the turnover occurs at low forces."
1767 @article { borgia08,
1768 author = Borgia #" and "# Williams #" and "# Clarke,
1769 title = "Single-Molecule Studies of Protein Folding",
1777 doi = "10.1146/annurev.biochem.77.060706.093102",
1778 eprint = "http://arjournals.annualreviews.org/doi/pdf/10.1146/annurev.bioch
1779 em.77.060706.093102",
1780 url = "http://arjournals.annualreviews.org/doi/abs/10.1146/annurev.biochem.
1782 abstract = "Although protein-folding studies began several decades ago, it
1783 is only recently that the tools to analyze protein folding at the
1784 single-molecule level have been developed. Advances in single-molecule
1785 fluorescence and force spectroscopy techniques allow investigation of
1786 the folding and dynamics of single protein molecules, both at
1787 equilibrium and as they fold and unfold. The experiments are far from
1788 simple, however, both in execution and in interpretation of the
1789 results. In this review, we discuss some of the highlights of the work
1790 so far and concentrate on cases where comparisons with the classical
1791 experiments can be made. We conclude that, although there have been
1792 relatively few startling insights from single-molecule studies, the
1793 rapid progress that has been made suggests that these experiments have
1794 significant potential to advance our understanding of protein folding.
1795 In particular, new techniques offer the possibility to explore regions
1796 of the energy landscape that are inaccessible to classical ensemble
1797 measurements and, perhaps, to observe rare events undetectable by other
1801 @article { braverman08,
1802 author = EBraverman #" and "# RMamdani,
1803 title = "Continuous versus pulse harvesting for population models in
1804 constant and variable environment",
1808 journal = JMathBiol,
1813 doi = "10.1007/s00285-008-0169-z",
1815 "http://www.springerlink.com/content/a1m23v50201m2401/fulltext.pdf",
1816 url = "http://www.springerlink.com/content/a1m23v50201m2401/",
1817 abstract = "We consider both autonomous and nonautonomous population models
1818 subject to either impulsive or continuous harvesting. It is
1819 demonstrated in the paper that the impulsive strategy can be as good as
1820 the continuous one, but cannot outperform it. We introduce a model,
1821 where certain harm to the population is incorporated in each harvesting
1822 event, and study it for the logistic and the Gompertz laws of growth.
1823 In this case, impulsive harvesting is not only the optimal strategy but
1824 is the only possible one.",
1825 note = "An example of non-exponential Gomperz law."
1828 @article { brochard-wyart99,
1829 author = FBrochard-Wyart #" and "# ABuguin #" and "# PGdeGennes,
1830 title = "Dynamics of taut {DNA} chains",
1837 "http://www.iop.org/EJ/article/0295-5075/47/2/171/epl_47_2_171.pdf",
1838 url = "http://stacks.iop.org/0295-5075/47/171",
1839 abstract = {We discuss the dynamics of stretched DNA chains, subjected to a
1840 tension force f, in a "taut" regime where ph = flp0/kBT $>$ 1 (lp0
1841 being the unperturbed persistence length). We deal with two variables:
1842 the local transverse displacements u, and the longitudinal position of
1843 a monomer u[?]. The variables u and u[?] follow two distinct Rouse
1844 equations, with diffusion coefficients D[?] = f/e (where e is the
1845 solvent viscosity) and D[?] = 4ph1/2D[?]. We apply these ideas to a
1846 discussion of various transient regimes.},
1847 note = "Theory for weakly bending relaxation modes in WLCs and FJCs."
1850 @article { brockwell02,
1851 author = DJBrockwell #" and "# GSBeddard #" and "# JClarkson #" and "#
1852 RCZinober #" and "# AWBlake #" and "# JTrinick #" and "# PDOlmsted #"
1853 and "# DASmith #" and "# SERadford,
1854 title = "The effect of core destabilization on the mechanical resistance of
1863 doi = "10.1016/S0006-3495(02)75182-5",
1864 eprint = "http://www.biophysj.org/cgi/reprint/83/1/458.pdf",
1865 url = "http://www.biophysj.org/cgi/content/abstract/83/1/458",
1866 keywords = "Amino Acid Sequence; Dose-Response Relationship, Drug;
1867 Kinetics; Magnetic Resonance Spectroscopy; Models, Molecular; Molecular
1868 Sequence Data; Monte Carlo Method; Muscle Proteins; Mutation; Peptide
1869 Fragments; Protein Denaturation; Protein Folding; Protein Kinases;
1870 Protein Structure, Secondary; Protein Structure, Tertiary; Proteins;
1872 abstract = "It is still unclear whether mechanical unfolding probes the
1873 same pathways as chemical denaturation. To address this point, we have
1874 constructed a concatamer of five mutant I27 domains (denoted (I27)(5)*)
1875 and used it for mechanical unfolding studies. This protein consists of
1876 four copies of the mutant C47S, C63S I27 and a single copy of C63S I27.
1877 These mutations severely destabilize I27 (DeltaDeltaG(UN) = 8.7 and
1878 17.9 kJ mol(-1) for C63S I27 and C47S, C63S I27, respectively). Both
1879 mutations maintain the hydrogen bond network between the A' and G
1880 strands postulated to be the major region of mechanical resistance for
1881 I27. Measuring the speed dependence of the force required to unfold
1882 (I27)(5)* in triplicate using the atomic force microscope allowed a
1883 reliable assessment of the intrinsic unfolding rate constant of the
1884 protein to be obtained (2.0 x 10(-3) s(-1)). The rate constant of
1885 unfolding measured by chemical denaturation is over fivefold faster
1886 (1.1 x 10(-2) s(-1)), suggesting that these techniques probe different
1887 unfolding pathways. Also, by comparing the parameters obtained from the
1888 mechanical unfolding of a wild-type I27 concatamer with that of
1889 (I27)(5)*, we show that although the observed forces are considerably
1890 lower, core destabilization has little effect on determining the
1891 mechanical sensitivity of this domain."
1894 @article { brockwell03,
1895 author = DJBrockwell #" and "# EPaci #" and "# RCZinober #" and "#
1896 GSBeddard #" and "# PDOlmsted #" and "# DASmith #" and "# RNPerham #"
1898 title = "Pulling geometry defines the mechanical resistance of a beta-sheet
1908 doi = "10.1038/nsb968",
1909 eprint = "http://www.nature.com/nsmb/journal/v10/n9/pdf/nsb968.pdf",
1910 url = "http://www.nature.com/nsmb/journal/v10/n9/abs/nsb968.html",
1911 keywords = "Anisotropy;Escherichia coli;Kinetics;Models, Molecular;Monte
1912 Carlo Method;Protein Folding;Protein Structure, Secondary;Protein
1913 Structure, Tertiary;Proteins;Software;Temperature;Thermodynamics",
1914 abstract = "Proteins show diverse responses when placed under mechanical
1915 stress. The molecular origins of their differing mechanical resistance
1916 are still unclear, although the orientation of secondary structural
1917 elements relative to the applied force vector is thought to have an
1918 important function. Here, by using a method of protein immobilization
1919 that allows force to be applied to the same all-beta protein, E2lip3,
1920 in two different directions, we show that the energy landscape for
1921 mechanical unfolding is markedly anisotropic. These results, in
1922 combination with molecular dynamics (MD) simulations, reveal that the
1923 unfolding pathway depends on the pulling geometry and is associated
1924 with unfolding forces that differ by an order of magnitude. Thus, the
1925 mechanical resistance of a protein is not dictated solely by amino acid
1926 sequence, topology or unfolding rate constant, but depends critically
1927 on the direction of the applied extension.",
1928 note = "Another scaffold effect paper.",
1931 @article { brower-toland02,
1932 author = BDBrowerToland #" and "# CSmith #" and "# RYeh #" and "# JLis #"
1933 and "# CPeterson #" and "# MDWang,
1934 title = "From the Cover: Mechanical disruption of individual nucleosomes
1935 reveals a reversible multistage release of {DNA}",
1940 pages = "1960--1965",
1941 doi = "10.1073/pnas.022638399",
1942 eprint = "http://www.pnas.org/cgi/reprint/99/4/1960.pdf",
1943 url = "http://www.pnas.org/cgi/content/abstract/99/4/1960",
1944 abstract = "The dynamic structure of individual nucleosomes was examined by
1945 stretching nucleosomal arrays with a feedback-enhanced optical trap.
1946 Forced disassembly of each nucleosome occurred in three stages.
1947 Analysis of the data using a simple worm-like chain model yields 76 bp
1948 of DNA released from the histone core at low stretching force.
1949 Subsequently, 80 bp are released at higher forces in two stages: full
1950 extension of DNA with histones bound, followed by detachment of
1951 histones. When arrays were relaxed before the dissociated state was
1952 reached, nucleosomes were able to reassemble and to repeat the
1953 disassembly process. The kinetic parameters for nucleosome disassembly
1954 also have been determined."
1957 @article { bryngelson87,
1958 author = JDBryngelson #" and "# PGWolynes,
1959 title = "Spin glasses and the statistical mechanics of protein folding",
1965 pages = "7524--7528",
1967 keywords = "Kinetics; Mathematics; Models, Theoretical; Protein
1968 Conformation; Proteins; Stochastic Processes",
1969 abstract = "The theory of spin glasses was used to study a simple model of
1970 protein folding. The phase diagram of the model was calculated, and the
1971 results of dynamics calculations are briefly reported. The relation of
1972 these results to folding experiments, the relation of these hypotheses
1973 to previous protein folding theories, and the implication of these
1974 hypotheses for protein folding prediction schemes are discussed.",
1975 note = "Seminal protein folding via energy landscape paper."
1978 @article { bryngelson95,
1979 author = JDBryngelson #" and "# JNOnuchic #" and "# NDSocci #" and "#
1981 title = "Funnels, pathways, and the energy landscape of protein folding: a
1990 doi = "10.1002/prot.340210302",
1991 keywords = "Amino Acid Sequence; Chemistry, Physical; Computer Simulation;
1992 Data Interpretation, Statistical; Kinetics; Models, Chemical; Molecular
1993 Sequence Data; Protein Biosynthesis; Protein Conformation; Protein
1994 Folding; Proteins; Thermodynamics",
1995 abstract = "The understanding, and even the description of protein folding
1996 is impeded by the complexity of the process. Much of this complexity
1997 can be described and understood by taking a statistical approach to the
1998 energetics of protein conformation, that is, to the energy landscape.
1999 The statistical energy landscape approach explains when and why unique
2000 behaviors, such as specific folding pathways, occur in some proteins
2001 and more generally explains the distinction between folding processes
2002 common to all sequences and those peculiar to individual sequences.
2003 This approach also gives new, quantitative insights into the
2004 interpretation of experiments and simulations of protein folding
2005 thermodynamics and kinetics. Specifically, the picture provides simple
2006 explanations for folding as a two-state first-order phase transition,
2007 for the origin of metastable collapsed unfolded states and for the
2008 curved Arrhenius plots observed in both laboratory experiments and
2009 discrete lattice simulations. The relation of these quantitative ideas
2010 to folding pathways, to uniexponential vs. multiexponential behavior in
2011 protein folding experiments and to the effect of mutations on folding
2012 is also discussed. The success of energy landscape ideas in protein
2013 structure prediction is also described. The use of the energy landscape
2014 approach for analyzing data is illustrated with a quantitative analysis
2015 of some recent simulations, and a qualitative analysis of experiments
2016 on the folding of three proteins. The work unifies several previously
2017 proposed ideas concerning the mechanism protein folding and delimits
2018 the regions of validity of these ideas under different thermodynamic
2022 @article { bullard06,
2023 author = BBullard #" and "# TGarcia #" and "# VBenes #" and "# MLeake #"
2024 and "# WALinke #" and "# AOberhauser,
2025 title = "The molecular elasticity of the insect flight muscle proteins
2026 projectin and kettin",
2031 pages = "4451--4456",
2032 doi = "10.1073/pnas.0509016103",
2033 eprint = "http://www.pnas.org/cgi/reprint/103/12/4451.pdf",
2034 url = "http://www.pnas.org/cgi/content/abstract/103/12/4451",
2035 abstract = "Projectin and kettin are titin-like proteins mainly responsible
2036 for the high passive stiffness of insect indirect flight muscles, which
2037 is needed to generate oscillatory work during flight. Here we report
2038 the mechanical properties of kettin and projectin by single-molecule
2039 force spectroscopy. Force-extension and force-clamp curves obtained
2040 from Lethocerus projectin and Drosophila recombinant projectin or
2041 kettin fragments revealed that fibronectin type III domains in
2042 projectin are mechanically weaker (unfolding force, Fu {approx} 50-150
2043 pN) than Ig-domains (Fu {approx} 150-250 pN). Among Ig domains in
2044 Sls/kettin, the domains near the N terminus are less stable than those
2045 near the C terminus. Projectin domains refolded very fast [85% at 15
2046 s-1 (25{degrees}C)] and even under high forces (15-30 pN). Temperature
2047 affected the unfolding forces with a Q10 of 1.3, whereas the refolding
2048 speed had a Q10 of 2-3, probably reflecting the cooperative nature of
2049 the folding mechanism. High bending rigidities of projectin and kettin
2050 indicated that straightening the proteins requires low forces. Our
2051 results suggest that titin-like proteins in indirect flight muscles
2052 could function according to a folding-based-spring mechanism."
2055 @article { bustamante08,
2056 author = CBustamante,
2057 title = "In singulo Biochemistry: When Less Is More",
2063 doi = "10.1146/annurev.biochem.012108.120952",
2064 eprint = "http://arjournals.annualreviews.org/doi/pdf/10.1146/annurev.bioch
2066 url = "http://arjournals.annualreviews.org/doi/abs/10.1146/annurev.biochem.
2068 abstract = "It has been over one-and-a-half decades since methods of
2069 single-molecule detection and manipulation were first introduced in
2070 biochemical research. Since then, the application of these methods to
2071 an expanding variety of problems has grown at a vertiginous pace. While
2072 initially many of these experiments led more to confirmatory results
2073 than to new discoveries, today single-molecule methods are often the
2074 methods of choice to establish new mechanism-based results in
2075 biochemical research. Throughout this process, improvements in the
2076 sensitivity, versatility, and both spatial and temporal resolution of
2077 these techniques has occurred hand in hand with their applications. We
2078 discuss here some of the advantages of single-molecule methods over
2079 their bulk counterparts and argue that these advantages should help
2080 establish them as essential tools in the technical arsenal of the
2084 @article { bustamante94,
2085 author = CBustamante #" and "# JFMarko #" and "# EDSiggia #" and "# SSmith,
2086 title = "Entropic elasticity of lambda-phage {DNA}",
2093 pages = "1599--1600",
2095 doi = "10.1126/science.8079175",
2096 eprint = "http://www.sciencemag.org/cgi/reprint/265/5178/1599.pdf",
2097 url = "http://www.sciencemag.org/cgi/content/abstract/265/5178/1599",
2098 keywords = "Bacteriophage lambda; DNA, Viral; Least-Squares Analysis;
2100 note = "WLC interpolation formula."
2103 @article { bustanji03,
2104 author = YBustanji #" and "# CArciola #" and "# MConti #" and "# EMandello
2105 #" and "# LMontanaro #" and "# BSamori,
2106 title = "Dynamics of the interaction between a fibronectin molecule and a
2107 living bacterium under mechanical force",
2112 pages = "13292--13297",
2113 doi = "10.1073/pnas.1735343100",
2114 eprint = "http://www.pnas.org/cgi/reprint/100/23/13292.pdf",
2115 url = "http://www.pnas.org/cgi/content/abstract/100/23/13292",
2116 abstract = "Fibronectin (Fn) is an important mediator of bacterial
2117 invasions and of persistent infections like that of Staphylococcus
2118 epidermis. Similar to many other types of cell-protein adhesion, the
2119 binding between Fn and S. epidermidis takes place under physiological
2120 shear rates. We investigated the dynamics of the interaction between
2121 individual living S. epidermidis cells and single Fn molecules under
2122 mechanical force by using the scanning force microscope. The mechanical
2123 strength of this interaction and the binding site in the Fn molecule
2124 were determined. The energy landscape of the binding/unbinding process
2125 was mapped, and the force spectrum and the association and dissociation
2126 rate constants of the binding pair were measured. The interaction
2127 between S. epidermidis cells and Fn molecules is compared with those of
2128 two other protein/ligand pairs known to mediate different dynamic
2129 states of adhesion of cells under a hydrodynamic flow: the firm
2130 adhesion mediated by biotin/avidin interactions, and the rolling
2131 adhesion, mediated by L-selectin/P-selectin glycoprotein ligand-1
2132 interactions. The inner barrier in the energy landscape of the Fn case
2133 characterizes a high-energy binding mode that can sustain larger
2134 deformations and for significantly longer times than the correspondent
2135 high-strength L-selectin/P-selectin glycoprotein ligand-1 binding mode.
2136 The association kinetics of the former interaction is much slower to
2137 settle than the latter. On this basis, the observations made at the
2138 macroscopic scale by other authors of a strong lability of the
2139 bacterial adhesions mediated by Fn under high turbulent flow are
2140 rationalized at the molecular level."
2144 author = YMartin #" and "# CCWilliams #" and "# HKWickramasinghe,
2145 title = {Atomic force microscope---force mapping and profiling on a
2153 pages = {4723--4729},
2155 issn_online = "1089-7550",
2156 doi = {10.1063/1.338807},
2157 url = {http://jap.aip.org/resource/1/japiau/v61/i10/p4723_s1},
2159 abstract = {A modified version of the atomic force microscope is
2160 introduced that enables a precise measurement of the force between
2161 a tip and a sample over a tip-sample distance range of 30--150
2162 \AA. As an application, the force signal is used to maintain the
2163 tip-sample spacing constant, so that profiling can be achieved
2164 with a spatial resolution of 50 \AA. A second scheme allows the
2165 simultaneous measurement of force and surface profile; this scheme
2166 has been used to obtain material-dependent information from
2167 surfaces of electronic materials.},
2171 author = HJButt #" and "# MJaschke,
2172 title = "Calculation of thermal noise in atomic force microscopy",
2178 doi = "10.1088/0957-4484/6/1/001",
2179 url = "http://stacks.iop.org/0957-4484/6/1",
2180 abstract = "Thermal fluctuations of the cantilever are a fundamental source
2181 of noise in atomic force microscopy. We calculated thermal noise using
2182 the equipartition theorem and considering all possible vibration modes
2183 of the cantilever. The measurable amplitude of thermal noise depends on
2184 the temperature, the spring constant K of the cantilever and on the
2185 method by which the cantilever defletion is detected. If the deflection
2186 is measured directly, e.g. with an interferometer or a scanning
2187 tunneling microscope, the thermal noise of a cantilever with a free end
2188 can be calculated from square root kT/K. If the end of the cantilever
2189 is supported by a hard surface no thermal fluctuations of the
2190 deflection are possible. If the optical lever technique is applied to
2191 measure the deflection, the thermal noise of a cantilever with a free
2192 end is square root 4kT/3K. When the cantilever is supported thermal
2193 noise decreases to square root kT/3K, but it does not vanish.",
2194 note = "Corrections to basic $kx^2 = kB T$ due to higher order modes in
2195 rectangular cantilevers.",
2196 project = "Cantilever Calibration"
2199 @article{ jaschke95,
2200 author = MJaschke #" and "# HJButt,
2201 title = {Height calibration of optical lever atomic force
2202 microscopes by simple laser interferometry},
2207 pages = {1258--1259},
2209 url = {http://rsi.aip.org/resource/1/rsinak/v66/i2/p1258_s1},
2210 doi = {10.1063/1.1146018},
2212 keywords = {atomic force microscopy;calibration;interferometry;laser
2213 beam applications;mirrors;spatial resolution},
2214 abstract = {A new and simple interferometric method for height
2215 calibration of AFM piezo scanners is presented. Except for a small
2216 mirror no additional equipment is required since the fixed
2217 wavelength of the laser diode is used as a calibration
2218 standard. The calibration is appliable in the range between
2219 several ten nm and several $\mu$m. Besides vertical calibration
2220 many problems of piezo elements like hysteresis, nonlinearity,
2221 creep, derating, etc. and their dependence on scan parameters or
2222 temperature can be investigated.},
2226 author = YCao #" and "# MBalamurali #" and "# DSharma #" and "# HLi,
2227 title = "A functional single-molecule binding assay via force spectroscopy",
2232 pages = "15677--15681",
2233 doi = "10.1073/pnas.0705367104",
2234 eprint = "http://www.pnas.org/cgi/reprint/104/40/15677.pdf",
2235 url = "http://www.pnas.org/cgi/content/abstract/104/40/15677",
2236 abstract = "Protein-ligand interactions, including protein-protein
2237 interactions, are ubiquitously essential in biological processes and
2238 also have important applications in biotechnology. A wide range of
2239 methodologies have been developed for quantitative analysis of protein-
2240 ligand interactions. However, most of them do not report direct
2241 functional/structural consequence of ligand binding. Instead they only
2242 detect the change of physical properties, such as fluorescence and
2243 refractive index, because of the colocalization of protein and ligand,
2244 and are susceptible to false positives. Thus, important information
2245 about the functional state of proteinligand complexes cannot be
2246 obtained directly. Here we report a functional single-molecule binding
2247 assay that uses force spectroscopy to directly probe the functional
2248 consequence of ligand binding and report the functional state of
2249 protein-ligand complexes. As a proof of principle, we used protein G
2250 and the Fc fragment of IgG as a model system in this study. Binding of
2251 Fc to protein G does not induce major structural changes in protein G
2252 but results in significant enhancement of its mechanical stability.
2253 Using mechanical stability of protein G as an intrinsic functional
2254 reporter, we directly distinguished and quantified Fc-bound and Fc-free
2255 forms of protein G on a single-molecule basis and accurately determined
2256 their dissociation constant. This single-molecule functional binding
2257 assay is label-free, nearly background-free, and can detect functional
2258 heterogeneity, if any, among proteinligand interactions. This
2259 methodology opens up avenues for studying protein-ligand interactions
2260 in a functional context, and we anticipate that it will find broad
2261 application in diverse protein-ligand systems."
2265 author = PCarl #" and "# CKwok #" and "# GManderson #" and "# DSpeicher #"
2267 title = "Forced unfolding modulated by disulfide bonds in the Ig domains of
2268 a cell adhesion molecule",
2273 pages = "1565--1570",
2274 doi = "10.1073/pnas.031409698",
2275 eprint = "http://www.pnas.org/cgi/reprint/98/4/1565.pdf",
2276 url = "http://www.pnas.org/cgi/content/abstract/98/4/1565",
2280 @article { carrion-vazquez00,
2281 author = MCarrionVazquez #" and "# AOberhauser #" and "# TEFisher #" and "#
2282 PMarszalek #" and "# HLi #" and "# JFernandez,
2283 title = "Mechanical design of proteins studied by single-molecule force
2284 spectroscopy and protein engineering",
2290 doi = "10.1016/S0079-6107(00)00017-1",
2292 eprint = "http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1302160&blo
2294 url = "http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1302160",
2295 keywords = "Elasticity;Hydrogen Bonding;Microscopy, Atomic Force;Protein
2296 Denaturation;Protein Engineering;Protein Folding;Recombinant
2297 Proteins;Signal Processing, Computer-Assisted",
2298 abstract = "Mechanical unfolding and refolding may regulate the molecular
2299 elasticity of modular proteins with mechanical functions. The
2300 development of the atomic force microscopy (AFM) has recently enabled
2301 the dynamic measurement of these processes at the single-molecule
2302 level. Protein engineering techniques allow the construction of
2303 homomeric polyproteins for the precise analysis of the mechanical
2304 unfolding of single domains. alpha-Helical domains are mechanically
2305 compliant, whereas beta-sandwich domains, particularly those that
2306 resist unfolding with backbone hydrogen bonds between strands
2307 perpendicular to the applied force, are more stable and appear
2308 frequently in proteins subject to mechanical forces. The mechanical
2309 stability of a domain seems to be determined by its hydrogen bonding
2310 pattern and is correlated with its kinetic stability rather than its
2311 thermodynamic stability. Force spectroscopy using AFM promises to
2312 elucidate the dynamic mechanical properties of a wide variety of
2313 proteins at the single molecule level and provide an important
2314 complement to other structural and dynamic techniques (e.g., X-ray
2315 crystallography, NMR spectroscopy, patch-clamp).",
2316 note = {Surface contact \fref{figure}{2} is a modified version of
2317 \xref{baljon96}{figure}{1}. They are both good pictures for
2318 explaining that the tip's radius of curvature ($\sim 20\U{nm}$) is
2319 larger than the I27 domains\citet{improta96} ($\sim 2\U{nm}$).},
2322 @article { carrion-vazquez03,
2323 author = MCarrionVazquez #" and "# HLi #" and "# HLu #" and "# PMarszalek
2324 #" and "# AOberhauser #" and "# JFernandez,
2325 title = "The mechanical stability of ubiquitin is linkage dependent",
2334 doi = "10.1038/nsb965",
2335 eprint = "http://www.nature.com/nsmb/journal/v10/n9/pdf/nsb965.pdf",
2336 url = "http://www.nature.com/nsmb/journal/v10/n9/abs/nsb965.html",
2337 keywords = "Humans;Hydrogen Bonding;Kinetics;Lysine;Microscopy, Atomic
2338 Force;Models, Molecular;Polyubiquitin;Protein Binding;Protein
2339 Folding;Protein Structure, Tertiary;Ubiquitin",
2340 abstract = "Ubiquitin chains are formed through the action of a set of
2341 enzymes that covalently link ubiquitin either through peptide bonds or
2342 through isopeptide bonds between their C terminus and any of four
2343 lysine residues. These naturally occurring polyproteins allow one to
2344 study the mechanical stability of a protein, when force is applied
2345 through different linkages. Here we used single-molecule force
2346 spectroscopy techniques to examine the mechanical stability of
2347 N-C-linked and Lys48-C-linked ubiquitin chains. We combined these
2348 experiments with steered molecular dynamics (SMD) simulations and found
2349 that the mechanical stability and unfolding pathway of ubiquitin
2350 strongly depend on the linkage through which the mechanical force is
2351 applied to the protein. Hence, a protein that is otherwise very stable
2352 may be easily unfolded by a relatively weak mechanical force applied
2353 through the right linkage. This may be a widespread mechanism in
2354 biological systems."
2357 @article { carrion-vazquez99a,
2358 author = MCarrionVazquez #" and "# PMarszalek #" and "# AOberhauser #" and
2360 title = "Atomic force microscopy captures length phenotypes in single
2366 pages = "11288--11292",
2367 doi = "10.1073/pnas.96.20.11288",
2368 eprint = "http://www.pnas.org/cgi/reprint/96/20/11288.pdf",
2369 url = "http://www.pnas.org/cgi/content/abstract/96/20/11288",
2373 @article { carrion-vazquez99b,
2374 author = MCarrionVazquez #" and "# AOberhauser #" and "# SFowler #" and "#
2375 PMarszalek #" and "# SBroedel #" and "# JClarke #" and "# JFernandez,
2376 title = "Mechanical and chemical unfolding of a single protein: A
2382 pages = "3694--3699",
2383 doi = "10.1073/pnas.96.7.3694",
2384 eprint = "http://www.pnas.org/cgi/reprint/96/7/3694.pdf",
2385 url = "http://www.pnas.org/cgi/content/abstract/96/7/3694"
2389 author = CLChyan #" and "# FCLin #" and "# HPeng #" and "# JMYuan #" and "#
2390 CHChang #" and "# SHLin #" and "# GYang,
2391 title = "Reversible mechanical unfolding of single ubiquitin molecules",
2395 address = "Department of Chemistry, National Dong Hwa University,
2400 pages = "3995--4006",
2402 doi = "10.1529/biophysj.104.042754",
2403 eprint = "http://download.cell.com/biophysj/pdf/PIIS0006349504738643.pdf",
2404 url = "http://www.cell.com/biophysj/abstract/S0006-3495(04)73864-3",
2406 keywords = "Computer
2407 Simulation;Elasticity;Mechanics;Micromanipulation;Microscopy, Atomic
2408 Force;Models, Chemical;Models, Molecular;Protein Conformation;Protein
2409 Denaturation;Protein Folding;Stress, Mechanical;Structure-Activity
2410 Relationship;Ubiquitin",
2411 abstract = "Single-molecule manipulation techniques have enabled the
2412 characterization of the unfolding and refolding process of individual
2413 protein molecules, using mechanical forces to initiate the unfolding
2414 transition. Experimental and computational results following this
2415 approach have shed new light on the mechanisms of the mechanical
2416 functions of proteins involved in several cellular processes, as well
2417 as revealed new information on the protein folding/unfolding free-
2418 energy landscapes. To investigate how protein molecules of different
2419 folds respond to a stretching force, and to elucidate the effects of
2420 solution conditions on the mechanical stability of a protein, we
2421 synthesized polymers of the protein ubiquitin and characterized the
2422 force-induced unfolding and refolding of individual ubiquitin molecules
2423 using an atomic-force-microscope-based single-molecule manipulation
2424 technique. The ubiquitin molecule was highly resistant to a stretching
2425 force, and the mechanical unfolding process was reversible. A model
2426 calculation based on the hydrogen-bonding pattern in the native
2427 structure was performed to explain the origin of this high mechanical
2428 stability. Furthermore, pH effects were studied and it was found that
2429 the forces required to unfold the protein remained constant within a pH
2430 range around the neutral value, and forces decreased as the solution pH
2431 was lowered to more acidic values.",
2432 note = "includes pH effects",
2435 @article { ciccotti86,
2436 author = GCiccotti #" and "# JPRyckaert,
2437 title = "Molecular dynamics simulation of rigid molecules",
2444 doi = "10.1016/0167-7977(86)90022-5",
2445 url = "http://dx.doi.org/10.1016/0167-7977(86)90022-5",
2446 note = "I haven't read this, but it looks like a nice review of MD with
2450 @article { claverie01,
2451 author = JMClaverie,
2452 title = "Gene number. What if there are only 30,000 human genes?",
2459 pages = "1255--1257",
2461 url = "http://www.sciencemag.org/cgi/content/full/291/5507/1255",
2462 keywords = "Animals;Computational Biology;Drug Industry;Expressed Sequence
2463 Tags;Gene Expression;Gene Expression Regulation;Genes;Genetic
2464 Techniques;Genome, Human;Genomics;Human Genome Project;Humans;Models,
2465 Genetic;Polymorphism, Single Nucleotide;Proteins;RNA, Messenger"
2468 @misc { codata-boltzmann,
2469 key = "codata-boltzmann",
2470 crossref = "codata06",
2471 url = "http://physics.nist.gov/cgi-bin/cuu/Value?k"
2474 @article { codata06,
2475 author = PJMohr #" and "# BNTaylor #" and "# DBNewell,
2477 title = "{CODATA} recommended values of the fundamental physical constants:
2487 doi = "10.1103/RevModPhys.80.633"
2490 @article { collins03,
2491 author = FSCollins #" and "# MMorgan #" and "# APatrinos,
2492 title = "The Human Genome Project: Lessons from large-scale biology.",
2501 doi = "10.1126/science.1084564",
2502 eprint = "http://www.sciencemag.org/cgi/reprint/300/5617/286.pdf",
2503 url = "http://www.sciencemag.org/cgi/content/summary/300/5617/277",
2504 keywords = "Access to Information;Computational Biology;Databases, Nucleic
2505 Acid;Genome, Human;Genomics;Government Agencies;History, 20th
2506 Century;Human Genome Project;Humans;International Cooperation;National
2507 Institutes of Health (U.S.);Private Sector;Public Policy;Public
2508 Sector;Publishing;Quality Control;Sequence Analysis, DNA;United States",
2509 note = "See also: \href{http://www.ornl.gov/sci/techresources/Human_Genome/
2510 project/journals/journals.shtml}{Landmark HPG Papers}"
2513 @article { cornish07,
2514 author = PVCornish #" and "# THa,
2515 title = "A survey of single-molecule techniques in chemical biology",
2519 journal = ACS:ChemBiol,
2524 doi = "10.1021/cb600342a",
2525 keywords = "Animals;Data Collection;Humans;Microscopy, Atomic
2526 Force;Microscopy, Fluorescence;Molecular Biology",
2527 abstract = "Single-molecule methods have revolutionized scientific research
2528 by rendering the investigation of once-inaccessible biological
2529 processes amenable to scientific inquiry. Several of the more
2530 established techniques will be emphasized in this Review, including
2531 single-molecule fluorescence microscopy, optical tweezers, and atomic
2532 force microscopy, which have been applied to many diverse biological
2533 processes. Serving as a taste of all the exciting research currently
2534 underway, recent examples will be discussed of translocation of RNA
2535 polymerase, myosin VI walking, protein folding, and enzyme activity. We
2536 will end by providing an assessment of what the future holds, including
2537 techniques that are currently in development."
2542 title = "Statistical Data Analysis",
2545 address = "New York",
2546 note = "Noise deconvolution in Chapter 11",
2547 project = "Cantilever Calibration"
2551 author = DCraig #" and "# AKrammer #" and "# KSchulten #" and "# VVogel,
2552 title = "Comparison of the early stages of forced unfolding for fibronectin
2553 type {III} modules",
2558 pages = "5590--5595",
2559 doi = "10.1073/pnas.101582198",
2560 eprint = "http://www.pnas.org/cgi/reprint/98/10/5590.pdf",
2561 url = "http://www.pnas.org/cgi/content/abstract/98/10/5590",
2565 @article { delpech01,
2566 author = BDelpech #" and "# MNCourel #" and "# CMaingonnat #" and "#
2567 CChauzy #" and "# RSesboue #" and "# GPratesi,
2568 title = "Hyaluronan digestion and synthesis in an experimental model of
2571 month = "September/October",
2572 journal = HistochemJ,
2577 keywords = "Animals;Culture Media;Humans;Hyaluronic
2578 Acid;Hyaluronoglucosaminidase;Mice;Mice, Nude;Neoplasm
2579 Metastasis;Neoplasm Transplantation;Neoplasms, Experimental;Tumor
2581 abstract = "To approach the question of hyaluronan catabolism in tumours,
2582 we have selected the cancer cell line H460M, a highly metastatic cell
2583 line in the nude mouse. H460M cells release hyaluronidase in culture
2584 media at a high rate of 57 pU/cell/h, without producing hyaluronan.
2585 Hyaluronidase was measured in the H460M cell culture medium at the
2586 optimum pH 3.8, and was not found above pH 4.5, with the enzyme-linked
2587 sorbent assay technique and zymography. Tritiated hyaluronan was
2588 digested at pH 3.8 by cells or cell membranes as shown by gel
2589 permeation chromatography, but no activity was recorded at pH 7 with
2590 this technique. Hyaluronan was digested in culture medium by tumour
2591 slices, prepared from tumours developed in nude mice grafted with H460M
2592 cells, showing that hyaluronan could be digested in complex tissue at
2593 physiological pH. Culture of tumour slices with tritiated acetate
2594 resulted in the accumulation within 2 days of radioactive
2595 macromolecules in the culture medium. The radioactive macromolecular
2596 material was mostly digested by Streptomyces hyaluronidase, showing
2597 that hyaluronan was its main component and that hyaluronan synthesis
2598 occurred together with its digestion. These results demonstrate that
2599 the membrane-associated hyaluronidase of H460M cells can act in vivo,
2600 and that hyaluronan, which is synthesised by the tumour stroma, can be
2601 made soluble and reduced to a smaller size by tumour cells before being
2602 internalised and further digested."
2605 @article { diCola05,
2606 author = EDCola #" and "# TAWaigh #" and "# JTrinick #" and "#
2607 LTskhovrebova #" and "# AHoumeida #" and "# WPyckhout-Hintzen #" and "#
2610 title = "Persistence length of titin from rabbit skeletal muscles measured
2611 with scattering and microrheology techniques",
2618 pages = "4095--4106",
2620 doi = "10.1529/biophysj.104.054908",
2621 eprint = "http://download.cell.com/biophysj/pdf/PIIS0006349505734603.pdf",
2622 url = "http://www.cell.com/biophysj/retrieve/pii/S0006349505734603",
2623 keywords = "Animals;Biophysics;Elasticity;Light;Muscle Proteins;Muscle,
2624 Skeletal;Neutrons;Protein Conformation;Protein
2625 Kinases;Rabbits;Rheology;Scattering, Radiation;Temperature",
2626 abstract = "The persistence length of titin from rabbit skeletal muscles
2627 was measured using a combination of static and dynamic light
2628 scattering, and neutron small angle scattering. Values of persistence
2629 length in the range 9-16 nm were found for titin-II, which corresponds
2630 to mainly physiologically inelastic A-band part of the protein, and for
2631 a proteolytic fragment with 100-nm contour length from the
2632 physiologically elastic I-band part. The ratio of the hydrodynamic
2633 radius to the static radius of gyration indicates that the proteins
2634 obey Gaussian statistics typical of a flexible polymer in a -solvent.
2635 Furthermore, measurements of the flexibility as a function of
2636 temperature demonstrate that titin-II and the I-band titin fragment
2637 experience a similar denaturation process; unfolding begins at 318 K
2638 and proceeds in two stages: an initial gradual 50\% change in
2639 persistence length is followed by a sharp unwinding transition at 338
2640 K. Complementary microrheology (video particle tracking) measurements
2641 indicate that the viscoelasticity in dilute solution behaves according
2642 to the Flory/Fox model, providing a value of the radius of gyration for
2643 titin-II (63 +/- 1 nm) in agreement with static light scattering and
2644 small angle neutron scattering results."
2648 author = HDietz #" and "# MRief,
2649 title = "Exploring the energy landscape of {GFP} by single-molecule
2650 mechanical experiments",
2655 pages = "16192--16197",
2656 doi = "10.1073/pnas.0404549101",
2657 eprint = "http://www.pnas.org/cgi/reprint/101/46/16192.pdf",
2658 url = "http://www.pnas.org/cgi/content/abstract/101/46/16192",
2659 abstract = "We use single-molecule force spectroscopy to drive
2660 single GFP molecules from the native state through their
2661 complex energy landscape into the completely unfolded
2662 state. Unlike many smaller proteins, mechanical GFP unfolding
2663 proceeds by means of two subsequent intermediate states. The
2664 transition from the native state to the first intermediate
2665 state occurs near thermal equilibrium at $\approx35\U{pN}$ and
2666 is characterized by detachment of a seven-residue N-terminal
2667 $\alpha$-helix from the beta barrel. We measure the
2668 equilibrium free energy cost associated with this transition
2669 as 22 kBT. Detachment of this small $\alpha$-helix completely
2670 destabilizes GFP thermodynamically even though the
2671 $\beta$-barrel is still intact and can bear load. Mechanical
2672 stability of the protein on the millisecond timescale,
2673 however, is determined by the activation barrier of unfolding
2674 the $\beta$-barrel out of this thermodynamically unstable
2675 intermediate state. High bandwidth, time-resolved measurements
2676 of the cantilever relaxation phase upon unfolding of the
2677 $\beta$-barrel revealed a second metastable mechanical
2678 intermediate with one complete $\beta$-strand detached from
2679 the barrel. Quantitative analysis of force distributions and
2680 lifetimes lead to a detailed picture of the complex mechanical
2681 unfolding pathway through a rough energy landscape.",
2682 note = "Towards use of Green Flourescent Protein (GFP) as an
2683 embedded force probe. Nice energy-landscape-to-one-dimension
2684 compression graphic.",
2685 project = "Energy landscape roughness"
2688 @article { dietz06a,
2689 author = HDietz #" and "# MRief,
2690 title = "Protein structure by mechanical triangulation",
2697 pages = "1244--1247",
2698 doi = "10.1073/pnas.0509217103",
2699 eprint = "http://www.pnas.org/cgi/reprint/103/5/1244.pdf",
2700 url = "http://www.pnas.org/cgi/content/abstract/103/5/1244",
2701 abstract = "Knowledge of protein structure is essential to understand
2702 protein function. High-resolution protein structure has so far been the
2703 domain of ensemble methods. Here, we develop a simple single-molecule
2704 technique to measure spatial position of selected residues within a
2705 folded and functional protein structure in solution. Construction and
2706 mechanical unfolding of cysteine-engineered polyproteins with
2707 controlled linkage topology allows measuring intramolecular distance
2708 with angstrom precision. We demonstrate the potential of this technique
2709 by determining the position of three residues in the structure of green
2710 fluorescent protein (GFP). Our results perfectly agree with the GFP
2711 crystal structure. Mechanical triangulation can find many applications
2712 where current bulk structural methods fail."
2715 @article { dietz06b,
2716 author = HDietz #" and "# FBerkemeier #" and "# MBertz #" and "# MRief,
2717 title = "Anisotropic deformation response of single protein molecules",
2724 pages = "12724--12728",
2725 doi = "10.1073/pnas.0602995103",
2726 eprint = "http://www.pnas.org/cgi/reprint/103/34/12724.pdf",
2727 url = "http://www.pnas.org/cgi/content/abstract/103/34/12724",
2728 abstract = "Single-molecule methods have given experimental access to the
2729 mechanical properties of single protein molecules. So far, access has
2730 been limited to mostly one spatial direction of force application.
2731 Here, we report single-molecule experiments that explore the mechanical
2732 properties of a folded protein structure in precisely controlled
2733 directions by applying force to selected amino acid pairs. We
2734 investigated the deformation response of GFP in five selected
2735 directions. We found fracture forces widely varying from 100 pN up to
2736 600 pN. We show that straining the GFP structure in one of the five
2737 directions induces partial fracture of the protein into a half-folded
2738 intermediate structure. From potential widths we estimated directional
2739 spring constants of the GFP structure and found values ranging from 1
2740 N/m up to 17 N/m. Our results show that classical continuum mechanics
2741 and simple mechanistic models fail to describe the complex mechanics of
2742 the GFP protein structure and offer insights into the mechanical design
2743 of protein materials."
2747 author = HDietz #" and "# MRief,
2748 title = "Detecting Molecular Fingerprints in Single Molecule Force
2749 Spectroscopy Using Pattern Recognition",
2754 pages = "5540--5542",
2756 doi = "10.1143/JJAP.46.5540",
2757 url = "http://jjap.ipap.jp/link?JJAP/46/5540/",
2758 keywords = "single molecule, protein mechanics, force spectroscopy, AFM,
2759 pattern recognition, GFP",
2760 abstract = "Single molecule force spectroscopy has given experimental
2761 access to the mechanical properties of protein molecules. Typically,
2762 less than 1% of the experimental recordings reflect true single
2763 molecule events due to abundant surface and multiple-molecule
2764 interactions. A key issue in single molecule force spectroscopy is thus
2765 to identify the characteristic mechanical `fingerprint' of a specific
2766 protein in noisy data sets. Here, we present an objective pattern
2767 recognition algorithm that is able to identify fingerprints in such
2769 note = "Automatic force curve selection. Seems a bit shoddy. Details
2773 @article{ berkemeier11,
2774 author = FBerkemeier #" and "# MBertz #" and "# SXiao #" and "#
2775 NPinotsis #" and "# MWilmanns #" and "# FGrater #" and "# MRief,
2776 title = "Fast-folding $\alpha$-helices as reversible strain absorbers
2777 in the muscle protein myomesin.",
2782 address = "Physik Department E22, Technische Universit{\"a}t
2783 M{\"u}nchen, James-Franck-Stra{\ss}e, 85748 Garching, Germany.",
2786 pages = "14139--14144",
2787 keywords = "Biomechanics",
2788 keywords = "Kinetics",
2789 keywords = "Microscopy, Atomic Force",
2790 keywords = "Molecular Dynamics Simulation",
2791 keywords = "Muscle Proteins",
2792 keywords = "Protein Folding",
2793 keywords = "Protein Multimerization",
2794 keywords = "Protein Stability",
2795 keywords = "Protein Structure, Secondary",
2796 keywords = "Protein Structure, Tertiary",
2797 keywords = "Protein Unfolding",
2798 abstract = "The highly oriented filamentous protein network of
2799 muscle constantly experiences significant mechanical load during
2800 muscle operation. The dimeric protein myomesin has been identified
2801 as an important M-band component supporting the mechanical
2802 integrity of the entire sarcomere. Recent structural studies have
2803 revealed a long $\alpha$-helical linker between the C-terminal
2804 immunoglobulin (Ig) domains My12 and My13 of myomesin. In this
2805 paper, we have used single-molecule force spectroscopy in
2806 combination with molecular dynamics simulations to characterize
2807 the mechanics of the myomesin dimer comprising immunoglobulin
2808 domains My12-My13. We find that at forces of approximately 30?pN
2809 the $\alpha$-helical linker reversibly elongates allowing the
2810 molecule to extend by more than the folded extension of a full
2811 domain. High-resolution measurements directly reveal the
2812 equilibrium folding/unfolding kinetics of the individual helix. We
2813 show that $\alpha$-helix unfolding mechanically protects the
2814 molecule homodimerization from dissociation at physiologically
2815 relevant forces. As fast and reversible molecular springs the
2816 myomesin $\alpha$-helical linkers are an essential component for
2817 the structural integrity of the M band.",
2819 doi = "10.1073/pnas.1105734108",
2820 URL = "http://www.ncbi.nlm.nih.gov/pubmed/21825161",
2825 author = KADill #" and "# HSChan,
2826 title = "From Levinthal to pathways to funnels.",
2834 doi = "10.1038/nsb0197-10",
2835 eprint = "http://www.nature.com/nsmb/journal/v4/n1/pdf/nsb0197-10.pdf",
2836 url = "http://www.nature.com/nsmb/journal/v4/n1/abs/nsb0197-10.html",
2837 keywords = "Kinetics;Models, Chemical;Protein Folding",
2838 abstract = "While the classical view of protein folding kinetics relies on
2839 phenomenological models, and regards folding intermediates in a
2840 structural way, the new view emphasizes the ensemble nature of protein
2841 conformations. Although folding has sometimes been regarded as a linear
2842 sequence of events, the new view sees folding as parallel microscopic
2843 multi-pathway diffusion-like processes. While the classical view
2844 invoked pathways to solve the problem of searching for the needle in
2845 the haystack, the pathway idea was then seen as conflicting with
2846 Anfinsen's experiments showing that folding is pathway-independent
2847 (Levinthal's paradox). In contrast, the new view sees no inherent
2848 paradox because it eliminates the pathway idea: folding can funnel to a
2849 single stable state by multiple routes in conformational space. The
2850 general energy landscape picture provides a conceptual framework for
2851 understanding both two-state and multi-state folding kinetics. Better
2852 tests of these ideas will come when new experiments become available
2853 for measuring not just averages of structural observables, but also
2854 correlations among their fluctuations. At that point we hope to learn
2855 much more about the real shapes of protein folding landscapes.",
2856 note = "Pretty folding funnel figures."
2859 @article { discher06,
2860 author = DDischer #" and "# NBhasin #" and "# CJohnson,
2861 title = "Covalent chemistry on distended proteins",
2866 pages = "7533--7534",
2867 doi = "10.1073/pnas.0602388103",
2868 eprint = "http://www.pnas.org/cgi/reprint/103/20/7533.pdf",
2869 url = "http://www.pnas.org/cgi/content/abstract/103/20/7533.pdf"
2873 author = OKDudko #" and "# AEFilippov #" and "# JKlafter #" and "# MUrbakh,
2874 title = "Beyond the conventional description of dynamic force spectroscopy
2882 pages = "11378--11381",
2884 doi = "10.1073/pnas.1534554100",
2885 eprint = "http://www.pnas.org/content/100/20/11378.full.pdf",
2886 url = "http://www.pnas.org/content/100/20/11378.abstract",
2887 keywords = "Spectrum Analysis;Temperature",
2888 abstract = "Dynamic force spectroscopy of single molecules is described by
2889 a model that predicts a distribution of rupture forces, the
2890 corresponding mean rupture force, and variance, which are all amenable
2891 to experimental tests. The distribution has a pronounced asymmetry,
2892 which has recently been observed experimentally. The mean rupture force
2893 follows a (lnV)2/3 dependence on the pulling velocity, V, and differs
2894 from earlier predictions. Interestingly, at low pulling velocities, a
2895 rebinding process is obtained whose signature is an intermittent
2896 behavior of the spring force, which delays the rupture. An extension to
2897 include conformational changes of the adhesion complex is proposed,
2898 which leads to the possibility of bimodal distributions of rupture
2903 author = OKDudko #" and "# GHummer #" and "# ASzabo,
2904 title = "Intrinsic rates and activation free energies from single-molecule
2905 pulling experiments",
2914 doi = "10.1103/PhysRevLett.96.108101",
2915 keywords = "Biophysics;Computer Simulation;Data Interpretation,
2916 Statistical;Kinetics;Micromanipulation;Models, Chemical;Models,
2917 Molecular;Molecular Conformation;Muscle Proteins;Nucleic Acid
2918 Conformation;Protein Binding;Protein Denaturation;Protein
2919 Folding;Protein Kinases;RNA;Stress, Mechanical;Thermodynamics;Time
2921 abstract = "We present a unified framework for extracting kinetic
2922 information from single-molecule pulling experiments at constant force
2923 or constant pulling speed. Our procedure provides estimates of not only
2924 (i) the intrinsic rate coefficient and (ii) the location of the
2925 transition state but also (iii) the free energy of activation. By
2926 analyzing simulated data, we show that the resulting rates of force-
2927 induced rupture are significantly more reliable than those obtained by
2928 the widely used approach based on Bell's formula. We consider the
2929 uniqueness of the extracted kinetic information and suggest guidelines
2930 to avoid over-interpretation of experiments."
2934 author = OKDudko #" and "# JMathe #" and "# ASzabo #" and "# AMeller #" and
2936 title = "Extracting kinetics from single-molecule force spectroscopy:
2937 Nanopore unzipping of {DNA} hairpins",
2944 pages = "4188--4195",
2946 doi = "10.1529/biophysj.106.102855",
2947 eprint = "http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1877759&blo
2949 keywords = "Computer
2950 Simulation;DNA;Elasticity;Mechanics;Micromanipulation;Microscopy,
2951 Atomic Force;Models, Chemical;Models, Molecular;Nanostructures;Nucleic
2952 Acid Conformation;Porosity;Stress, Mechanical",
2953 abstract = "Single-molecule force experiments provide powerful new tools to
2954 explore biomolecular interactions. Here, we describe a systematic
2955 procedure for extracting kinetic information from force-spectroscopy
2956 experiments, and apply it to nanopore unzipping of individual DNA
2957 hairpins. Two types of measurements are considered: unzipping at
2958 constant voltage, and unzipping at constant voltage-ramp speeds. We
2959 perform a global maximum-likelihood analysis of the experimental data
2960 at low-to-intermediate ramp speeds. To validate the theoretical models,
2961 we compare their predictions with two independent sets of data,
2962 collected at high ramp speeds and at constant voltage, by using a
2963 quantitative relation between the two types of measurements.
2964 Microscopic approaches based on Kramers theory of diffusive barrier
2965 crossing allow us to estimate not only intrinsic rates and transition
2966 state locations, as in the widely used phenomenological approach based
2967 on Bell's formula, but also free energies of activation. The problem of
2968 extracting unique and accurate kinetic parameters of a molecular
2969 transition is discussed in light of the apparent success of the
2970 microscopic theories in reproducing the experimental data."
2974 author = OKDudko #" and "# GHummer #" and "# ASzabo,
2975 title = "Theory, analysis, and interpretation of single-molecule
2976 force spectroscopy experiments.",
2981 address = "Department of Physics and Center for Theoretical
2982 Biological Physics, University of California at San Diego, La
2983 Jolla, CA 92093, USA.
2984 dudko@physics.ucsd.edu",
2987 pages = "15755--15760",
2989 keywords = "Half-Life",
2990 keywords = "Kinetics",
2991 keywords = "Microscopy, Atomic Force",
2992 keywords = "Motion",
2993 keywords = "Nucleic Acid Conformation",
2994 keywords = "Nucleic Acid Denaturation",
2995 keywords = "Protein Folding",
2996 keywords = "Thermodynamics",
2997 abstract = "Dynamic force spectroscopy probes the kinetic and
2998 thermodynamic properties of single molecules and molecular
2999 assemblies. Here, we propose a simple procedure to extract kinetic
3000 information from such experiments. The cornerstone of our method
3001 is a transformation of the rupture-force histograms obtained at
3002 different force-loading rates into the force-dependent lifetimes
3003 measurable in constant-force experiments. To interpret the
3004 force-dependent lifetimes, we derive a generalization of Bell's
3005 formula that is formally exact within the framework of Kramers
3006 theory. This result complements the analytical expression for the
3007 lifetime that we derived previously for a class of model
3008 potentials. We illustrate our procedure by analyzing the nanopore
3009 unzipping of DNA hairpins and the unfolding of a protein attached
3010 by flexible linkers to an atomic force microscope. Our procedure
3011 to transform rupture-force histograms into the force-dependent
3012 lifetimes remains valid even when the molecular extension is a
3013 poor reaction coordinate and higher-dimensional free-energy
3014 surfaces must be considered. In this case the microscopic
3015 interpretation of the lifetimes becomes more challenging because
3016 the lifetimes can reveal richer, and even nonmonotonic, dependence
3019 doi = "10.1073/pnas.0806085105",
3020 URL = "http://www.ncbi.nlm.nih.gov/pubmed/18852468",
3026 title = "Probing the relation between force--lifetime--and chemistry in
3027 single molecular bonds",
3033 doi = "10.1146/annurev.biophys.30.1.105",
3034 url = "http://arjournals.annualreviews.org/doi/abs/10.1146%2Fannurev.biophys.30.1.105",
3035 keywords = "Biophysics;Kinetics;Microscopy, Atomic Force;Models,
3036 Chemical;Protein Binding;Spectrum Analysis;Time Factors",
3037 abstract = "On laboratory time scales, the energy landscape of a weak bond
3038 along a dissociation pathway is fully explored through Brownian-thermal
3039 excitations, and energy barriers become encoded in a dissociation time
3040 that varies with applied force. Probed with ramps of force over an
3041 enormous range of rates (force/time), this kinetic profile is
3042 transformed into a dynamic spectrum of bond rupture force as a function
3043 of loading rate. On a logarithmic scale in loading rate, the force
3044 spectrum provides an easy-to-read map of the prominent energy barriers
3045 traversed along the force-driven pathway and exposes the differences in
3046 energy between barriers. In this way, the method of dynamic force
3047 spectroscopy (DFS) is being used to probe the complex relation between
3048 force-lifetime-and chemistry in single molecular bonds. Most important,
3049 DFS probes the inner world of molecular interactions to reveal barriers
3050 that are difficult or impossible to detect in assays of near
3051 equilibrium dissociation but that determine bond lifetime and strength
3052 under rapid detachment. To use an ultrasensitive force probe as a
3053 spectroscopic tool, we need to understand the physics of bond
3054 dissociation under force, the impact of experimental technique on the
3055 measurement of detachment force (bond strength), the consequences of
3056 complex interactions in macromolecular bonds, and effects of multiply-
3057 bonded attachments."
3060 @article { evans91a,
3061 author = EEvans #" and "# DBerk #" and "# ALeung,
3062 title = "Detachment of agglutinin-bonded red blood cells. {I}. Forces to
3063 rupture molecular-point attachments",
3071 keywords = "ABO Blood-Group System;Animals;Antibodies,
3072 Monoclonal;Erythrocyte Deformability;Erythrocyte
3073 Membrane;Erythrocytes;Glycophorin;Helix
3074 (Snails);Hemagglutinins;Humans;Immune Sera;Lectins;Mathematics;Models,
3076 abstract = "A simple micromechanical method has been developed to measure
3077 the rupture strength of a molecular-point attachment (focal bond)
3078 between two macroscopically smooth membrane capsules. In the procedure,
3079 one capsule is prepared with a low density coverage of adhesion
3080 molecules, formed as a stiff sphere, and held at fixed position by a
3081 micropipette. The second capsule without adhesion molecules is
3082 pressurized into a spherical shape with low suction by another pipette.
3083 This capsule is maneuvered to initiate point contact at the pole
3084 opposite the stiff capsule which leads to formation of a few (or even
3085 one) molecular attachments. Then, the deformable capsule is slowly
3086 withdrawn by displacement of the pipette. Analysis shows that the end-
3087 to-end extension of the capsule provides a direct measure of the force
3088 at the point contact and, therefore, the rupture strength when
3089 detachment occurs. The range for point forces accessible to this
3090 technique depends on the elastic moduli of the membrane, membrane
3091 tension, and the size of the capsule. For biological and synthetic
3092 vesicle membranes, the range of force lies between 10(-7)-10(-5) dyn
3093 (10(-12)-10(-10) N) which is 100-fold less than presently measurable by
3094 Atomic Force Microscopy! Here, the approach was used to study the
3095 forces required to rupture microscopic attachments between red blood
3096 cells formed by a monoclonal antibody to red cell membrane glycophorin,
3097 anti-A serum, and a lectin from the snail-helix pomatia. Failure of the
3098 attachments appeared to be a stochastic function of the magnitude and
3099 duration of the detachment force. We have correlated the statistical
3100 behavior observed for rupture with a random process model for failure
3101 of small numbers of molecular attachments. The surprising outcome of
3102 the measurements and analysis was that the forces deduced for short-
3103 time failure of 1-2 molecular attachments were nearly the same for all
3104 of the agglutinin, i.e., 1-2 x 10(-6) dyn. Hence, microfluorometric
3105 tests were carried out to determine if labeled agglutinins and/or
3106 labeled surface molecules were transferred between surfaces after
3107 separation of large areas of adhesive contact. The results showed that
3108 the attachments failed because receptors were extracted from the
3112 @article { evans91b,
3113 author = EEvans #" and "# DBerk #" and "# ALeung #" and "# NMohandas,
3114 title = "Detachment of agglutinin-bonded red blood cells. {II}. Mechanical
3115 energies to separate large contact areas",
3123 keywords = "Animals;Antibodies, Monoclonal;Cell Adhesion;Erythrocyte
3124 Membrane;Erythrocytes;Helix
3125 (Snails);Hemagglutination;Hemagglutinins;Humans;Immune
3126 Sera;Kinetics;Lectins;Mathematics",
3127 abstract = "As detailed in a companion paper (Berk, D., and E. Evans. 1991.
3128 Biophys. J. 59:861-872), a method was developed to quantitate the
3129 strength of adhesion between agglutinin-bonded membranes without
3130 ambiguity due to mechanical compliance of the cell body. The
3131 experimental method and analysis were formulated around controlled
3132 assembly and detachment of a pair of macroscopically smooth red blood
3133 cell surfaces. The approach provides precise measurement of the
3134 membrane tension applied at the perimeter of an adhesive contact and
3135 the contact angle theta c between membrane surfaces which defines the
3136 mechanical leverage factor (1-cos theta c) important in the definition
3137 of the work to separate a unit area of contact. Here, the method was
3138 applied to adhesion and detachment of red cells bound together by
3139 different monoclonal antibodies to red cell membrane glycophorin and
3140 the snail-helix pomatia-lectin. For these tests, one of the two red
3141 cells was chemically prefixed in the form of a smooth sphere then
3142 equilibrated with the agglutinin before the adhesion-detachment
3143 procedure. The other cell was not exposed to the agglutinin until it
3144 was forced into contact with the rigid cell surface by mechanical
3145 impingement. Large regions of agglutinin bonding were produced by
3146 impingement but no spontaneous spreading was observed beyond the forced
3147 contact. Measurements of suction force to detach the deformable cell
3148 yielded consistent behavior for all of the agglutinins: i.e., the
3149 strength of adhesion increased progressively with reduction in contact
3150 diameter throughout detachment. This tension-contact diameter behavior
3151 was not altered over a ten-fold range of separation rates. In special
3152 cases, contacts separated smoothly after critical tensions were
3153 reached; these were the highest values attained for tension. Based on
3154 measurements reported in another paper (Evans et al. 1991. Biophys. J.
3155 59:838-848) of the forces required to rupture molecular-point
3156 attachments, the density of cross-bridges was estimated with the
3157 assumption that the tension was proportional to the discrete rupture
3158 force x the number of attachments per unit length. These estimates
3159 showed that only a small fraction of agglutinin formed cross-bridges at
3160 initial assembly and increased progressively with separation. When
3161 critical tension levels were reached, it appeared that nearly all local
3162 agglutinin was involved as cross-bridges. Because one cell surface was
3163 chemically fixed, receptor accumulation was unlikely; thus, microscopic
3164 ``roughness'' and steric repulsion probably modulated formation of
3165 cross-bridges on initial contact.(ABSTRACT TRUNCATED AT 400 WORDS)"
3169 author = EEvans #" and "# KRitchie,
3170 title = "Dynamic strength of molecular adhesion bonds",
3176 pages = "1541--1555",
3178 eprint = "http://www.biophysj.org/cgi/reprint/72/4/1541.pdf",
3179 url = "http://www.biophysj.org/cgi/content/abstract/72/4/1541",
3180 keywords = "Avidin; Biotin; Chemistry, Physical; Computer Simulation;
3181 Mathematics; Monte Carlo Method; Protein Binding",
3182 abstract = "In biology, molecular linkages at, within, and beneath cell
3183 interfaces arise mainly from weak noncovalent interactions. These bonds
3184 will fail under any level of pulling force if held for sufficient time.
3185 Thus, when tested with ultrasensitive force probes, we expect cohesive
3186 material strength and strength of adhesion at interfaces to be time-
3187 and loading rate-dependent properties. To examine what can be learned
3188 from measurements of bond strength, we have extended Kramers' theory
3189 for reaction kinetics in liquids to bond dissociation under force and
3190 tested the predictions by smart Monte Carlo (Brownian dynamics)
3191 simulations of bond rupture. By definition, bond strength is the force
3192 that produces the most frequent failure in repeated tests of breakage,
3193 i.e., the peak in the distribution of rupture forces. As verified by
3194 the simulations, theory shows that bond strength progresses through
3195 three dynamic regimes of loading rate. First, bond strength emerges at
3196 a critical rate of loading (> or = 0) at which spontaneous dissociation
3197 is just frequent enough to keep the distribution peak at zero force. In
3198 the slow-loading regime immediately above the critical rate, strength
3199 grows as a weak power of loading rate and reflects initial coupling of
3200 force to the bonding potential. At higher rates, there is crossover to
3201 a fast regime in which strength continues to increase as the logarithm
3202 of the loading rate over many decades independent of the type of
3203 attraction. Finally, at ultrafast loading rates approaching the domain
3204 of molecular dynamics simulations, the bonding potential is quickly
3205 overwhelmed by the rapidly increasing force, so that only naked
3206 frictional drag on the structure remains to retard separation. Hence,
3207 to expose the energy landscape that governs bond strength, molecular
3208 adhesion forces must be examined over an enormous span of time scales.
3209 However, a significant gap exists between the time domain of force
3210 measurements in the laboratory and the extremely fast scale of
3211 molecular motions. Using results from a simulation of biotin-avidin
3212 bonds (Izrailev, S., S. Stepaniants, M. Balsera, Y. Oono, and K.
3213 Schulten. 1997. Molecular dynamics study of unbinding of the avidin-
3214 biotin complex. Biophys. J., this issue), we describe how Brownian
3215 dynamics can help bridge the gap between molecular dynamics and probe
3217 project = "sawtooth simulation"
3221 author = EEvans #" and "# KRitchie,
3222 title = "Strength of a weak bond connecting flexible polymer chains",
3228 pages = "2439--2447",
3230 eprint = "http://www.biophysj.org/cgi/reprint/76/5/2439.pdf",
3231 url = "http://www.biophysj.org/cgi/content/abstract/76/5/2439",
3232 keywords = "Animals; Biophysics; Biopolymers; Microscopy, Atomic Force;
3233 Models, Chemical; Muscle Proteins; Protein Folding; Protein Kinases;
3234 Stochastic Processes; Stress, Mechanical; Thermodynamics",
3235 abstract = "Bond dissociation under steadily rising force occurs most
3236 frequently at a time governed by the rate of loading (Evans and
3237 Ritchie, 1997 Biophys. J. 72:1541-1555). Multiplied by the loading
3238 rate, the breakage time specifies the force for most frequent failure
3239 (called bond strength) that obeys the same dependence on loading rate.
3240 The spectrum of bond strength versus log(loading rate) provides an
3241 image of the energy landscape traversed in the course of unbonding.
3242 However, when a weak bond is connected to very compliant elements like
3243 long polymers, the load applied to the bond does not rise steadily
3244 under constant pulling speed. Because of nonsteady loading, the most
3245 frequent breakage force can differ significantly from that of a bond
3246 loaded at constant rate through stiff linkages. Using generic models
3247 for wormlike and freely jointed chains, we have analyzed the kinetic
3248 process of failure for a bond loaded by pulling the polymer linkages at
3249 constant speed. We find that when linked by either type of polymer
3250 chain, a bond is likely to fail at lower force under steady separation
3251 than through stiff linkages. Quite unexpectedly, a discontinuous jump
3252 can occur in bond strength at slow separation speed in the case of long
3253 polymer linkages. We demonstrate that the predictions of strength
3254 versus log(loading rate) can rationalize conflicting results obtained
3255 recently for unfolding Ig domains along muscle titin with different
3257 note = "Develops Kramers improvement on Bell model for domain unfolding.
3258 Presents unfolding under variable loading rates. Often cited as the
3259 ``Bell--Evans'' model. They derive a unitless treatment, scaling force
3260 by $f_\beta$, time by $\tau_f$, and elasiticity by compliance
3261 $c(f)$. The appendix has relaxation time formulas for WLC and FJC
3263 project = "sawtooth simulation"
3266 @article { fernandez04,
3267 author = JFernandez #" and "# HLi,
3268 title = "Force-clamp spectroscopy monitors the folding trajectory of a
3276 pages = "1674--1678",
3278 doi = "10.1126/science.1092497",
3279 eprint = "http://www.sciencemag.org/cgi/reprint/303/5664/1674.pdf",
3280 url = "http://www.sciencemag.org/cgi/content/abstract/303/5664/1674",
3281 keywords = "Chemistry, Physical;Microscopy, Atomic Force;Physicochemical
3282 Phenomena;Polyubiquitin;Protein Conformation;Protein
3283 Denaturation;Protein Folding;Protein Structure, Secondary;Time
3285 abstract = "We used force-clamp atomic force microscopy to measure the end-
3286 to-end length of the small protein ubiquitin during its folding
3287 reaction at the single-molecule level. Ubiquitin was first unfolded and
3288 extended at a high force, then the stretching force was quenched and
3289 protein folding was observed. The folding trajectories were continuous
3290 and marked by several distinct stages. The time taken to fold was
3291 dependent on the contour length of the unfolded protein and the
3292 stretching force applied during folding. The folding collapse was
3293 marked by large fluctuations in the end-to-end length of the protein,
3294 but these fluctuations vanished upon the final folding contraction.
3295 These direct observations of the complete folding trajectory of a
3296 protein provide a benchmark to determine the physical basis of the
3301 author = JHoward #" and "# AJHudspeth,
3302 title = {Mechanical relaxation of the hair bundle mediates
3303 adaptation in mechanoelectrical transduction by the
3304 bullfrog's saccular hair cell.},
3310 pages = {3064--3068},
3312 url = {http://www.ncbi.nlm.nih.gov/pubmed/3495007},
3313 keywords = {Acclimatization},
3314 keywords = {Animals},
3315 keywords = {Electric Conductivity},
3316 keywords = {Electric Stimulation},
3317 keywords = {Hair Cells, Auditory},
3318 keywords = {Membrane Potentials},
3319 keywords = {Microelectrodes},
3320 keywords = {Physical Stimulation},
3321 keywords = {Rana catesbeiana},
3322 keywords = {Saccule and Utricle},
3323 abstract = {Mechanoelectrical transduction by hair cells of the
3324 frog's internal ear displays adaptation: the electrical response
3325 to a maintained deflection of the hair bundle declines over a
3326 period of tens of milliseconds. We investigated the role of
3327 mechanics in adaptation by measuring changes in hair-bundle
3328 stiffness following the application of force stimuli. Following
3329 step stimulation with a glass fiber, the hair bundle of a saccular
3330 hair cell initially had a stiffness of approximately equal to
3331 $1\U{mN/m}$. The stiffness then declined to a steady-state level
3332 near $0.6\U{mN/m}$ with a time course comparable to that of
3333 adaptation in the receptor current. The hair bundle may be modeled
3334 as the parallel combination of a spring, which represents the
3335 rotational stiffness of the stereocilia, and a series spring and
3336 dashpot, which respectively, represent the elastic element
3337 responsible for channel gating and the apparatus for adaptation.},
3342 author = JHoward #" and "# AJHudspeth,
3343 title = {Compliance of the Hair Bundle Associated with Gating of
3344 Mechanoelectrical Transduction Channels in the Bullfrog's Saccular
3351 doi = {10.1016/0896-6273(88)90139-0},
3352 url = {http://www.cell.com/neuron/retrieve/pii/0896627388901390},
3353 eprint = {http://download.cell.com/neuron/pdf/PII0896627388901390.pdf},
3354 note = {Initial thermal calibration paper as cited by
3355 \citet{florin95}. This is not an AFM paper, but it uses the
3356 equipartition theorem to calculate the spring constant of hair
3357 fibers by measuring their tip displacement variance. The
3358 discussion occurs in the \emph{Manufacture and Calibration of
3359 Fibers} section on pages 197--198. Actual details are scarce, but
3360 I believe this is the original source of the ``Lorentzian'' and
3361 ``10\% accuracy'' ideas that have haunted themal calibration ever
3366 author = ELFlorin #" and "# VMoy #" and "# HEGaub,
3367 title = {Adhesion forces between individual ligand-receptor pairs},
3375 doi = {10.1126/science.8153628},
3376 url = {http://www.sciencemag.org/content/264/5157/415.abstract},
3377 eprint = {http://www.sciencemag.org/content/264/5157/415.full.pdf},
3378 abstract ={The adhesion force between the tip of an atomic force
3379 microscope cantilever derivatized with avidin and agarose beads
3380 functionalized with biotin, desthiobiotin, or iminobiotin was
3381 measured. Under conditions that allowed only a limited number of
3382 molecular pairs to interact, the force required to separate tip
3383 and bead was found to be quantized in integer multiples of
3384 $160\pm20$ piconewtons for biotin and $85\pm15$ piconewtons for
3385 iminobiotin. The measured force quanta are interpreted as the
3386 unbinding forces of individual molecular pairs.},
3389 @article { florin95,
3390 author = ELFlorin #" and "# MRief #" and "# HLehmann #" and "# MLudwig #"
3391 and "# CDornmair #" and "# VMoy #" and "# HEGaub,
3392 title = "Sensing specific molecular interactions with the atomic force
3400 doi = "10.1016/0956-5663(95)99227-C",
3401 url = "http://dx.doi.org/10.1016/0956-5663(95)99227-C",
3402 abstract = "One of the unique features of the atomic force microscope (AFM)
3403 is its capacity to measure interactions between tip and sample with
3404 high sensitivity and unparal leled spatial resolution. Since the
3405 development of methods for the functionaliza tion of the tips, the
3406 versatility of the AFM has been expanded to experiments wh ere specific
3407 molecular interactions are measured. For illustration, we present m
3408 easurements of the interaction between complementary strands of DNA. A
3409 necessary prerequisite for the quantitative analysis of the interaction
3410 force is knowledg e of the spring constant of the cantilevers. Here, we
3411 compare different techniqu es that allow for the in situ measurement of
3412 the absolute value of the spring co nstant of cantilevers.",
3413 note = {Good review of calibration to 1995, with experimental
3414 comparison between resonance-shift, reference-spring, and
3415 thermal methods. They incorrectly cite \citet{hutter93} as
3416 being published in 1994.},
3417 project = "Cantilever Calibration"
3420 @article{ burnham03,
3421 author = NABurnham #" and "# XiChen #" and "# CSHodges #" and "#
3422 GAMatei #" and "# EJThoreson #" and "# CJRoberts #" and "#
3423 MCDavies #" and "# SJBTendler,
3424 title = {Comparison of calibration methods for atomic-force
3425 microscopy cantilevers},
3432 url = {http://stacks.iop.org/0957-4484/14/i=1/a=301},
3433 abstract = {The scientific community needs a rapid and reliable way
3434 of accurately determining the stiffness of atomic-force microscopy
3435 cantilevers. We have compared the experimentally determined values
3436 of stiffness for ten cantilever probes using four different
3437 methods. For rectangular silicon cantilever beams of well defined
3438 geometry, the approaches all yield values within 17\% of the
3439 manufacturer's nominal stiffness. One of the methods is new, based
3440 on the acquisition and analysis of thermal distribution functions
3441 of the oscillator's amplitude fluctuations. We evaluate this
3442 method in comparison to the three others and recommend it for its
3443 ease of use and broad applicability.},
3444 note = {Contains both the overdamped (\fref{equation}{6}) and
3445 general (\fref{equation}{8}) power spectral densities used in
3446 thermal cantilever calibration, but punts to textbooks for the
3451 author = NRForde #" and "# DIzhaky #" and "# GRWoodcock #" and "# GJLWuite
3452 #" and "# CBustamante,
3453 title = "Using mechanical force to probe the mechanism of pausing and
3454 arrest during continuous elongation by Escherichia coli {RNA}
3462 pages = "11682--11687",
3464 doi = "10.1073/pnas.142417799",
3465 eprint = "http://www.pnas.org/cgi/reprint/99/18/11682.pdf",
3466 url = "http://www.pnas.org/content/99/18/11682",
3467 keywords = "DNA-Directed RNA Polymerases;Escherichia
3468 coli;Kinetics;Transcription, Genetic",
3469 abstract = "Escherichia coli RNA polymerase translocates along the DNA
3470 discontinuously during the elongation phase of transcription, spending
3471 proportionally more time at some template positions, known as pause and
3472 arrest sites, than at others. Current models of elongation suggest that
3473 the enzyme backtracks at these locations, but the dynamics are
3474 unresolved. Here, we study the role of lateral displacement in pausing
3475 and arrest by applying force to individually transcribing molecules. We
3476 find that an assisting mechanical force does not alter the
3477 translocation rate of the enzyme, but does reduce the efficiency of
3478 both pausing and arrest. Moreover, arrested molecules cannot be rescued
3479 by force, suggesting that arrest occurs by a bipartite mechanism: the
3480 enzyme backtracks along the DNA followed by a conformational change of
3481 the ternary complex (RNA polymerase, DNA and transcript), which cannot
3482 be reversed mechanically."
3485 @article { freitag97,
3486 author = SFreitag #" and "# ILTrong #" and "# LKlumb #" and "# PSStayton #"
3488 title = "Structural studies of the streptavidin binding loop.",
3494 pages = "1157--1166",
3496 doi = "10.1002/pro.5560060604",
3497 keywords = "Allosteric Regulation;Bacterial Proteins;Binding
3498 Sites;Biotin;Crystallography, X-Ray;Hydrogen Bonding;Ligands;Models,
3499 Molecular;Molecular Conformation;Streptavidin;Tryptophan",
3500 abstract = "The streptavidin-biotin complex provides the basis for many
3501 important biotechnological applications and is an interesting model
3502 system for studying high-affinity protein-ligand interactions. We
3503 report here crystallographic studies elucidating the conformation of
3504 the flexible binding loop of streptavidin (residues 45 to 52) in the
3505 unbound and bound forms. The crystal structures of unbound streptavidin
3506 have been determined in two monoclinic crystal forms. The binding loop
3507 generally adopts an open conformation in the unbound species. In one
3508 subunit of one crystal form, the flexible loop adopts the closed
3509 conformation and an analysis of packing interactions suggests that
3510 protein-protein contacts stabilize the closed loop conformation. In the
3511 other crystal form all loops adopt an open conformation. Co-
3512 crystallization of streptavidin and biotin resulted in two additional,
3513 different crystal forms, with ligand bound in all four binding sites of
3514 the first crystal form and biotin bound in only two subunits in a
3515 second. The major change associated with binding of biotin is the
3516 closure of the surface loop incorporating residues 45 to 52. Residues
3517 49 to 52 display a 3(10) helical conformation in unbound subunits of
3518 our structures as opposed to the disordered loops observed in other
3519 structure determinations of streptavidin. In addition, the open
3520 conformation is stabilized by a beta-sheet hydrogen bond between
3521 residues 45 and 52, which cannot occur in the closed conformation. The
3522 3(10) helix is observed in nearly all unbound subunits of both the co-
3523 crystallized and ligand-free structures. An analysis of the temperature
3524 factors of the binding loop regions suggests that the mobility of the
3525 closed loops in the complexed structures is lower than in the open
3526 loops of the ligand-free structures. The two biotin bound subunits in
3527 the tetramer found in the MONO-b1 crystal form are those that
3528 contribute Trp 120 across their respective binding pockets, suggesting
3529 a structural link between these binding sites in the tetramer. However,
3530 there are no obvious signatures of binding site communication observed
3531 upon ligand binding, such as quaternary structure changes or shifts in
3532 the region of Trp 120. These studies demonstrate that while
3533 crystallographic packing interactions can stabilize both the open and
3534 closed forms of the flexible loop, in their absence the loop is open in
3535 the unbound state and closed in the presence of biotin. If present in
3536 solution, the helical structure in the open loop conformation could
3537 moderate the entropic penalty associated with biotin binding by
3538 contributing an order-to-disorder component to the loop closure.",
3539 note = "\href{http://www.rcsb.org/pdb/explore.do?structureId=1SWE}{PDB ID:
3541 \href{http://dx.doi.org/10.2210/pdb1swe/pdb}{10.2210/pdb1swe/pdb}."
3544 @article { friddle08,
3545 author = RWFriddle #" and "# PPodsiadlo #" and "# ABArtyukhin #" and "#
3547 title = "Near-Equilibrium Chemical Force Microscopy",
3552 pages = "4986--4990",
3553 doi = "10.1021/jp7095967",
3554 eprint = "http://pubs.acs.org/doi/pdf/10.1021/jp7095967",
3555 url = "http://pubs.acs.org/doi/abs/10.1021/jp7095967"
3559 author = TFujii #" and "# YLSun #" and "# KNAn #" and "# ZPLuo,
3560 title = "Mechanical properties of single hyaluronan molecules",
3568 keywords = "Biomechanics;Cross-Linking Reagents;Elasticity;Extracellular
3569 Matrix;Humans;Hyaluronic Acid;Lasers;Microspheres;Nanotechnology",
3570 abstract = "Hyaluronan (HA) is a major component of the extracellular
3571 matrix. It plays an important role in the mechanical functions of the
3572 extracellular matrix and stabilization of cells. Currently, its
3573 mechanical properties have been investigated only at the gross level.
3574 In this study, the mechanical properties of single HA molecules were
3575 directly measured with an optical tweezer technique, yielding a
3576 persistence length of 4.5 +/- 1.2 nm. This information may help us to
3577 understand the mechanical roles in the extracellular matrix
3578 infrastructure, cell attachment, and to design tissue engineering and
3579 drug delivery systems where the mechanical functions of HA are
3583 @article { ganchev08,
3584 author = DNGanchev #" and "# NJCobb #" and "# KSurewicz #" and "#
3586 title = "Nanomechanical properties of human prion protein amyloid as probed
3587 by force spectroscopy",
3594 pages = "2909--2915",
3596 doi = "10.1529/biophysj.108.133108",
3597 abstract = "Amyloids are associated with a number of protein misfolding
3598 disorders, including prion diseases. In this study, we used single-
3599 molecule force spectroscopy to characterize the nanomechanical
3600 properties and molecular structure of amyloid fibrils formed by human
3601 prion protein PrP90-231. Force-extension curves obtained by specific
3602 attachment of a gold-covered atomic force microscope tip to engineered
3603 Cys residues could be described by the worm-like chain model for
3604 entropic elasticity of a polymer chain, with the size of the N-terminal
3605 segment that could be stretched entropically depending on the tip
3606 attachment site. The data presented here provide direct information
3607 about the forces required to extract an individual monomer from the
3608 core of the PrP90-231 amyloid, and indicate that the beta-sheet core of
3609 this amyloid starts at residue approximately 164-169. The latter
3610 finding has important implications for the ongoing debate regarding the
3611 structure of PrP amyloid."
3615 author = MGao #" and "# DCraig #" and "# OLequin #" and "# ICampbell #" and
3616 "# VVogel #" and "# KSchulten,
3617 title = "Structure and functional significance of mechanically unfolded
3618 fibronectin type {III1} intermediates",
3623 pages = "14784--14789",
3624 doi = "10.1073/pnas.2334390100",
3625 eprint = "http://www.pnas.org/cgi/reprint/100/25/14784.pdf",
3626 url = "http://www.pnas.org/cgi/content/abstract/100/25/14784",
3627 abstract = "Fibronectin (FN) forms fibrillar networks coupling cells to the
3628 extracellular matrix. The formation of FN fibrils, fibrillogenesis, is
3629 a tightly regulated process involving the exposure of cryptic binding
3630 sites in individual FN type III (FN-III) repeats presumably exposed by
3631 mechanical tension. The FN-III1 module has been previously proposed to
3632 contain such cryptic sites that promote the assembly of extracellular
3633 matrix FN fibrils. We have combined NMR and steered molecular dynamics
3634 simulations to study the structure and mechanical unfolding pathway of
3635 FN-III1. This study finds that FN-III1 consists of a {beta}-sandwich
3636 structure that unfolds to a mechanically stable intermediate about four
3637 times the length of the native folded state. Considering previous
3638 experimental findings, our studies provide a structural model by which
3639 mechanical stretching of FN-III1 may induce fibrillogenesis through
3640 this partially unfolded intermediate."
3643 @article { gavrilov01,
3644 author = LAGavrilov #" and "# NSGavrilova,
3645 title = "The reliability theory of aging and longevity",
3654 doi = "10.1006/jtbi.2001.2430",
3655 keywords = "Adult;Aged;Aging;Animals;Humans;Longevity;Middle Aged;Models,
3656 Biological;Survival Rate;Systems Theory",
3657 abstract = "Reliability theory is a general theory about systems failure.
3658 It allows researchers to predict the age-related failure kinetics for a
3659 system of given architecture (reliability structure) and given
3660 reliability of its components. Reliability theory predicts that even
3661 those systems that are entirely composed of non-aging elements (with a
3662 constant failure rate) will nevertheless deteriorate (fail more often)
3663 with age, if these systems are redundant in irreplaceable elements.
3664 Aging, therefore, is a direct consequence of systems redundancy.
3665 Reliability theory also predicts the late-life mortality deceleration
3666 with subsequent leveling-off, as well as the late-life mortality
3667 plateaus, as an inevitable consequence of redundancy exhaustion at
3668 extreme old ages. The theory explains why mortality rates increase
3669 exponentially with age (the Gompertz law) in many species, by taking
3670 into account the initial flaws (defects) in newly formed systems. It
3671 also explains why organisms ``prefer'' to die according to the Gompertz
3672 law, while technical devices usually fail according to the Weibull
3673 (power) law. Theoretical conditions are specified when organisms die
3674 according to the Weibull law: organisms should be relatively free of
3675 initial flaws and defects. The theory makes it possible to find a
3676 general failure law applicable to all adult and extreme old ages, where
3677 the Gompertz and the Weibull laws are just special cases of this more
3678 general failure law. The theory explains why relative differences in
3679 mortality rates of compared populations (within a given species) vanish
3680 with age, and mortality convergence is observed due to the exhaustion
3681 of initial differences in redundancy levels. Overall, reliability
3682 theory has an amazing predictive and explanatory power with a few, very
3683 general and realistic assumptions. Therefore, reliability theory seems
3684 to be a promising approach for developing a comprehensive theory of
3685 aging and longevity integrating mathematical methods with specific
3686 biological knowledge.",
3687 note = "An example of exponential (standard) Gomperz law."
3690 @article { gergely00,
3691 author = CGergely #" and "# JCVoegel #" and "# PSchaaf #" and "# BSenger #"
3692 and "# MMaaloum #" and "# JHorber #" and "# JHemmerle,
3693 title = "Unbinding process of adsorbed proteins under external stress
3694 studied by atomic force microscopy spectroscopy",
3699 pages = "10802--10807",
3700 doi = "10.1073/pnas.180293097",
3701 eprint = "http://www.pnas.org/cgi/reprint/97/20/10802.pdf",
3702 url = "http://www.pnas.org/cgi/content/abstract/97/20/10802"
3705 @article { gompertz25,
3707 title = "On the Nature of the Function Expressive of the Law of Human
3708 Mortality, and on a New Mode of Determining the Value of Life
3717 copyright = "Copyright \copy\ 1825 The Royal Society",
3718 url = "http://www.jstor.org/stable/107756",
3720 jstor_articletype = "primary_article",
3721 jstor_formatteddate = 1825,
3722 jstor_issuetitle = ""
3727 title = {The significance of the difference between two means when
3728 the population variances are unequal},
3735 keywords = "Population",
3737 url = "http://www.jstor.org/stable/2332010",
3743 title = {The generalization of {Student's} problems when several
3744 different population variances are involved},
3751 keywords = "Population",
3753 url = "http://www.ncbi.nlm.nih.gov/pubmed/20287819",
3754 jstor_url = "http://www.jstor.org/stable/2332510",
3758 @article { granzier97,
3759 author = HLGranzier #" and "# MSKellermayer #" and "# MHelmes #" and "#
3761 title = "Titin elasticity and mechanism of passive force development in rat
3762 cardiac myocytes probed by thin-filament extraction",
3768 pages = "2043--2053",
3770 doi = "10.1016/S0006-3495(97)78234-1",
3771 url = "http://www.cell.com/biophysj/retrieve/pii/S0006349597782341",
3772 keywords = "Amino Acid Sequence;Animals;Biomechanics;Biophysical
3773 Phenomena;Biophysics;Cell Fractionation;Elasticity;Gelsolin;Microscopy,
3774 Immunoelectron;Models, Cardiovascular;Molecular Structure;Muscle
3775 Proteins;Myocardial Contraction;Myocardium;Protein
3776 Kinases;Rats;Sarcomeres",
3777 abstract = "Titin (also known as connectin) is a giant filamentous protein
3778 whose elastic properties greatly contribute to the passive force in
3779 muscle. In the sarcomere, the elastic I-band segment of titin may
3780 interact with the thin filaments, possibly affecting the molecule's
3781 elastic behavior. Indeed, several studies have indicated that
3782 interactions between titin and actin occur in vitro and may occur in
3783 the sarcomere as well. To explore the properties of titin alone, one
3784 must first eliminate the modulating effect of the thin filaments by
3785 selectively removing them. In the present work, thin filaments were
3786 selectively removed from the cardiac myocyte by using a gelsolin
3787 fragment. Partial extraction left behind approximately 100-nm-long thin
3788 filaments protruding from the Z-line, whereas the rest of the I-band
3789 became devoid of thin filaments, exposing titin. By applying a much
3790 more extensive gelsolin treatment, we also removed the remaining short
3791 thin filaments near the Z-line. After extraction, the extensibility of
3792 titin was studied by using immunoelectron microscopy, and the passive
3793 force-sarcomere length relation was determined by using mechanical
3794 techniques. Titin's regional extensibility was not detectably affected
3795 by partial thin-filament extraction. Passive force, on the other hand,
3796 was reduced at sarcomere lengths longer than approximately 2.1 microm,
3797 with a 33 +/- 9\% reduction at 2.6 microm. After a complete extraction,
3798 the slack sarcomere length was reduced to approximately 1.7 microm. The
3799 segment of titin near the Z-line, which is otherwise inextensible,
3800 collapsed toward the Z-line in sarcomeres shorter than approximately
3801 2.0 microm, but it was extended in sarcomeres longer than approximately
3802 2.3 microm. Passive force became elevated at sarcomere lengths between
3803 approximately 1.7 and approximately 2.1 microm, but was reduced at
3804 sarcomere lengths of >2.3 microm. These changes can be accounted for by
3805 modeling titin as two wormlike chains in series, one of which increases
3806 its contour length by recruitment of the titin segment near the Z-line
3807 into the elastic pool."
3810 @article { grossman05,
3811 author = CGrossman #" and "# AStout,
3812 title = "Optical Tweezers Advanced Lab",
3816 eprint = "http://chirality.swarthmore.edu/PHYS81/OpticalTweezers.pdf",
3817 note = {Fairly complete overdamped PSD derivation in
3818 \fref{section}{4.3}. Cites \citet{tlusty98} and
3819 \citet{bechhoefer02} for further details. However, Tlusty
3820 (listed as reference 8) doesn't contain the thermal response
3821 fn.\ derivation it was cited for. Also, the single sided PSD
3822 definition credited to reference 9 (listed as Bechhoefer)
3823 looks more like Press (listed as reference 10). I imagine
3824 Grossman and Stout mixed up their references, and meant to
3825 refer to \citet{bechhoefer02} and \citet{press92} respectively
3827 project = "Cantilever Calibration"
3830 @article { halvorsen09,
3831 author = KHalvorsen #" and "# WPWong,
3832 title = "Massively parallel single-molecule manipulation using centrifugal
3836 url = "http://arxiv.org/abs/0912.5370",
3837 abstract = {Precise manipulation of single molecules has already led to
3838 remarkable insights in physics, chemistry, biology and medicine.
3839 However, widespread adoption of single-molecule techniques has been
3840 impeded by equipment cost and the laborious nature of making
3841 measurements one molecule at a time. We have solved these issues with a
3842 new approach: massively parallel single-molecule force measurements
3843 using centrifugal force. This approach is realized in a novel
3844 instrument that we call the Centrifuge Force Microscope (CFM), in which
3845 objects in an orbiting sample are subjected to a calibration-free,
3846 macroscopically uniform force-field while their micro-to-nanoscopic
3847 motions are observed. We demonstrate high-throughput single-molecule
3848 force spectroscopy with this technique by performing thousands of
3849 rupture experiments in parallel, characterizing force-dependent
3850 unbinding kinetics of an antibody-antigen pair in minutes rather than
3851 days. Additionally, we verify the force accuracy of the instrument by
3852 measuring the well-established DNA overstretching transition at 66
3853 $\pm$ 3 pN. With significant benefits in efficiency, cost, simplicity,
3854 and versatility, "single-molecule centrifugation" has the potential to
3855 revolutionize single-molecule experimentation, and open access to a
3856 wider range of researchers and experimental systems.}
3859 @article { hanggi90,
3860 author = PHanggi #" and "# PTalkner #" and "# MBorkovec,
3861 title = "Reaction-rate theory: Fifty years after {K}ramers",
3870 doi = "10.1103/RevModPhys.62.251",
3871 eprint = "http://www.physik.uni-augsburg.de/theo1/hanggi/Papers/112.pdf",
3872 url = "http://prola.aps.org/abstract/RMP/v62/i2/p251_1",
3873 note = "\emph{The} Kramers' theory review article. See pages 268--279 for
3874 the Kramers-specific introduction.",
3875 project = "sawtooth simulation"
3878 @article { hatfield99,
3879 author = JWHatfield #" and "# SRQuake,
3880 title = "Dynamic Properties of an Extended Polymer in Solution",
3886 pages = "3548--3551",
3889 doi = "10.1103/PhysRevLett.82.3548",
3890 url = "http://link.aps.org/abstract/PRL/v82/p3548",
3891 note = "Defines WLC and FJC models, citing textbooks.",
3892 project = "sawtooth simulation"
3895 @article { heymann00,
3896 author = BHeymann #" and "# HGrubmuller,
3897 title = "Dynamic force spectroscopy of molecular adhesion bonds",
3904 pages = "6126--6129",
3906 doi = "10.1103/PhysRevLett.84.6126",
3907 eprint = "http://prola.aps.org/pdf/PRL/v84/i26/p6126_1",
3908 url = "http://prola.aps.org/abstract/PRL/v84/p6126",
3909 abstract = "Recent advances in atomic force microscopy, biomembrane force
3910 probe experiments, and optical tweezers allow one to measure the
3911 response of single molecules to mechanical stress with high precision.
3912 Such experiments, due to limited spatial resolution, typically access
3913 only one single force value in a continuous force profile that
3914 characterizes the molecular response along a reaction coordinate. We
3915 develop a theory that allows one to reconstruct force profiles from
3916 force spectra obtained from measurements at varying loading rates,
3917 without requiring increased resolution. We show that spectra obtained
3918 from measurements with different spring constants contain complementary
3922 @article { hummer01,
3923 author = GHummer #" and "# ASzabo,
3924 title = "From the Cover: Free energy reconstruction from nonequilibrium
3925 single-molecule pulling experiments",
3930 pages = "3658--3661",
3931 doi = "10.1073/pnas.071034098",
3932 eprint = "http://www.pnas.org/cgi/reprint/98/7/3658.pdf",
3933 url = "http://www.pnas.org/cgi/content/abstract/98/7/3658",
3937 @article { hummer03,
3938 author = GHummer #" and "# ASzabo,
3939 title = "Kinetics from nonequilibrium single-molecule pulling experiments",
3947 eprint = "http://www.biophysj.org/cgi/reprint/85/1/5.pdf",
3948 url = "http://www.biophysj.org/cgi/content/abstract/85/1/5",
3949 keywords = "Computer Simulation; Crystallography; Energy Transfer;
3950 Kinetics; Lasers; Micromanipulation; Microscopy, Atomic Force; Models,
3951 Molecular; Molecular Conformation; Motion; Muscle Proteins;
3952 Nanotechnology; Physical Stimulation; Protein Conformation; Protein
3953 Denaturation; Protein Folding; Protein Kinases; Stress, Mechanical",
3954 abstract = "Mechanical forces exerted by laser tweezers or atomic force
3955 microscopes can be used to drive rare transitions in single molecules,
3956 such as unfolding of a protein or dissociation of a ligand. The
3957 phenomenological description of pulling experiments based on Bell's
3958 expression for the force-induced rupture rate is found to be inadequate
3959 when tested against computer simulations of a simple microscopic model
3960 of the dynamics. We introduce a new approach of comparable complexity
3961 to extract more accurate kinetic information about the molecular events
3962 from pulling experiments. Our procedure is based on the analysis of a
3963 simple stochastic model of pulling with a harmonic spring and
3964 encompasses the phenomenological approach, reducing to it in the
3965 appropriate limit. Our approach is tested against computer simulations
3966 of a multimodule titin model with anharmonic linkers and then an
3967 illustrative application is made to the forced unfolding of I27
3968 subunits of the protein titin. Our procedure to extract kinetic
3969 information from pulling experiments is simple to implement and should
3970 prove useful in the analysis of experiments on a variety of systems.",
3972 project = "sawtooth simulation"
3975 @article { hutter05,
3977 title = "Comment on tilt of atomic force microscope cantilevers: Effect on
3978 spring constant and adhesion measurements.",
3985 pages = "2630--2632",
3987 doi = "10.1021/la047670t",
3988 note = "Tilted cantilever corrections (not needed? see Ohler/VEECO note)",
3989 project = "Cantilever Calibration"
3992 @article { hutter93,
3993 author = JHutter #" and "# JBechhoefer,
3994 title = "Calibration of atomic-force microscope tips",
3999 pages = "1868--1873",
4001 doi = "10.1063/1.1143970",
4002 url = "http://link.aip.org/link/?RSI/64/1868/1",
4003 keywords = {atomic force microscopy; calibration; quality factor; probes;
4004 resonance; silicon nitrides; mica; van der waals forces},
4005 note = {Original equipartition-based calibration method (thermal
4006 calibration), after the brief mention in \citet{howard88}.
4007 This is the first paper I've found that works out the theory
4008 in detail, although they punt to page 431 of \citet{heer72}
4009 instead of listing a formula for their ``Lorentzian''. The
4010 experimental data uses high-$Q$ cantilevers in air, and their
4011 figure 2 shows clear water-layer snap-off. There is a
4012 published erratum\citep{hutter93-erratum}.},
4013 project = "Cantilever Calibration"
4016 @article{ hutter93-erratum,
4017 author = JHutter #" and "# JBechhoefer,
4018 title = "Erratum: Calibration of atomic-force microscope tips",
4026 doi = "10.1063/1.1144449",
4027 url = "http://rsi.aip.org/resource/1/rsinak/v64/i11/p3342_s1",
4028 note = {V.~Croquette pointed out that they should calibrate the
4029 response of their optical-detection electronics.},
4030 project = "Cantilever Calibration",
4035 title = {Statistical mechanics, kinetic theory, and stochastic processes},
4038 address = {New York},
4040 isbn = {0-123-36550-3},
4041 language = {English},
4042 keywords = {Statistical mechanics.; Kinetic theory of gases.; Stochastic processes.},
4046 author = CHyeon #" and "# DThirumalai,
4047 title = "Can energy landscape roughness of proteins and {RNA} be measured
4048 by using mechanical unfolding experiments?",
4055 pages = "10249--10253",
4057 doi = "10.1073/pnas.1833310100",
4058 eprint = "http://www.pnas.org/cgi/reprint/100/18/10249.pdf",
4059 url = "http://www.pnas.org/cgi/content/abstract/100/18/10249",
4060 keywords = "Protein Folding; Proteins; RNA; Temperature; Thermodynamics",
4061 abstract = "By considering temperature effects on the mechanical unfolding
4062 rates of proteins and RNA, whose energy landscape is rugged, the
4063 question posed in the title is answered in the affirmative. Adopting a
4064 theory by Zwanzig [Zwanzig, R. (1988) Proc. Natl. Acad. Sci. USA 85,
4065 2029-2030], we show that, because of roughness characterized by an
4066 energy scale epsilon, the unfolding rate at constant force is retarded.
4067 Similarly, in nonequilibrium experiments done at constant loading
4068 rates, the most probable unfolding force increases because of energy
4069 landscape roughness. The effects are dramatic at low temperatures. Our
4070 analysis suggests that, by using temperature as a variable in
4071 mechanical unfolding experiments of proteins and RNA, the ruggedness
4072 energy scale epsilon, can be directly measured.",
4073 note = "Derives the major theory behind my thesis. The Kramers rate
4074 equation is \xref{hanggi90}{equation}{4.56c} (page 275).",
4075 project = "Energy Landscape Roughness"
4078 @article { improta96,
4079 author = SImprota #" and "# ASPolitou #" and "# APastore,
4080 title = "Immunoglobulin-like modules from titin {I}-band: Extensible
4081 components of muscle elasticity.",
4090 doi = "10.1016/S0969-2126(96)00036-6",
4091 keywords = "Amino Acid Sequence;Immunoglobulins;Magnetic Resonance
4092 Spectroscopy;Models, Molecular;Molecular Sequence Data;Molecular
4093 Structure;Muscle Proteins;Protein Kinases;Protein Structure,
4094 Secondary;Protein Structure, Tertiary;Sequence Alignment",
4095 abstract = "BACKGROUND. The giant muscle protein titin forms a filament
4096 which spans half of the sarcomere and performs, along its length, quite
4097 diverse functions. The region of titin located in the sarcomere I-band
4098 is believed to play a major role in extensibility and passive
4099 elasticity of muscle. In the I-band, the titin sequence consists mostly
4100 of repetitive motifs of tandem immunoglobulin-like (Ig) modules
4101 intercalated by a potentially non-globular region. The highly
4102 repetitive titin architecture suggests that the molecular basis of its
4103 mechanical properties be approached through the characterization of the
4104 isolated components of the I-band and their interfaces. In the present
4105 paper, we report on the structure determination in solution of a
4106 representative Ig module from the I-band (I27) as solved by NMR
4107 techniques. RESULTS. The structure of I27 consists of a beta sandwich
4108 formed by two four-stranded sheets (named ABED and A'GFC). This fold
4109 belongs to the intermediate frame (I frame) of the immunoglobulin
4110 superfamily. Comparison of I27 with another titin module from the
4111 region located in the M-line (M5) shows that two loops (between the B
4112 and C and the F and G strands) are shorter in I27, conferring a less
4113 elongated appearance to this structure. Such a feature is specific to
4114 the Ig domains in the I-band and might therefore be related to the
4115 functions of the protein in this region. The structure of tandem Ig
4116 domains as modeled from I27 suggests the presence of hinge regions
4117 connecting contiguous modules. CONCLUSIONS. We suggest that titin Ig
4118 domains in the I-band function as extensible components of muscle
4119 elasticity by stretching the hinge regions.",
4120 note = "\href{http://www.rcsb.org/pdb/explore.do?structureId=1TIT}{PDB ID:
4122 \href{http://dx.doi.org/10.2210/pdb1tit/pdb}{10.2210/pdb1tit/pdb}."
4125 @article { irback05,
4126 author = AIrback #" and "# SMitternacht #" and "# SMohanty,
4127 title = "Dissecting the mechanical unfolding of ubiquitin",
4132 pages = "13427--13432",
4133 doi = "10.1073/pnas.0501581102",
4134 eprint = "http://www.pnas.org/cgi/reprint/102/38/13427.pdf",
4135 url = "http://www.pnas.org/cgi/content/abstract/102/38/13427",
4136 abstract = "The unfolding behavior of ubiquitin under the influence of a
4137 stretching force recently was investigated experimentally by single-
4138 molecule constant-force methods. Many observed unfolding traces had a
4139 simple two-state character, whereas others showed clear evidence of
4140 intermediate states. Here, we use Monte Carlo simulations to
4141 investigate the force-induced unfolding of ubiquitin at the atomic
4142 level. In agreement with experimental data, we find that the unfolding
4143 process can occur either in a single step or through intermediate
4144 states. In addition to this randomness, we find that many quantities,
4145 such as the frequency of occurrence of intermediates, show a clear
4146 systematic dependence on the strength of the applied force. Despite
4147 this diversity, one common feature can be identified in the simulated
4148 unfolding events, which is the order in which the secondary-structure
4149 elements break. This order is the same in two- and three-state events
4150 and at the different forces studied. The observed order remains to be
4151 verified experimentally but appears physically reasonable."
4154 @article{ grubmuller96,
4155 author = HGrubmuller #" and "# BHeymann #" and "# PTavan,
4156 title = {Ligand binding: molecular mechanics calculation of the
4157 streptavidin-biotin rupture force.},
4161 address = {Theoretische Biophysik, Institut f{\"u}r Medizinische
4162 Optik, Ludwig- Maximilians-Universit{\"a}t M{\"u}nchen,
4163 Germany. Helmut.Grubmueller@ Physik.uni-muenchen.de},
4169 url = {http://www.ncbi.nlm.nih.gov/pubmed/8584939},
4170 eprint = {http://pubman.mpdl.mpg.de/pubman/item/escidoc:1690312:2/component/escidoc:1690313/1690312.pdf},
4172 keywords = {Bacterial Proteins},
4173 keywords = {Biotin},
4174 keywords = {Chemistry, Physical},
4175 keywords = {Computer Simulation},
4176 keywords = {Hydrogen Bonding},
4177 keywords = {Ligands},
4178 keywords = {Microscopy, Atomic Force},
4179 keywords = {Models, Chemical},
4180 keywords = {Molecular Conformation},
4181 keywords = {Physicochemical Phenomena},
4182 keywords = {Protein Conformation},
4183 keywords = {Streptavidin},
4184 keywords = {Thermodynamics},
4185 abstract = {The force required to rupture the streptavidin-biotin
4186 complex was calculated here by computer simulations.
4187 The computed force agrees well with that obtained by
4188 recent single molecule atomic force microscope
4189 experiments. These simulations suggest a detailed
4190 multiple-pathway rupture mechanism involving five major
4191 unbinding steps. Binding forces and specificity are
4192 attributed to a hydrogen bond network between the
4193 biotin ligand and residues within the binding pocket of
4194 streptavidin. During rupture, additional water bridges
4195 substantially enhance the stability of the complex and
4196 even dominate the binding interactions. In contrast,
4197 steric restraints do not appear to contribute to the
4198 binding forces, although conformational motions were
4203 @article { izrailev97,
4204 author = SIzrailev #" and "# SStepaniants #" and "# MBalsera #" and "#
4205 YOono #" and "# KSchulten,
4206 title = "Molecular dynamics study of unbinding of the avidin-biotin
4213 pages = "1568--1581",
4215 eprint = "http://www.biophysj.org/cgi/reprint/72/4/1568.pdf",
4216 url = "http://www.biophysj.org/cgi/content/abstract/72/4/1568",
4217 keywords = "Avidin;Binding Sites;Biotin;Computer Simulation;Hydrogen
4218 Bonding;Mathematics;Microscopy, Atomic Force;Microspheres;Models,
4219 Molecular;Molecular Structure;Protein Binding;Protein
4220 Conformation;Protein Folding;Sepharose",
4221 abstract = "We report molecular dynamics simulations that induce, over
4222 periods of 40-500 ps, the unbinding of biotin from avidin by means of
4223 external harmonic forces with force constants close to those of AFM
4224 cantilevers. The applied forces are sufficiently large to reduce the
4225 overall binding energy enough to yield unbinding within the measurement
4226 time. Our study complements earlier work on biotin-streptavidin that
4227 employed a much larger harmonic force constant. The simulations reveal
4228 a variety of unbinding pathways, the role of key residues contributing
4229 to adhesion as well as the spatial range over which avidin binds
4230 biotin. In contrast to the previous studies, the calculated rupture
4231 forces exceed by far those observed. We demonstrate, in the framework
4232 of models expressed in terms of one-dimensional Langevin equations with
4233 a schematic binding potential, the associated Smoluchowski equations,
4234 and the theory of first passage times, that picosecond to nanosecond
4235 simulation of ligand unbinding requires such strong forces that the
4236 resulting protein-ligand motion proceeds far from the thermally
4237 activated regime of millisecond AFM experiments, and that simulated
4238 unbinding cannot be readily extrapolated to the experimentally observed
4242 @article { janshoff00,
4243 author = AJanshoff #" and "# MNeitzert #" and "# YOberdorfer #" and "#
4245 title = "Force Spectroscopy of Molecular Systems-Single Molecule
4246 Spectroscopy of Polymers and Biomolecules.",
4253 pages = "3212--3237",
4255 doi = "10.1002/1521-3773(20000915)39:18<3212::AID-ANIE3212>3.0.CO;2-X",
4257 url = "http://dx.doi.org/10.1002/1521-3773(20000915)39:18<3212::AID-ANIE3212>3.0.CO;2-X",
4258 abstract = "How do molecules interact with each other? What happens if a
4259 neurotransmitter binds to a ligand-operated ion channel? How do
4260 antibodies recognize their antigens? Molecular recognition events play
4261 a pivotal role in nature: in enzymatic catalysis and during the
4262 replication and transcription of the genome; it is also important for
4263 the cohesion of cellular structures and in numerous metabolic reactions
4264 that molecules interact with each other in a specific manner.
4265 Conventional methods such as calorimetry provide very precise values of
4266 binding enthalpies; these are, however, average values obtained from a
4267 large ensemble of molecules without knowledge of the dynamics of the
4268 molecular recognition event. Which forces occur when a single molecular
4269 couple meets and forms a bond? Since the development of the scanning
4270 force microscope and force spectroscopy a couple of years ago, tools
4271 have now become available for measuring the forces between interfaces
4272 with high precision-starting from colloidal forces to the interaction
4273 of single molecules. The manipulation of individual molecules using
4274 force spectroscopy is also possible. In this way, the mechanical
4275 properties on a molecular scale are measurable. The study of single
4276 molecules is not an exclusive domain of force spectroscopy; it can also
4277 be performed with a surface force apparatus, laser tweezers, or the
4278 micropipette technique. Regardless of these techniques, force
4279 spectroscopy has been proven as an extraordinary versatile tool. The
4280 intention of this review article is to present a critical evaluation of
4281 the actual development of static force spectroscopy. The article mainly
4282 focuses on experiments dealing with inter- and intramolecular forces-
4283 starting with ``simple'' electrostatic forces, then ligand-receptor
4284 systems, and finally the stretching of individual molecules."
4287 @article { jollymore09,
4288 author = AJollymore #" and "# CLethias #" and "# QPeng #" and "# YCao #"
4290 title = "Nanomechanical properties of tenascin-{X} revealed by single-
4291 molecule force spectroscopy",
4298 pages = "1277--1286",
4300 doi = "10.1016/j.jmb.2008.11.038",
4301 url = "http://dx.doi.org/10.1016/j.jmb.2008.11.038",
4302 keywords = "Animals;Biomechanics;Cattle;Fibronectins;Kinetics;Microscopy,
4303 Atomic Force;Protein Folding;Protein Structure, Tertiary;Spectrum
4305 abstract = "Tenascin-X is an extracellular matrix protein and binds a
4306 variety of molecules in extracellular matrix and on cell membrane.
4307 Tenascin-X plays important roles in regulating the structure and
4308 mechanical properties of connective tissues. Using single-molecule
4309 atomic force microscopy, we have investigated the mechanical properties
4310 of bovine tenascin-X in detail. Our results indicated that tenascin-X
4311 is an elastic protein and the fibronectin type III (FnIII) domains can
4312 unfold under a stretching force and refold to regain their mechanical
4313 stability upon the removal of the stretching force. All the 30 FnIII
4314 domains of tenascin-X show similar mechanical stability, mechanical
4315 unfolding kinetics, and contour length increment upon domain unfolding,
4316 despite their large sequence diversity. In contrast to the homogeneity
4317 in their mechanical unfolding behaviors, FnIII domains fold at
4318 different rates. Using the 10th FnIII domain of tenascin-X (TNXfn10) as
4319 a model system, we constructed a polyprotein chimera composed of
4320 alternating TNXfn10 and GB1 domains and used atomic force microscopy to
4321 confirm that the mechanical properties of TNXfn10 are consistent with
4322 those of the FnIII domains of tenascin-X. These results lay the
4323 foundation to further study the mechanical properties of individual
4324 FnIII domains and establish the relationship between point mutations
4325 and mechanical phenotypic effect on tenascin-X. Moreover, our results
4326 provided the opportunity to compare the mechanical properties and
4327 design of different forms of tenascins. The comparison between
4328 tenascin-X and tenascin-C revealed interesting common as well as
4329 distinguishing features for mechanical unfolding and folding of
4330 tenascin-C and tenascin-X and will open up new avenues to investigate
4331 the mechanical functions and architectural design of different forms of
4336 author = REJones #" and "# DPHart,
4337 title = "Force interactions between substrates and {SPM} cantilevers
4338 immersed in fluids",
4345 doi = "10.1016/j.triboint.2004.08.016",
4346 url = "http://dx.doi.org/10.1016/j.triboint.2004.08.016",
4347 keywords = "AFM;Liquid;Hydrodynamic;Lubrication",
4348 abstract = "With the availability of equipment used in Scanning Probe
4349 Microscopy (SPM), researchers have been able to probe the local fluid-
4350 substrate force interactions with resolutions of pN using a variety of
4351 SPM cantilevers. When using such methods, it is essential to
4352 differentiate between contributions to the net force on the cantilever.
4353 Specifically, the interaction between the cantilever, substrate and
4354 fluid, quantified while generating force curves, are discussed and
4355 compared with theoretical models for squeeze-film effects and drag on
4356 the SPM cantilevers. In addition we have demonstrated a simple method
4357 for utilizing the system as a micro-viscometer, independently measuring
4358 the viscosity of the lubricant for each test."
4361 @article { juckett93,
4362 author = DAJuckett #" and "# BRosenberg,
4363 title = "Comparison of the {G}ompertz and {W}eibull functions as
4364 descriptors for human mortality distributions and their intersections",
4372 doi = "10.1016/0047-6374(93)90068-3",
4373 keywords = "Adolescent;Adult;Aged;Aged, 80 and
4374 over;Aging;Biometry;Child;Child, Preschool;Data Interpretation,
4375 Statistical;Female;Humans;Infant;Infant, Newborn;Longitudinal
4376 Studies;Male;Middle Aged;Models, Biological;Models,
4377 Statistical;Mortality",
4378 abstract = "The Gompertz and Weibull functions are compared with respect to
4379 goodness-of-fit to human mortality distributions; ability to describe
4380 mortality curve intersections; and, parameter interpretation. The
4381 Gompertz function is shown to be a better descriptor for 'all-causes'
4382 of deaths and combined disease categories while the Weibull function is
4383 shown to be a better descriptor of purer, single causes-of-death. A
4384 modified form of the Weibull function maps directly to the inherent
4385 degrees of freedom of human mortality distributions while the Gompertz
4386 function does not. Intersections in the old-age tails of mortality are
4387 explored in the context of both functions and, in particular, the
4388 relationship between distribution intersections, and the Gompertz
4389 ln[R0] versus alpha regression is examined. Evidence is also presented
4390 that mortality intersections are fundamental to the survivorship form
4391 and not the rate (hazard) form. Finally, comparisons are made to the
4392 parameter estimates in recent longitudinal Gompertzian analyses and the
4393 probable errors in those analyses are discussed.",
4394 note = "Nice table of various functions associated with Gompertz and
4398 @article { kaplan58,
4399 author = ELKaplan #" and "# PMeier,
4400 title = "Nonparametric Estimation from Incomplete Observations",
4409 copyright = "Copyright \copy\ 1958 American Statistical Association",
4410 url = "http://www.jstor.org/stable/2281868",
4414 @article { kellermayer03,
4415 author = MSKellermayer #" and "# CBustamante #" and "# HLGranzier,
4416 title = "Mechanics and structure of titin oligomers explored with atomic
4424 doi = "10.1016/S0005-2728(03)00029-X",
4425 url = "http://dx.doi.org/10.1016/S0005-2728(03)00029-X",
4426 keywords = "Titin;Wormlike chain;Unfolding;Elasticity;AFM;Molecular force
4428 abstract = "Titin is a giant polypeptide that spans half of the striated
4429 muscle sarcomere and generates passive force upon stretch. To explore
4430 the elastic response and structure of single molecules and oligomers of
4431 titin, we carried out molecular force spectroscopy and atomic force
4432 microscopy (AFM) on purified full-length skeletal-muscle titin. From
4433 the force data, apparent persistence lengths as long as ~1.5 nm were
4434 obtained for the single, unfolded titin molecule. Furthermore, data
4435 suggest that titin molecules may globally associate into oligomers
4436 which mechanically behave as independent wormlike chains (WLCs).
4437 Consistent with this, AFM of surface-adsorbed titin molecules revealed
4438 the presence of oligomers. Although oligomers may form globally via
4439 head-to-head association of titin, the constituent molecules otherwise
4440 appear independent from each other along their contour. Based on the
4441 global association but local independence of titin molecules, we
4442 discuss a mechanical model of the sarcomere in which titin molecules
4443 with different contour lengths, corresponding to different isoforms,
4444 are held in a lattice. The net force response of aligned titin
4445 molecules is determined by the persistence length of the tandemly
4446 arranged, different WLC components of the individual molecules, the
4447 ratio of their overall contour lengths, and by domain unfolding events.
4448 Biased domain unfolding in mechanically selected constituent molecules
4449 may serve as a compensatory mechanism for contour- and persistence-
4450 length differences. Variation in the ratio and contour length of the
4451 component chains may provide mechanisms for the fine-tuning of the
4452 sarcomeric passive force response.",
4456 @article { kellermayer97,
4457 author = MSKellermayer #" and "# SBSmith #" and "# HLGranzier #" and "#
4459 title = "Folding-unfolding transitions in single titin molecules
4460 characterized with laser tweezers",
4467 pages = "1112--1116",
4469 keywords = "Amino Acid
4470 Sequence;Elasticity;Entropy;Immunoglobulins;Lasers;Models,
4471 Chemical;Muscle Contraction;Muscle Proteins;Muscle Relaxation;Muscle,
4472 Skeletal;Protein Denaturation;Protein Folding;Protein Kinases;Stress,
4474 abstract = "Titin, a giant filamentous polypeptide, is believed to play a
4475 fundamental role in maintaining sarcomeric structural integrity and
4476 developing what is known as passive force in muscle. Measurements of
4477 the force required to stretch a single molecule revealed that titin
4478 behaves as a highly nonlinear entropic spring. The molecule unfolds in
4479 a high-force transition beginning at 20 to 30 piconewtons and refolds
4480 in a low-force transition at approximately 2.5 piconewtons. A fraction
4481 of the molecule (5 to 40 percent) remains permanently unfolded,
4482 behaving as a wormlike chain with a persistence length (a measure of
4483 the chain's bending rigidity) of 20 angstroms. Force hysteresis arises
4484 from a difference between the unfolding and refolding kinetics of the
4485 molecule relative to the stretch and release rates in the experiments,
4486 respectively. Scaling the molecular data up to sarcomeric dimensions
4487 reproduced many features of the passive force versus extension curve of
4492 author = WKing #" and "# MSu #" and "# GYang,
4493 title = "{M}onte {C}arlo simulation of mechanical unfolding of proteins
4494 based on a simple two-state model",
4498 address = "Department of Physics, Drexel University, 3141
4499 Chestnut Street, Philadelphia, PA 19104, USA.",
4505 alternative_issn = "1879-0003",
4506 doi = "10.1016/j.ijbiomac.2009.12.001",
4507 url = "http://dx.doi.org/10.1016/j.ijbiomac.2009.12.001",
4509 keywords = "Atomic force microscopy;Mechanical unfolding;Monte Carlo
4510 simulation;Worm-like chain;Single molecule methods",
4511 abstract = "Single molecule methods are becoming routine biophysical
4512 techniques for studying biological macromolecules. In mechanical
4513 unfolding of proteins, an externally applied force is used to induce
4514 the unfolding of individual protein molecules. Such experiments have
4515 revealed novel information that has significantly enhanced our
4516 understanding of the function and folding mechanisms of several types
4517 of proteins. To obtain information on the unfolding kinetics and the
4518 free energy landscape of the protein molecule from mechanical unfolding
4519 data, a Monte Carlo simulation based on a simple two-state kinetic
4520 model is often used. In this paper, we provide a detailed description
4521 of the procedure to perform such simulations and discuss the
4522 approximations and assumptions involved. We show that the appearance of
4523 the force versus extension curves from mechanical unfolding of proteins
4524 is affected by a variety of experimental parameters, such as the length
4525 of the protein polymer and the force constant of the cantilever. We
4526 also analyze the errors associated with different methods of data
4527 pooling and present a quantitative measure of how well the simulation
4528 results fit experimental data. These findings will be helpful in
4529 experimental design, artifact identification, and data analysis for
4530 single molecule studies of various proteins using the mechanical
4532 note = "Sawsim is available at \url{http://blog.tremily.us/posts/sawsim/}.",
4535 @article { kleiner07,
4536 author = AKleiner #" and "# EShakhnovich,
4537 title = "The mechanical unfolding of ubiquitin through all-atom Monte Carlo
4538 simulation with a Go-type potential",
4545 pages = "2054--2061",
4547 doi = "10.1529/biophysj.106.081257",
4548 eprint = "http://www.biophysj.org/cgi/reprint/92/6/2054",
4549 url = "http://www.biophysj.org/cgi/content/full/92/6/2054",
4550 keywords = "Computer Simulation; Models, Chemical; Models, Molecular;
4551 Models, Statistical; Monte Carlo Method; Motion; Protein Conformation;
4552 Protein Denaturation; Protein Folding; Ubiquitin",
4553 abstract = "The mechanical unfolding of proteins under a stretching force
4554 has an important role in living systems and is a logical extension of
4555 the more general protein folding problem. Recent advances in
4556 experimental methodology have allowed the stretching of single
4557 molecules, thus rendering this process ripe for computational study. We
4558 use all-atom Monte Carlo simulation with a G?-type potential to study
4559 the mechanical unfolding pathway of ubiquitin. A detailed, robust,
4560 well-defined pathway is found, confirming existing results in this vein
4561 though using a different model. Additionally, we identify the protein's
4562 fundamental stabilizing secondary structure interactions in the
4563 presence of a stretching force and show that this fundamental
4564 stabilizing role does not persist in the absence of mechanical stress.
4565 The apparent success of simulation methods in studying ubiquitin's
4566 mechanical unfolding pathway indicates their potential usefulness for
4567 future study of the stretching of other proteins and the relationship
4568 between protein structure and the response to mechanical deformation."
4571 @article { klimov00,
4572 author = DKlimov #" and "# DThirumalai,
4573 title = "Native topology determines force-induced unfolding pathways in
4581 pages = "7254--7259",
4583 doi = "10.1073/pnas.97.13.7254",
4584 eprint = "http://www.pnas.org/cgi/reprint/97/13/7254.pdf",
4585 url = "http://www.pnas.org/cgi/content/abstract/97/13/7254",
4586 keywords = "Animals; Humans; Protein Folding; Proteins; Spectrin",
4587 abstract = "Single-molecule manipulation techniques reveal that stretching
4588 unravels individually folded domains in the muscle protein titin and
4589 the extracellular matrix protein tenascin. These elastic proteins
4590 contain tandem repeats of folded domains with beta-sandwich
4591 architecture. Herein, we propose by stretching two model sequences (S1
4592 and S2) with four-stranded beta-barrel topology that unfolding forces
4593 and pathways in folded domains can be predicted by using only the
4594 structure of the native state. Thermal refolding of S1 and S2 in the
4595 absence of force proceeds in an all-or-none fashion. In contrast, phase
4596 diagrams in the force-temperature (f,T) plane and steered Langevin
4597 dynamics studies of these sequences, which differ in the native
4598 registry of the strands, show that S1 unfolds in an allor-none fashion,
4599 whereas unfolding of S2 occurs via an obligatory intermediate. Force-
4600 induced unfolding is determined by the native topology. After proving
4601 that the simulation results for S1 and S2 can be calculated by using
4602 native topology alone, we predict the order of unfolding events in Ig
4603 domain (Ig27) and two fibronectin III type domains ((9)FnIII and
4604 (10)FnIII). The calculated unfolding pathways for these proteins, the
4605 location of the transition states, and the pulling speed dependence of
4606 the unfolding forces reflect the differences in the way the strands are
4607 arranged in the native states. We also predict the mechanisms of force-
4608 induced unfolding of the coiled-coil spectrin (a three-helix bundle
4609 protein) for all 20 structures deposited in the Protein Data Bank. Our
4610 approach suggests a natural way to measure the phase diagram in the
4611 (f,C) plane, where C is the concentration of denaturants.",
4612 note = {Simulated unfolding time scales for Ig27-like S1 and S2 domains.},
4615 @article { klimov99,
4616 author = DKlimov #" and "# DThirumalai,
4617 title = "Stretching single-domain proteins: Phase diagram and kinetics of
4618 force-induced unfolding",
4625 pages = "6166--6170",
4627 keywords = "Amino Acid Sequence;Kinetics;Models, Chemical;Protein
4628 Denaturation;Protein Folding;Proteins;Thermodynamics;Time Factors",
4629 abstract = "Single-molecule force spectroscopy reveals unfolding of domains
4630 in titin on stretching. We provide a theoretical framework for these
4631 experiments by computing the phase diagrams for force-induced unfolding
4632 of single-domain proteins using lattice models. The results show that
4633 two-state folders (at zero force) unravel cooperatively, whereas
4634 stretching of non-two-state folders occurs through intermediates. The
4635 stretching rates of individual molecules show great variations
4636 reflecting the heterogeneity of force-induced unfolding pathways. The
4637 approach to the stretched state occurs in a stepwise ``quantized''
4638 manner. Unfolding dynamics and forces required to stretch proteins
4639 depend sensitively on topology. The unfolding rates increase
4640 exponentially with force f till an optimum value, which is determined
4641 by the barrier to unfolding when f = 0. A mapping of these results to
4642 proteins shows qualitative agreement with force-induced unfolding of
4643 Ig-like domains in titin. We show that single-molecule force
4644 spectroscopy can be used to map the folding free energy landscape of
4645 proteins in the absence of denaturants."
4648 @article { kosztin06,
4649 author = IKosztin #" and "# BBarz #" and "# LJanosi,
4650 title = "Calculating potentials of mean force and diffusion coefficients
4651 from nonequilibrium processes without Jarzynski's equality",
4659 doi = "10.1063/1.2166379",
4660 url = "http://link.aip.org/link/?JCPSA6/124/064106/1"
4663 @article { kramers40,
4665 title = "Brownian motion in a field of force and the diffusion model of
4666 chemical reactions",
4674 doi = "10.1016/S0031-8914(40)90098-2",
4675 url = "http://dx.doi.org/10.1016/S0031-8914(40)90098-2",
4676 abstract = "A particle which is caught in a potential hole and which,
4677 through the shuttling action of Brownian motion, can escape over a
4678 potential barrier yields a suitable model for elucidating the
4679 applicability of the transition state method for calculating the rate
4680 of chemical reactions.",
4681 note = "Seminal paper on thermally activated barrier crossings."
4684 @article { krammer99,
4685 author = AKrammer #" and "# HLu #" and "# BIsralewitz #" and "# KSchulten
4687 title = "Forced unfolding of the fibronectin type {III} module reveals a
4688 tensile molecular recognition switch",
4695 pages = "1351--1356",
4697 keywords = "Amino Acid Sequence;Binding Sites;Computer
4698 Simulation;Crystallography, X-Ray;Disulfides;Fibronectins;Hydrogen
4699 Bonding;Integrins;Models, Molecular;Oligopeptides;Protein
4700 Conformation;Protein Denaturation;Protein Folding;Protein Structure,
4701 Secondary;Protein Structure, Tertiary;Software;Tensile Strength",
4702 abstract = "The 10th type III module of fibronectin possesses a beta-
4703 sandwich structure consisting of seven beta-strands (A-G) that are
4704 arranged in two antiparallel sheets. It mediates cell adhesion to
4705 surfaces via its integrin binding motif, Arg78, Gly79, and Asp80 (RGD),
4706 which is placed at the apex of the loop connecting beta-strands F and
4707 G. Steered molecular dynamics simulations in which tension is applied
4708 to the protein's terminal ends reveal that the beta-strand G is the
4709 first to break away from the module on forced unfolding whereas the
4710 remaining fold maintains its structural integrity. The separation of
4711 strand G from the remaining fold results in a gradual shortening of the
4712 distance between the apex of the RGD-containing loop and the module
4713 surface, which potentially reduces the loop's accessibility to surface-
4714 bound integrins. The shortening is followed by a straightening of the
4715 RGD-loop from a tight beta-turn into a linear conformation, which
4716 suggests a further decrease of affinity and selectivity to integrins.
4717 The RGD-loop therefore is located strategically to undergo strong
4718 conformational changes in the early stretching stages of the module and
4719 thus constitutes a mechanosensitive control of ligand recognition."
4722 @article { kreuzer01,
4723 author = HJKreuzer #" and "# SHPayne,
4724 title = "Stretching a macromolecule in an atomic force microscope:
4725 statistical mechanical analysis",
4734 eprint = "http://www.biophysj.org/cgi/reprint/80/6/2505.pdf",
4735 url = "http://www.biophysj.org/cgi/content/abstract/80/6/2505",
4736 keywords = "Biophysics;Macromolecular Substances;Microscopy, Atomic
4737 Force;Models, Statistical;Models, Theoretical;Statistics as Topic",
4738 abstract = "We formulate the proper statistical mechanics to describe the
4739 stretching of a macromolecule under a force provided by the cantilever
4740 of an atomic force microscope. In the limit of a soft cantilever the
4741 generalized ensemble of the coupled molecule/cantilever system reduces
4742 to the Gibbs ensemble for an isolated molecule subject to a constant
4743 force in which the extension is fluctuating. For a stiff cantilever we
4744 obtain the Helmholtz ensemble for an isolated molecule held at a fixed
4745 extension with the force fluctuating. Numerical examples are given for
4746 poly (ethylene glycol) chains."
4750 author = KKroy #" and "# JGlaser,
4751 title = "The glassy wormlike chain",
4757 doi = "10.1088/1367-2630/9/11/416",
4758 eprint = "http://www.iop.org/EJ/article/1367-2630/9/11/416/njp7_11_416.pdf",
4759 url = "http://stacks.iop.org/1367-2630/9/416",
4760 abstract = "We introduce a new model for the dynamics of a wormlike chain
4761 (WLC) in an environment that gives rise to a rough free energy
4762 landscape, which we name the glassy WLC. It is obtained from the common
4763 WLC by an exponential stretching of the relaxation spectrum of its
4764 long-wavelength eigenmodes, controlled by a single parameter
4765 \\boldsymbol{\\cal E} . Predictions for pertinent observables such as
4766 the dynamic structure factor and the microrheological susceptibility
4767 exhibit the characteristics of soft glassy rheology and compare
4768 favourably with experimental data for reconstituted cytoskeletal
4769 networks and live cells. We speculate about the possible microscopic
4770 origin of the stretching, implications for the nonlinear rheology, and
4771 the potential physiological significance of our results.",
4772 note = "Has short section on WLC relaxation time in the weakly bending
4776 @article { labeit03,
4777 author = DLabeit #" and "# KWatanabe #" and "# CWitt #" and "# HFujita #"
4778 and "# YWu #" and "# SLahmers #" and "# TFunck #" and "# SLabeit #" and
4780 title = "Calcium-dependent molecular spring elements in the giant protein
4786 pages = "13716--13721",
4787 doi = "10.1073/pnas.2235652100",
4788 eprint = "http://www.pnas.org/cgi/reprint/100/23/13716.pdf",
4789 url = "http://www.pnas.org/cgi/content/abstract/100/23/13716",
4790 abstract = "Titin (also known as connectin) is a giant protein with a wide
4791 range of cellular functions, including providing muscle cells with
4792 elasticity. Its physiological extension is largely derived from the
4793 PEVK segment, rich in proline (P), glutamate (E), valine (V), and
4794 lysine (K) residues. We studied recombinant PEVK molecules containing
4795 the two conserved elements: {approx}28-residue PEVK repeats and E-rich
4796 motifs. Single molecule experiments revealed that calcium-induced
4797 conformational changes reduce the bending rigidity of the PEVK
4798 fragments, and site-directed mutagenesis identified four glutamate
4799 residues in the E-rich motif that was studied (exon 129), as critical
4800 for this process. Experiments with muscle fibers showed that titin-
4801 based tension is calcium responsive. We propose that the PEVK segment
4802 contains E-rich motifs that render titin a calcium-dependent molecular
4803 spring that adapts to the physiological state of the cell."
4807 author = SLabeit #" and "# BKolmerer,
4808 title = "Titins: Giant proteins in charge of muscle ultrastructure
4814 address = "European Molecular Biology Laboratory, Heidelberg, Germany.",
4818 keywords = "Actin Cytoskeleton",
4819 keywords = "Amino Acid Sequence",
4820 keywords = "Animals",
4821 keywords = "DNA, Complementary",
4822 keywords = "Elasticity",
4823 keywords = "Fibronectins",
4824 keywords = "Humans",
4825 keywords = "Immunoglobulins",
4826 keywords = "Molecular Sequence Data",
4827 keywords = "Muscle Contraction",
4828 keywords = "Muscle Proteins",
4829 keywords = "Muscle, Skeletal",
4830 keywords = "Myocardium",
4831 keywords = "Protein Kinases",
4832 keywords = "Rabbits",
4833 keywords = "Repetitive Sequences, Nucleic Acid",
4834 keywords = "Sarcomeres",
4835 abstract = "In addition to thick and thin filaments, vertebrate
4836 striated muscle contains a third filament system formed by the
4837 giant protein titin. Single titin molecules extend from Z discs to
4838 M lines and are longer than 1 micrometer. The titin filament
4839 contributes to muscle assembly and resting tension, but more
4840 details are not known because of the large size of the
4841 protein. The complete complementary DNA sequence of human cardiac
4842 titin was determined. The 82-kilobase complementary DNA predicts a
4843 3-megadalton protein composed of 244 copies of immunoglobulin and
4844 fibronectin type III (FN3) domains. The architecture of sequences
4845 in the A band region of titin suggests why thick filament
4846 structure is conserved among vertebrates. In the I band region,
4847 comparison of titin sequences from muscles of different passive
4848 tension identifies two elements that correlate with tissue
4849 stiffness. This suggests that titin may act as two springs in
4850 series. The differential expression of the springs provides a
4851 molecular explanation for the diversity of sarcomere length and
4852 resting tension in vertebrate striated muscles.",
4854 URL = "http://www.ncbi.nlm.nih.gov/pubmed/7569978",
4859 author = RLaw #" and "# GLiao #" and "# SHarper #" and "# GYang #" and "#
4860 DSpeicher #" and "# DDischer,
4861 title = "Pathway shifts and thermal softening in temperature-coupled forced
4862 unfolding of spectrin domains",
4863 address = "Biophysical Engineering Lab, Institute for Medicine and
4864 Engineering, and School of Engineering and Applied Science,
4865 University of Pennsylvania, Philadelphia, Pennsylvania
4872 pages = "3286--3293",
4874 keywords = "Circular Dichroism;Elasticity;Heat;Microscopy, Atomic
4875 Force;Physical Stimulation;Protein Conformation;Protein
4876 Denaturation;Protein Folding;Protein Structure,
4877 Tertiary;Spectrin;Stress, Mechanical;Temperature",
4878 abstract = "Pathways of unfolding a protein depend in principle on the
4879 perturbation-whether it is temperature, denaturant, or even forced
4880 extension. Widely-shared, helical-bundle spectrin repeats are known to
4881 melt at temperatures as low as 40-45 degrees C and are also known to
4882 unfold via multiple pathways as single molecules in atomic force
4883 microscopy. Given the varied roles of spectrin family proteins in cell
4884 deformability, we sought to determine the coupled effects of
4885 temperature on forced unfolding. Bimodal distributions of unfolding
4886 intervals are seen at all temperatures for the four-repeat beta(1-4)
4887 spectrin-an alpha-actinin homolog. The major unfolding length
4888 corresponds to unfolding of a single repeat, and a minor peak at twice
4889 the length corresponds to tandem repeats. Increasing temperature shows
4890 fewer tandem events but has no effect on unfolding intervals. As T
4891 approaches T(m), however, mean unfolding forces in atomic force
4892 microscopy also decrease; and circular dichroism studies demonstrate a
4893 nearly proportional decrease of helical content in solution. The
4894 results imply a thermal softening of a helical linker between repeats
4895 which otherwise propagates a helix-to-coil transition to adjacent
4896 repeats. In sum, structural changes with temperature correlate with
4897 both single-molecule unfolding forces and shifts in unfolding
4899 doi = "10.1016/S0006-3495(03)74747-X",
4900 URL = "http://www.ncbi.nlm.nih.gov/pubmed/14581229",
4904 @article { levinthal68,
4905 author = CLevinthal,
4906 title = "Are there pathways for protein folding?",
4913 "http://www.biochem.wisc.edu/courses/biochem704/Reading/Levinthal1968.p
4915 note = "\emph{Not} Levinthal's paradox."
4918 @inproceedings { levinthal69,
4919 editor = PDebrunner #" and "# JCMTsibris #" and "# EMunck,
4920 author = CLevinthal,
4921 title = "How to Fold Graciously.",
4922 booktitle = "Mossbauer Spectroscopy in Biological Systems",
4925 publisher = UIP:Urbana,
4926 address = "Allerton House, Monticello, IL",
4927 url = "http://www-miller.ch.cam.ac.uk/levinthal/levinthal.html"
4931 author = RLevy #" and "# MMaaloum,
4932 title = "Measuring the spring constant of atomic force microscope
4933 cantilevers: Thermal fluctuations and other methods",
4939 doi = "10.1088/0957-4484/13/1/307",
4940 url = "http://stacks.iop.org/0957-4484/13/33",
4941 abstract = "Knowledge of the interaction forces between surfaces gained
4942 using an atomic force microscope (AFM) is crucial in a variety of
4943 industrial and scientific applications and necessitates a precise
4944 knowledge of the cantilever spring constant. Many methods have been
4945 devised to experimentally determine the spring constants of AFM
4946 cantilevers. The thermal fluctuation method is elegant but requires a
4947 theoretical model of the bending modes. For a rectangular cantilever,
4948 this model is available (Butt and Jaschke). Detailed thermal
4949 fluctuation measurements of a series of AFM cantilever beams have been
4950 performed in order to test the validity and accuracy of the recent
4951 theoretical models. The spring constant of rectangular cantilevers can
4952 also be determined easily with the method of Sader and White. We found
4953 very good agreement between the two methods. In the case of the
4954 V-shaped cantilever, we have shown that the thermal fluctuation method
4955 is a valid and accurate approach to the evaluation of the spring
4956 constant. A comparison between this method and those of Sader-
4957 Neumeister and of Ducker has been established. In some cases, we found
4958 disagreement between these two methods; the effect of non-conservation
4959 of material properties over all cantilevers from a single chip is
4960 qualitatively invoked.",
4961 note = "Good review of thermal calibration to 2002, but not much on the
4962 derviation of the Lorentzian fit.",
4963 project = "Cantilever Calibration"
4967 author = HLi #" and "# AOberhauser #" and "# SFowler #" and "# JClarke #"
4969 title = "Atomic force microscopy reveals the mechanical design of a modular
4975 pages = "6527--6531",
4976 doi = "10.1073/pnas.120048697",
4977 eprint = "http://www.pnas.org/cgi/reprint/97/12/6527.pdf",
4978 url = "http://www.pnas.org/cgi/content/abstract/97/12/6527",
4980 note = "Unfolding order not from protein-surface interactions. Mechanical
4981 unfolding of a chain of interleaved domains $ABABAB\ldots$ yielded a
4982 run of $A$ unfoldings followed by a run of $B$ unfoldings."
4986 author = HLi #" and "# AOberhauser #" and "# SRedick #" and "#
4987 MCarrionVazquez #" and "# HErickson #" and "# JFernandez,
4988 title = "Multiple conformations of {PEVK} proteins detected by single-
4989 molecule techniques",
4994 pages = "10682--10686",
4995 doi = "10.1073/pnas.191189098",
4996 eprint = "http://www.pnas.org/cgi/reprint/98/19/10682.pdf",
4997 url = "http://www.pnas.org/cgi/content/abstract/98/19/10682",
4998 abstract = "An important component of muscle elasticity is the PEVK region
4999 of titin, so named because of the preponderance of these amino acids.
5000 However, the PEVK region, similar to other elastomeric proteins, is
5001 thought to form a random coil and therefore its structure cannot be
5002 determined by standard techniques. Here we combine single-molecule
5003 electron microscopy and atomic force microscopy to examine the
5004 conformations of the human cardiac titin PEVK region. In contrast to a
5005 simple random coil, we have found that cardiac PEVK shows a wide range
5006 of elastic conformations with end-to-end distances ranging from 9 to 24
5007 nm and persistence lengths from 0.4 to 2.5 nm. Individual PEVK
5008 molecules retained their distinctive elastic conformations through many
5009 stretch-relaxation cycles, consistent with the view that these PEVK
5010 conformers cannot be interconverted by force. The multiple elastic
5011 conformations of cardiac PEVK may result from varying degrees of
5012 proline isomerization. The single-molecule techniques demonstrated here
5013 may help elucidate the conformation of other proteins that lack a well-
5018 author = HLi #" and "# JFernandez,
5019 title = "Mechanical design of the first proximal Ig domain of human cardiac
5020 titin revealed by single molecule force spectroscopy",
5029 doi = "10.1016/j.jmb.2003.09.036",
5030 keywords = "Amino Acid Sequence;Disulfides;Humans;Immunoglobulins;Models,
5031 Molecular;Molecular Sequence Data;Muscle Proteins;Myocardium;Protein
5032 Denaturation;Protein Engineering;Protein Kinases;Protein Structure,
5033 Tertiary;Spectrum Analysis",
5034 abstract = "The elastic I-band part of muscle protein titin contains two
5035 tandem immunoglobulin (Ig) domain regions of distinct mechanical
5036 properties. Until recently, the only known structure was that of the
5037 I27 module of the distal region, whose mechanical properties have been
5038 reported in detail. Recently, the structure of the first proximal
5039 domain, I1, has been resolved at 2.1A. In addition to the
5040 characteristic beta-sandwich structure of all titin Ig domains, the
5041 crystal structure of I1 showed an internal disulfide bridge that was
5042 proposed to modulate its mechanical extensibility in vivo. Here, we use
5043 single molecule force spectroscopy and protein engineering to examine
5044 the mechanical architecture of this domain. In contrast to the
5045 predictions made from the X-ray crystal structure, we find that the
5046 formation of a disulfide bridge in I1 is a relatively rare event in
5047 solution, even under oxidative conditions. Furthermore, our studies of
5048 the mechanical stability of I1 modules engineered with point mutations
5049 reveal significant differences between the mechanical unfolding of the
5050 I1 and I27 modules. Our study illustrates the varying mechanical
5051 architectures of the titin Ig modules."
5055 author = LeLi #" and "# HHuang #" and "# CBadilla #" and "# JFernandez,
5056 title = "Mechanical unfolding intermediates observed by single-molecule
5057 force spectroscopy in a fibronectin type {III} module",
5066 doi = "10.1016/j.jmb.2004.11.021",
5067 keywords = "Fibronectins;Kinetics;Microscopy, Atomic Force;Models,
5068 Molecular;Mutagenesis, Site-Directed;Protein Denaturation;Protein
5069 Folding;Protein Structure, Tertiary;Recombinant Fusion Proteins",
5070 abstract = "Domain 10 of type III fibronectin (10FNIII) is known to play a
5071 pivotal role in the mechanical interactions between cell surface
5072 integrins and the extracellular matrix. Recent molecular dynamics
5073 simulations have predicted that 10FNIII, when exposed to a stretching
5074 force, unfolds along two pathways, each with a distinct, mechanically
5075 stable intermediate. Here, we use single-molecule force spectroscopy
5076 combined with protein engineering to test these predictions by probing
5077 the mechanical unfolding pathway of 10FNIII. Stretching single
5078 polyproteins containing the 10FNIII module resulted in sawtooth
5079 patterns where 10FNIII was seen unfolding in two consecutive steps. The
5080 native state unfolded at 100(+/-20) pN, elongating (10)FNIII by
5081 12(+/-2) nm and reaching a clearly marked intermediate that unfolded at
5082 50(+/-20) pN. Unfolding of the intermediate completed the elongation of
5083 the molecule by extending another 19(+/-2) nm. Site-directed
5084 mutagenesis of residues in the A and B beta-strands (E9P and L19P)
5085 resulted in sawtooth patterns with all-or-none unfolding events that
5086 elongated the molecule by 19(+/-2) nm. In contrast, mutating residues
5087 in the G beta-strand gave results that were dependent on amino acid
5088 position. The mutation I88P in the middle of the G beta-strand resulted
5089 in native like unfolding sawtooth patterns showing an intact
5090 intermediate state. The mutation Y92P, which is near the end of G beta-
5091 strand, produced sawtooth patterns with all-or-none unfolding events
5092 that lengthened the molecule by 17(+/-2) nm. These results are
5093 consistent with the view that 10FNIII can unfold in two different ways.
5094 Along one pathway, the detachment of the A and B beta-strands from the
5095 body of the folded module constitute the first unfolding event,
5096 followed by the unfolding of the remaining beta-sandwich structure.
5097 Along the second pathway, the detachment of the G beta-strands is
5098 involved in the first unfolding event. These results are in excellent
5099 agreement with the sequence of events predicted by molecular dynamics
5100 simulations of the 10FNIII module."
5104 author = MSLi #" and "# CKHu #" and "# DKlimov #" and "# DThirumalai,
5105 title = "Multiple stepwise refolding of immunoglobulin domain {I27} upon
5106 force quench depends on initial conditions",
5112 doi = "10.1073/pnas.0503758103",
5113 eprint = "http://www.pnas.org/cgi/reprint/103/1/93.pdf",
5114 url = "http://www.pnas.org/cgi/content/abstract/103/1/93",
5115 abstract = "Mechanical folding trajectories for polyproteins starting from
5116 initially stretched conformations generated by single-molecule atomic
5117 force microscopy experiments [Fernandez, J. M. & Li, H. (2004) Science
5118 303, 1674-1678] show that refolding, monitored by the end-to-end
5119 distance, occurs in distinct multiple stages. To clarify the molecular
5120 nature of folding starting from stretched conformations, we have probed
5121 the folding dynamics, upon force quench, for the single I27 domain from
5122 the muscle protein titin by using a C{alpha}-Go model. Upon temperature
5123 quench, collapse and folding of I27 are synchronous. In contrast,
5124 refolding from stretched initial structures not only increases the
5125 folding and collapse time scales but also decouples the two kinetic
5126 processes. The increase in the folding times is associated primarily
5127 with the stretched state to compact random coil transition.
5128 Surprisingly, force quench does not alter the nature of the refolding
5129 kinetics, but merely increases the height of the free-energy folding
5130 barrier. Force quench refolding times scale as f1.gif, where {Delta}xf
5131 {approx} 0.6 nm is the location of the average transition state along
5132 the reaction coordinate given by end-to-end distance. We predict that
5133 {tau}F and the folding mechanism can be dramatically altered by the
5134 initial and/or final values of force. The implications of our results
5135 for design and analysis of experiments are discussed."
5140 title = "Divergence measures based on the {S}hannon entropy",
5148 doi = "10.1109/18.61115",
5149 url = "http://ieeexplore.ieee.org/xpl/freeabs_all.jsp?isnumber=2227&arnumbe
5150 r=61115&count=35&index=9",
5151 keywords = "divergence;dissimilarity measure;discrimintation
5152 information;entropy;probability of error bounds",
5153 abstract = "A novel class of information-theoretic divergence measures
5154 based on the Shannon entropy is introduced. Unlike the well-known
5155 Kullback divergences, the new measures do not require the condition of
5156 absolute continuity to be satisfied by the probability distributions
5157 involved. More importantly, their close relationship with the
5158 variational distance and the probability of misclassification error are
5159 established in terms of bounds. These bounds are crucial in many
5160 applications of divergence measures. The measures are also well
5161 characterized by the properties of nonnegativity, finiteness,
5162 semiboundedness, and boundedness."
5166 author = WALinke #" and "# AGrutzner,
5167 title = "Pulling single molecules of titin by {AFM}--recent advances and
5168 physiological implications",
5177 doi = "10.1007/s00424-007-0389-x",
5178 abstract = "Perturbation of a protein away from its native state by
5179 mechanical stress is a physiological process immanent to many cells.
5180 The mechanical stability and conformational diversity of proteins under
5181 force therefore are important parameters in nature. Molecular-level
5182 investigations of ``mechanical proteins'' have enjoyed major
5183 breakthroughs over the last decade, a development to which atomic force
5184 microscopy (AFM) force spectroscopy has been instrumental. The giant
5185 muscle protein titin continues to be a paradigm model in this field. In
5186 this paper, we review how single-molecule mechanical measurements of
5187 titin using AFM have served to elucidate key aspects of protein
5188 unfolding-refolding and mechanisms by which biomolecular elasticity is
5189 attained. We outline recent work combining protein engineering and AFM
5190 force spectroscopy to establish the mechanical behavior of titin
5191 domains using molecular ``fingerprinting.'' Furthermore, we summarize
5192 AFM force-extension data demonstrating different mechanical stabilities
5193 of distinct molecular-spring elements in titin, compare AFM force-
5194 extension to novel force-ramp/force-clamp studies, and elaborate on
5195 exciting new results showing that AFM force clamp captures the
5196 unfolding and refolding trajectory of single mechanical proteins. Along
5197 the way, we discuss the physiological implications of the findings, not
5198 least with respect to muscle mechanics. These studies help us
5199 understand how proteins respond to forces in cells and how
5200 mechanosensing and mechanosignaling events may proceed in vivo."
5203 @article { linke98a,
5204 author = WALinke #" and "# MRStockmeier #" and "# MIvemeyer #" and "#
5205 HHosser #" and "# PMundel,
5206 title = "Characterizing titin's {I}-band {Ig} domain region as an entropic
5211 volume = "111 (Pt 11)",
5212 pages = "1567--1574",
5215 eprint = "http://jcs.biologists.org/cgi/reprint/111/11/1567",
5216 url = "http://jcs.biologists.org/cgi/content/abstract/111/11/1567",
5217 keywords = "Animals;Elasticity;Immunoglobulins;Male;Muscle Proteins;Muscle,
5218 Skeletal;Protein Kinases;Rats;Rats, Wistar;Structure-Activity
5220 abstract = "The poly-immunoglobulin domain region of titin, located within
5221 the elastic section of this giant muscle protein, determines the
5222 extensibility of relaxed myofibrils mainly at shorter physiological
5223 lengths. To elucidate this region's contribution to titin elasticity,
5224 we measured the elastic properties of the N-terminal I-band Ig region
5225 by using immunofluorescence/immunoelectron microscopy and myofibril
5226 mechanics and tried to simulate the results with a model of entropic
5227 polymer elasticity. Rat psoas myofibrils were stained with titin-
5228 specific antibodies flanking the Ig region at the N terminus and C
5229 terminus, respectively, to record the extension behaviour of that titin
5230 segment. The segment's end-to-end length increased mainly at small
5231 stretch, reaching approximately 90\% of the native contour length of
5232 the Ig region at a sarcomere length of 2.8 microm. At this extension,
5233 the average force per single titin molecule, deduced from the steady-
5234 state passive length-tension relation of myofibrils, was approximately
5235 5 or 2.5 pN, depending on whether we assumed a number of 3 or 6 titins
5236 per half thick filament. When the force-extension curve constructed for
5237 the Ig region was simulated by the wormlike chain model, best fits were
5238 obtained for a persistence length, a measure of the chain's bending
5239 rigidity, of 21 or 42 nm (for 3 or 6 titins/half thick filament), which
5240 correctly reproduced the curve for sarcomere lengths up to 3.4 microm.
5241 Systematic deviations between data and fits above that length indicated
5242 that forces of >30 pN per titin strand may induce unfolding of Ig
5243 modules. We conclude that stretches of at least 5-6 Ig domains, perhaps
5244 coinciding with known super repeat patterns of these titin modules in
5245 the I-band, may represent the unitary lengths of the wormlike chain.
5246 The poly-Ig regions might thus act as compliant entropic springs that
5247 determine the minute levels of passive tension at low extensions of a
5251 @article { linke98b,
5252 author = WALinke #" and "# MIvemeyer #" and "# PMundel #" and "#
5253 MRStockmeier #" and "# BKolmerer,
5254 title = "Nature of {PEVK}-titin elasticity in skeletal muscle",
5261 pages = "8052--8057",
5263 keywords = "Animals;Elasticity;Fluorescent Antibody
5264 Technique;Male;Microscopy, Immunoelectron;Muscle Proteins;Muscle,
5265 Skeletal;Protein Kinases;Rats;Rats, Wistar;Stress, Mechanical",
5266 abstract = "A unique sequence within the giant titin molecule, the PEVK
5267 domain, has been suggested to greatly contribute to passive force
5268 development of relaxed skeletal muscle during stretch. To explore the
5269 nature of PEVK elasticity, we used titin-specific antibodies to stain
5270 both ends of the PEVK region in rat psoas myofibrils and determined the
5271 region's force-extension relation by combining immunofluorescence and
5272 immunoelectron microscopy with isolated myofibril mechanics. We then
5273 tried to fit the results with recent models of polymer elasticity. The
5274 PEVK segment elongated substantially at sarcomere lengths above 2.4
5275 micro(m) and reached its estimated contour length at approximately 3.5
5276 micro(m). In immunofluorescently labeled sarcomeres stretched and
5277 released repeatedly above 3 micro(m), reversible PEVK lengthening could
5278 be readily visualized. At extensions near the contour length, the
5279 average force per titin molecule was calculated to be approximately 45
5280 pN. Attempts to fit the force-extension curve of the PEVK segment with
5281 a standard wormlike chain model of entropic elasticity were successful
5282 only for low to moderate extensions. In contrast, the experimental data
5283 also could be correctly fitted at high extensions with a modified
5284 wormlike chain model that incorporates enthalpic elasticity. Enthalpic
5285 contributions are likely to arise from electrostatic stiffening, as
5286 evidenced by the ionic-strength dependency of titin-based myofibril
5287 stiffness; at high stretch, hydrophobic effects also might become
5288 relevant. Thus, at physiological muscle lengths, the PEVK region does
5289 not function as a pure entropic spring. Rather, PEVK elasticity may
5290 have both entropic and enthalpic origins characterizable by a polymer
5291 persistence length and a stretch modulus."
5295 author = WLiu #" and "# VMontana #" and "# EChapman #" and "# UMohideen #"
5297 title = "Botulinum toxin type {B} micromechanosensor",
5302 pages = "13621--13625",
5303 doi = "10.1073/pnas.2233819100",
5304 eprint = "http://www.pnas.org/cgi/reprint/100/23/13621.pdf",
5305 url = "http://www.pnas.org/cgi/content/abstract/100/23/13621",
5306 abstract = "Botulinum neurotoxin (BoNT) types A, B, E, and F are toxic to
5307 humans; early and rapid detection is essential for adequate medical
5308 treatment. Presently available tests for detection of BoNTs, although
5309 sensitive, require hours to days. We report a BoNT-B sensor whose
5310 properties allow detection of BoNT-B within minutes. The technique
5311 relies on the detection of an agarose bead detachment from the tip of a
5312 micromachined cantilever resulting from BoNT-B action on its
5313 substratum, the synaptic protein synaptobrevin 2, attached to the
5314 beads. The mechanical resonance frequency of the cantilever is
5315 monitored for the detection. To suspend the bead off the cantilever we
5316 use synaptobrevin's molecular interaction with another synaptic
5317 protein, syntaxin 1A, that was deposited onto the cantilever tip.
5318 Additionally, this bead detachment technique is general and can be used
5319 in any displacement reaction, such as in receptor-ligand pairs, where
5320 the introduction of one chemical leads to the displacement of another.
5321 The technique is of broad interest and will find uses outside
5326 author = GLois #" and "# JBlawzdziewicz #" and "# CSOHern,
5327 title = "Reliable protein folding on complex energy landscapes: the free
5328 energy reaction path",
5335 pages = "2692--2701",
5337 doi = "10.1529/biophysj.108.133132",
5338 abstract = "A theoretical framework is developed to study the dynamics of
5339 protein folding. The key insight is that the search for the native
5340 protein conformation is influenced by the rate r at which external
5341 parameters, such as temperature, chemical denaturant, or pH, are
5342 adjusted to induce folding. A theory based on this insight predicts
5343 that 1), proteins with complex energy landscapes can fold reliably to
5344 their native state; 2), reliable folding can occur as an equilibrium or
5345 out-of-equilibrium process; and 3), reliable folding only occurs when
5346 the rate r is below a limiting value, which can be calculated from
5347 measurements of the free energy. We test these predictions against
5348 numerical simulations of model proteins with a single energy scale."
5352 author = HLu #" and "# AKrammer #" and "# BIsralewitz #" and "# VVogel #"
5354 title = "Computer modeling of force-induced titin domain unfolding",
5356 journal = AdvExpMedBiol,
5360 url = {http://www.ncbi.nlm.nih.gov/pubmed/10987071},
5361 keywords = "Amino Acid Sequence;Animals;Computer
5362 Simulation;Elasticity;Fibronectins;Humans;Hydrogen
5363 Bonding;Immunoglobulins;Models, Molecular;Muscle Proteins;Muscle,
5364 Skeletal;Myofibrils;Protein Conformation;Protein Denaturation;Protein
5366 abstract = "Titin, a 1 micron long protein found in striated muscle
5367 myofibrils, possesses unique elastic and extensibility properties, and
5368 is largely composed of a PEVK region and beta-sandwich immunoglobulin
5369 (Ig) and fibronectin type III (FnIII) domains. The extensibility
5370 behavior of titin has been shown in atomic force microscope and optical
5371 tweezer experiments to partially depend on the reversible unfolding of
5372 individual Ig and FnIII domains. We performed steered molecular
5373 dynamics simulations to stretch single titin Ig domains in solution
5374 with pulling speeds of 0.1-1.0 A/ps, and FnIII domains with a pulling
5375 speed of 0.5 A/ps. Resulting force-extension profiles exhibit a single
5376 dominant peak for each domain unfolding, consistent with the
5377 experimentally observed sequential, as opposed to concerted, unfolding
5378 of Ig and FnIII domains under external stretching forces. The force
5379 peaks can be attributed to an initial burst of a set of backbone
5380 hydrogen bonds connected to the domains' terminal beta-strands.
5381 Constant force stretching simulations, applying 500-1000 pN of force,
5382 were performed on Ig domains. The resulting domain extensions are
5383 halted at an initial extension of 10 A until the set of all six
5384 hydrogen bonds connecting terminal beta-strands break simultaneously.
5385 This behavior is accounted for by a barrier separating folded and
5386 unfolded states, the shape of which is consistent with AFM and chemical
5387 denaturation data.",
5388 note = "discussion in journal on pages 161--2"
5392 author = HLu #" and "# KSchulten,
5393 title = "The key event in force-induced unfolding of Titin's immunoglobulin
5402 doi = {10.1016/S0006-3495(00)76273-4},
5403 url = {http://www.cell.com/biophysj/abstract/S0006-3495%2800%2976273-4},
5404 eprint = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1300915/pdf/10866937.pdf},
5405 keywords = "Amino Acid Sequence;Computer Simulation;Double Bind
5406 Interaction;Hydrogen Bonding;Immunoglobulins;Microscopy, Atomic
5407 Force;Models, Chemical;Models, Molecular;Molecular Sequence Data;Muscle
5408 Proteins;Protein Folding;Protein Kinases;Protein Structure,
5409 Tertiary;Stress, Mechanical;Water",
5410 abstract = "Steered molecular dynamics simulation of force-induced titin
5411 immunoglobulin domain I27 unfolding led to the discovery of a
5412 significant potential energy barrier at an extension of approximately
5413 14 A on the unfolding pathway that protects the domain against
5414 stretching. Previous simulations showed that this barrier is due to the
5415 concurrent breaking of six interstrand hydrogen bonds (H-bonds) between
5416 beta-strands A' and G that is preceded by the breaking of two to three
5417 hydrogen bonds between strands A and B, the latter leading to an
5418 unfolding intermediate. The simulation results are supported by
5419 Angstrom-resolution atomic force microscopy data. Here we perform a
5420 structural and energetic analysis of the H-bonds breaking. It is
5421 confirmed that H-bonds between strands A and B break rapidly. However,
5422 the breaking of the H-bond between strands A' and G needs to be
5423 assisted by fluctuations of water molecules. In nanosecond simulations,
5424 water molecules are found to repeatedly interact with the protein
5425 backbone atoms, weakening individual interstrand H-bonds until all six
5426 A'-G H-bonds break simultaneously under the influence of external
5427 stretching forces. Only when those bonds are broken can the generic
5428 unfolding take place, which involves hydrophobic interactions of the
5429 protein core and exerts weaker resistance against stretching than the
5434 author = HLu #" and "# BIsralewitz #" and "# AKrammer #" and "# VVogel #"
5436 title = "Unfolding of titin immunoglobulin domains by steered molecular
5437 dynamics simulation",
5445 doi = "10.1016/S0006-3495(98)77556-3",
5446 eprint = "http://download.cell.com/biophysj/pdf/PIIS0006349598775563.pdf",
5447 url = "http://www.cell.com/biophysj/abstract/S0006-3495(98)77556-3",
5448 keywords = "Amino Acid Sequence;Animals;Computer Simulation;Glutamic
5449 Acid;Immunoglobulins;Lysine;Macromolecular Substances;Models,
5450 Molecular;Molecular Sequence Data;Muscle
5451 Proteins;Myocardium;Proline;Protein Denaturation;Protein
5452 Folding;Protein Kinases;Protein Structure, Secondary;Sequence
5453 Alignment;Sequence Homology, Amino Acid;Valine",
5454 abstract = "Titin, a 1-microm-long protein found in striated muscle
5455 myofibrils, possesses unique elastic and extensibility properties in
5456 its I-band region, which is largely composed of a PEVK region (70\%
5457 proline, glutamic acid, valine, and lysine residue) and seven-strand
5458 beta-sandwich immunoglobulin-like (Ig) domains. The behavior of titin
5459 as a multistage entropic spring has been shown in atomic force
5460 microscope and optical tweezer experiments to partially depend on the
5461 reversible unfolding of individual Ig domains. We performed steered
5462 molecular dynamics simulations to stretch single titin Ig domains in
5463 solution with pulling speeds of 0.5 and 1.0 A/ps. Resulting force-
5464 extension profiles exhibit a single dominant peak for each Ig domain
5465 unfolding, consistent with the experimentally observed sequential, as
5466 opposed to concerted, unfolding of Ig domains under external stretching
5467 forces. This force peak can be attributed to an initial burst of
5468 backbone hydrogen bonds, which takes place between antiparallel beta-
5469 strands A and B and between parallel beta-strands A' and G. Additional
5470 features of the simulations, including the position of the force peak
5471 and relative unfolding resistance of different Ig domains, can be
5472 related to experimental observations."
5476 author = HLu #" and "# KSchulten,
5477 title = "Steered molecular dynamics simulations of force-induced protein
5487 doi = "10.1002/(SICI)1097-0134(19990601)35:4<453::AID-PROT9>3.0.CO;2-M",
5488 eprint = "http://www3.interscience.wiley.com/cgi-bin/fulltext/65000328/PDFSTART",
5489 url = "http://www3.interscience.wiley.com/journal/65000328/abstract",
5490 keywords = "Computer Simulation;Fibronectins;Hydrogen Bonding;Microscopy,
5491 Atomic Force;Models, Molecular;Protein Denaturation",
5492 abstract = "Steered molecular dynamics (SMD), a computer simulation method
5493 for studying force-induced reactions in biopolymers, has been applied
5494 to investigate the response of protein domains to stretching apart of
5495 their terminal ends. The simulations mimic atomic force microscopy and
5496 optical tweezer experiments, but proceed on much shorter time scales.
5497 The simulations on different domains for 0.6 nanosecond each reveal two
5498 types of protein responses: the first type, arising in certain beta-
5499 sandwich domains, exhibits nanosecond unfolding only after a force
5500 above 1,500 pN is applied; the second type, arising in a wider class of
5501 protein domain structures, requires significantly weaker forces for
5502 nanosecond unfolding. In the first case, strong forces are needed to
5503 concertedly break a set of interstrand hydrogen bonds which protect the
5504 domains against unfolding through stretching; in the second case,
5505 stretching breaks backbone hydrogen bonds one by one, and does not
5506 require strong forces for this purpose. Stretching of beta-sandwich
5507 (immunoglobulin) domains has been investigated further revealing a
5508 specific relationship between response to mechanical strain and the
5509 architecture of beta-sandwich domains."
5512 @article { makarov01,
5513 author = DEMakarov #" and "# PHansma #" and "# HMetiu,
5514 title = "Kinetic Monte Carlo simulation of titin unfolding",
5520 pages = "9663--9673",
5522 doi = "10.1063/1.1369622",
5523 eprint = "http://hansmalab.physics.ucsb.edu/pdf/297%20-%20Makarov,%20D.E._J
5524 .Chem.Phys._2001.pdf",
5525 url = "http://link.aip.org/link/?JCP/114/9663/1",
5526 keywords = "proteins; hydrogen bonds; digital simulation; Monte Carlo
5527 methods; molecular biophysics; intramolecular mechanics;
5528 macromolecules; atomic force microscopy"
5532 author = JFMarko #" and "# EDSiggia,
5533 title = "Stretching {DNA}",
5539 pages = "8759--8770",
5541 eprint = "http://pubs.acs.org/cgi-
5542 bin/archive.cgi/mamobx/1995/28/i26/pdf/ma00130a008.pdf",
5544 "http://pubs3.acs.org/acs/journals/doilookup?in_doi=10.1021/ma00130a008
5547 note = "Derivation of the Worm-like Chain interpolation function."
5550 @article { marszalek02,
5551 author = PMarszalek #" and "# HLi #" and "# AOberhauser #" and "#
5553 title = "Chair-boat transitions in single polysaccharide molecules observed
5554 with force-ramp {AFM}",
5559 pages = "4278--4283",
5560 doi = "10.1073/pnas.072435699",
5561 eprint = "http://www.pnas.org/cgi/reprint/99/7/4278.pdf",
5562 url = "http://www.pnas.org/cgi/content/abstract/99/7/4278",
5563 abstract = "Under a stretching force, the sugar ring of polysaccharide
5564 molecules switches from the chair to the boat-like or inverted chair
5565 conformation. This conformational change can be observed by stretching
5566 single polysaccharide molecules with an atomic force microscope. In
5567 those early experiments, the molecules were stretched at a constant
5568 rate while the resulting force changed over wide ranges. However,
5569 because the rings undergo force-dependent transitions, an experimental
5570 arrangement where the force is the free variable introduces an
5571 undesirable level of complexity in the results. Here we demonstrate the
5572 use of force-ramp atomic force microscopy to capture the conformational
5573 changes in single polysaccharide molecules. Force-ramp atomic force
5574 microscopy readily captures the ring transitions under conditions where
5575 the entropic elasticity of the molecule is separated from its
5576 conformational transitions, enabling a quantitative analysis of the
5577 data with a simple two-state model. This analysis directly provides the
5578 physico-chemical characteristics of the ring transitions such as the
5579 width of the energy barrier, the relative energy of the conformers, and
5580 their enthalpic elasticity. Our experiments enhance the ability of
5581 single-molecule force spectroscopy to make high-resolution measurements
5582 of the conformations of single polysaccharide molecules under a
5583 stretching force, making an important addition to polysaccharide
5587 @article { marszalek99,
5588 author = PMarszalek #" and "# HLu #" and "# HLi #" and "# MCarrionVazquez
5589 #" and "# AOberhauser #" and "# KSchulten #" and "# JFernandez,
5590 title = "Mechanical unfolding intermediates in titin modules",
5599 doi = "10.1038/47083",
5600 eprint = "http://www.nature.com/nature/journal/v402/n6757/pdf/402100a0.pdf",
5601 url = "http://www.nature.com/nature/journal/v402/n6757/abs/402100a0.html",
5602 keywords = "Biomechanics;Computer Simulation;Humans;Hydrogen
5603 Bonding;Microscopy, Atomic Force;Models, Molecular;Muscle
5604 Proteins;Myocardium;Protein Folding;Protein Kinases;Recombinant
5606 abstract = "The modular protein titin, which is responsible for the passive
5607 elasticity of muscle, is subjected to stretching forces. Previous work
5608 on the experimental elongation of single titin molecules has suggested
5609 that force causes consecutive unfolding of each domain in an all-or-
5610 none fashion. To avoid problems associated with the heterogeneity of
5611 the modular, naturally occurring titin, we engineered single proteins
5612 to have multiple copies of single immunoglobulin domains of human
5613 cardiac titin. Here we report the elongation of these molecules using
5614 the atomic force microscope. We find an abrupt extension of each domain
5615 by approximately 7 A before the first unfolding event. This fast
5616 initial extension before a full unfolding event produces a reversible
5617 'unfolding intermediate' Steered molecular dynamics simulations show
5618 that the rupture of a pair of hydrogen bonds near the amino terminus of
5619 the protein domain causes an extension of about 6 A, which is in good
5620 agreement with our observations. Disruption of these hydrogen bonds by
5621 site-directed mutagenesis eliminates the unfolding intermediate. The
5622 unfolding intermediate extends titin domains by approximately 15\% of
5623 their slack length, and is therefore likely to be an important
5624 previously unrecognized component of titin elasticity."
5627 @article { mcpherson01,
5628 author = JDMcPherson #" and "# MMarra #" and "# LHillier #" and "#
5629 RHWaterston #" and "# AChinwalla #" and "# JWallis #" and "# MSekhon #"
5630 and "# KWylie #" and "# ERMardis #" and "# RKWilson #" and "# RFulton
5631 #" and "# TAKucaba #" and "# CWagner-McPherson #" and "# WBBarbazuk #"
5632 and "# SGGregory #" and "# SJHumphray #" and "# LFrench #" and "#
5633 RSEvans #" and "# GBethel #" and "# AWhittaker #" and "# JLHolden #"
5634 and "# OTMcCann #" and "# ADunham #" and "# CSoderlund #" and "#
5635 CEScott #" and "# DRBentley #" and "# GSchuler #" and "# HCChen #" and
5636 "# WJang #" and "# EDGreen #" and "# JRIdol #" and "# VVMaduro #" and
5637 "# KTMontgomery #" and "# ELee #" and "# AMiller #" and "# SEmerling #"
5638 and "# Kucherlapati #" and "# RGibbs #" and "# SScherer #" and "#
5639 JHGorrell #" and "# ESodergren #" and "# KClerc-Blankenburg #" and "#
5640 PTabor #" and "# SNaylor #" and "# DGarcia #" and "# PJdeJong #" and "#
5641 JJCatanese #" and "# NNowak #" and "# KOsoegawa #" and "# SQin #" and
5642 "# LRowen #" and "# AMadan #" and "# MDors #" and "# LHood #" and "#
5643 BTrask #" and "# CFriedman #" and "# HMassa #" and "# VGCheung #" and
5644 "# IRKirsch #" and "# TReid #" and "# RYonescu #" and "# JWeissenbach
5645 #" and "# TBruls #" and "# RHeilig #" and "# EBranscomb #" and "#
5646 AOlsen #" and "# NDoggett #" and "# JFCheng #" and "# THawkins #" and
5647 "# RMMyers #" and "# JShang #" and "# LRamirez #" and "# JSchmutz #"
5648 and "# OVelasquez #" and "# KDixon #" and "# NEStone #" and "# DRCox #"
5649 and "# DHaussler #" and "# WJKent #" and "# TFurey #" and "# SRogic #"
5650 and "# SKennedy #" and "# SJones #" and "# ARosenthal #" and "# GWen #"
5651 and "# MSchilhabel #" and "# GGloeckner #" and "# GNyakatura #" and "#
5652 RSiebert #" and "# BSchlegelberger #" and "# JKorenberg #" and "#
5653 XNChen #" and "# AFujiyama #" and "# MHattori #" and "# AToyoda #" and
5654 "# TYada #" and "# HSPark #" and "# YSakaki #" and "# NShimizu #" and
5655 "# SAsakawa #" and "# KKawasaki #" and "# TSasaki #" and "# AShintani
5656 #" and "# AShimizu #" and "# KShibuya #" and "# JKudoh #" and "#
5657 SMinoshima #" and "# JRamser #" and "# PSeranski #" and "# CHoff #" and
5658 "# APoustka #" and "# RReinhardt #" and "# HLehrach,
5659 title = "A physical map of the human genome.",
5668 doi = "10.1038/35057157",
5669 eprint = "http://www.nature.com/nature/journal/v409/n6822/pdf/409934a0.pdf",
5670 url = "http://www.nature.com/nature/journal/v409/n6822/full/409934a0.html",
5671 keywords = "Chromosomes, Artificial, Bacterial;Cloning, Molecular;Contig
5672 Mapping;DNA Fingerprinting;Gene Duplication;Genome, Human;Humans;In
5673 Situ Hybridization, Fluorescence;Repetitive Sequences, Nucleic Acid",
5674 abstract = "The human genome is by far the largest genome to be sequenced,
5675 and its size and complexity present many challenges for sequence
5676 assembly. The International Human Genome Sequencing Consortium
5677 constructed a map of the whole genome to enable the selection of clones
5678 for sequencing and for the accurate assembly of the genome sequence.
5679 Here we report the construction of the whole-genome bacterial
5680 artificial chromosome (BAC) map and its integration with previous
5681 landmark maps and information from mapping efforts focused on specific
5682 chromosomal regions. We also describe the integration of sequence data
5687 author = CCMello #" and "# DBarrick,
5688 title = "An experimentally determined protein folding energy landscape",
5695 pages = "14102--14107",
5697 doi = "10.1073/pnas.0403386101",
5698 keywords = "Animals; Ankyrin Repeat; Circular Dichroism; Drosophila
5699 Proteins; Drosophila melanogaster; Gene Deletion; Models, Chemical;
5700 Models, Molecular; Protein Denaturation; Protein Folding; Protein
5701 Structure, Tertiary; Spectrometry, Fluorescence; Thermodynamics; Urea",
5702 abstract = "Energy landscapes have been used to conceptually describe and
5703 model protein folding but have been difficult to measure
5704 experimentally, in large part because of the myriad of partly folded
5705 protein conformations that cannot be isolated and thermodynamically
5706 characterized. Here we experimentally determine a detailed energy
5707 landscape for protein folding. We generated a series of overlapping
5708 constructs containing subsets of the seven ankyrin repeats of the
5709 Drosophila Notch receptor, a protein domain whose linear arrangement of
5710 modular structural units can be fragmented without disrupting
5711 structure. To a good approximation, stabilities of each construct can
5712 be described as a sum of energy terms associated with each repeat. The
5713 magnitude of each energy term indicates that each repeat is
5714 intrinsically unstable but is strongly stabilized by interactions with
5715 its nearest neighbors. These linear energy terms define an equilibrium
5716 free energy landscape, which shows an early free energy barrier and
5717 suggests preferred low-energy routes for folding."
5720 @article { merkel99,
5721 author = RMerkel #" and "# PNassoy #" and "# ALeung #" and "# KRitchie #"
5723 title = "Energy landscapes of receptor-ligand bonds explored with dynamic
5724 force spectroscopy",
5733 doi = "10.1038/16219",
5734 url = "http://www.nature.com/nature/journal/v397/n6714/full/397050a0.html",
5735 keywords = "Biotin;Microscopy, Atomic Force;Protein Binding;Streptavidin",
5736 abstract = "Atomic force microscopy (AFM) has been used to measure the
5737 strength of bonds between biological receptor molecules and their
5738 ligands. But for weak noncovalent bonds, a dynamic spectrum of bond
5739 strengths is predicted as the loading rate is altered, with the
5740 measured strength being governed by the prominent barriers traversed in
5741 the energy landscape along the force-driven bond-dissociation pathway.
5742 In other words, the pioneering early AFM measurements represent only a
5743 single point in a continuous spectrum of bond strengths, because theory
5744 predicts that these will depend on the rate at which the load is
5745 applied. Here we report the strength spectra for the bonds between
5746 streptavidin (or avidin) and biotins-the prototype of receptor-ligand
5747 interactions used in earlier AFM studies, and which have been modelled
5748 by molecular dynamics. We have probed bond formation over six orders of
5749 magnitude in loading rate, and find that the bond survival time
5750 diminished from about 1 min to 0.001 s with increasing loading rate
5751 over this range. The bond strength, meanwhile, increased from about 5
5752 pN to 170 pN. Thus, although they are among the strongest noncovalent
5753 linkages in biology (affinity of 10(13) to 10(15) M(-1)), these bonds
5754 in fact appear strong or weak depending on how fast they are loaded. We
5755 are also able to relate the activation barriers derived from our
5756 strength spectra to the shape of the energy landscape derived from
5757 simulations of the biotin-avidin complex."
5760 @article { metropolis87,
5761 author = NMetropolis,
5762 title = "The Beginning of the {M}onte {C}arlo Method",
5768 url = "http://library.lanl.gov/cgi-bin/getfile?15-12.pdf"
5771 @article { mickler07,
5772 author = MMickler #" and "# RDima #" and "# HDietz #" and "# CHyeon #" and
5773 "# DThirumalai #" and "# MRief,
5774 title = "Revealing the bifurcation in the unfolding pathways of {GFP} by
5775 using single-molecule experiments and simulations",
5780 pages = "20268--20273",
5781 doi = "10.1073/pnas.0705458104",
5782 eprint = "http://www.pnas.org/cgi/reprint/104/51/20268.pdf",
5783 url = "http://www.pnas.org/cgi/content/abstract/104/51/20268",
5784 keywords = "AFM experiments, coarse-grained simulations, cross-link
5785 mutants, pathway bifurcation, plasticity of energy landscape",
5786 abstract = "Nanomanipulation of biomolecules by using single-molecule
5787 methods and computer simulations has made it possible to visualize the
5788 energy landscape of biomolecules and the structures that are sampled
5789 during the folding process. We use simulations and single-molecule
5790 force spectroscopy to map the complex energy landscape of GFP that is
5791 used as a marker in cell biology and biotechnology. By engineering
5792 internal disulfide bonds at selected positions in the GFP structure,
5793 mechanical unfolding routes are precisely controlled, thus allowing us
5794 to infer features of the energy landscape of the wild-type GFP. To
5795 elucidate the structures of the unfolding pathways and reveal the
5796 multiple unfolding routes, the experimental results are complemented
5797 with simulations of a self-organized polymer (SOP) model of GFP. The
5798 SOP representation of proteins, which is a coarse-grained description
5799 of biomolecules, allows us to perform forced-induced simulations at
5800 loading rates and time scales that closely match those used in atomic
5801 force microscopy experiments. By using the combined approach, we show
5802 that forced unfolding of GFP involves a bifurcation in the pathways to
5803 the stretched state. After detachment of an N-terminal {alpha}-helix,
5804 unfolding proceeds along two distinct pathways. In the dominant
5805 pathway, unfolding starts from the detachment of the primary N-terminal
5806 -strand, while in the minor pathway rupture of the last, C-terminal
5807 -strand initiates the unfolding process. The combined approach has
5808 allowed us to map the features of the complex energy landscape of GFP
5809 including a characterization of the structures, albeit at a coarse-
5810 grained level, of the three metastable intermediates.",
5811 note = {Hiccup in unfolding leg corresponds to unfolding
5812 intermediate (\fref{figure}{2}). The unfolding time scale in GFP
5813 is about $6\U{ms}$.},
5817 author = RNevo #" and "# CStroh #" and "# FKienberger #" and "# DKaftan #"
5818 and "# VBrumfeld #" and "# MElbaum #" and "# ZReich #" and "#
5820 title = "A molecular switch between alternative conformational states in
5821 the complex of {Ran} and importin beta1",
5829 doi = "10.1038/nsb940",
5830 eprint = "http://www.nature.com/nsmb/journal/v10/n7/pdf/nsb940.pdf",
5831 url = "http://www.nature.com/nsmb/journal/v10/n7/abs/nsb940.html",
5832 keywords = "Guanosine Diphosphate; Guanosine Triphosphate; Microscopy,
5833 Atomic Force; Protein Binding; Protein Conformation; beta Karyopherins;
5834 ran GTP-Binding Protein",
5835 abstract = "Several million macromolecules are exchanged each minute
5836 between the nucleus and cytoplasm by receptor-mediated transport. Most
5837 of this traffic is controlled by the small GTPase Ran, which regulates
5838 assembly and disassembly of the receptor-cargo complexes in the
5839 appropriate cellular compartment. Here we applied dynamic force
5840 spectroscopy to study the interaction of Ran with the nuclear import
5841 receptor importin beta1 (impbeta) at the single-molecule level. We
5842 found that the complex alternates between two distinct conformational
5843 states of different adhesion strength. The application of an external
5844 mechanical force shifts equilibrium toward one of these states by
5845 decreasing the height of the interstate activation energy barrier. The
5846 other state can be stabilized by a functional Ran mutant that increases
5847 this barrier. These results support a model whereby functional control
5848 of Ran-impbeta is achieved by a population shift between pre-existing
5849 alternative conformations."
5853 author = RNevo #" and "# VBrumfeld #" and "# MElbaum #" and "#
5854 PHinterdorfer #" and "# ZReich,
5855 title = "Direct discrimination between models of protein activation by
5856 single-molecule force measurements",
5862 pages = "2630--2634",
5864 doi = "10.1529/biophysj.104.041889",
5865 eprint = "http://www.biophysj.org/cgi/reprint/87/4/2630.pdf",
5866 url = "http://www.biophysj.org/cgi/content/abstract/87/4/2630",
5867 keywords = "Elasticity; Enzyme Activation; Micromanipulation; Microscopy,
5868 Atomic Force; Models, Chemical; Models, Molecular; Multiprotein
5869 Complexes; Nuclear Proteins; Physical Stimulation; Protein Binding;
5870 Stress, Mechanical; Structure-Activity Relationship; beta Karyopherins;
5871 ran GTP-Binding Protein",
5872 abstract = "The limitations imposed on the analyses of complex chemical and
5873 biological systems by ensemble averaging can be overcome by single-
5874 molecule experiments. Here, we used a single-molecule technique to
5875 discriminate between two generally accepted mechanisms of a key
5876 biological process--the activation of proteins by molecular effectors.
5877 The two mechanisms, namely induced-fit and population-shift, are
5878 normally difficult to discriminate by ensemble approaches. As a model,
5879 we focused on the interaction between the nuclear transport effector,
5880 RanBP1, and two related complexes consisting of the nuclear import
5881 receptor, importin beta, and the GDP- or GppNHp-bound forms of the
5882 small GTPase, Ran. We found that recognition by the effector proceeds
5883 through either an induced-fit or a population-shift mechanism,
5884 depending on the substrate, and that the two mechanisms can be
5885 differentiated by the data."
5889 author = RNevo #" and "# VBrumfeld #" and "# RKapon #" and "# PHinterdorfer
5891 title = "Direct measurement of protein energy landscape roughness",
5899 doi = "10.1038/sj.embor.7400403",
5900 eprint = "http://www.nature.com/embor/journal/v6/n5/pdf/7400403.pdf",
5901 url = "http://www.nature.com/embor/journal/v6/n5/abs/7400403.html",
5902 keywords = "Models, Molecular; Protein Binding; Protein Folding; Spectrum
5903 Analysis; Thermodynamics; beta Karyopherins; ran GTP-Binding Protein",
5904 abstract = "The energy landscape of proteins is thought to have an
5905 intricate, corrugated structure. Such roughness should have important
5906 consequences on the folding and binding kinetics of proteins, as well
5907 as on their equilibrium fluctuations. So far, no direct measurement of
5908 protein energy landscape roughness has been made. Here, we combined a
5909 recent theory with single-molecule dynamic force spectroscopy
5910 experiments to extract the overall energy scale of roughness epsilon
5911 for a complex consisting of the small GTPase Ran and the nuclear
5912 transport receptor importin-beta. The results gave epsilon > 5k(B)T,
5913 indicating a bumpy energy surface, which is consistent with the ability
5914 of importin-beta to accommodate multiple conformations and to interact
5915 with different, structurally distinct ligands.",
5916 note = "Applies \citet{hyeon03} to ligand-receptor binding.",
5917 project = "Energy Landscape Roughness"
5921 author = SNg #" and "# KBillings #" and "# TOhashi #" and "# MAllen #" and
5922 "# RBest #" and "# LRandles #" and "# HErickson #" and "# JClarke,
5923 title = "Designing an extracellular matrix protein with enhanced mechanical
5931 pages = "9633--9637",
5932 doi = "10.1073/pnas.0609901104",
5933 eprint = "http://www.pnas.org/cgi/reprint/104/23/9633.pdf",
5934 url = "http://www.pnas.org/cgi/content/abstract/104/23/9633",
5935 abstract = "The extracellular matrix proteins tenascin and fibronectin
5936 experience significant mechanical forces in vivo. Both contain a number
5937 of tandem repeating homologous fibronectin type III (fnIII) domains,
5938 and atomic force microscopy experiments have demonstrated that the
5939 mechanical strength of these domains can vary significantly. Previous
5940 work has shown that mutations in the core of an fnIII domain from human
5941 tenascin (TNfn3) reduce the unfolding force of that domain
5942 significantly: The composition of the core is apparently crucial to the
5943 mechanical stability of these proteins. Based on these results, we have
5944 used rational redesign to increase the mechanical stability of the 10th
5945 fnIII domain of human fibronectin, FNfn10, which is directly involved
5946 in integrin binding. The hydrophobic core of FNfn10 was replaced with
5947 that of the homologous, mechanically stronger TNfn3 domain. Despite the
5948 extensive substitution, FNoTNc retains both the three-dimensional
5949 structure and the cell adhesion activity of FNfn10. Atomic force
5950 microscopy experiments reveal that the unfolding forces of the
5951 engineered protein FNoTNc increase by {approx}20% to match those of
5952 TNfn3. Thus, we have specifically designed a protein with increased
5953 mechanical stability. Our results demonstrate that core engineering can
5954 be used to change the mechanical strength of proteins while retaining
5955 functional surface interactions."
5959 author = SNg #" and "# JClarke,
5960 title = "Experiments Suggest that Simulations May Overestimate
5961 Electrostatic Contributions to the Mechanical Stability of a
5962 Fibronectin Type {III} Domain",
5966 pages = "851–854",
5971 doi = "10.1016/j.jmb.2007.06.015",
5972 url = "http://dx.doi.org/10.1016/j.jmb.2007.06.015",
5974 keywords = "MD simulations",
5976 keywords = "forced unfolding",
5977 keywords = "extracellular matrix",
5978 abstract = "Steered molecular dynamics simulations have previously
5979 been used to investigate the mechanical properties of the
5980 extracellular matrix protein fibronectin. The simulations
5981 suggest that the mechanical stability of the tenth type III
5982 domain from fibronectin (FNfn10) is largely determined by a
5983 number of critical hydrogen bonds in the peripheral
5984 strands. Interestingly, the simulations predict that lowering
5985 the pH from 7 to ∼4.7 will increase the mechanical stability
5986 of FNfn10 significantly (by ∼33 %) due to the protonation of a
5987 few key acidic residues in the A and B strands. To test this
5988 simulation prediction, we used single-molecule atomic force
5989 microscopy (AFM) to investigate the mechanical stability of
5990 FNfn10 at neutral pH and at lower pH where these key residues
5991 have been shown to be protonated. Our AFM experimental results
5992 show no difference in the mechanical stability of FNfn10 at
5993 these different pH values. These results suggest that some
5994 simulations may overestimate the role played by electrostatic
5995 interactions in determining the mechanical stability of
6000 author = RNome #" and "# JZhao #" and "# WHoff #" and "# NScherer,
6001 title = "Axis-dependent anisotropy in protein unfolding from integrated
6002 nonequilibrium single-molecule experiments, analysis, and simulation",
6009 pages = "20799--20804",
6011 doi = "10.1073/pnas.0701281105",
6012 eprint = "http://www.pnas.org/cgi/reprint/104/52/20799.pdf",
6013 url = "http://www.pnas.org/cgi/content/abstract/104/52/20799",
6014 keywords = "Anisotropy; Bacterial Proteins; Biophysics; Computer
6015 Simulation; Cysteine; Halorhodospira halophila; Hydrogen Bonding;
6016 Kinetics; Luminescent Proteins; Microscopy, Atomic Force; Molecular
6017 Conformation; Protein Binding; Protein Conformation; Protein
6018 Denaturation; Protein Folding; Protein Structure, Secondary",
6019 abstract = "We present a comprehensive study that integrates experimental
6020 and theoretical nonequilibrium techniques to map energy landscapes
6021 along well defined pull-axis specific coordinates to elucidate
6022 mechanisms of protein unfolding. Single-molecule force-extension
6023 experiments along two different axes of photoactive yellow protein
6024 combined with nonequilibrium statistical mechanical analysis and
6025 atomistic simulation reveal energetic and mechanistic anisotropy.
6026 Steered molecular dynamics simulations and free-energy curves
6027 constructed from the experimental results reveal that unfolding along
6028 one axis exhibits a transition-state-like feature where six hydrogen
6029 bonds break simultaneously with weak interactions observed during
6030 further unfolding. The other axis exhibits a constant (unpeaked) force
6031 profile indicative of a noncooperative transition, with enthalpic
6032 (e.g., H-bond) interactions being broken throughout the unfolding
6033 process. Striking qualitative agreement was found between the force-
6034 extension curves derived from steered molecular dynamics calculations
6035 and the equilibrium free-energy curves obtained by JarzynskiHummerSzabo
6036 analysis of the nonequilibrium work data. The anisotropy persists
6037 beyond pulling distances of more than twice the initial dimensions of
6038 the folded protein, indicating a rich energy landscape to the
6039 mechanically fully unfolded state. Our findings challenge the notion
6040 that cooperative unfolding is a universal feature in protein
6046 title = "Handbook of Molecular Force Spectroscopy",
6048 isbn = "978-0-387-49987-1",
6049 publisher = SPRINGER,
6050 note = "The first book about force spectroscopy. Discusses the scaffold
6051 effect in section 8.4.1."
6054 @article { nummela07,
6055 author = JNummela #" and "# IAndricioaei,
6056 title = "{Exact Low-Force Kinetics from High-Force Single-Molecule
6062 pages = "3373--3381",
6063 doi = "10.1529/biophysj.107.111658",
6064 eprint = "http://www.biophysj.org/cgi/reprint/93/10/3373.pdf",
6065 url = "http://www.biophysj.org/cgi/content/abstract/93/10/3373",
6066 abstract = "Mechanical forces play a key role in crucial cellular processes
6067 involving force-bearing biomolecules, as well as in novel single-
6068 molecule pulling experiments. We present an exact method that enables
6069 one to extrapolate, to low (or zero) forces, entire time-correlation
6070 functions and kinetic rate constants from the conformational dynamics
6071 either simulated numerically or measured experimentally at a single,
6072 relatively higher, external force. The method has twofold relevance:
6073 1), to extrapolate the kinetics at physiological force conditions from
6074 molecular dynamics trajectories generated at higher forces that
6075 accelerate conformational transitions; and 2), to extrapolate unfolding
6076 rates from experimental force-extension single-molecule curves. The
6077 theoretical formalism, based on stochastic path integral weights of
6078 Langevin trajectories, is presented for the constant-force, constant
6079 loading rate, and constant-velocity modes of the pulling experiments.
6080 For the first relevance, applications are described for simulating the
6081 conformational isomerization of alanine dipeptide; and for the second
6082 relevance, the single-molecule pulling of RNA is considered. The
6083 ability to assign a weight to each trace in the single-molecule data
6084 also suggests a means to quantitatively compare unfolding pathways
6085 under different conditions."
6088 @article { oberhauser01,
6089 author = AOberhauser #" and "# PHansma #" and "# MCarrionVazquez #" and "#
6091 title = "Stepwise unfolding of titin under force-clamp atomic force
6098 doi = "10.1073/pnas.021321798",
6099 eprint = "http://www.pnas.org/cgi/reprint/98/2/468.pdf",
6100 url = "http://www.pnas.org/cgi/content/abstract/98/2/468",
6106 title = "Cantilever spring constant calibration using laser Doppler
6116 doi = "10.1063/1.2743272",
6117 url = "http://link.aip.org/link/?RSI/78/063701/1",
6118 keywords = "calibration; vibration measurement; measurement by laser beam;
6119 Doppler measurement; measurement uncertainty; atomic force microscopy",
6120 note = "Excellent review of thermal calibration to 2007, but nothing in the
6121 way of derivations. Compares thermal tune and Sader method with laser
6122 Doppler vibrometry.",
6123 project = "Cantilever Calibration"
6126 @article { olshansky97,
6127 author = SJOlshansky #" and "# BACarnes,
6128 title = "Ever since {G}ompertz",
6131 journal = Demography,
6136 url = "http://www.jstor.org/stable/2061656",
6137 keywords = "Aging;Biometry;History, 19th Century;History, 20th
6138 Century;Humans;Life Tables;Mortality;Sexual Maturation",
6139 abstract = "In 1825 British actuary Benjamin Gompertz made a simple but
6140 important observation that a law of geometrical progression pervades
6141 large portions of different tables of mortality for humans. The simple
6142 formula he derived describing the exponential rise in death rates
6143 between sexual maturity and old age is commonly, referred to as the
6144 Gompertz equation-a formula that remains a valuable tool in demography
6145 and in other scientific disciplines. Gompertz's observation of a
6146 mathematical regularity in the life table led him to believe in the
6147 presence of a low of mortality that explained why common age patterns
6148 of death exist. This law of mortality has captured the attention of
6149 scientists for the past 170 years because it was the first among what
6150 are now several reliable empirical tools for describing the dying-out
6151 process of many living organisms during a significant portion of their
6152 life spans. In this paper we review the literature on Gompertz's law of
6153 mortality and discuss the importance of his observations and insights
6154 in light of research on aging that has taken place since then.",
6155 note = "Hardly any actual math, but the references might be interesting.
6156 I'll look into them if I have the time. Available through several
6160 @article { onuchic96,
6161 author = JNOnuchic #" and "# NDSocci #" and "# ZLuthey-Schulten #" and "#
6163 title = "Protein folding funnels: the nature of the transition state
6171 keywords = "Animals; Cytochrome c Group; Humans; Infant; Protein Folding",
6172 abstract = "BACKGROUND: Energy landscape theory predicts that the folding
6173 funnel for a small fast-folding alpha-helical protein will have a
6174 transition state half-way to the native state. Estimates of the
6175 position of the transition state along an appropriate reaction
6176 coordinate can be obtained from linear free energy relationships
6177 observed for folding and unfolding rate constants as a function of
6178 denaturant concentration. The experimental results of Huang and Oas for
6179 lambda repressor, Fersht and collaborators for C12, and Gray and
6180 collaborators for cytochrome c indicate a free energy barrier midway
6181 between the folded and unfolded regions. This barrier arises from an
6182 entropic bottleneck for the folding process. RESULTS: In keeping with
6183 the experimental results, lattice simulations based on the folding
6184 funnel description show that the transition state is not just a single
6185 conformation, but rather an ensemble of a relatively large number of
6186 configurations that can be described by specific values of one or a few
6187 order parameters (e.g. the fraction of native contacts). Analysis of
6188 this transition state or bottleneck region from our lattice simulations
6189 and from atomistic models for small alpha-helical proteins by Boczko
6190 and Brooks indicates a broad distribution for native contact
6191 participation in the transition state ensemble centered around 50\%.
6192 Importantly, however, the lattice-simulated transition state ensemble
6193 does include some particularly hot contacts, as seen in the
6194 experiments, which have been termed by others a folding nucleus.
6195 CONCLUSIONS: Linear free energy relations provide a crude spectroscopy
6196 of the transition state, allowing us to infer the values of a reaction
6197 coordinate based on the fraction of native contacts. This bottleneck
6198 may be thought of as a collection of delocalized nuclei where different
6199 native contacts will have different degrees of participation. The
6200 agreement between the experimental results and the theoretical
6201 predictions provides strong support for the landscape analysis."
6205 author = COpitz #" and "# MKulke #" and "# MLeake #" and "# CNeagoe #" and
6206 "# HHinssen #" and "# RHajjar #" and "# WALinke,
6207 title = "Damped elastic recoil of the titin spring in myofibrils of human
6213 pages = "12688--12693",
6214 doi = "10.1073/pnas.2133733100",
6215 eprint = "http://www.pnas.org/cgi/reprint/100/22/12688.pdf",
6216 url = "http://www.pnas.org/cgi/content/abstract/100/22/12688",
6217 abstract = "The giant protein titin functions as a molecular spring in
6218 muscle and is responsible for most of the passive tension of
6219 myocardium. Because the titin spring is extended during diastolic
6220 stretch, it will recoil elastically during systole and potentially may
6221 influence the overall shortening behavior of cardiac muscle. Here,
6222 titin elastic recoil was quantified in single human heart myofibrils by
6223 using a high-speed charge-coupled device-line camera and a
6224 nanonewtonrange force sensor. Application of a slack-test protocol
6225 revealed that the passive shortening velocity (Vp) of nonactivated
6226 cardiomyofibrils depends on: (i) initial sarcomere length, (ii)
6227 release-step amplitude, and (iii) temperature. Selective digestion of
6228 titin, with low doses of trypsin, decelerated myofibrillar passive
6229 recoil and eventually stopped it. Selective extraction of actin
6230 filaments with a Ca2+-independent gelsolin fragment greatly reduced the
6231 dependency of Vp on release-step size and temperature. These results
6232 are explained by the presence of viscous forces opposing myofibrillar
6233 passive recoil that are caused mainly by weak actin-titin interactions.
6234 Thus, Vp is determined by two distinct factors: titin elastic recoil
6235 and internal viscous drag forces. The recoil could be modeled as that
6236 of a damped entropic spring consisting of independent worm-like chains.
6237 The functional importance of myofibrillar elastic recoil was addressed
6238 by comparing instantaneous Vp to unloaded shortening velocity, which
6239 was measured in demembranated, fully Ca2+-activated, human cardiac
6240 fibers. Titin-driven passive recoil was much faster than active
6241 unloaded shortening velocity in early phases of isotonic contraction.
6242 Damped myofibrillar elastic recoil could help accelerate active
6243 contraction speed of human myocardium during early systolic
6247 @article { oroudjev02,
6248 author = EOroudjev #" and "# JSoares #" and "# SArcidiacono #" and "#
6249 JThompson #" and "# SFossey #" and "# HHansma,
6250 title = "Segmented nanofibers of spider dragline silk: Atomic force
6251 microscopy and single-molecule force spectroscopy",
6256 pages = "6460--6465",
6257 doi = "10.1073/pnas.082526499",
6258 eprint = "http://www.pnas.org/cgi/reprint/99/suppl_2/6460.pdf",
6259 url = "http://www.pnas.org/cgi/content/abstract/99/suppl_2/6460",
6260 abstract = "Despite its remarkable materials properties, the structure of
6261 spider dragline silk has remained unsolved. Results from two probe
6262 microscopy techniques provide new insights into the structure of spider
6263 dragline silk. A soluble synthetic protein from dragline silk
6264 spontaneously forms nanofibers, as observed by atomic force microscopy.
6265 These nanofibers have a segmented substructure. The segment length and
6266 amino acid sequence are consistent with a slab-like shape for
6267 individual silk protein molecules. The height and width of nanofiber
6268 segments suggest a stacking pattern of slab-like molecules in each
6269 nanofiber segment. This stacking pattern produces nano-crystals in an
6270 amorphous matrix, as observed previously by NMR and x-ray diffraction
6271 of spider dragline silk. The possible importance of nanofiber formation
6272 to native silk production is discussed. Force spectra for single
6273 molecules of the silk protein demonstrate that this protein unfolds
6274 through a number of rupture events, indicating a modular substructure
6275 within single silk protein molecules. A minimal unfolding module size
6276 is estimated to be around 14 nm, which corresponds to the extended
6277 length of a single repeated module, 38 amino acids long. The structure
6278 of this spider silk protein is distinctly different from the structures
6279 of other proteins that have been analyzed by single-molecule force
6280 spectroscopy, and the force spectra show correspondingly novel
6285 author = EPaci #" and "# MKarplus,
6286 title = "Unfolding proteins by external forces and temperature: The
6287 importance of topology and energetics",
6292 pages = "6521--6526",
6293 doi = "10.1073/pnas.100124597",
6294 eprint = "http://www.pnas.org/cgi/reprint/97/12/6521.pdf",
6295 url = "http://www.pnas.org/cgi/content/abstract/97/12/6521"
6299 author = EPaci #" and "# MKarplus,
6300 title = "Forced unfolding of fibronectin type 3 modules: an analysis by
6301 biased molecular dynamics simulations",
6310 doi = "10.1006/jmbi.1999.2670",
6311 keywords = "Dimerization;Fibronectins;Humans;Hydrogen Bonding;Microscopy,
6312 Atomic Force;Protein Denaturation;Protein Folding",
6313 abstract = "Titin, an important constituent of vertebrate muscles, is a
6314 protein of the order of a micrometer in length in the folded state.
6315 Atomic force microscopy and laser tweezer experiments have been used to
6316 stretch titin molecules to more than ten times their folded lengths. To
6317 explain the observed relation between force and extension, it has been
6318 suggested that the immunoglobulin and fibronectin domains unfold one at
6319 a time in an all-or-none fashion. We use molecular dynamics simulations
6320 to study the forced unfolding of two different fibronectin type 3
6321 domains (the ninth, 9Fn3, and the tenth, 10Fn3, from human fibronectin)
6322 and of their heterodimer of known structure. An external biasing
6323 potential on the N to C distance is employed and the protein is treated
6324 in the polar hydrogen representation with an implicit solvation model.
6325 The latter provides an adiabatic solvent response, which is important
6326 for the nanosecond unfolding simulation method used here. A series of
6327 simulations is performed for each system to obtain meaningful results.
6328 The two different fibronectin domains are shown to unfold in the same
6329 way along two possible pathways. These involve the partial separation
6330 of the ``beta-sandwich'', an essential structural element, and the
6331 unfolding of the individual sheets in a stepwise fashion. The biasing
6332 potential results are confirmed by constant force unfolding
6333 simulations. For the two connected domains, there is complete unfolding
6334 of one domain (9Fn3) before major unfolding of the second domain
6335 (10Fn3). Comparison of different models for the potential energy
6336 function demonstrates that the dominant cohesive element in both
6337 proteins is due to the attractive van der Waals interactions;
6338 electrostatic interactions play a structural role but appear to make
6339 only a small contribution to the stabilization of the domains, in
6340 agreement with other studies of beta-sheet stability. The unfolding
6341 forces found in the simulations are of the order of those observed
6342 experimentally, even though the speed of the former is more than six
6343 orders of magnitude greater than that used in the latter."
6347 author = QPeng #" and "# HLi,
6348 title = "Atomic force microscopy reveals parallel mechanical unfolding
6349 pathways of T4 lysozyme: Evidence for a kinetic partitioning mechanism",
6354 pages = "1885--1890",
6355 doi = "10.1073/pnas.0706775105",
6356 eprint = "http://www.pnas.org/cgi/reprint/105/6/1885.pdf",
6357 url = "http://www.pnas.org/cgi/content/abstract/105/6/1885",
6358 abstract = "Kinetic partitioning is predicted to be a general mechanism for
6359 proteins to fold into their well defined native three-dimensional
6360 structure from unfolded states following multiple folding pathways.
6361 However, experimental evidence supporting this mechanism is still
6362 limited. By using single-molecule atomic force microscopy, here we
6363 report experimental evidence supporting the kinetic partitioning
6364 mechanism for mechanical unfolding of T4 lysozyme, a small protein
6365 composed of two subdomains. We observed that on stretching from its N
6366 and C termini, T4 lysozyme unfolds by multiple distinct unfolding
6367 pathways: the majority of T4 lysozymes unfold in an all-or-none fashion
6368 by overcoming a dominant unfolding kinetic barrier; and a small
6369 fraction of T4 lysozymes unfold in three-state fashion involving
6370 unfolding intermediate states. The three-state unfolding pathways do
6371 not follow well defined routes, instead they display variability and
6372 diversity in individual unfolding pathways. The unfolding intermediate
6373 states are local energy minima along the mechanical unfolding pathways
6374 and are likely to result from the residual structures present in the
6375 two subdomains after crossing the main unfolding barrier. These results
6376 provide direct evidence for the kinetic partitioning of the mechanical
6377 unfolding pathways of T4 lysozyme, and the complex unfolding behaviors
6378 reflect the stochastic nature of kinetic barrier rupture in mechanical
6379 unfolding processes. Our results demonstrate that single-molecule
6380 atomic force microscopy is an ideal tool to investigate the
6381 folding/unfolding dynamics of complex multimodule proteins that are
6382 otherwise difficult to study using traditional methods."
6386 author = WPress #" and "# STeukolsky #" and "# WVetterling #" and "#
6388 title = "Numerical Recipies in {C}: The Art of Scientific Computing",
6392 address = "New York",
6393 eprint = "http://www.nrbook.com/a/bookcpdf.php",
6394 note = "See Sections 12.0, 12.1, 12.3, and 13.4 for a good introduction to
6395 Fourier transforms and power spectrum estimation.",
6396 project = "Cantilever Calibration"
6399 @article { puchner08,
6400 author = EPuchner #" and "# GFranzen #" and "# MGautel #" and "# HEGaub,
6401 title = "Comparing proteins by their unfolding pattern.",
6409 doi = "10.1529/biophysj.108.129999",
6410 eprint = "http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2426622/pdf/426.pdf",
6411 url = "http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2426622/",
6412 keywords = "Algorithms;Computer Simulation;Microscopy, Atomic Force;Models,
6413 Chemical;Models, Molecular;Protein Denaturation;Protein
6415 abstract = "Single molecule force spectroscopy has evolved into an
6416 important and extremely powerful technique for investigating the
6417 folding potentials of biomolecules. Mechanical tension is applied to
6418 individual molecules, and the subsequent, often stepwise unfolding is
6419 recorded in force extension traces. However, because the energy
6420 barriers of the folding potentials are often close to the thermal
6421 energy, both the extensions and the forces at which these barriers are
6422 overcome are subject to marked fluctuations. Therefore, force extension
6423 traces are an inadequate representation despite widespread use
6424 particularly when large populations of proteins need to be compared and
6425 analyzed. We show in this article that contour length, which is
6426 independent of fluctuations and alterable experimental parameters, is a
6427 more appropriate variable than extension. By transforming force
6428 extension traces into contour length space, histograms are obtained
6429 that directly represent the energy barriers. In contrast to force
6430 extension traces, such barrier position histograms can be averaged to
6431 investigate details of the unfolding potential. The cross-superposition
6432 of barrier position histograms allows us to detect and visualize the
6433 order of unfolding events. We show with this approach that in contrast
6434 to the sequential unfolding of bacteriorhodopsin, two main steps in the
6435 unfolding of the enzyme titin kinase are independent of each other. The
6436 potential of this new method for accurate and automated analysis of
6437 force spectroscopy data and for novel automated screening techniques is
6438 shown with bacteriorhodopsin and with protein constructs containing GFP
6440 note = {Contour length space and barrier position fingerprinting.
6441 There are errors in \fref{equation}{3}, propagated from
6442 \citet{livadaru03}. I contacted Elias Puchner and pointed out the
6443 typos, and he revised his FRC fit parameters from $\gamma=22\dg$
6444 and $b=0.4\U{nm}$ to $\gamma=41\dg$ and $b=0.11\U{nm}$. The
6445 combined effect on \fref{figure}{3} of fixing the equation typos
6446 and adjusting the fit parameters was small, so their conclusions
6450 @article { raible04,
6451 author = MRaible #" and "# MEvstigneev #" and "# PReimann #" and "#
6452 FWBartels #" and "# RRos,
6453 title = "Theoretical analysis of dynamic force spectroscopy experiments on
6454 ligand-receptor complexes",
6463 doi = "10.1016/j.jbiotec.2004.04.017",
6464 keywords = "Binding Sites;Computer Simulation;DNA;DNA-Binding
6465 Proteins;Elasticity;Ligands;Macromolecular
6466 Substances;Micromanipulation;Microscopy, Atomic Force;Models,
6467 Chemical;Molecular Biology;Nucleic Acid Conformation;Physical
6468 Stimulation;Protein Binding;Protein Conformation;Stress, Mechanical",
6469 abstract = "The forced rupture of single chemical bonds in biomolecular
6470 compounds (e.g. ligand-receptor systems) as observed in dynamic force
6471 spectroscopy experiments is addressed. Under the assumption that the
6472 probability of bond rupture depends only on the instantaneously acting
6473 force, a data collapse onto a single master curve is predicted. For
6474 rupture data obtained experimentally by dynamic AFM force spectroscopy
6475 of a ligand-receptor bond between a DNA and a regulatory protein we do
6476 not find such a collapse. We conclude that the above mentioned,
6477 generally accepted assumption is not satisfied and we discuss possible
6481 @article { raible06,
6482 author = MRaible #" and "# MEvstigneev #" and "# FWBartels #" and "# REckel
6483 #" and "# MNguyen-Duong #" and "# RMerkel #" and "# RRos #" and "#
6484 DAnselmetti #" and "# PReimann,
6485 title = "Theoretical analysis of single-molecule force spectroscopy
6486 experiments: heterogeneity of chemical bonds",
6493 pages = "3851--3864",
6495 doi = "10.1529/biophysj.105.077099",
6496 eprint = "http://www.biophysj.org/cgi/reprint/90/11/3851.pdf",
6497 url = "http://www.biophysj.org/cgi/content/abstract/90/11/3851",
6498 keywords = "Biomechanics;Microscopy, Atomic Force;Models,
6499 Molecular;Statistical Distributions;Thermodynamics",
6500 abstract = "We show that the standard theoretical framework in single-
6501 molecule force spectroscopy has to be extended to consistently describe
6502 the experimental findings. The basic amendment is to take into account
6503 heterogeneity of the chemical bonds via random variations of the force-
6504 dependent dissociation rates. This results in a very good agreement
6505 between theory and rupture data from several different experiments."
6508 @article{ bartels03,
6509 author = FWBartels #" and "# BBaumgarth #" and "# DAnselmetti
6510 #" and "# RRos #" and "# ABecker,
6511 title = "Specific binding of the regulatory protein Exp{G} to
6512 promoter regions of the galactoglucan biosynthesis gene cluster of
6513 Sinorhizobium meliloti--a combined molecular biology and force
6514 spectroscopy investigation.",
6515 journal = JStructBiol,
6518 address = "Experimentelle Biophysik, Fakult{\"a}t f{\"u}r Physik,
6519 Universit{\"a}t Bielefeld, 33615 Bielefeld, Germany.",
6523 keywords = "Base Sequence",
6524 keywords = "Binding Sites",
6525 keywords = "Conserved Sequence",
6526 keywords = "Fungal Proteins",
6527 keywords = "Galactans",
6528 keywords = "Glucans",
6529 keywords = "Kinetics",
6530 keywords = "Microscopy, Atomic Force",
6531 keywords = "Multigene Family",
6532 keywords = "Polysaccharides, Bacterial",
6533 keywords = "Promoter Regions, Genetic",
6534 keywords = "Protein Binding",
6535 keywords = "Sinorhizobium meliloti",
6536 keywords = "Trans-Activators",
6537 abstract = "Specific protein-DNA interaction is fundamental for all
6538 aspects of gene transcription. We focus on a regulatory
6539 DNA-binding protein in the Gram-negative soil bacterium
6540 Sinorhizobium meliloti 2011, which is capable of fixing molecular
6541 nitrogen in a symbiotic interaction with alfalfa plants. The ExpG
6542 protein plays a central role in regulation of the biosynthesis of
6543 the exopolysaccharide galactoglucan, which promotes the
6544 establishment of symbiosis. ExpG is a transcriptional activator of
6545 exp gene expression. We investigated the molecular mechanism of
6546 binding of ExpG to three associated target sequences in the exp
6547 gene cluster with standard biochemical methods and single molecule
6548 force spectroscopy based on the atomic force microscope
6549 (AFM). Binding of ExpG to expA1, expG-expD1, and expE1 promoter
6550 fragments in a sequence specific manner was demonstrated, and a 28
6551 bp conserved region was found. AFM force spectroscopy experiments
6552 confirmed the specific binding of ExpG to the promoter regions,
6553 with unbinding forces ranging from 50 to 165 pN in a logarithmic
6554 dependence from the loading rates of 70-79000 pN/s. Two different
6555 regimes of loading rate-dependent behaviour were
6556 identified. Thermal off-rates in the range of k(off)=(1.2+/-1.0) x
6557 10(-3)s(-1) were derived from the lower loading rate regime for
6558 all promoter regions. In the upper loading rate regime, however,
6559 these fragments exhibited distinct differences which are
6560 attributed to the molecular binding mechanism.",
6562 URL = "http://www.ncbi.nlm.nih.gov/pubmed/12972351",
6567 author = MRief #" and "# HGrubmuller,
6568 title = "Force spectroscopy of single biomolecules",
6577 doi = "10.1002/1439-7641(20020315)3:3<255::AID-CPHC255>3.0.CO;2-M",
6578 url = "http://www3.interscience.wiley.com/journal/91016383/abstract",
6579 keywords = "Ligands;Microscopy, Atomic Force;Polysaccharides;Protein
6580 Denaturation;Proteins",
6581 abstract = "Many processes in the body are effected and regulated by highly
6582 specialized protein molecules: These molecules certainly deserve the
6583 name ``biochemical nanomachines''. Recent progress in single-molecule
6584 experiments and corresponding simulations with supercomputers enable us
6585 to watch these ``nanomachines'' at work, revealing a host of astounding
6586 mechanisms. Examples are the fine-tuned movements of the binding pocket
6587 of a receptor protein locking into its ligand molecule and the forced
6588 unfolding of titin, which acts as a molecular shock absorber to protect
6589 muscle cells. At present, we are not capable of designing such high
6590 precision machines, but we are beginning to understand their working
6591 principles and to simulate and predict their function.",
6592 note = "Nice, general review of force spectroscopy to 2002, but not much
6598 title = "Fundamentals of Statistical and Thermal Physics",
6600 publisher = McGraw-Hill,
6601 address = "New York",
6602 note = "Thermal noise for simple harmonic oscillators, in Chapter
6603 15, Sections 6 and 10.",
6604 project = "Cantilever Calibration"
6608 author = MRief #" and "# MGautel #" and "# FOesterhelt #" and "# JFernandez
6610 title = "Reversible Unfolding of Individual Titin Immunoglobulin Domains by
6616 pages = "1109--1112",
6617 doi = "10.1126/science.276.5315.1109",
6618 eprint = "http://www.sciencemag.org/cgi/reprint/276/5315/1109.pdf",
6619 url = "http://www.sciencemag.org/cgi/content/abstract/276/5315/1109",
6620 note = "Seminal paper for force spectroscopy on Titin. Cited by
6621 \citet{dietz04} (ref 9) as an example of how unfolding large proteins
6622 is easily interpreted (vs.\ confusing unfolding in bulk), but Titin is
6623 a rather simple example of that, because of its globular-chain
6625 project = "Energy Landscape Roughness"
6629 author = MRief #" and "# FOesterhelt #" and "# BHeymann #" and "# HEGaub,
6630 title = "Single Molecule Force Spectroscopy on Polysaccharides by Atomic
6638 pages = "1295--1297",
6640 doi = "10.1126/science.275.5304.1295",
6641 eprint = "http://www.sciencemag.org/cgi/reprint/275/5304/1295.pdf",
6642 url = "http://www.sciencemag.org/cgi/content/abstract/275/5304/1295",
6643 abstract = "Recent developments in piconewton instrumentation allow the
6644 manipulation of single molecules and measurements of intermolecular as
6645 well as intramolecular forces. Dextran filaments linked to a gold
6646 surface were probed with the atomic force microscope tip by vertical
6647 stretching. At low forces the deformation of dextran was found to be
6648 dominated by entropic forces and can be described by the Langevin
6649 function with a 6 angstrom Kuhn length. At elevated forces the strand
6650 elongation was governed by a twist of bond angles. At higher forces the
6651 dextran filaments underwent a distinct conformational change. The
6652 polymer stiffened and the segment elasticity was dominated by the
6653 bending of bond angles. The conformational change was found to be
6654 reversible and was corroborated by molecular dynamics calculations."
6658 author = MRief #" and "# JFernandez #" and "# HEGaub,
6659 title = "Elastically Coupled Two-Level Systems as a Model for Biopolymer
6666 pages = "4764--4767",
6669 doi = "10.1103/PhysRevLett.81.4764",
6670 eprint = "http://prola.aps.org/pdf/PRL/v81/i21/p4764_1",
6671 url = "http://prola.aps.org/abstract/PRL/v81/i21/p4764_1",
6672 note = "Original details on mechanical unfolding analysis via Monte Carlo
6677 author = MRief #" and "# HClausen-Schaumann #" and "# HEGaub,
6678 title = "Sequence-dependent mechanics of single {DNA} molecules",
6686 doi = "10.1038/7582",
6687 eprint = "http://www.nature.com/nsmb/journal/v6/n4/pdf/nsb0499_346.pdf",
6688 url = "http://www.nature.com/nsmb/journal/v6/n4/abs/nsb0499_346.html",
6689 keywords = "Bacteriophage lambda;Base Pairing;DNA;DNA, Single-Stranded;DNA,
6690 Viral;Gold;Mechanics;Microscopy, Atomic Force;Nucleotides;Spectrum
6691 Analysis;Thermodynamics",
6692 abstract = "Atomic force microscope-based single-molecule force
6693 spectroscopy was employed to measure sequence-dependent mechanical
6694 properties of DNA by stretching individual DNA double strands attached
6695 between a gold surface and an AFM tip. We discovered that in lambda-
6696 phage DNA the previously reported B-S transition, where 'S' represents
6697 an overstretched conformation, at 65 pN is followed by a nonequilibrium
6698 melting transition at 150 pN. During this transition the DNA is split
6699 into single strands that fully recombine upon relaxation. The sequence
6700 dependence was investigated in comparative studies with poly(dG-dC) and
6701 poly(dA-dT) DNA. Both the B-S and the melting transition occur at
6702 significantly lower forces in poly(dA-dT) compared to poly(dG-dC). We
6703 made use of the melting transition to prepare single poly(dG-dC) and
6704 poly(dA-dT) DNA strands that upon relaxation reannealed into hairpins
6705 as a result of their self-complementary sequence. The unzipping of
6706 these hairpins directly revealed the base pair-unbinding forces for G-C
6707 to be 20 +/- 3 pN and for A-T to be 9 +/- 3 pN."
6710 @article{ schmitt00,
6711 author = LSchmitt #" and "# MLudwig #" and "# HEGaub #" and "# RTampe,
6712 title = "A metal-chelating microscopy tip as a new toolbox for
6713 single-molecule experiments by atomic force microscopy.",
6717 address = "Institut f{\"u}r Physiologische Chemie,
6718 Philipps-Universit{\"a}t Marburg, 35033 Marburg,
6719 Germany. schmittl@mailer.uni-marburg.de",
6722 pages = "3275--3285",
6723 keywords = "Chelating Agents",
6724 keywords = "Edetic Acid",
6725 keywords = "Histidine",
6726 keywords = "Metals",
6727 keywords = "Microscopy, Atomic Force",
6728 keywords = "Nitrilotriacetic Acid",
6729 keywords = "Peptides",
6730 keywords = "Recombinant Fusion Proteins",
6731 abstract = "In recent years, the atomic force microscope (AFM) has
6732 contributed much to our understanding of the molecular forces
6733 involved in various high-affinity receptor-ligand
6734 systems. However, a universal anchor system for such measurements
6735 is still required. This would open up new possibilities for the
6736 study of biological recognition processes and for the
6737 establishment of high-throughput screening applications. One such
6738 candidate is the N-nitrilo-triacetic acid (NTA)/His-tag system,
6739 which is widely used in molecular biology to isolate and purify
6740 histidine-tagged fusion proteins. Here the histidine tag acts as a
6741 high-affinity recognition site for the NTA chelator. Accordingly,
6742 we have investigated the possibility of using this approach in
6743 single-molecule force measurements. Using a histidine-peptide as a
6744 model system, we have determined the binding force for various
6745 metal ions. At a loading rate of 0.5 microm/s, the determined
6746 forces varied from 22 +/- 4 to 58 +/- 5 pN. Most importantly, no
6747 interaction was detected for Ca(2+) and Mg(2+) up to
6748 concentrations of 10 mM. Furthermore, EDTA and a metal ion
6749 reloading step demonstrated the reversibility of the
6750 approach. Here the molecular interactions were turned off (EDTA)
6751 and on (metal reloading) in a switch-like fashion. Our results
6752 show that the NTA/His-tag system will expand the ``molecular
6753 toolboxes'' with which receptor-ligand systems can be investigated
6754 at the single-molecule level.",
6756 doi = "10.1016/S0006-3495(00)76863-9",
6757 URL = "http://www.ncbi.nlm.nih.gov/pubmed/10828003",
6761 @article { roters96,
6762 author = ARoters #" and "# DJohannsmann,
6763 title = "Distance-dependent noise measurements in scanning force
6769 pages = "7561-7577",
6770 doi = "10.1088/0953-8984",
6771 eprint = "http://www.iop.org/EJ/article/0953-8984/8/41/006/c64103.pdf",
6772 url = "http://stacks.iop.org/0953-8984/8/7561",
6773 abstract = "The changes in the thermal noise spectrum of a scanning-force-
6774 microscope cantilever upon approach of the tip to the sample were used
6775 to investigate the interactions between the cantilever and the sample.
6776 The investigation of thermal noise is the natural choice for dynamic
6777 measurements with little disturbance of the sample. In particular, the
6778 small amplitudes involved ensure linear dynamic response. It is
6779 possible to discriminate between viscous coupling, elastic coupling and
6780 changes in the effective mass. The technique is versatile in terms of
6781 substrates and environments. Hydrodynamic long-range interactions
6782 depending on the sample, the geometry and the ambient medium are
6783 observed. The dependence of hydrodynamic interaction on various
6784 parameters such as the viscosity and the density of the medium is
6785 described. For sufficiently soft surfaces, the method is sensitive to
6786 viscoelastic properties of the surface. For example, the viscous
6787 coupling to the surface is strongly increased when the surface is
6788 covered with a swollen `polymer brush'.",
6789 note = "They actually write down a Lagrangian formula and give a decent
6790 derivation of PSD, but don't show or work out the integrals.",
6791 project = "Cantilever Calibration"
6795 author = FGittes #" and "# CFSchmidt,
6796 title = {Thermal noise limitations on micromechanical experiments},
6803 doi = {10.1007/s002490050113},
6804 url = {http://dx.doi.org/10.1007/s002490050113},
6806 publisher = SPRINGER:V,
6807 keywords = {Key words Thermal noise; Optical tweezers; Atomic force
6808 microscopy; Single molecules; Micromechanics},
6809 language = {English},
6812 @article { ryckaert77,
6813 author = JPRyckaert #" and "# GCiccotti #" and "# HJCBerendsen,
6814 title = "Numerical integration of the cartesian equations of motion of a
6815 system with constraints: molecular dynamics of n-alkanes",
6822 doi = "10.1016/0021-9991(77)90098-5",
6823 url = "http://dx.doi.org/10.1016/0021-9991(77)90098-5",
6824 abstract = "A numerical algorithm integrating the 3N Cartesian equations of
6825 motion of a system of N points subject to holonomic constraints is
6826 formulated. The relations of constraint remain perfectly fulfilled at
6827 each step of the trajectory despite the approximate character of
6828 numerical integration. The method is applied to a molecular dynamics
6829 simulation of a liquid of 64 n-butane molecules and compared to a
6830 simulation using generalized coordinates. The method should be useful
6831 for molecular dynamics calculations on large molecules with internal
6832 degrees of freedom.",
6833 note = "Entry-level explaination of MD with rigid constraints. Explicit
6834 Verlet integrator example."
6837 @article { sarkar04,
6838 author = ASarkar #" and "# RRobertson #" and "# JFernandez,
6839 title = "Simultaneous atomic force microscope and fluorescence measurements
6840 of protein unfolding using a calibrated evanescent wave",
6845 pages = "12882--12886",
6846 doi = "10.1073/pnas.0403534101",
6847 eprint = "http://www.pnas.org/cgi/reprint/101/35/12882.pdf",
6848 url = "http://www.pnas.org/cgi/content/abstract/101/35/12882",
6849 abstract = "Fluorescence techniques for monitoring single-molecule dynamics
6850 in the vertical dimension currently do not exist. Here we use an atomic
6851 force microscope to calibrate the distance-dependent intensity decay of
6852 an evanescent wave. The measured evanescent wave transfer function was
6853 then used to convert the vertical motions of a fluorescent particle
6854 into displacement ($SD =< 1$ nm). We demonstrate the use of the
6855 calibrated evanescent wave to resolve the 20.1 {+/-} 0.5-nm step
6856 increases in the length of the small protein ubiquitin during forced
6857 unfolding. The experiments that we report here make an important
6858 contribution to fluorescence microscopy by demonstrating the
6859 unambiguous optical tracking of a single molecule with a resolution
6860 comparable to that of an atomic force microscope."
6864 author = TSato #" and "# MEsaki #" and "# JFernandez #" and "# TEndo,
6865 title = "{Comparison of the protein-unfolding pathways between
6866 mitochondrial protein import and atomic-force microscopy measurements}",
6871 pages = "17999--18004",
6872 doi = "10.1073/pnas.0504495102",
6873 eprint = "http://www.pnas.org/cgi/reprint/102/50/17999.pdf",
6874 url = "http://www.pnas.org/cgi/content/abstract/102/50/17999",
6875 abstract = "Many newly synthesized proteins have to become unfolded during
6876 translocation across biological membranes. We have analyzed the effects
6877 of various stabilization/destabilization mutations in the Ig-like
6878 module of the muscle protein titin upon its import from the N terminus
6879 or C terminus into mitochondria. The effects of mutations on the import
6880 of the titin module from the C terminus correlate well with those on
6881 forced mechanical unfolding in atomic-force microscopy (AFM)
6882 measurements. On the other hand, as long as turnover of the
6883 mitochondrial Hsp70 system is not rate-limiting for the import, import
6884 of the titin module from the N terminus is sensitive to mutations in
6885 the N-terminal region but not the ones in the C-terminal region that
6886 affect resistance to global unfolding in AFM experiments. We propose
6887 that the mitochondrial-import system can catalyze precursor-unfolding
6888 by reducing the stability of unfolding intermediates."
6891 @article { schlierf04,
6892 author = MSchlierf #" and "# HLi #" and "# JFernandez,
6893 title = "The unfolding kinetics of ubiquitin captured with single-molecule
6894 force-clamp techniques",
6901 pages = "7299--7304",
6903 doi = "10.1073/pnas.0400033101",
6904 eprint = "http://www.pnas.org/cgi/reprint/101/19/7299.pdf",
6905 url = "http://www.pnas.org/cgi/content/abstract/101/19/7299",
6906 keywords = "Kinetics;Microscopy, Atomic Force;Probability;Ubiquitin",
6907 abstract = "We use single-molecule force spectroscopy to study the kinetics
6908 of unfolding of the small protein ubiquitin. Upon a step increase in
6909 the stretching force, a ubiquitin polyprotein extends in discrete steps
6910 of 20.3 +/- 0.9 nm marking each unfolding event. An average of the time
6911 course of these unfolding events was well described by a single
6912 exponential, which is a necessary condition for a memoryless Markovian
6913 process. Similar ensemble averages done at different forces showed that
6914 the unfolding rate was exponentially dependent on the stretching force.
6915 Stretching a ubiquitin polyprotein with a force that increased at a
6916 constant rate (force-ramp) directly measured the distribution of
6917 unfolding forces. This distribution was accurately reproduced by the
6918 simple kinetics of an all-or-none unfolding process. Our force-clamp
6919 experiments directly demonstrate that an ensemble average of ubiquitin
6920 unfolding events is well described by a two-state Markovian process
6921 that obeys the Arrhenius equation. However, at the single-molecule
6922 level, deviant behavior that is not well represented in the ensemble
6923 average is readily observed. Our experiments make an important addition
6924 to protein spectroscopy by demonstrating an unambiguous method of
6925 analysis of the kinetics of protein unfolding by a stretching force."
6928 @article { schlierf06,
6929 author = MSchlierf #" and "# MRief,
6930 title = "Single-molecule unfolding force distributions reveal a funnel-
6931 shaped energy landscape",
6940 doi = "10.1529/biophysj.105.077982",
6941 url = "http://www.biophysj.org/cgi/content/abstract/90/4/L33",
6942 keywords = "Models, Molecular; Protein Folding; Proteins; Thermodynamics",
6943 abstract = "The protein folding process is described as diffusion on a
6944 high-dimensional energy landscape. Experimental data showing details of
6945 the underlying energy surface are essential to understanding folding.
6946 So far in single-molecule mechanical unfolding experiments a simplified
6947 model assuming a force-independent transition state has been used to
6948 extract such information. Here we show that this so-called Bell model,
6949 although fitting well to force velocity data, fails to reproduce full
6950 unfolding force distributions. We show that by applying Kramers'
6951 diffusion model, we were able to reconstruct a detailed funnel-like
6952 curvature of the underlying energy landscape and establish full
6953 agreement with the data. We demonstrate that obtaining spatially
6954 resolved details of the unfolding energy landscape from mechanical
6955 single-molecule protein unfolding experiments requires models that go
6956 beyond the Bell model.",
6957 note = {The inspiration behind my sawtooth simulation. Bell model
6958 fit to $f_{unfold}(v)$, but Kramers model fit to unfolding
6959 distribution for a given $v$. \fref{equation}{3} in the
6960 supplement is \xref{evans99}{equation}{2}, but it is just
6961 $[\text{dying percent}] \cdot [\text{surviving population}]
6963 $\nu \equiv k$ is the force/time-dependent off rate. The Kramers'
6964 rate equation (on page L34, the second equation in the paper) is
6965 \xref{hanggi90}{equation}{4.56b} (page 275) and
6966 \xref{socci96}{equation}{2} but \citet{schlierf06} gets the minus
6967 sign wrong in the exponent. $U_F(x=0)\gg 0$ and
6968 $U_F(x_\text{max})\ll 0$ (\cf~\xref{schlierf06}{figure}{1}).
6969 Schlierf's integral (as written) contains
6970 $\exp{-U_F(x_\text{max})}\cdot\exp{U_F(0)}$, which is huge, when
6971 it should contain $\exp{U_F(x_\text{max})}\cdot\exp{-U_F(0)}$,
6972 which is tiny. For more details and a picture of the peak that
6973 forms the bulk of the integrand, see
6974 \cref{eq:kramers,fig:kramers:integrand}. I pointed out this
6975 problem to Michael Schlierf, but he was unconvinced.},
6978 @article { schwaiger04,
6979 author = ISchwaiger #" and "# AKardinal #" and "# MSchleicher #" and "#
6980 AANoegel #" and "# MRief,
6981 title = "A mechanical unfolding intermediate in an actin-crosslinking
6991 doi = "10.1038/nsmb705",
6992 eprint = "http://www.nature.com/nsmb/journal/v11/n1/pdf/nsmb705.pdf",
6993 url = "http://www.nature.com/nsmb/journal/v11/n1/full/nsmb705.html",
6994 keywords = "Actins; Animals; Contractile Proteins; Cross-Linking Reagents;
6995 Dictyostelium; Dimerization; Microfilament Proteins; Microscopy, Atomic
6996 Force; Mutagenesis, Site-Directed; Protein Denaturation; Protein
6997 Folding; Protein Structure, Tertiary; Protozoan Proteins",
6998 abstract = "Many F-actin crosslinking proteins consist of two actin-binding
6999 domains separated by a rod domain that can vary considerably in length
7000 and structure. In this study, we used single-molecule force
7001 spectroscopy to investigate the mechanics of the immunoglobulin (Ig)
7002 rod domains of filamin from Dictyostelium discoideum (ddFLN). We find
7003 that one of the six Ig domains unfolds at lower forces than do those of
7004 all other domains and exhibits a stable unfolding intermediate on its
7005 mechanical unfolding pathway. Amino acid inserts into various loops of
7006 this domain lead to contour length changes in the single-molecule
7007 unfolding pattern. These changes allowed us to map the stable core of
7008 approximately 60 amino acids that constitutes the unfolding
7009 intermediate. Fast refolding in combination with low unfolding forces
7010 suggest a potential in vivo role for this domain as a mechanically
7011 extensible element within the ddFLN rod.",
7012 note = "ddFLN unfolding with WLC params for sacrificial domains. Gives
7013 persistence length $p = 0.5\mbox{ nm}$ in ``high force regime'', $p =
7014 0.9\mbox{ nm}$ in ``low force regime'', with a transition at $F =
7016 project = "sawtooth simulation"
7019 @article { schwaiger05,
7020 author = ISchwaiger #" and "# MSchleicher #" and "# AANoegel #" and "#
7022 title = "The folding pathway of a fast-folding immunoglobulin domain
7023 revealed by single-molecule mechanical experiments",
7031 doi = "10.1038/sj.embor.7400317",
7032 eprint = "http://www.nature.com/embor/journal/v6/n1/pdf/7400317.pdf",
7033 url = "http://www.nature.com/embor/journal/v6/n1/index.html",
7034 keywords = "Animals; Contractile Proteins; Dictyostelium; Immunoglobulins;
7035 Kinetics; Microfilament Proteins; Models, Molecular; Protein Folding;
7036 Protein Structure, Tertiary",
7037 abstract = "The F-actin crosslinker filamin from Dictyostelium discoideum
7038 (ddFLN) has a rod domain consisting of six structurally similar
7039 immunoglobulin domains. When subjected to a stretching force, domain 4
7040 unfolds at a lower force than all the other domains in the chain.
7041 Moreover, this domain shows a stable intermediate along its mechanical
7042 unfolding pathway. We have developed a mechanical single-molecule
7043 analogue to a double-jump stopped-flow experiment to investigate the
7044 folding kinetics and pathway of this domain. We show that an obligatory
7045 and productive intermediate also occurs on the folding pathway of the
7046 domain. Identical mechanical properties suggest that the unfolding and
7047 refolding intermediates are closely related. The folding process can be
7048 divided into two consecutive steps: in the first step 60 C-terminal
7049 amino acids form an intermediate at the rate of 55 s(-1); and in the
7050 second step the remaining 40 amino acids are packed on this core at the
7051 rate of 179 s(-1). This division increases the overall folding rate of
7052 this domain by a factor of ten compared with all other homologous
7053 domains of ddFLN that lack the folding intermediate."
7056 @article { sharma07,
7057 author = DSharma #" and "# OPerisic #" and "# QPeng #" and "# YCao #" and
7058 "# CLam #" and "# HLu #" and "# HLi,
7059 title = "Single-molecule force spectroscopy reveals a mechanically stable
7060 protein fold and the rational tuning of its mechanical stability",
7065 pages = "9278--9283",
7066 doi = "10.1073/pnas.0700351104",
7067 eprint = "http://www.pnas.org/cgi/reprint/104/22/9278.pdf",
7068 url = "http://www.pnas.org/cgi/content/abstract/104/22/9278",
7069 abstract = "It is recognized that shear topology of two directly connected
7070 force-bearing terminal [beta]-strands is a common feature among the
7071 vast majority of mechanically stable proteins known so far. However,
7072 these proteins belong to only two distinct protein folds, Ig-like
7073 [beta] sandwich fold and [beta]-grasp fold, significantly hindering
7074 delineating molecular determinants of mechanical stability and rational
7075 tuning of mechanical properties. Here we combine single-molecule atomic
7076 force microscopy and steered molecular dynamics simulation to reveal
7077 that the de novo designed Top7 fold [Kuhlman B, Dantas G, Ireton GC,
7078 Varani G, Stoddard BL, Baker D (2003) Science 302:13641368] represents
7079 a mechanically stable protein fold that is distinct from Ig-like [beta]
7080 sandwich and [beta]-grasp folds. Although the two force-bearing [beta]
7081 strands of Top7 are not directly connected, Top7 displays significant
7082 mechanical stability, demonstrating that the direct connectivity of
7083 force-bearing [beta] strands in shear topology is not mandatory for
7084 mechanical stability. This finding broadens our understanding of the
7085 design of mechanically stable proteins and expands the protein fold
7086 space where mechanically stable proteins can be screened. Moreover, our
7087 results revealed a substructure-sliding mechanism for the mechanical
7088 unfolding of Top7 and the existence of two possible unfolding pathways
7089 with different height of energy barrier. Such insights enabled us to
7090 rationally tune the mechanical stability of Top7 by redesigning its
7091 mechanical unfolding pathway. Our study demonstrates that computational
7092 biology methods (including de novo design) offer great potential for
7093 designing proteins of defined topology to achieve significant and
7094 tunable mechanical properties in a rational and systematic fashion."
7098 author = YJSheng #" and "# SJiang #" and "# HKTsao,
7099 title = "Forced Kramers escape in single-molecule pulling experiments",
7109 doi = "10.1063/1.2046632",
7110 url = "http://link.aip.org/link/?JCP/123/091102/1",
7111 keywords = "molecular biophysics; bonds (chemical); proteins",
7112 note = "Gives appropriate Einstein-S... relation for diffusion to damping",
7113 project = "sawtooth simulation"
7116 @article { shillcock98,
7117 author = JShillcock #" and "# USeifert,
7118 title = "Escape from a metastable well under a time-ramped force",
7124 pages = "7301--7304",
7127 doi = "10.1103/PhysRevE.57.7301",
7128 eprint = "http://prola.aps.org/pdf/PRE/v57/i6/p7301_1",
7129 url = "http://link.aps.org/abstract/PRE/v57/p7301",
7130 project = "sawtooth simulation"
7134 author = GESims #" and "# SRJun #" and "# GAWu #" and "# SHKim,
7135 title = "Alignment-free genome comparison with feature frequency profiles
7136 ({FFP}) and optimal resolutions",
7143 pages = "2677--2682",
7145 doi = "10.1073/pnas.0813249106",
7146 eprint = "http://www.pnas.org/cgi/reprint/106/31/12826",
7147 url = "http://www.pnas.org/content/106/8/2677",
7148 keywords = "Genome;Introns;Phylogeny",
7149 abstract = "For comparison of whole-genome (genic + nongenic) sequences,
7150 multiple sequence alignment of a few selected genes is not appropriate.
7151 One approach is to use an alignment-free method in which feature (or
7152 l-mer) frequency profiles (FFP) of whole genomes are used for
7153 comparison-a variation of a text or book comparison method, using word
7154 frequency profiles. In this approach it is critical to identify the
7155 optimal resolution range of l-mers for the given set of genomes
7156 compared. The optimum FFP method is applicable for comparing whole
7157 genomes or large genomic regions even when there are no common genes
7158 with high homology. We outline the method in 3 stages: (i) We first
7159 show how the optimal resolution range can be determined with English
7160 books which have been transformed into long character strings by
7161 removing all punctuation and spaces. (ii) Next, we test the robustness
7162 of the optimized FFP method at the nucleotide level, using a mutation
7163 model with a wide range of base substitutions and rearrangements. (iii)
7164 Finally, to illustrate the utility of the method, phylogenies are
7165 reconstructed from concatenated mammalian intronic genomes; the FFP
7166 derived intronic genome topologies for each l within the optimal range
7167 are all very similar. The topology agrees with the established
7168 mammalian phylogeny revealing that intron regions contain a similar
7169 level of phylogenic signal as do coding regions."
7173 author = SBSmith #" and "# LFinzi #" and "# CBustamante,
7174 title = "Direct mechanical measurements of the elasticity of single {DNA}
7175 molecules by using magnetic beads",
7182 pages = "1122--1126",
7184 doi = "10.1126/science.1439819",
7185 eprint = "http://www.sciencemag.org/cgi/reprint/258/5085/1122.pdf",
7186 url = "http://www.sciencemag.org/cgi/content/abstract/258/5085/1122",
7187 keywords = "Chemistry,
7188 Physical;Cisplatin;DNA;Elasticity;Ethidium;Glass;Indoles;Intercalating
7189 Agents;Magnetics;Mathematics;Microspheres",
7190 abstract = "Single DNA molecules were chemically attached by one end to a
7191 glass surface and by their other end to a magnetic bead. Equilibrium
7192 positions of the beads were observed in an optical microscope while the
7193 beads were acted on by known magnetic and hydrodynamic forces.
7194 Extension versus force curves were obtained for individual DNA
7195 molecules at three different salt concentrations with forces between
7196 10(-14) and 10(-11) newtons. Deviations from the force curves predicted
7197 by the freely jointed chain model suggest that DNA has significant
7198 local curvature in solution. Ethidium bromide and
7199 4',6-diamidino-2-phenylindole had little effect on the elastic response
7200 of the molecules, but their extent of intercalation was directly
7201 measured. Conversely, the effect of bend-inducing cis-
7202 diamminedichloroplatinum (II) was large and supports the hypothesis of
7203 natural curvature in DNA."
7207 author = SBSmith #" and "# YCui #" and "# CBustamante,
7208 title = "Overstretching {B}-{DNA}: the elastic response of individual
7209 double-stranded and single-stranded {DNA} molecules",
7218 keywords = "Base Composition;Chemistry, Physical;DNA;DNA, Single-
7219 Stranded;Elasticity;Nucleic Acid Conformation;Osmolar
7220 Concentration;Thermodynamics",
7221 abstract = "Single molecules of double-stranded DNA (dsDNA) were stretched
7222 with force-measuring laser tweezers. Under a longitudinal stress of
7223 approximately 65 piconewtons (pN), dsDNA molecules in aqueous buffer
7224 undergo a highly cooperative transition into a stable form with 5.8
7225 angstroms rise per base pair, that is, 70\% longer than B form dsDNA.
7226 When the stress was relaxed below 65 pN, the molecules rapidly and
7227 reversibly contracted to their normal contour lengths. This transition
7228 was affected by changes in the ionic strength of the medium and the
7229 water activity or by cross-linking of the two strands of dsDNA.
7230 Individual molecules of single-stranded DNA were also stretched giving
7231 a persistence length of 7.5 angstroms and a stretch modulus of 800 pN.
7232 The overstretched form may play a significant role in the energetics of
7237 author = NDSocci #" and "# JNOnuchic #" and "# PGWolynes,
7238 title = "Diffusive dynamics of the reaction coordinate for protein folding
7245 pages = "5860--5868",
7247 doi = "10.1063/1.471317",
7248 eprint = "http://arxiv.org/pdf/cond-mat/9601091",
7249 url = "http://link.aip.org/link/?JCP/104/5860/1",
7250 keywords = "PROTEINS; FOLDS; DIFFUSION; MONTE CARLO METHOD; SIMULATION;
7252 abstract = "The quantitative description of model protein folding kinetics
7253 using a diffusive collective reaction coordinate is examined. Direct
7254 folding kinetics, diffusional coefficients and free energy profiles are
7255 determined from Monte Carlo simulations of a 27-mer, 3 letter code
7256 lattice model, which corresponds roughly to a small helical protein.
7257 Analytic folding calculations, using simple diffusive rate theory,
7258 agree extremely well with the full simulation results. Folding in this
7259 system is best seen as a diffusive, funnel-like process.",
7260 note = "A nice introduction to some quantitative ramifications of the
7261 funnel energy landscape. There's also a bit of Kramers' theory and
7262 graph theory thrown in for good measure."
7266 author = NDSocci #" and "# JNOnuchic #" and "# PGWolynes,
7267 title = "Stretching lattice models of protein folding",
7274 pages = "2031--2035",
7276 keywords = "Amino Acid Sequence;Drug Stability;Kinetics;Models,
7277 Theoretical;Molecular Sequence Data;Peptides;Protein
7278 Denaturation;Protein Folding",
7279 abstract = "A new class of experiments that probe folding of individual
7280 protein domains uses mechanical stretching to cause the transition. We
7281 show how stretching forces can be incorporated in lattice models of
7282 folding. For fast folding proteins, the analysis suggests a complex
7283 relation between the force dependence and the reaction coordinate for
7287 @article { staple08,
7288 author = DBStaple #" and "# SHPayne #" and "# ALCReddin #" and "# HJKreuzer,
7289 title = "Model for stretching and unfolding the giant multidomain muscle
7290 protein using single-molecule force spectroscopy.",
7299 doi = "10.1103/PhysRevLett.101.248301",
7300 url = "http://dx.doi.org/10.1103/PhysRevLett.101.248301",
7301 keywords = "Kinetics;Microscopy, Atomic Force;Models, Chemical;Muscle
7302 Proteins;Protein Conformation;Protein Folding;Protein Kinases;Protein
7303 Structure, Tertiary;Thermodynamics",
7304 abstract = "Single-molecule manipulation has allowed the forced unfolding
7305 of multidomain proteins. Here we outline a theory that not only
7306 explains these experiments but also points out a number of difficulties
7307 in their interpretation and makes suggestions for further experiments.
7308 For titin we reproduce force-extension curves, the dependence of break
7309 force on pulling speed, and break-force distributions and also validate
7310 two common experimental views: Unfolding titin Ig domains can be
7311 explained as stepwise increases in contour length, and increasing force
7312 peaks in native Ig sequences represent a hierarchy of bond strengths.
7313 Our theory is valid for essentially any molecule that can be unfolded
7314 in atomic force microscopy; as a further example, we present force-
7315 extension curves for the unfolding of RNA hairpins."
7319 author = RStark #" and "# TDrobek #" and "# WHeckl,
7320 title = "Thermomechanical noise of a free v-shaped cantilever for atomic-
7329 doi = "http://dx.doi.org/10.1016/S0304-3991(00)00077-2",
7330 abstract = "We have calculated the thermal noise of a v-shaped AFM
7331 cantilever (Microlever, Type E, Thermomicroscopes) by means of a finite
7332 element analysis. The modal shapes of the first 10 eigenmodes are
7333 displayed as well as the numerical constants, which are needed for the
7334 calibration using the thermal noise method. In the first eigenmode,
7335 values for the thermomechanical noise of the z-displacement at 22
7336 degrees C temperature of square root of u2(1) = A/square root of
7337 c(cant) and the photodiode signal (normal-force) of S2(1) = A/square
7338 root of c(cant) were obtained. The results also indicate a systematic
7339 deviation ofthe spectral density of the thermomechanical noise of
7340 v-shaped cantilevers as compared to rectangular beam-shaped
7342 note = "Higher mode adjustments for v-shaped cantilevers from simulation.",
7343 project = "Cantilever Calibration"
7346 @article { strick96,
7347 author = TRStrick #" and "# JFAllemand #" and "# DBensimon #" and "#
7348 ABensimon #" and "# VCroquette,
7349 title = "The elasticity of a single supercoiled {DNA} molecule",
7356 pages = "1835--1837",
7358 keywords = "Bacteriophage lambda;DNA, Superhelical;DNA,
7359 Viral;Elasticity;Magnetics;Nucleic Acid Conformation;Temperature",
7360 abstract = "Single linear DNA molecules were bound at multiple sites at one
7361 extremity to a treated glass cover slip and at the other to a magnetic
7362 bead. The DNA was therefore torsionally constrained. A magnetic field
7363 was used to rotate the beads and thus to coil and pull the DNA. The
7364 stretching force was determined by analysis of the Brownian
7365 fluctuations of the bead. Here the elastic behavior of individual
7366 lambda DNA molecules over- and underwound by up to 500 turns was
7367 studied. A sharp transition was discovered from a low to a high
7368 extension state at a force of approximately 0.45 piconewtons for
7369 underwound molecules and at a force of approximately 3 piconewtons for
7370 overwound ones. These transitions, probably reflecting the formation of
7371 alternative structures in stretched coiled DNA molecules, might be
7372 relevant for DNA transcription and replication."
7375 @article { strunz99,
7376 author = TStrunz #" and "# KOroszlan #" and "# RSchafer #" and "#
7378 title = "Dynamic force spectroscopy of single {DNA} molecules",
7383 pages = "11277--11282",
7384 doi = "10.1073/pnas.96.20.11277",
7385 eprint = "http://www.pnas.org/cgi/reprint/96/20/11277.pdf",
7386 url = "http://www.pnas.org/cgi/content/abstract/96/20/11277"
7390 author = ASzabo #" and "# KSchulten #" and "# ZSchulten,
7391 title = "First passage time approach to diffusion controlled reactions",
7397 pages = "4350--4357",
7399 doi = "10.1063/1.439715",
7400 url = "http://link.aip.org/link/?JCP/72/4350/1",
7401 keywords = "DIFFUSION; CHEMICAL REACTIONS; CHEMICAL REACTION KINETICS;
7402 PROBABILITY; DIFFERENTIAL EQUATIONS"
7405 @article { talaga00,
7406 author = DTalaga #" and "# WLau #" and "# HRoder #" and "# JTang #" and "#
7407 YJia #" and "# WDeGrado #" and "# RHochstrasser,
7408 title = "Dynamics and folding of single two-stranded coiled-coil peptides
7409 studied by fluorescent energy transfer confocal microscopy",
7414 pages = "13021--13026",
7415 doi = "10.1073/pnas.97.24.13021",
7416 eprint = "http://www.pnas.org/cgi/reprint/97/24/13021.pdf",
7417 url = "http://www.pnas.org/cgi/content/abstract/97/24/13021"
7420 @article { thirumalai05,
7421 author = DThirumalai #" and "# CHyeon,
7422 title = "{RNA} and Protein Folding: Common Themes and Variations",
7423 affiliation = "Biophysics Program, and Department of Chemistry and
7424 Biochemistry, Institute for Physical Science and Technology, University
7425 of Maryland, College Park, Maryland 20742",
7430 pages = "4957--4970",
7433 "http://pubs3.acs.org/acs/journals/doilookup?in_doi=10.1021/bi047314+",
7434 abstract = "Visualizing the navigation of an ensemble of unfolded molecules
7435 through the bumpy energy landscape in search of the native state gives
7436 a pictorial view of biomolecular folding. This picture, when combined
7437 with concepts in polymer theory, provides a unified theory of RNA and
7438 protein folding. Just as for proteins, the major folding free energy
7439 barrier for RNA scales sublinearly with the number of nucleotides,
7440 which allows us to extract the elusive prefactor for RNA folding.
7441 Several folding scenarios can be anticipated by considering variations
7442 in the energy landscape that depend on sequence, native topology, and
7443 external conditions. RNA and protein folding mechanism can be described
7444 by the kinetic partitioning mechanism (KPM) according to which a
7445 fraction () of molecules reaches the native state directly, whereas the
7446 remaining fraction gets kinetically trapped in metastable
7447 conformations. For two-state folders 1. Molecular chaperones are
7448 recruited to assist protein folding whenever is small. We show that the
7449 iterative annealing mechanism, introduced to describe chaperonin-
7450 mediated folding, can be generalized to understand protein-assisted RNA
7451 folding. The major differences between the folding of proteins and RNA
7452 arise in the early stages of folding. For RNA, folding can only begin
7453 after the polyelectrolyte problem is solved, whereas protein collapse
7454 requires burial of hydrophobic residues. Cross-fertilization of ideas
7455 between the two fields should lead to an understanding of how RNA and
7456 proteins solve their folding problems.",
7457 note = "unfolding-refolding"
7461 author = SThornton #" and "# JMarion,
7462 title = "Classical Dynamics of Particles and Systems",
7465 isbn = "0-534-40896-6",
7466 publisher = BrooksCole,
7467 address = "Belmont, CA"
7470 @article { tlusty98,
7471 author = TTlusty #" and "# AMeller #" and "# RBar-Ziv,
7472 title = "Optical Gradient Forces of Strongly Localized Fields",
7478 pages = "1738--1741",
7481 doi = "10.1103/PhysRevLett.81.1738",
7482 eprint = "http://prola.aps.org/pdf/PRL/v81/i8/p1738_1",
7484 \url{http://nanoscience.bu.edu/papers/p1738_1_Meller.pdf}.
7485 Cited by \citet{grossman05} for derivation of thermal response
7486 functions. However, I only see a referenced thermal energy when
7487 they list the likelyhood of a small partical (radius $<R_c$)
7488 escaping due to thermal energy, where $R_c$ is roughly $R_c \sim
7489 (k_B T / \alpha I_0)^{1/3}$, $\alpha$ is a dielectric scaling
7490 term, and $I_0$ is the maximum beam energy density. I imagine
7491 Grossman and Stout mixed up this reference.",
7492 project = "Cantilever Calibration"
7495 @article { tshiprut08,
7496 author = ZTshiprut #" and "# JKlafter #" and "# MUrbakh,
7497 title = "Single-molecule pulling experiments: when the stiffness of the
7498 pulling device matters",
7507 doi = "10.1529/biophysj.108.141580",
7508 eprint = "http://www.biophysj.org/cgi/reprint/95/6/L42.pdf",
7509 abstract = "Using Langevin modeling, we investigate the role of the
7510 experimental setup on the unbinding forces measured in single-molecule
7511 pulling experiments. We demonstrate that the stiffness of the pulling
7512 device, K(eff), may influence the unbinding forces through its effect
7513 on the barrier heights for both unbinding and rebinding processes.
7514 Under realistic conditions the effect of K(eff) on the rebinding
7515 barrier is shown to play the most important role. This results in a
7516 significant increase of the mean unbinding force with the stiffness for
7517 a given loading rate. Thus, in contrast to the phenomenological Bell
7518 model, we find that the loading rate (the multiplicative value K(eff)V,
7519 V being the pulling velocity) is not the only control parameter that
7520 determines the mean unbinding force. If interested in intrinsic
7521 properties of a molecular system, we recommend probing the system in
7522 the parameter range corresponding to a weak spring and relatively high
7523 loading rates where rebinding is negligible.",
7524 note = "Cites \citet{dudko03} for Kramers' description of irreversible
7525 rupture, and claims it is required to explain the deviations in
7526 $\avg{F}$ at the same loading rate. Proposes Moese equation as an
7527 example potential. Cites \citet{walton08} for experimental evidence of
7528 $\avg{F}$ increasing with linker stiffness."
7531 @article { uniprot10,
7532 author = UniProtConsort,
7534 title = "The Universal Protein Resource (UniProt) in 2010.",
7540 number = "Database issue",
7541 pages = "D142--D148",
7543 doi = "10.1093/nar/gkp846",
7544 url = "http://nar.oxfordjournals.org/cgi/content/abstract/38/suppl_1/D142",
7545 keywords = "Algorithms;Animals;Computational Biology;Databases, Nucleic
7546 Acid;Databases, Protein;Europe;Genome, Fungal;Genome,
7547 Viral;Humans;Information Storage and Retrieval;Internet;Protein
7548 Isoforms;Proteome;Proteomics;Software",
7549 abstract = "The primary mission of UniProt is to support biological
7550 research by maintaining a stable, comprehensive, fully classified,
7551 richly and accurately annotated protein sequence knowledgebase, with
7552 extensive cross-references and querying interfaces freely accessible to
7553 the scientific community. UniProt is produced by the UniProt Consortium
7554 which consists of groups from the European Bioinformatics Institute
7555 (EBI), the Swiss Institute of Bioinformatics (SIB) and the Protein
7556 Information Resource (PIR). UniProt is comprised of four major
7557 components, each optimized for different uses: the UniProt Archive, the
7558 UniProt Knowledgebase, the UniProt Reference Clusters and the UniProt
7559 Metagenomic and Environmental Sequence Database. UniProt is updated and
7560 distributed every 3 weeks and can be accessed online for searches or
7561 download at http://www.uniprot.org."
7564 @misc { uniprot:STRAV,
7565 key = "uniprot:STRAV",
7566 url = "http://www.uniprot.org/uniprot/P22629"
7569 @book { vanKampen07,
7570 author = NGvanKampen,
7571 title = "Stochastic Processes in Physics and Chemistry",
7575 address = "Amsterdam",
7577 project = "sawtooth simulation"
7580 @article { venter01,
7581 author = JCVenter #" and "# MDAdams #" and "# EWMyers #" and "# PWLi #" and
7582 "# RJMural #" and "# GGSutton #" and "# HOSmith #" and "# MYandell #"
7583 and "# CAEvans #" and "# RAHolt #" and "# JDGocayne #" and "#
7584 PAmanatides #" and "# RMBallew #" and "# DHHuson #" and "# JRWortman #"
7585 and "# QZhang #" and "# CDKodira #" and "# XHZheng #" and "# LChen #"
7586 and "# MSkupski #" and "# GSubramanian #" and "# PDThomas #" and "#
7587 JZhang #" and "# GLGaborMiklos #" and "# CNelson #" and "# SBroder #"
7588 and "# AGClark #" and "# JNadeau #" and "# VAMcKusick #" and "# NZinder
7589 #" and "# AJLevine #" and "# RJRoberts #" and "# MSimon #" and "#
7590 CSlayman #" and "# MHunkapiller #" and "# RBolanos #" and "# ADelcher
7591 #" and "# IDew #" and "# DFasulo #" and "# MFlanigan #" and "# LFlorea
7592 #" and "# AHalpern #" and "# SHannenhalli #" and "# SKravitz #" and "#
7593 SLevy #" and "# CMobarry #" and "# KReinert #" and "# KRemington #" and
7594 "# JAbu-Threideh #" and "# EBeasley #" and "# KBiddick #" and "#
7595 VBonazzi #" and "# RBrandon #" and "# MCargill #" and "#
7596 IChandramouliswaran #" and "# RCharlab #" and "# KChaturvedi #" and "#
7597 ZDeng #" and "# VDiFrancesco #" and "# PDunn #" and "# KEilbeck #" and
7598 "# CEvangelista #" and "# AEGabrielian #" and "# WGan #" and "# WGe #"
7599 and "# FGong #" and "# ZGu #" and "# PGuan #" and "# TJHeiman #" and "#
7600 MEHiggins #" and "# RRJi #" and "# ZKe #" and "# KAKetchum #" and "#
7601 ZLai #" and "# YLei #" and "# ZLi #" and "# JLi #" and "# YLiang #" and
7602 "# XLin #" and "# FLu #" and "# GVMerkulov #" and "# NMilshina #" and
7603 "# HMMoore #" and "# AKNaik #" and "# VANarayan #" and "# BNeelam #"
7604 and "# DNusskern #" and "# DBRusch #" and "# SSalzberg #" and "# WShao
7605 #" and "# BShue #" and "# JSun #" and "# ZWang #" and "# AWang #" and
7606 "# XWang #" and "# JWang #" and "# MWei #" and "# RWides #" and "#
7607 CXiao #" and "# CYan #" and "# AYao #" and "# JYe #" and "# MZhan #"
7608 and "# WZhang #" and "# HZhang #" and "# QZhao #" and "# LZheng #" and
7609 "# FZhong #" and "# WZhong #" and "# SZhu #" and "# SZhao #" and "#
7610 DGilbert #" and "# SBaumhueter #" and "# GSpier #" and "# CCarter #"
7611 and "# ACravchik #" and "# TWoodage #" and "# FAli #" and "# HAn #" and
7612 "# AAwe #" and "# DBaldwin #" and "# HBaden #" and "# MBarnstead #" and
7613 "# IBarrow #" and "# KBeeson #" and "# DBusam #" and "# ACarver #" and
7614 "# ACenter #" and "# MLCheng #" and "# LCurry #" and "# SDanaher #" and
7615 "# LDavenport #" and "# RDesilets #" and "# SDietz #" and "# KDodson #"
7616 and "# LDoup #" and "# SFerriera #" and "# NGarg #" and "# AGluecksmann
7617 #" and "# BHart #" and "# JHaynes #" and "# CHaynes #" and "# CHeiner
7618 #" and "# SHladun #" and "# DHostin #" and "# JHouck #" and "# THowland
7619 #" and "# CIbegwam #" and "# JJohnson #" and "# FKalush #" and "#
7620 LKline #" and "# SKoduru #" and "# ALove #" and "# FMann #" and "# DMay
7621 #" and "# SMcCawley #" and "# TMcIntosh #" and "# IMcMullen #" and "#
7622 MMoy #" and "# LMoy #" and "# BMurphy #" and "# KNelson #" and "#
7623 CPfannkoch #" and "# EPratts #" and "# VPuri #" and "# HQureshi #" and
7624 "# MReardon #" and "# RRodriguez #" and "# YHRogers #" and "# DRomblad
7625 #" and "# BRuhfel #" and "# RScott #" and "# CSitter #" and "#
7626 MSmallwood #" and "# EStewart #" and "# RStrong #" and "# ESuh #" and
7627 "# RThomas #" and "# NNTint #" and "# STse #" and "# CVech #" and "#
7628 GWang #" and "# JWetter #" and "# SWilliams #" and "# MWilliams #" and
7629 "# SWindsor #" and "# EWinn-Deen #" and "# KWolfe #" and "# JZaveri #"
7630 and "# KZaveri #" and "# JFAbril #" and "# RGuigo #" and "# MJCampbell
7631 #" and "# KVSjolander #" and "# BKarlak #" and "# AKejariwal #" and "#
7632 HMi #" and "# BLazareva #" and "# THatton #" and "# ANarechania #" and
7633 "# KDiemer #" and "# AMuruganujan #" and "# NGuo #" and "# SSato #" and
7634 "# VBafna #" and "# SIstrail #" and "# RLippert #" and "# RSchwartz #"
7635 and "# BWalenz #" and "# SYooseph #" and "# DAllen #" and "# ABasu #"
7636 and "# JBaxendale #" and "# LBlick #" and "# MCaminha #" and "#
7637 JCarnes-Stine #" and "# PCaulk #" and "# YHChiang #" and "# MCoyne #"
7638 and "# CDahlke #" and "# AMays #" and "# MDombroski #" and "# MDonnelly
7639 #" and "# DEly #" and "# SEsparham #" and "# CFosler #" and "# HGire #"
7640 and "# SGlanowski #" and "# KGlasser #" and "# AGlodek #" and "#
7641 MGorokhov #" and "# KGraham #" and "# BGropman #" and "# MHarris #" and
7642 "# JHeil #" and "# SHenderson #" and "# JHoover #" and "# DJennings #"
7643 and "# CJordan #" and "# JJordan #" and "# JKasha #" and "# LKagan #"
7644 and "# CKraft #" and "# ALevitsky #" and "# MLewis #" and "# XLiu #"
7645 and "# JLopez #" and "# DMa #" and "# WMajoros #" and "# JMcDaniel #"
7646 and "# SMurphy #" and "# MNewman #" and "# TNguyen #" and "# NNguyen #"
7647 and "# MNodell #" and "# SPan #" and "# JPeck #" and "# MPeterson #"
7648 and "# WRowe #" and "# RSanders #" and "# JScott #" and "# MSimpson #"
7649 and "# TSmith #" and "# ASprague #" and "# TStockwell #" and "# RTurner
7650 #" and "# EVenter #" and "# MWang #" and "# MWen #" and "# DWu #" and
7651 "# MWu #" and "# AXia #" and "# AZandieh #" and "# XZhu,
7652 title = "The sequence of the human genome.",
7659 pages = "1304--1351",
7661 doi = "10.1126/science.1058040",
7662 eprint = "http://www.sciencemag.org/cgi/content/pdf/291/5507/1304",
7663 url = "http://www.sciencemag.org/cgi/content/short/291/5507/1304",
7664 keywords = "Algorithms;Animals;Chromosome Banding;Chromosome
7665 Mapping;Chromosomes, Artificial, Bacterial;Computational
7666 Biology;Consensus Sequence;CpG Islands;DNA, Intergenic;Databases,
7667 Factual;Evolution, Molecular;Exons;Female;Gene
7668 Duplication;Genes;Genetic Variation;Genome, Human;Human Genome
7669 Project;Humans;Introns;Male;Phenotype;Physical Chromosome
7670 Mapping;Polymorphism, Single Nucleotide;Proteins;Pseudogenes;Repetitive
7671 Sequences, Nucleic Acid;Retroelements;Sequence Analysis, DNA;Species
7673 abstract = "A 2.91-billion base pair (bp) consensus sequence of the
7674 euchromatic portion of the human genome was generated by the whole-
7675 genome shotgun sequencing method. The 14.8-billion bp DNA sequence was
7676 generated over 9 months from 27,271,853 high-quality sequence reads
7677 (5.11-fold coverage of the genome) from both ends of plasmid clones
7678 made from the DNA of five individuals. Two assembly strategies-a whole-
7679 genome assembly and a regional chromosome assembly-were used, each
7680 combining sequence data from Celera and the publicly funded genome
7681 effort. The public data were shredded into 550-bp segments to create a
7682 2.9-fold coverage of those genome regions that had been sequenced,
7683 without including biases inherent in the cloning and assembly procedure
7684 used by the publicly funded group. This brought the effective coverage
7685 in the assemblies to eightfold, reducing the number and size of gaps in
7686 the final assembly over what would be obtained with 5.11-fold coverage.
7687 The two assembly strategies yielded very similar results that largely
7688 agree with independent mapping data. The assemblies effectively cover
7689 the euchromatic regions of the human chromosomes. More than 90\% of the
7690 genome is in scaffold assemblies of 100,000 bp or more, and 25\% of the
7691 genome is in scaffolds of 10 million bp or larger. Analysis of the
7692 genome sequence revealed 26,588 protein-encoding transcripts for which
7693 there was strong corroborating evidence and an additional approximately
7694 12,000 computationally derived genes with mouse matches or other weak
7695 supporting evidence. Although gene-dense clusters are obvious, almost
7696 half the genes are dispersed in low G+C sequence separated by large
7697 tracts of apparently noncoding sequence. Only 1.1\% of the genome is
7698 spanned by exons, whereas 24\% is in introns, with 75\% of the genome
7699 being intergenic DNA. Duplications of segmental blocks, ranging in size
7700 up to chromosomal lengths, are abundant throughout the genome and
7701 reveal a complex evolutionary history. Comparative genomic analysis
7702 indicates vertebrate expansions of genes associated with neuronal
7703 function, with tissue-specific developmental regulation, and with the
7704 hemostasis and immune systems. DNA sequence comparisons between the
7705 consensus sequence and publicly funded genome data provided locations
7706 of 2.1 million single-nucleotide polymorphisms (SNPs). A random pair of
7707 human haploid genomes differed at a rate of 1 bp per 1250 on average,
7708 but there was marked heterogeneity in the level of polymorphism across
7709 the genome. Less than 1\% of all SNPs resulted in variation in
7710 proteins, but the task of determining which SNPs have functional
7711 consequences remains an open challenge."
7714 @article { verdier70,
7716 title = "Relaxation Behavior of the Freely Jointed Chain",
7722 pages = "5512--5517",
7724 doi = "10.1063/1.1672818",
7725 url = "http://link.aip.org/link/?JCP/52/5512/1"
7728 @article { walther07,
7729 author = KWalther #" and "# FGrater #" and "# LDougan #" and "# CBadilla #"
7730 and "# BBerne #" and "# JFernandez,
7731 title = "Signatures of hydrophobic collapse in extended proteins captured
7732 with force spectroscopy",
7737 pages = "7916--7921",
7738 doi = "10.1073/pnas.0702179104",
7739 eprint = "http://www.pnas.org/cgi/reprint/104/19/7916.pdf",
7740 url = "http://www.pnas.org/cgi/content/abstract/104/19/7916",
7741 abstract = "We unfold and extend single proteins at a high force and then
7742 linearly relax the force to probe their collapse mechanisms. We observe
7743 a large variability in the extent of their recoil. Although chain
7744 entropy makes a small contribution, we show that the observed
7745 variability results from hydrophobic interactions with randomly varying
7746 magnitude from protein to protein. This collapse mechanism is common to
7747 highly extended proteins, including nonfolding elastomeric proteins
7748 like PEVK from titin. Our observations explain the puzzling differences
7749 between the folding behavior of highly extended proteins, from those
7750 folding after chemical or thermal denaturation. Probing the collapse of
7751 highly extended proteins with force spectroscopy allows separation of
7752 the different driving forces in protein folding."
7755 @mastersthesis{ lee05,
7757 title = {Chemical Functionalization of AFM Cantilevers},
7761 url = {http://dspace.mit.edu/handle/1721.1/34205},
7762 abstract = {Atomic force microscopy (AFM) has been a powerful
7763 instrument that provides nanoscale imaging of surface features,
7764 mainly of rigid metal or ceramic surfaces that can be insulators
7765 as well as conductors. Since it has been demonstrated that AFM
7766 could be used in aqueous environment such as in water or various
7767 buffers from which physiological condition can be maintained, the
7768 scope of the application of this imaging technique has been
7769 expanded to soft biological materials. In addition, the main usage
7770 of AFM has been to image the material and provide the shape of
7771 surface, which has also been diversified to molecular-recognition
7772 imaging - functional force imaging through force spectroscopy and
7773 modification of AFM cantilevers. By immobilizing of certain
7774 molecules at the end of AFM cantilever, specific molecules or
7775 functionalities can be detected by the combination of intrinsic
7776 feature of AFM and chemical modification technique of AFM
7777 cantilever. The surface molecule that is complementary to the
7778 molecule at the end of AFM probe can be investigated via
7779 specificity of molecule-molecule interaction.(cont.) Thus, this
7780 AFM cantilever chemistry, or chemical functionalization of AFM
7781 cantilever for the purpose of chemomechanical surface
7782 characterization, can be considered as an infinite source of
7783 applications important to understanding biological materials and
7784 material interactions. This thesis is mainly focused on three
7785 parts: (1) AFM cantilever chemistry that introduces specific
7786 protocols in details such as adsorption method, gold chemistry,
7787 and silicon nitride cantilever modification; (2) validation of
7788 cantilever chemistry such as X-ray photoelectron spectroscopy
7789 (XPS), AFM blocking experiment, and fluorescence microscopy,
7790 through which various AFM cantilever chemistry is verified; and
7791 (3) application of cantilever chemistry, especially toward the
7792 potential of force spectroscopy and the imaging of biological
7793 material surfaces.},
7795 note = {Binding proteins to gold-coated cantilevers via EDC (among
7796 other things in this thesis.},
7799 @article { walton08,
7800 author = EBWalton #" and "# SLee #" and "# KJVanVliet,
7801 title = "Extending {B}ell's model: How force transducer stiffness alters
7802 measured unbinding forces and kinetics of molecular complexes",
7809 pages = "2621--2630",
7811 doi = "10.1529/biophysj.107.114454",
7812 keywords = "Biotin;Computer
7813 Simulation;Elasticity;Kinetics;Mechanotransduction, Cellular;Models,
7814 Chemical;Models, Molecular;Molecular Motor
7815 Proteins;Motion;Streptavidin;Stress, Mechanical;Transducers",
7816 abstract = "Forced unbinding of complementary macromolecules such as
7817 ligand-receptor complexes can reveal energetic and kinetic details
7818 governing physiological processes ranging from cellular adhesion to
7819 drug metabolism. Although molecular-level experiments have enabled
7820 sampling of individual ligand-receptor complex dissociation events,
7821 disparities in measured unbinding force F(R) among these methods lead
7822 to marked variation in inferred binding energetics and kinetics at
7823 equilibrium. These discrepancies are documented for even the ubiquitous
7824 ligand-receptor pair, biotin-streptavidin. We investigated these
7825 disparities and examined atomic-level unbinding trajectories via
7826 steered molecular dynamics simulations, as well as via molecular force
7827 spectroscopy experiments on biotin-streptavidin. In addition to the
7828 well-known loading rate dependence of F(R) predicted by Bell's model,
7829 we find that experimentally accessible parameters such as the effective
7830 stiffness of the force transducer k can significantly perturb the
7831 energy landscape and the apparent unbinding force of the complex for
7832 sufficiently stiff force transducers. Additionally, at least 20\%
7833 variation in unbinding force can be attributed to minute differences in
7834 initial atomic positions among energetically and structurally
7835 comparable complexes. For force transducers typical of molecular force
7836 spectroscopy experiments and atomistic simulations, this energy barrier
7837 perturbation results in extrapolated energetic and kinetic parameters
7838 of the complex that depend strongly on k. We present a model that
7839 explicitly includes the effect of k on apparent unbinding force of the
7840 ligand-receptor complex, and demonstrate that this correction enables
7841 prediction of unbinding distances and dissociation rates that are
7842 decoupled from the stiffness of actual or simulated molecular linkers.",
7843 note = "Some detailed estimates at U(x)."
7846 @article { walton86,
7848 title = "The Abbe theory of imaging: an alternative derivation of the
7855 url = "http://stacks.iop.org/0143-0807/7/62"
7858 @article { watanabe05,
7859 author = HWatanabe #" and "# TInoue,
7860 title = "Conformational dynamics of Rouse chains during creep/recovery
7861 processes: a review",
7866 pages = "R607--R636",
7867 doi = "10.1088/0953-8984/17/19/R01",
7868 eprint = "http://www.iop.org/EJ/article/0953-8984/17/19/R01/cm5_19_R01.pdf",
7869 url = "http://stacks.iop.org/0953-8984/17/R607",
7870 abstract = "The Rouse model is a well-established model for non-entangled
7871 polymer chains and also serves as a fundamental model for entangled
7872 chains. The dynamic behaviour of this model under strain-controlled
7873 conditions has been fully analysed in the literature. However, despite
7874 the importance of the Rouse model, no analysis has been made so far of
7875 the orientational anisotropy of the Rouse eigenmodes during the stress-
7876 controlled, creep and recovery processes. For completeness of the
7877 analysis of the model, the Rouse equation of motion is solved to
7878 calculate this anisotropy for monodisperse chains and their binary
7879 blends during the creep/recovery processes. The calculation is simple
7880 and straightforward, but the result is intriguing in the sense that
7881 each Rouse eigenmode during these processes has a distribution in the
7882 retardation times. This behaviour, reflecting the interplay/correlation
7883 among the Rouse eigenmodes of different orders (and for different
7884 chains in the blends) under the constant stress condition, is quite
7885 different from the behaviour under rate-controlled flow (where each
7886 eigenmode exhibits retardation/relaxation associated with a single
7887 characteristic time). Furthermore, the calculation indicates that the
7888 Rouse chains exhibit affine deformation on sudden imposition/removal of
7889 the stress and the magnitude of this deformation is inversely
7890 proportional to the number of bond vectors per chain. In relation to
7891 these results, a difference between the creep and relaxation properties
7892 is also discussed for chains obeying multiple relaxation mechanisms
7893 (Rouse and reptation mechanisms).",
7894 note = "Middly-detailed Rouse model review."
7898 author = AWiita #" and "# SAinavarapu #" and "# HHuang #" and "# JFernandez,
7899 title = "From the Cover: Force-dependent chemical kinetics of disulfide
7900 bond reduction observed with single-molecule techniques",
7905 pages = "7222--7227",
7906 doi = "10.1073/pnas.0511035103",
7907 eprint = "http://www.pnas.org/cgi/reprint/103/19/7222.pdf",
7908 url = "http://www.pnas.org/cgi/content/abstract/103/19/7222",
7909 abstract = "The mechanism by which mechanical force regulates the kinetics
7910 of a chemical reaction is unknown. Here, we use single-molecule force-
7911 clamp spectroscopy and protein engineering to study the effect of force
7912 on the kinetics of thiol/disulfide exchange. Reduction of disulfide
7913 bonds through the thiol/disulfide exchange chemical reaction is crucial
7914 in regulating protein function and is known to occur in mechanically
7915 stressed proteins. We apply a constant stretching force to single
7916 engineered disulfide bonds and measure their rate of reduction by DTT.
7917 Although the reduction rate is linearly dependent on the concentration
7918 of DTT, it is exponentially dependent on the applied force, increasing
7919 10-fold over a 300-pN range. This result predicts that the disulfide
7920 bond lengthens by 0.34 A at the transition state of the thiol/disulfide
7921 exchange reaction. Our work at the single bond level directly
7922 demonstrates that thiol/disulfide exchange in proteins is a force-
7923 dependent chemical reaction. Our findings suggest that mechanical force
7924 plays a role in disulfide reduction in vivo, a property that has never
7925 been explored by traditional biochemistry. Furthermore, our work also
7926 indicates that the kinetics of any chemical reaction that results in
7927 bond lengthening will be force-dependent."
7930 @article { wilcox05,
7931 author = AWilcox #" and "# JChoy #" and "# CBustamante #" and "#
7933 title = "Effect of protein structure on mitochondrial import",
7938 pages = "15435--15440",
7939 doi = "10.1073/pnas.0507324102",
7940 eprint = "http://www.pnas.org/cgi/reprint/102/43/15435.pdf",
7941 url = "http://www.pnas.org/cgi/content/abstract/102/43/15435",
7942 abstract = "Most proteins that are to be imported into the mitochondrial
7943 matrix are synthesized as precursors, each composed of an N-terminal
7944 targeting sequence followed by a mature domain. Precursors are
7945 recognized through their targeting sequences by receptors at the
7946 mitochondrial surface and are then threaded through import channels
7947 into the matrix. Both the targeting sequence and the mature domain
7948 contribute to the efficiency with which proteins are imported into
7949 mitochondria. Precursors must be in an unfolded conformation during
7950 translocation. Mitochondria can unfold some proteins by changing their
7951 unfolding pathways. The effectiveness of this unfolding mechanism
7952 depends on the local structure of the mature domain adjacent to the
7953 targeting sequence. This local structure determines the extent to which
7954 the unfolding pathway can be changed and, therefore, the unfolding rate
7955 increased. Atomic force microscopy studies find that the local
7956 structures of proteins near their N and C termini also influence their
7957 resistance to mechanical unfolding. Thus, protein unfolding during
7958 import resembles mechanical unfolding, and the specificity of import is
7959 determined by the resistance of the mature domain to unfolding as well
7960 as by the properties of the targeting sequence."
7963 @article { wolfsberg01,
7964 author = TGWolfsberg #" and "# JMcEntyre #" and "# GDSchuler,
7965 title = "Guide to the draft human genome.",
7974 doi = "10.1038/35057000",
7975 eprint = "http://www.nature.com/nature/journal/v409/n6822/pdf/409824a0.pdf",
7976 url = "http://www.nature.com/nature/journal/v409/n6822/full/409824a0.html",
7977 keywords = "Amino Acid Sequence;Chromosome Mapping;Computational
7978 Biology;Genes;Genetic Variation;Genome, Human;Human Genome
7979 Project;Humans;Internet;Molecular Sequence Data;Sequence Analysis, DNA",
7980 abstract = "There are a number of ways to investigate the structure,
7981 function and evolution of the human genome. These include examining the
7982 morphology of normal and abnormal chromosomes, constructing maps of
7983 genomic landmarks, following the genetic transmission of phenotypes and
7984 DNA sequence variations, and characterizing thousands of individual
7985 genes. To this list we can now add the elucidation of the genomic DNA
7986 sequence, albeit at 'working draft' accuracy. The current challenge is
7987 to weave together these disparate types of data to produce the
7988 information infrastructure needed to support the next generation of
7989 biomedical research. Here we provide an overview of the different
7990 sources of information about the human genome and how modern
7991 information technology, in particular the internet, allows us to link
7996 author = JWWu #" and "# WLHung #" and "# CHTsai,
7997 title = "Estimation of parameters of the {G}ompertz distribution using the
7998 least squares method",
8007 doi = "10.1016/j.amc.2003.08.086",
8008 url = "http://dx.doi.org/10.1016/j.amc.2003.08.086",
8009 keywords = "Gompertz distribution; Least squares estimate; Maximum
8010 likelihood estimate; First failure-censored; Series system",
8011 abstract = "The Gompertz distribution has been used to describe human
8012 mortality and establish actuarial tables. Recently, this distribution
8013 has been again studied by some authors. The maximum likelihood
8014 estimates for the parameters of the Gompertz distribution has been
8015 discussed by Garg et al. [J. R. Statist. Soc. C 19 (1970) 152]. The
8016 purpose of this paper is to propose unweighted and weighted least
8017 squares estimates for parameters of the Gompertz distribution under the
8018 complete data and the first failure-censored data (series systems; see
8019 [J. Statist. Comput. Simulat. 52 (1995) 337]). A simulation study is
8020 carried out to compare the proposed estimators and the maximum
8021 likelihood estimators. Results of the simulation studies show that the
8022 performance of the weighted least squares estimators is acceptable."
8026 author = GYang #" and "# CCecconi #" and "# WBaase #" and "# IVetter #" and
8027 "# WBreyer #" and "# JHaack #" and "# BMatthews #" and "# FDahlquist #"
8029 title = "Solid-state synthesis and mechanical unfolding of polymers of {T4}
8036 doi = "10.1073/pnas.97.1.139",
8037 eprint = "http://www.pnas.org/cgi/reprint/97/1/139.pdf",
8038 url = "http://www.pnas.org/cgi/content/abstract/97/1/139"
8042 author = YYang #" and "# FCLin #" and "# GYang,
8043 title = "Temperature control device for single molecule measurements using
8044 the atomic force microscope",
8054 doi = "10.1063/1.2204580",
8055 url = "http://link.aip.org/link/?RSI/77/063701/1",
8056 keywords = "temperature control; atomic force microscopy; thermocouples;
8058 note = "Introduces our temperature control system",
8059 project = "Energy Landscape Roughness"
8063 author = WYu #" and "# JLamb #" and "# FHan #" and "# JBirchler,
8064 title = "Telomere-mediated chromosomal truncation in maize",
8069 pages = "17331--17336",
8070 doi = "10.1073/pnas.0605750103",
8071 eprint = "http://www.pnas.org/cgi/reprint/103/46/17331.pdf",
8072 url = "http://www.pnas.org/cgi/content/abstract/103/46/17331",
8073 abstract = "Direct repeats of Arabidopsis telomeric sequence were
8074 constructed to test telomere-mediated chromosomal truncation in maize.
8075 Two constructs with 2.6 kb of telomeric sequence were used to transform
8076 maize immature embryos by Agrobacterium-mediated transformation. One
8077 hundred seventy-six transgenic lines were recovered in which 231
8078 transgene loci were revealed by a FISH analysis. To analyze chromosomal
8079 truncations that result in transgenes located near chromosomal termini,
8080 Southern hybridization analyses were performed. A pattern of smear in
8081 truncated lines was seen as compared with discrete bands for internal
8082 integrations, because telomeres in different cells are elongated
8083 differently by telomerase. When multiple restriction enzymes were used
8084 to map the transgene positions, the size of the smears shifted in
8085 accordance with the locations of restriction sites on the construct.
8086 This result demonstrated that the transgene was present at the end of
8087 the chromosome immediately before the integrated telomere sequence.
8088 Direct evidence for chromosomal truncation came from the results of
8089 FISH karyotyping, which revealed broken chromosomes with transgene
8090 signals at the ends. These results demonstrate that telomere-mediated
8091 chromosomal truncation operates in plant species. This technology will
8092 be useful for chromosomal engineering in maize as well as other plant
8097 author = JZhao #" and "# HLee #" and "# RNome #" and "# SMajid #" and "#
8098 NScherer #" and "# WHoff,
8099 title = "Single-molecule detection of structural changes during
8100 {P}er-{A}rnt-{S}im ({PAS}) domain activation",
8105 pages = "11561--11566",
8106 doi = "10.1073/pnas.0601567103",
8107 eprint = "http://www.pnas.org/cgi/reprint/103/31/11561.pdf",
8108 url = "http://www.pnas.org/cgi/content/abstract/103/31/11561",
8109 abstract = "The Per-Arnt-Sim (PAS) domain is a ubiquitous protein module
8110 with a common three-dimensional fold involved in a wide range of
8111 regulatory and sensory functions in all domains of life. The activation
8112 of these functions is thought to involve partial unfolding of N- or
8113 C-terminal helices attached to the PAS domain. Here we use atomic force
8114 microscopy to probe receptor activation in single molecules of
8115 photoactive yellow protein (PYP), a prototype of the PAS domain family.
8116 Mechanical unfolding of Cys-linked PYP multimers in the presence and
8117 absence of illumination reveals that, in contrast to previous studies,
8118 the PAS domain itself is extended by {approx}3 nm (at the 10-pN
8119 detection limit of the measurement) and destabilized by {approx}30% in
8120 the light-activated state of PYP. Comparative measurements and steered
8121 molecular dynamics simulations of two double-Cys PYP mutants that probe
8122 different regions of the PAS domain quantify the anisotropy in
8123 stability and changes in local structure, thereby demonstrating the
8124 partial unfolding of their PAS domain upon activation. These results
8125 establish a generally applicable single-molecule approach for mapping
8126 functional conformational changes to selected regions of a protein. In
8127 addition, the results have profound implications for the molecular
8128 mechanism of PAS domain activation and indicate that stimulus-induced
8129 partial protein unfolding can be used as a signaling mechanism."
8132 @article { zhuang06,
8133 author = WZhuang #" and "# DAbramavicius #" and "# SMukamel,
8134 title = "Two-dimensional vibrational optical probes for peptide fast
8135 folding investigation",
8140 pages = "18934--18938",
8141 doi = "10.1073/pnas.0606912103",
8142 eprint = "http://www.pnas.org/cgi/reprint/103/50/18934.pdf",
8143 url = "http://www.pnas.org/cgi/content/abstract/103/50/18934",
8144 abstract = "A simulation study shows that early protein folding events may
8145 be investigated by using a recently developed family of nonlinear
8146 infrared techniques that combine the high temporal and spatial
8147 resolution of multidimensional spectroscopy with the chirality-specific
8148 sensitivity of amide vibrations to structure. We demonstrate how the
8149 structural sensitivity of cross-peaks in two-dimensional correlation
8150 plots of chiral signals of an {alpha} helix and a [beta] hairpin may be
8151 used to clearly resolve structural and dynamical details undetectable
8152 by one-dimensional techniques (e.g. circular dichroism) and identify
8153 structures indistinguishable by NMR."
8156 @article { zinober02,
8157 author = RCZinober #" and "# DJBrockwell #" and "# GSBeddard #" and "#
8158 AWBlake #" and "# PDOlmsted #" and "# SERadford #" and "# DASmith,
8159 title = "Mechanically unfolding proteins: the effect of unfolding history
8160 and the supramolecular scaffold",
8166 pages = "2759--2765",
8168 doi = "10.1110/ps.0224602",
8169 eprint = "http://www.proteinscience.org/cgi/reprint/11/12/2759.pdf",
8170 url = "http://www.proteinscience.org/cgi/content/abstract/11/12/2759",
8171 keywords = "Computer Simulation; Models, Molecular; Monte Carlo Method;
8172 Protein Folding; Protein Structure, Tertiary; Proteins",
8173 abstract = "The mechanical resistance of a folded domain in a polyprotein
8174 of five mutant I27 domains (C47S, C63S I27)(5)is shown to depend on the
8175 unfolding history of the protein. This observation can be understood on
8176 the basis of competition between two effects, that of the changing
8177 number of domains attempting to unfold, and the progressive increase in
8178 the compliance of the polyprotein as domains unfold. We present Monte
8179 Carlo simulations that show the effect and experimental data that
8180 verify these observations. The results are confirmed using an
8181 analytical model based on transition state theory. The model and
8182 simulations also predict that the mechanical resistance of a domain
8183 depends on the stiffness of the surrounding scaffold that holds the
8184 domain in vivo, and on the length of the unfolded domain. Together,
8185 these additional factors that influence the mechanical resistance of
8186 proteins have important consequences for our understanding of natural
8187 proteins that have evolved to withstand force.",
8188 note = "Introduces unfolding-order \emph{scaffold effect} on average
8190 project = "sawtooth simulation"
8193 @article { zwanzig92,
8194 author = RZwanzig #" and "# ASzabo #" and "# BBagchi,
8195 title = "Levinthal's paradox.",
8205 "http://www.ncbi.nlm.nih.gov/pmc/articles/PMC48166/pdf/pnas01075-0036.p
8207 url = "http://www.ncbi.nlm.nih.gov/pmc/articles/PMC48166/",
8208 keywords = "Mathematics;Models, Theoretical;Protein Conformation;Proteins",
8209 abstract = "Levinthal's paradox is that finding the native folded state of
8210 a protein by a random search among all possible configurations can take
8211 an enormously long time. Yet proteins can fold in seconds or less.
8212 Mathematical analysis of a simple model shows that a small and
8213 physically reasonable energy bias against locally unfavorable
8214 configurations, of the order of a few kT, can reduce Levinthal's time
8215 to a biologically significant size."
8219 author = XHong #" and "# XChu #" and "# PZou #" and "# YLiu
8221 title = "Magnetic-field-assisted rapid ultrasensitive
8222 immunoassays using Fe3{O4}/Zn{O}/Au nanorices as Raman
8228 address = "Centre for Advanced Optoelectronic Functional
8229 Materials Research, Key Laboratory for UV
8230 Light-Emitting Materials and Technology of Ministry of
8231 Education, Northeast Normal University, Changchun
8236 keywords = "Biosensing Techniques",
8237 keywords = "Electromagnetic Fields",
8238 keywords = "Equipment Design",
8239 keywords = "Equipment Failure Analysis",
8240 keywords = "Immunoassay",
8241 keywords = "Magnetite Nanoparticles",
8242 keywords = "Spectrum Analysis, Raman",
8243 keywords = "Zinc Oxide",
8244 abstract = "Rapid and ultrasensitive immunoassays were developed
8245 by using biofunctional Fe3O4/ZnO/Au nanorices as Raman
8246 probes. Taking advantage of the superparamagnetic
8247 property of the nanorices, the labeled proteins can
8248 rapidly be separated and purified with a commercial
8249 permanent magnet. The unsusceptible multiphonon
8250 resonant Raman scattering of the nanorices provided a
8251 characteristic spectroscopic fingerprint function,
8252 which allowed an accurate detection of the analyte.
8253 High specificity and selectivity of the assay were
8254 demonstrated. It was found that the diffusion barriers
8255 and the boundary layer effects had a great influence on
8256 the detection limit. Manipulation of the nanorice
8257 probes using an external magnetic field can enhance the
8258 assay sensitivity by several orders of magnitude, and
8259 reduce the detection time from 1 h to 3 min. This
8260 magnetic-field-assisted rapid and ultrasensitive
8261 immunoassay based on the resonant Raman scatting of
8262 semiconductor shows significant value for potential
8263 applications in biomedicine, food safety, and
8264 environmental defence.",
8266 doi = "10.1016/j.bios.2010.06.066",
8267 URL = "http://www.ncbi.nlm.nih.gov/pubmed/20667438",
8272 author = LZhao #" and "# ABulhassan #" and "# GYang #" and "#
8274 title = "Real-time detection of the morphological change in
8275 cellulose by a nanomechanical sensor.",
8280 address = "Department of Physics, Drexel University,
8281 Philadelphia, Pennsylvania, USA.",
8285 keywords = "Cellulose",
8286 keywords = "Computer Systems",
8287 keywords = "Equipment Design",
8288 keywords = "Equipment Failure Analysis",
8289 keywords = "Micro-Electrical-Mechanical Systems",
8290 keywords = "Molecular Conformation",
8291 keywords = "Nanotechnology",
8292 keywords = "Transducers",
8293 abstract = "Up to now, experimental limitations have prevented
8294 researchers from achieving the molecular-level
8295 understanding for the initial steps of the enzymatic
8296 hydrolysis of cellulose, where cellulase breaks down
8297 the crystal structure on the surface region of
8298 cellulose and exposes cellulose chains for the
8299 subsequent hydrolysis by cellulase. Because one of
8300 these non-hydrolytic enzymatic steps could be the
8301 rate-limiting step for the entire enzymatic hydrolysis
8302 of crystalline cellulose by cellulase, being able to
8303 analyze and understand these steps is instrumental in
8304 uncovering novel leads for improving the efficiency of
8305 cellulase. In this communication, we report an
8306 innovative application of the microcantilever technique
8307 for a real-time assessment of the morphological change
8308 of cellulose induced by a treatment of sodium chloride.
8309 This sensitive nanomechanical approach to define
8310 changes in surface structure of cellulose has the
8311 potential to permit a real-time assessment of the
8312 effect of the non-hydrolytic activities of cellulase on
8313 cellulose and thereby to provide a comprehensive
8314 understanding of the initial steps of the enzymatic
8315 hydrolysis of cellulose.",
8317 doi = "10.1002/bit.22754",
8318 URL = "http://www.ncbi.nlm.nih.gov/pubmed/20653025",
8323 author = RLiu #" and "# MRoman #" and "# GYang,
8324 title = "Correction of the viscous drag induced errors in
8325 macromolecular manipulation experiments using atomic
8330 address = "Department of Physics, Drexel University,
8331 Philadelphia, Pennsylvania 19104, USA.",
8335 keywords = "Algorithms",
8336 keywords = "Artifacts",
8337 keywords = "Macromolecular Substances",
8338 keywords = "Mechanical Processes",
8339 keywords = "Microscopy, Atomic Force",
8340 keywords = "Models, Theoretical",
8341 keywords = "Motion",
8342 keywords = "Protein Folding",
8343 keywords = "Signal Processing, Computer-Assisted",
8344 keywords = "Viscosity",
8345 abstract = "We describe a method to correct the errors induced by
8346 viscous drag on the cantilever in macromolecular
8347 manipulation experiments using the atomic force
8348 microscope. The cantilever experiences a viscous drag
8349 force in these experiments because of its motion
8350 relative to the surrounding liquid. This viscous force
8351 superimposes onto the force generated by the
8352 macromolecule under study, causing ambiguity in the
8353 experimental data. To remove this artifact, we analyzed
8354 the motions of the cantilever and the liquid in
8355 macromolecular manipulation experiments, and developed
8356 a novel model to treat the viscous drag on the
8357 cantilever as the superposition of the viscous force on
8358 a static cantilever in a moving liquid and that on a
8359 bending cantilever in a static liquid. The viscous
8360 force was measured under both conditions and the
8361 results were used to correct the viscous drag induced
8362 errors from the experimental data. The method will be
8363 useful for many other cantilever based techniques,
8364 especially when high viscosity and high cantilever
8365 speed are involved.",
8367 doi = "10.1063/1.3436646",
8368 URL = "http://www.ncbi.nlm.nih.gov/pubmed/20590242",
8372 @phdthesis { roman12,
8374 title = "Macromolecular crowding effects in the mechanical unfolding
8375 forces of proteins",
8379 url = "http://hdl.handle.net/1860/3854",
8380 eprint = "http://idea.library.drexel.edu/bitstream/1860/3854/1/Roman_Marisa.pdf",
8381 keywords = "Physics",
8382 keywords = "Biophysics",
8383 keywords = "Protein folding",
8384 abstract = "Macromolecules can occupy a large fraction of the volume
8385 of a cell and this crowded environment influences the behavior and
8386 properties of the proteins, such as mechanical unfolding forces,
8387 thermal stability and rates of folding and diffusion. Although
8388 much is already known about molecular crowding, it is not well
8389 understood how it affects a protein’s resistance to mechanical
8390 stress in a crowded environment and how the size of the crowders
8391 affect those changes. An atomic force microscope-based single
8392 molecule method was used to measure the effects of the crowding on
8393 the mechanical stability of a model protein, in this case I-27. As
8394 proteins tend to aggregate, single molecule methods provided a way
8395 to prevent aggregation because of the very low concentration of
8396 proteins in the solution under study. Dextran was used as the
8397 crowding agent with three different molecular weights 6kDa, 10 kDa
8398 and 40 kDa, with concentrations varying from zero to 300 grams per
8399 liter in a pH neutral buffer solution at room temperature. Results
8400 showed that the forces required to unfold biomolecules were
8401 increased when a high concentration of crowder molecules were
8402 added to the buffer solution and that the maximum force required
8403 to unfold a domain was when the crowder size was 10 kDa, which is
8404 comparable to the protein size. Unfolding rates obtained from
8405 Monte Carlo simulations showed that they were also affected in the
8406 presence of crowders. As a consequence, the energy barrier was
8407 also affected. These effects were most notable when the size of
8408 the crowder was 10 kDa, comparable to the size of the protein. On
8409 the other hand, distances to the transition state did not seem to
8410 change when crowders were added to the solution. The effect of
8411 Dextran on the energy barrier was modeled by using established
8412 theories such as Ogston’s and scaled particle theory, neither of
8413 which was completely convincing at describing the results. It can
8414 be hypothesized that the composition of Dextran plays a role in
8415 the deviation of the predicted behavior with respect to the
8416 experimental data.",
8420 @article { measey09,
8421 author = TMeasey #" and "# KBSmith #" and "# SDecatur #" and "#
8422 LZhao #" and "# GYang #" and "# RSchweitzerStenner,
8423 title = "Self-aggregation of a polyalanine octamer promoted by
8424 its {C}-terminal tyrosine and probed by a strongly
8425 enhanced vibrational circular dichroism signal.",
8430 address = "Department of Chemistry, Drexel University, 3141
8431 Chestnut Street, Philadelphia, Pennsylvania 19104,
8435 pages = "18218--18219",
8436 keywords = "Amyloid",
8437 keywords = "Circular Dichroism",
8438 keywords = "Dimerization",
8439 keywords = "Oligopeptides",
8440 keywords = "Peptides",
8441 keywords = "Protein Conformation",
8442 keywords = "Tyrosine",
8443 abstract = "The eight-residue alanine oligopeptide
8444 Ac-A(4)KA(2)Y-NH(2) (AKY8) was found to form
8445 amyloid-like fibrils upon incubation at room
8446 temperature in acidified aqueous solution at peptide
8447 concentrations >10 mM. The fibril solution exhibits an
8448 enhanced vibrational circular dichroism (VCD) couplet
8449 in the amide I' band region that is nearly 2 orders of
8450 magnitude larger than typical polypeptide/protein
8451 signals in this region. The UV-CD spectrum of the
8452 fibril solution shows CD in the region associated with
8453 the tyrosine side chain absorption. A similar peptide,
8454 Ac-A(4)KA(2)-NH(2) (AK7), which lacks a terminal
8455 tyrosine residue, does not aggregate. These results
8456 suggest a pivotal role for the C-terminal tyrosine
8457 residue in stabilizing the aggregation state of this
8458 peptide. It is speculated that interactions between the
8459 lysine and tyrosine side chains of consecutive strands
8460 in an antiparallel arrangement (e.g., cation-pi
8461 interactions) are responsible for the stabilization of
8462 the resulting fibrils. These results offer
8463 considerations and insight regarding the de novo design
8464 of self-assembling oligopeptides for biomedical and
8465 biotechnological applications and highlight the
8466 usefulness of VCD as a tool for probing amyloid fibril
8469 doi = "10.1021/ja908324m",
8470 URL = "http://www.ncbi.nlm.nih.gov/pubmed/19958029",
8475 author = GShan #" and "# SWang #" and "# XFei #" and "# YLiu
8477 title = "Heterostructured Zn{O}/Au nanoparticles-based resonant
8478 Raman scattering for protein detection.",
8483 address = "Center for Advanced Optoelectronic Functional
8484 Materials Research, Northeast Normal University,
8485 Changchun 130024, P. R. China.",
8488 pages = "1468--1472",
8489 keywords = "Animals",
8491 keywords = "Humans",
8492 keywords = "Immunoglobulin G",
8493 keywords = "Metal Nanoparticles",
8494 keywords = "Microscopy, Electron, Transmission",
8495 keywords = "Spectrum Analysis, Raman",
8496 keywords = "Zinc Oxide",
8497 abstract = "A new method of protein detection was explored on the
8498 resonant Raman scattering signal of ZnO nanoparticles.
8499 A probe for the target protein was constructed by
8500 binding the ZnO/Au nanoparticles to secondary protein
8501 by eletrostatic interaction. The detection of proteins
8502 was achieved by an antibody-based sandwich assay. A
8503 first antibody, which could be specifically recognized
8504 by target protein, was attached to a solid silicon
8505 surface. The ZnO/Au protein probe could specifically
8506 recognize and bind to the complex of the target protein
8507 and first antibody. This method on the resonant Raman
8508 scattering signal of ZnO nanoparticles showed good
8509 selectivity and sensitivity for the target protein.",
8511 doi = "10.1021/jp8046032",
8512 URL = "http://www.ncbi.nlm.nih.gov/pubmed/19138135",
8517 author = JMYuan #" and "# CLChyan #" and "# HXZhou #" and "#
8518 TYChung #" and "# HPeng #" and "# GPing #" and "#
8520 title = "The effects of macromolecular crowding on the
8521 mechanical stability of protein molecules.",
8526 address = "Department of Physics, Drexel University,
8527 Philadelphia, Pennsylvania 19104, USA.",
8530 pages = "2156--2166",
8531 keywords = "Circular Dichroism",
8532 keywords = "Dextrans",
8533 keywords = "Kinetics",
8534 keywords = "Microscopy, Atomic Force",
8535 keywords = "Microscopy, Scanning Probe",
8536 keywords = "Protein Folding",
8537 keywords = "Protein Stability",
8538 keywords = "Protein Structure, Secondary",
8539 keywords = "Thermodynamics",
8540 keywords = "Ubiquitin",
8541 abstract = "Macromolecular crowding, a common phenomenon in the
8542 cellular environments, can significantly affect the
8543 thermodynamic and kinetic properties of proteins. A
8544 single-molecule method based on atomic force microscopy
8545 (AFM) was used to investigate the effects of
8546 macromolecular crowding on the forces required to
8547 unfold individual protein molecules. It was found that
8548 the mechanical stability of ubiquitin molecules was
8549 enhanced by macromolecular crowding from added dextran
8550 molecules. The average unfolding force increased from
8551 210 pN in the absence of dextran to 234 pN in the
8552 presence of 300 g/L dextran at a pulling speed of 0.25
8553 microm/sec. A theoretical model, accounting for the
8554 effects of macromolecular crowding on the native and
8555 transition states of the protein molecule by applying
8556 the scaled-particle theory, was used to quantitatively
8557 explain the crowding-induced increase in the unfolding
8558 force. The experimental results and interpretation
8559 presented could have wide implications for the many
8560 proteins that experience mechanical stresses and
8561 perform mechanical functions in the crowded environment
8564 doi = "10.1110/ps.037325.108",
8565 URL = "http://www.ncbi.nlm.nih.gov/pubmed/18780817",
8570 author = YLiu #" and "# MZhong #" and "# GShan #" and "# YLi
8571 #" and "# BHuang #" and "# GYang,
8572 title = "Biocompatible Zn{O}/Au nanocomposites for
8573 ultrasensitive {DNA} detection using resonance Raman
8579 address = "Centre for Advanced Optoelectronic Functional
8580 Materials Research, Institute of Genetics and Cytology,
8581 Northeast Normal University, Changchun, People's
8582 Republic of China. ycliu@nenu.edu.cn",
8585 pages = "6484--6489",
8586 keywords = "Base Sequence",
8589 keywords = "Microscopy, Electron, Transmission",
8590 keywords = "Nanocomposites",
8591 keywords = "Sensitivity and Specificity",
8592 keywords = "Spectrum Analysis, Raman",
8593 keywords = "Zinc Oxide",
8594 abstract = "A novel method for identifying DNA microarrays based
8595 on ZnO/Au nanocomposites functionalized with
8596 thiol-oligonucleotide as probes is descried here. DNA
8597 labeled with ZnO/Au nanocomposites has a strong Raman
8598 signal even without silver acting as a surface-enhanced
8599 Raman scattering promoter. X-ray photoelectron spectra
8600 confirmed the formation of a three-component sandwich
8601 assay, i.e., constituted DNA and ZnO/Au nanocomposites.
8602 The resonance multiple-phonon Raman signal of the
8603 ZnO/Au nanocomposites as a spectroscopic fingerprint is
8604 used to detect a target sequence of oligonucleotide.
8605 This method exhibits extraordinary sensitivity and the
8606 detection limit is at least 1 fM.",
8608 doi = "10.1021/jp710399d",
8609 URL = "http://www.ncbi.nlm.nih.gov/pubmed/18444675",
8614 author = YGuo #" and "# AMylonakis #" and "# ZZhang #" and "#
8615 GYang #" and "# PLelkes #" and "# SChe #" and "#
8617 title = "Templated synthesis of electroactive periodic
8618 mesoporous organosilica bridged with oligoaniline.",
8621 address = "Department of Chemistry, Drexel University,
8622 Philadelphia, Pennsylvania 19104, USA.",
8625 pages = "2909--2917",
8626 keywords = "Aniline Compounds",
8627 keywords = "Cetrimonium Compounds",
8628 keywords = "Electrochemistry",
8629 keywords = "Hydrolysis",
8630 keywords = "Microscopy, Electron, Transmission",
8631 keywords = "Molecular Structure",
8632 keywords = "Organosilicon Compounds",
8633 keywords = "Particle Size",
8634 keywords = "Porosity",
8635 keywords = "Spectroscopy, Fourier Transform Infrared",
8636 keywords = "Surface Properties",
8637 keywords = "Thermogravimetry",
8638 keywords = "X-Ray Diffraction",
8639 abstract = "The synthesis and characterization of novel
8640 electroactive periodic mesoporous organosilica (PMO)
8641 are reported. The silsesquioxane precursor,
8642 N,N'-bis(4'-(3-triethoxysilylpropylureido)phenyl)-1,4-quinonene-diimine
8643 (TSUPQD), was prepared from the emeraldine base of
8644 amino-capped aniline trimer (EBAT) using a one-step
8645 coupling reaction and was used as an organic silicon
8646 source in the co-condensation with tetraethyl
8647 orthosilicate (TEOS) in proper ratios. By means of a
8648 hydrothermal sol-gel approach with the cationic
8649 surfactant cetyltrimethyl-ammonium bromide (CTAB) as
8650 the structure-directing template and acetone as the
8651 co-solvent for the dissolution of TSUPQD, a series of
8652 novel MCM-41 type siliceous materials (TSU-PMOs) were
8653 successfully prepared under mild alkaline conditions.
8654 The resultant mesoporous organosilica were
8655 characterized by Fourier transform infrared (FT-IR)
8656 spectroscopy, thermogravimetry, X-ray diffraction,
8657 nitrogen sorption, and transmission electron microscopy
8658 (TEM) and showed that this series of TSU-PMOs exhibited
8659 hexagonally patterned mesostructures with pore
8660 diameters of 2.1-2.8 nm. Although the structural
8661 regularity and pore parameters gradually deteriorated
8662 with increasing loading of organic bridges, the
8663 electrochemical behavior of TSU-PMOs monitored by
8664 cyclic voltammetry demonstrated greater
8665 electroactivities for samples with higher concentration
8666 of the incorporated TSU units.",
8668 doi = "10.1002/chem.200701605",
8669 URL = "http://www.ncbi.nlm.nih.gov/pubmed/18224650",
8674 author = LiLi #" and "# BLi #" and "# GYang #" and "# CYLi,
8675 title = "Polymer decoration on carbon nanotubes via physical
8681 address = "A. J. Drexel Nanotechnology Institute and Department
8682 of Materials Science and Engineering, Drexel
8683 University, Philadelphia, Pennsylvania 19104, USA.",
8686 pages = "8522--8525",
8687 keywords = "Microscopy, Atomic Force",
8688 keywords = "Microscopy, Electron, Transmission",
8689 keywords = "Nanotubes, Carbon",
8690 keywords = "Polymers",
8691 keywords = "Surface Properties",
8692 keywords = "Volatilization",
8693 abstract = "The polymer decoration technique has been widely used
8694 to study the chain folding behavior of polymer single
8695 crystals. In this article, we demonstrate that this
8696 method can be successfully adopted to pattern a variety
8697 of polymers on carbon nanotubes (CNTs). The resulting
8698 structure is a two-dimensional nanohybrid shish kebab
8699 (2D NHSK), wherein the CNT forms the shish and the
8700 polymer crystals form the kebabs. 2D NHSKs consisting
8701 of CNTs and polymers such as polyethylene, nylon 66,
8702 polyvinylidene fluoride and poly(L-lysine) have been
8703 achieved. Transmission electron microscopy and atomic
8704 force microscopy were used to study the nanoscale
8705 morphology of these hybrid materials. Relatively
8706 periodic decoration of polymers on both single-walled
8707 and multi-walled CNTs was observed. It is envisaged
8708 that this unique method offers a facile means to
8709 achieve patterned CNTs for nanodevice applications.",
8711 doi = "10.1021/la700480z",
8712 URL = "http://www.ncbi.nlm.nih.gov/pubmed/17602575",
8717 author = MSu #" and "# YYang #" and "# GYang,
8718 title = "Quantitative measurement of hydroxyl radical induced
8719 {DNA} double-strand breaks and the effect of
8720 {N}-acetyl-{L}-cysteine.",
8725 address = "Department of Physics, Drexel University,
8726 Philadelphia, PA 19104, USA.",
8729 pages = "4136--4142",
8730 keywords = "Acetylcysteine",
8731 keywords = "Animals",
8732 keywords = "DNA Damage",
8733 keywords = "Humans",
8734 keywords = "Hydroxyl Radical",
8735 keywords = "Microscopy, Atomic Force",
8736 keywords = "Nucleic Acid Conformation",
8737 keywords = "Plasmids",
8738 abstract = "Reactive oxygen species, such as hydroxyl or
8739 superoxide radicals, can be generated by exogenous
8740 agents as well as from normal cellular metabolism.
8741 Those radicals are known to induce various lesions in
8742 DNA, including strand breaks and base modifications.
8743 These lesions have been implicated in a variety of
8744 diseases such as cancer, arteriosclerosis, arthritis,
8745 neurodegenerative disorders and others. To assess these
8746 oxidative DNA damages and to evaluate the effects of
8747 the antioxidant N-acetyl-L-cysteine (NAC), atomic force
8748 microscopy (AFM) was used to image DNA molecules
8749 exposed to hydroxyl radicals generated via Fenton
8750 chemistry. AFM images showed that the circular DNA
8751 molecules became linear after incubation with hydroxyl
8752 radicals, indicating the development of double-strand
8753 breaks. The occurrence of the double-strand breaks was
8754 found to depend on the concentration of the hydroxyl
8755 radicals and the duration of the reaction. Under the
8756 conditions of the experiments, NAC was found to
8757 exacerbate the free radical-induced DNA damage.",
8759 doi = "10.1016/j.febslet.2006.06.060",
8760 URL = "http://www.ncbi.nlm.nih.gov/pubmed/16828758",
8765 author = LiLi #" and "# YYang #" and "# GYang #" and "# XuChen
8766 #" and "# BHsiao #" and "# BChu #" and "#
8767 JSpanier #" and "# CYLi,
8768 title = "Patterning polyethylene oligomers on carbon nanotubes
8769 using physical vapor deposition.",
8773 address = "A. J. Drexel Nanotechnology Institute and Department
8774 of Materials Science and Engineering, Drexel
8775 University, Philadelphia, Pennsylvania 19104, USA.",
8778 pages = "1007--1012",
8779 keywords = "Microscopy, Atomic Force",
8780 keywords = "Nanotechnology",
8781 keywords = "Nanotubes, Carbon",
8782 keywords = "Polyethylenes",
8783 keywords = "Volatilization",
8784 abstract = "Periodic patterning on one-dimensional (1D) carbon
8785 nanotubes (CNTs) is of great interest from both
8786 scientific and technological points of view. In this
8787 letter, we report using a facile physical vapor
8788 deposition method to achieve periodic polyethylene (PE)
8789 oligomer patterning on individual CNTs. Upon heating
8790 under vacuum, PE degraded into oligomers and
8791 crystallized into rod-shaped single crystals. These PE
8792 rods periodically decorate on CNTs with their long axes
8793 perpendicular to the CNT axes. The formation mechanism
8794 was attributed to ``soft epitaxy'' growth of PE
8795 oligomer crystals on CNTs. Both SWNTs and MWNTs were
8796 decorated successfully with PE rods. The intermediate
8797 state of this hybrid structure, MWNTs absorbed with a
8798 thin layer of PE, was captured successfully by
8799 depositing PE vapor on MWNTs detached from the solid
8800 substrate, and was observed using high-resolution
8801 transmission electron microscopy. Furthermore, this
8802 hybrid structure formation depends critically on CNT
8803 surface chemistry: alkane-modification of the MWNT
8804 surface prohibited the PE single-crystal growth on the
8805 CNTs. We anticipate that this work could open a gateway
8806 for creating complex CNT-based nanoarchitectures for
8807 nanodevice applications.",
8809 doi = "10.1021/nl060276q",
8810 URL = "http://www.ncbi.nlm.nih.gov/pubmed/16683841",
8815 author = MKuhn #" and "# HJanovjak #" and "# MHubain #" and "# DJMuller,
8816 title = {Automated alignment and pattern recognition of
8817 single-molecule force spectroscopy data.},
8820 address = {Division of Computer Science, California Institute of
8821 Technology, Pasadena, California 91125, USA.},
8827 doi = {10.1111/j.1365-2818.2005.01478.x},
8828 URL = {http://www.ncbi.nlm.nih.gov/pubmed/15857374},
8830 keywords = {Algorithms},
8831 keywords = {Bacteriorhodopsins},
8832 keywords = {Data Interpretation, Statistical},
8833 keywords = {Escherichia coli Proteins},
8834 keywords = {Microscopy, Atomic Force},
8835 keywords = {Protein Folding},
8836 keywords = {Sodium-Hydrogen Antiporter},
8837 keywords = {Software},
8838 abstract = {Recently, direct measurements of forces stabilizing
8839 single proteins or individual receptor-ligand bonds became
8840 possible with ultra-sensitive force probe methods like the atomic
8841 force microscope (AFM). In force spectroscopy experiments using
8842 AFM, a single molecule or receptor-ligand pair is tethered between
8843 the tip of a micromachined cantilever and a supporting
8844 surface. While the molecule is stretched, forces are measured by
8845 the deflection of the cantilever and plotted against extension,
8846 yielding a force spectrum characteristic for each biomolecular
8847 system. In order to obtain statistically relevant results, several
8848 hundred to thousand single-molecule experiments have to be
8849 performed, each resulting in a unique force spectrum. We developed
8850 software and algorithms to analyse large numbers of force
8851 spectra. Our algorithms include the fitting polymer extension
8852 models to force peaks as well as the automatic alignment of
8853 spectra. The aligned spectra allowed recognition of patterns of
8854 peaks across different spectra. We demonstrate the capabilities of
8855 our software by analysing force spectra that were recorded by
8856 unfolding single transmembrane proteins such as bacteriorhodopsin
8857 and NhaA. Different unfolding pathways were detected by
8858 classifying peak patterns. Deviant spectra, e.g. those with no
8859 attachment or erratic peaks, can be easily identified. The
8860 software is based on the programming language C++, the GNU
8861 Scientific Library (GSL), the software WaveMetrics IGOR Pro and
8862 available open-source at http://bioinformatics.org/fskit/.},
8863 note = {Development stalled in 2005 after Michael graduated.},
8866 @article{ janovjak05,
8867 author = HJanovjak #" and "# JStruckmeier #" and "# DJMuller,
8868 title = {Hydrodynamic effects in fast {AFM} single-molecule
8869 force measurements.},
8873 address = {BioTechnological Center, University of Technology
8874 Dresden, 01307 Dresden, Germany.},
8880 doi = {10.1007/s00249-004-0430-3},
8881 url = {http://www.ncbi.nlm.nih.gov/pubmed/15257425},
8883 keywords = {Algorithms},
8884 keywords = {Computer Simulation},
8885 keywords = {Elasticity},
8886 keywords = {Microfluidics},
8887 keywords = {Microscopy, Atomic Force},
8888 keywords = {Models, Chemical},
8889 keywords = {Models, Molecular},
8890 keywords = {Physical Stimulation},
8891 keywords = {Protein Binding},
8892 keywords = {Proteins},
8893 keywords = {Stress, Mechanical},
8894 keywords = {Viscosity},
8895 abstract = {Atomic force microscopy (AFM) allows the critical forces
8896 that unfold single proteins and rupture individual receptor-ligand
8897 bonds to be measured. To derive the shape of the energy landscape,
8898 the dynamic strength of the system is probed at different force
8899 loading rates. This is usually achieved by varying the pulling
8900 speed between a few nm/s and a few $\mu$m/s, although for a more
8901 complete investigation of the kinetic properties higher speeds are
8902 desirable. Above 10 $\mu$m/s, the hydrodynamic drag force acting
8903 on the AFM cantilever reaches the same order of magnitude as the
8904 molecular forces. This has limited the maximum pulling speed in
8905 AFM single-molecule force spectroscopy experiments. Here, we
8906 present an approach for considering these hydrodynamic effects,
8907 thereby allowing a correct evaluation of AFM force measurements
8908 recorded over an extended range of pulling speeds (and thus
8909 loading rates). To support and illustrate our theoretical
8910 considerations, we experimentally evaluated the mechanical
8911 unfolding of a multi-domain protein recorded at $30\U{$mu$m/s}$
8916 author = MSandal #" and "# FValle #" and "# ITessari #" and "#
8917 SMammi #" and "# EBergantino #" and "# FMusiani #" and "#
8918 MBrucale #" and "# LBubacco #" and "# BSamori,
8919 title = {Conformational Equilibria in Monomeric $\alpha$-Synuclein
8920 at the Single-Molecule Level},
8923 address = {Department of Biochemistry G. Moruzzi,
8924 University of Bologna, Bologna, Italy.},
8930 doi = {10.1371/journal.pbio.0060006},
8931 url = {http://www.ncbi.nlm.nih.gov/pubmed/18198943},
8933 keywords = {Buffers},
8934 keywords = {Circular Dichroism},
8935 keywords = {Copper},
8936 keywords = {Entropy},
8937 keywords = {Models, Molecular},
8938 keywords = {Molecular Sequence Data},
8939 keywords = {Mutation},
8940 keywords = {Protein Structure, Secondary},
8941 keywords = {Protein Structure, Tertiary},
8942 keywords = {alpha-Synuclein},
8943 abstract = {Human $\alpha$-Synuclein ($\alpha$Syn) is a natively
8944 unfolded protein whose aggregation into amyloid fibrils is
8945 involved in the pathology of Parkinson disease. A full
8946 comprehension of the structure and dynamics of early intermediates
8947 leading to the aggregated states is an unsolved problem of
8948 essential importance to researchers attempting to decipher the
8949 molecular mechanisms of $\alpha$Syn aggregation and formation of
8950 fibrils. Traditional bulk techniques used so far to solve this
8951 problem point to a direct correlation between $\alpha$Syn's unique
8952 conformational properties and its propensity to aggregate, but
8953 these techniques can only provide ensemble-averaged information
8954 for monomers and oligomers alike. They therefore cannot
8955 characterize the full complexity of the conformational equilibria
8956 that trigger the aggregation process. We applied atomic force
8957 microscopy-based single-molecule mechanical unfolding methodology
8958 to study the conformational equilibrium of human wild-type and
8959 mutant $\alpha$Syn. The conformational heterogeneity of monomeric
8960 $\alpha$Syn was characterized at the single-molecule level. Three
8961 main classes of conformations, including disordered and
8962 ``$\beta$-like'' structures, were directly observed and quantified
8963 without any interference from oligomeric soluble forms. The
8964 relative abundance of the ``$\beta$-like'' structures
8965 significantly increased in different conditions promoting the
8966 aggregation of $\alpha$Syn: the presence of \Cu, the pathogenic
8967 A30P mutation, and high ionic strength. This methodology can
8968 explore the full conformational space of a protein at the
8969 single-molecule level, detecting even poorly populated conformers
8970 and measuring their distribution in a variety of biologically
8971 important conditions. To the best of our knowledge, we present
8972 for the first time evidence of a conformational equilibrium that
8973 controls the population of a specific class of monomeric
8974 $\alpha$Syn conformers, positively correlated with conditions
8975 known to promote the formation of aggregates. A new tool is thus
8976 made available to test directly the influence of mutations and
8977 pharmacological strategies on the conformational equilibrium of
8978 monomeric $\alpha$Syn.},
8982 author = MSandal #" and "# FBenedetti #" and "# MBrucale #" and "#
8983 AGomezCasado #" and "# BSamori,
8984 title = "Hooke: An open software platform for force spectroscopy.",
8989 address = "Department of Biochemistry, University of Bologna,
8990 Bologna, Italy. massimo.sandal@unibo.it",
8993 pages = "1428--1430",
8994 keywords = "Algorithms",
8995 keywords = "Computational Biology",
8996 keywords = "Internet",
8997 keywords = "Microscopy, Atomic Force",
8998 keywords = "Proteome",
8999 keywords = "Proteomics",
9000 keywords = "Software",
9001 abstract = "SUMMARY: Hooke is an open source, extensible software
9002 intended for analysis of atomic force microscope (AFM)-based
9003 single molecule force spectroscopy (SMFS) data. We propose it as a
9004 platform on which published and new algorithms for SMFS analysis
9005 can be integrated in a standard, open fashion, as a general
9006 solution to the current lack of a standard software for SMFS data
9007 analysis. Specific features and support for file formats are coded
9008 as independent plugins. Any user can code new plugins, extending
9009 the software capabilities. Basic automated dataset filtering and
9010 semi-automatic analysis facilities are included. AVAILABILITY:
9011 Software and documentation are available at
9012 (http://code.google.com/p/hooke). Hooke is a free software under
9013 the GNU Lesser General Public License.",
9015 doi = "10.1093/bioinformatics/btp180",
9016 URL = "http://www.ncbi.nlm.nih.gov/pubmed/19336443",
9020 @article{ materassi09,
9021 author = DMaterassi #" and "# PBaschieri #" and "# BTiribilli #" and "#
9022 GZuccheri #" and "# BSamori,
9023 title = {An open source/real-time atomic force microscope
9024 architecture to perform customizable force spectroscopy
9028 address = {Department of Electrical and Computer Engineering,
9029 University of Minnesota, 200 Union St. SE, Minneapolis,
9030 Minnesota 55455, USA. mater013@umn.edu},
9036 doi = "10.1063/1.3194046",
9037 url = "http://www.ncbi.nlm.nih.gov/pubmed/19725671",
9039 keywords = {Algorithms},
9040 keywords = {Animals},
9041 keywords = {Calibration},
9043 keywords = {Microscopy, Atomic Force},
9044 keywords = {Muscle Proteins},
9045 keywords = {Myocardium},
9046 keywords = {Optics and Photonics},
9047 keywords = {Ownership},
9048 keywords = {Protein Kinases},
9049 keywords = {Software},
9050 keywords = {Spectrum Analysis},
9051 keywords = {Time Factors},
9052 abstract = {We describe the realization of an atomic force
9053 microscope architecture designed to perform customizable
9054 experiments in a flexible and automatic way. Novel technological
9055 contributions are given by the software implementation platform
9056 (RTAI-LINUX), which is free and open source, and from a functional
9057 point of view, by the implementation of hard real-time control
9058 algorithms. Some other technical solutions such as a new way to
9059 estimate the optical lever constant are described as well. The
9060 adoption of this architecture provides many degrees of freedom in
9061 the device behavior and, furthermore, allows one to obtain a
9062 flexible experimental instrument at a relatively low cost. In
9063 particular, we show how such a system has been employed to obtain
9064 measures in sophisticated single-molecule force spectroscopy
9065 experiments\citep{fernandez04}. Experimental results on proteins
9066 already studied using the same methodologies are provided in order
9067 to show the reliability of the measure system.},
9068 note = {Although this paper claims to present an open source
9069 experiment control framework (on Linux!), it doesn't actually link
9070 to any source code. This is puzzling and frusterating.},
9073 @article{ aioanei11,
9074 author = DAioanei #" and "# MBrucale #" and "# BSamori,
9075 title = {Open source platform for the execution and analysis of
9076 mechanical refolding experiments.},
9080 address = {Department of Biochemistry G.~Moruzzi,
9081 University of Bologna, Via Irnerio 48, 40126 Bologna, Italy.
9082 aioaneid@gmail.com},
9088 doi = {10.1093/bioinformatics/btq663},
9089 url = {http://www.ncbi.nlm.nih.gov/pubmed/21123222},
9091 keywords = {Computational Biology},
9092 keywords = {Kinetics},
9093 keywords = {Protein Denaturation},
9094 keywords = {Protein Refolding},
9095 keywords = {Software},
9096 abstract = {Single-molecule force spectroscopy has facilitated the
9097 experimental investigation of biomolecular force-coupled kinetics,
9098 from which the kinetics at zero force can be extrapolated via
9099 explicit theoretical models. The atomic force microscope (AFM) in
9100 particular is routinely used to study protein unfolding kinetics,
9101 but only rarely protein folding kinetics. The discrepancy arises
9102 because mechanical protein refolding studies are more technically
9104 note = {\href{http://code.google.com/p/refolding/}{Refolding} is a
9105 suite for performing and analyzing double-pulse refolding
9106 experiments. The experiment-driver is mostly written in Java with
9107 the analysis code in Python. The driver is curious; it uses the
9108 NanoScope scripting interface to drive the experiment through the
9109 NanoScope software by impersonating a mouse-wielding user (like
9110 Selenium does for web browsers). See the
9111 \imint{sh}|RobotNanoDriver.java| code for details. There is also
9112 support for automatic velocity clamp analysis.},
9115 @article{ benedetti11,
9116 author = FBenedetti #" and "# CMicheletti #" and "# GBussi #" and "#
9117 SKSekatskii #" and "# GDietler,
9118 title = {Nonkinetic modeling of the mechanical unfolding of
9119 multimodular proteins: theory and experiments.},
9123 address = {Laboratory of Physics of Living Matter,
9124 Ecole Polytechnique F{\'e}d{\'e}rale de Lausanne,
9125 Lausanne, Switzerland.},
9129 pages = {1504--1512},
9131 doi = {10.1016/j.bpj.2011.07.047},
9132 url = {http://www.ncbi.nlm.nih.gov/pubmed/21943432},
9134 keywords = {Kinetics},
9135 keywords = {Microscopy, Atomic Force},
9136 keywords = {Models, Molecular},
9137 keywords = {Monte Carlo Method},
9138 keywords = {Protein Unfolding},
9139 keywords = {Stochastic Processes},
9140 abstract = {We introduce and discuss a novel approach called
9141 back-calculation for analyzing force spectroscopy experiments on
9142 multimodular proteins. The relationship between the histograms of
9143 the unfolding forces for different peaks, corresponding to a
9144 different number of not-yet-unfolded protein modules, is exploited
9145 in such a manner that the sole distribution of the forces for one
9146 unfolding peak can be used to predict the unfolding forces for
9147 other peaks. The scheme is based on a bootstrap prediction method
9148 and does not rely on any specific kinetic model for multimodular
9149 unfolding. It is tested and validated in both
9150 theoretical/computational contexts (based on stochastic
9151 simulations) and atomic force microscopy experiments on (GB1)(8)
9152 multimodular protein constructs. The prediction accuracy is so
9153 high that the predicted average unfolding forces corresponding to
9154 each peak for the GB1 construct are within only 5 pN of the
9155 averaged directly-measured values. Experimental data are also used
9156 to illustrate how the limitations of standard kinetic models can
9157 be aptly circumvented by the proposed approach.},
9160 @phdthesis{ benedetti12,
9161 author = FBenedetti,
9162 title = {Statistical Study of the Unfolding of Multimodular Proteins
9163 and their Energy Landscape by Atomic Force Microscopy},
9165 address = {Lausanne},
9166 affiliation = {EPFL},
9169 doi = {10.5075/epfl-thesis-5440},
9170 url = {http://infoscience.epfl.ch/record/181215},
9171 eprint = {http://infoscience.epfl.ch/record/181215/files/EPFL_TH5440.pdf},
9172 keywords = {atomic force microscope (AFM); single molecule force
9173 spectrosopy; velocity clamp AFM; Monte carlo simulations; force
9174 modulation spectroscopy; energy barrier model; non kinetic methods
9175 for force spectroscopy},
9176 abstract = {The aim of the present thesis is to investigate several
9177 aspects of: the proteins mechanics, interprotein interactions and
9178 to study also new techniques, theoretical and technical, to obtain
9179 and analyze the force spectroscopy experiments. The first section
9180 is dedicated to the statistical properties of the unfolding forces
9181 in a chain of homomeric multimodular proteins. The basic idea of
9182 this kind of statistic is to divide the peaks observed in a force
9183 extension curve in separate groups and then analyze these groups
9184 considering their position in the force curves. In fact in a
9185 multimodular homomeric protein the unfolding force is related to
9186 the number of not yet unfolded modules (we call it "N"). Such
9187 effect yields to a linear dependence of the most probable
9188 unfolding force of a peak on ln(N). We demonstrate how such
9189 dependence can be used to extract the kinetic parameters and how,
9190 ignoring it, could lead to significant errors. Following this
9191 topic we continue with non kinetic methods that, using the
9192 resampling from the rupture forces of any peak, could reconstruct
9193 the rupture forces for all the other peaks in a chain. Then a
9194 discussion about the Monte Carlo simulation for protein pulling is
9195 present. In fact a theoretical framework for such methodology has
9196 to be introduced to understand the various simulations done. In
9197 this chapter we also introduce a methodology to study the ligand
9198 receptor interactions when we directly functionalize the AFM tip
9199 and the substrate. In fact, in many of our experiments, we see a
9200 "cloud of points" in the force vs loading rate graph. We have
9201 modeled a system composed by "N" parallel springs, and studying
9202 the distribution of forces obtained in the force vs loading rate
9203 graph we have establish a procedure to restore the kinetic
9204 parameters used. Such procedure has then been used to discuss real
9205 experiments similar to biotin-avidin interaction. In the following
9206 chapter we discuss a first order approximation of the Bell-Evans
9207 model where a more explicit form of the potential is
9208 considered. In particular the dependence of the curvature of the
9209 potential on the applied force at the minimum and at the
9210 metastable state is considered. In the well known Bell-Evans model
9211 the prefactors of the transition rate are fixed at any force,
9212 however this is not what happen in nature, where the prefactors
9213 (that are the second local derivative of the interacting energy
9214 with respect to the reaction coordinate in its minimum and
9215 maximum) depend on the force applied. The results obtained with
9216 the force spectroscopy of the Laminin-binding-protein are
9217 discussed, in particular this protein showed a phase transition
9218 when the pH was changed. The behavior of this protein changes,
9219 from a normal WLC behavior to a plateau behavior. The analysis of
9220 the force spectroscopy curves shows a distribution of length where
9221 the maximum of the first prominent peak correspond to the full
9222 length of the protein. However, length that could be associated
9223 with dimers and trymers are also present in this
9224 distribution. Later a new approach to study the lock and key
9225 mechanism, using "handles" with a specific force extension
9226 pattern, is introduced. In particular handles of (I27)3 and
9227 (I27–SNase)3 were biochemically attached to: strept-actin
9228 molecules, biotin molecules, RNase and Angiogenin. The main idea
9229 is to have a system composed by "handle-(molecule A)-(molecule
9230 B)-handle" where the handles are covalently attached to the
9231 respective molecules and the two molecules "A and B" are attached
9232 by secondary bonds. This approach allows a better recognition of
9233 the protein-protein interaction enabling us to filter out spurious
9234 events. Doing a statistic on the rupture forces and comparing this
9235 with the statistic of the detachments of the system of the bare
9236 handles, we are able to extract the information of the interaction
9237 between the molecule A and B. The two last chapters are of more
9238 preliminary character that the previous part of the thesis. A
9239 section is dedicated to the estimation of effective mass and
9240 viscous drag of the cantilevers studied by autocorrelation and
9241 noise power spectrum. Usually the noise power spectrum method is
9242 the most used, however the autocorrelation should give
9243 approximately the same information. The parameters obtained are
9244 important in high frequency modulation techniques. In fact, they
9245 are needed to interpret the results. The results of these two
9246 methods show a good agreement in the estimation of the mass and
9247 the viscous drag of the various cantilever used. Afterwards a
9248 chapter is dedicated to the discussion of the force spectroscopy
9249 experiments using a low frequency modulation of the cantilever
9250 base. Such experiments allow us to record the phase and the
9251 amplitude shift of the modulation signal used. Using the amplitude
9252 channel we managed to restore the static force signal with a lower
9253 level of noise. Moreover these signals give us direct information
9254 about the dynamic stiffness and the lose of energy in the system,
9255 information that, using the standard technique would be difficult
9256 (or even impossible) to obtain.},
9260 author = TKempe #" and "# SBHKent #" and "# FChow #" and "# SMPeterson
9261 #" and "# WSundquist #" and "# JLItalien #" and "# DHarbrecht
9262 #" and "# DPlunkett #" and "# WDeLorbe,
9263 title = "Multiple-copy genes: Production and modification of
9264 monomeric peptides from large multimeric fusion proteins.",
9270 keywords = "Cloning, Molecular",
9271 keywords = "Cyanogen Bromide",
9272 keywords = "DNA, Recombinant",
9273 keywords = "Escherichia coli",
9274 keywords = "Gene Expression Regulation",
9275 keywords = "Genetic Vectors",
9276 keywords = "Humans",
9277 keywords = "Molecular Weight",
9278 keywords = "Peptide Fragments",
9279 keywords = "Plasmids",
9280 keywords = "Substance P",
9281 keywords = "beta-Galactosidase",
9282 abstract = "A vector system has been designed for obtaining high
9283 yields of polypeptides synthesized in Escherichia coli. Multiple
9284 copies of a synthetic gene encoding the neuropeptide substance P
9285 (SP) (Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2) have been
9286 linked and fused to the lacZ gene. Each copy of the SP gene was
9287 flanked by codons for methionine to create sites for cleavage by
9288 cyanogen bromide (CNBr). The isolated multimeric SP fusion
9289 protein was converted to monomers of SP analog, each containing a
9290 carboxyl-terminal homoserine lactone (Hse-lactone) residue
9291 (Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Hse-lactone), upon
9292 treatment with CNBr in formic acid. The Hse-lactone moiety was
9293 subjected to chemical modifications to produce an SP Hse
9294 amide. This method permits synthesis of peptide amide analogs and
9295 other peptide derivatives by combining recombinant DNA techniques
9296 and chemical methods.",
9298 URL = "http://www.ncbi.nlm.nih.gov/pubmed/2419204",
9303 author = MHonda #" and "# YBaba #" and "# NHiaro #" and "# TSekiguchi,
9304 title = "Metal-molecular interface of sulfur-containing amino acid
9305 and thiophene on gold surface",
9310 url = "http://dx.doi.org/10.1088/1742-6596/100/5/052071",
9312 abstract = "Chemical-bonding states of metal-molecular interface
9313 have been investigated for L-cysteine and thiophene on gold by
9314 x-ray photoelectron spectroscopy (XPS) and near edge x-ray
9315 adsorption fine structure (NEXAFS). A remarkable difference in
9316 Au-S bonding states was found between L-cysteine and
9317 thiophene. For mono-layered L-cysteine on gold, the binding energy
9318 of S 1s in XPS and the resonance energy at the S K-edge in NEXAFS
9319 are higher by 8–9 eV than those for multi-layered film (molecular
9320 L-cysteine). In contrast, the S K-edge resonance energy for
9321 mono-layered thiophene on gold was 2475.0 eV, which is the same as
9322 that for molecular L-cysteine. In S 1s XPS for mono-layered
9323 thiophene, two peaks were observed. The higher binging-energy and
9324 more intense peak at 2473.4 eV are identified as gold sulfide. The
9325 binding energy of smaller peak, whose intensity is less than 1/3
9326 of the higher binding energy peak, is 2472.2 eV, which is the same
9327 as that for molecular thiophene. These observations indicate that
9328 Au-S interface behavior shows characteristic chemical bond only
9329 for the Au-S interface of L-cysteine monolayer on gold
9335 title = "Formation and Structure of Self-Assembled Monolayers.",
9340 address = "Department of Chemical Engineering, Chemistry and
9341 Materials Science, and the Herman F. Mark Polymer Research
9342 Institute, Polytechnic University, Six MetroTech Center, Brooklyn,
9346 pages = "1533--1554",
9348 URL = "http://www.ncbi.nlm.nih.gov/pubmed/11848802",
9353 author = GHager #" and "# ABrolo,
9354 title = "Adsorption/desorption behaviour of cysteine and cystine in
9355 neutral and basic media: electrochemical evidence for differing
9356 thiol and disulfide adsorption to a {Au(111)} single crystal
9359 volume = "550--551",
9364 doi = "10.1016/S0022-0728(03)00052-4",
9365 url = "http://dx.doi.org/10.1016/S0022-0728(03)00052-4",
9367 keywords = "Disulfide",
9368 keywords = "Thiol adsorption",
9369 keywords = "Self-assembled monolayers",
9370 keywords = "Au(111) single crystal electrode",
9371 keywords = "Cysteine",
9372 keywords = "Cystine",
9373 abstract = "The adsorption/desorption behaviour of the
9374 thiol/disulfide redox couple, cysteine/cystine, was monitored at a
9375 Au(111) single crystal electrode. The monolayers were formed
9376 electrochemically from 0.1 M KClO4 and 0.1 M NaOH solutions
9377 containing either the thiol or the disulfide. Distinct features in
9378 the adsorption potential were noted. An adsorption peak was
9379 observed in the cyclic voltammograms (CVs) from Au(111) in 0.1 M
9380 KClO4 solutions containing cystine at $-0.57$ V vs. saturated
9381 calomel electrode. Under the same conditions, the CVs from
9382 solutions containing cysteine showed an adsorption peak at $-0.43$
9383 V (0.14 V more positive than the corresponding peak from disulfide
9384 solutions). This showed that the thiol and disulfide species have
9385 different adsorption properties. Similar behaviour was observed in
9386 0.1 M NaOH. Cyclic voltammetric and chronocoulometric data were
9387 employed to determine the surface coverage of the different
9388 monolayers. Cysteine solutions prepared in 0.1 M KClO4 provided
9389 coverages of $3.0\times10^{-10}$ and $2.5\times10^{-10}$
9390 mol~cm$^{-2}$ for the L and the D--L species, respectively as
9391 evaluated from the desorption peaks. Desorption of cystine in the
9392 same medium yielded coverages of $1.2\times10^{-10}$ mol~cm$^{-2}$
9393 for both L and D--L solutions (or $2.4\times10^{-10}$
9394 mol~cm$^{-2}$ in cysteine equivalents). Surface coverages obtained
9395 from Au(111) in 0.1 M NaOH corresponded to $3.9\times10^{10}$
9396 mol~cm$^{-2}$ for L-cysteine, and $1.2\times10^{-10}$
9397 mol~cm$^{-2}$ (or $2.4\times10^{-10}$ mol~cm$^{-2}$ cysteine
9398 equivalents) for L and D--L cystine.",
9403 title = "The Nanomechanics of Polycystin-1: A Kidney Mechanosensor",
9407 url = "http://etd.utmb.edu/theses/available/etd-07072010-132038/",
9409 keywords = "Polycystin-1",
9410 keywords = "Missense mutations",
9411 keywords = "Atomic Force Microscopy",
9412 keywords = "Osmolyte",
9413 keywords = "Mechanosensor",
9414 abstract = "Mutations in polycystin-1 (PC1) can cause Autosomal
9415 Dominant Polycystic Kidney Disease (ADPKD), which is a leading
9416 cause of renal failure. The available evidence suggests that PC1
9417 acts as a mechanosensor, receiving signals from the primary cilia,
9418 neighboring cells, and extracellular matrix. PC1 is a large
9419 membrane protein that has a long N-terminal extracellular region
9420 (about 3000 aa) with a multimodular structure including sixteen
9421 Ig-like PKD domains, which are targeted by many naturally
9422 occurring missense mutations. Nothing is known about the effects
9423 of these mutations on the biophysical properties of PKD
9424 domains. In addition, PC1 is expressed along the renal tubule,
9425 where it is exposed to a wide range of concentration of urea. Urea
9426 is known to destabilize proteins. Other osmolytes found in the
9427 kidney such as sorbitol, betaine and TMAO are known to counteract
9428 urea's negative effects on proteins. Nothing is known about how
9429 the mechanical properties of PC1 are affected by these
9430 osmolytes. Here I use nano-mechanical techniques to study the
9431 effects of missense mutations and effects of denaturants and
9432 various osmolytes on the mechanical properties of PKD
9433 domains. Several missense mutations were found to alter the
9434 mechanical stability of PKD domains resulting in distinct
9435 mechanical phenotypes. Based on these findings, I hypothesize that
9436 missense mutations may cause ADPKD by altering the stability of
9437 the PC1 ectodomain, thereby perturbing its ability to sense
9438 mechanical signals. I also found that urea has a significant
9439 impact on both the mechanical stability and refolding rate of PKD
9440 domains. It not only lowers their mechanical stability, but also
9441 slows down their refolding rate. Moreover, several osmolytes were
9442 found to effectively counteract the effects of urea. Our data
9443 provide the evidence that naturally occurring osmolytes can help
9444 to maintain Polycystin-1 mechanical stability and folding
9445 kinetics. This study has the potential to provide new therapeutic
9446 approaches (e.g. through the use of osmolytes or chemical
9447 chaperones) for rescuing destabilized and misfolded PKD domains.",
9451 @article{ sundberg03,
9452 author = MSundberg #" and "# JRosengren #" and "# RBunk
9453 #" and "# JLindahl #" and "# INicholls #" and "# STagerud
9454 #" and "# POmling #" and "# LMontelius #" and "# AMansson,
9455 title = "Silanized surfaces for in vitro studies of actomyosin
9456 function and nanotechnology applications.",
9461 address = "Department of Chemistry and Biomedical Sciences,
9462 University of Kalmar, SE-391 82 Kalmar, Sweden.",
9466 keywords = "Actomyosin",
9467 keywords = "Adsorption",
9468 keywords = "Animals",
9469 keywords = "Collodion",
9470 keywords = "Kinetics",
9471 keywords = "Methods",
9472 keywords = "Movement",
9473 keywords = "Nanotechnology",
9474 keywords = "Rabbits",
9475 keywords = "Silicon",
9476 keywords = "Surface Properties",
9477 keywords = "Trimethylsilyl Compounds",
9478 abstract = "We have previously shown that selective heavy meromyosin
9479 (HMM) adsorption to predefined regions of nanostructured polymer
9480 resist surfaces may be used to produce a nanostructured in vitro
9481 motility assay. However, actomyosin function was of lower quality
9482 than on conventional nitrocellulose films. We have therefore
9483 studied actomyosin function on differently derivatized glass
9484 surfaces with the aim to find a substitute for the polymer
9485 resists. We have found that surfaces derivatized with
9486 trimethylchlorosilane (TMCS) were superior to all other surfaces
9487 tested, including nitrocellulose. High-quality actin filament
9488 motility was observed up to 6 days after incubation with HMM and
9489 the fraction of motile actin filaments and the velocity of smooth
9490 sliding were generally higher on TMCS than on nitrocellulose. The
9491 actomyosin function on TMCS-derivatized glass and nitrocellulose
9492 is considered in relation to roughness and hydrophobicity of these
9493 surfaces. The results suggest that TMCS is an ideal substitute for
9494 polymer resists in the nanostructured in vitro motility
9495 assay. Furthermore, TMCS derivatized glass also seems to offer
9496 several advantages over nitrocellulose for HMM adsorption in the
9497 ordinary in /vitro motility assay.",
9499 URL = "http://www.ncbi.nlm.nih.gov/pubmed/14622967",
9500 doi = "10.1016/j.ab.2003.07.022",
9505 author = HItoh #" and "# ATakahashi #" and "# KAdachi #" and "#
9506 HNoji #" and "# RYasuda #" and "# MYoshida #" and "#
9508 title = "Mechanically driven {ATP} synthesis by {F1}-{ATP}ase.",
9513 address = "Tsukuba Research Laboratory, Hamamatsu Photonics KK,
9514 Joko, Hamamatsu 431-3103, Japan.
9515 hiritoh@hpk.trc-net.co.jp",
9519 keywords = "Adenosine Diphosphate",
9520 keywords = "Adenosine Triphosphate",
9521 keywords = "Bacillus",
9522 keywords = "Catalysis",
9524 keywords = "Magnetics",
9525 keywords = "Microchemistry",
9526 keywords = "Microspheres",
9527 keywords = "Molecular Motor Proteins",
9528 keywords = "Proton-Translocating ATPases",
9529 keywords = "Rotation",
9530 keywords = "Torque",
9531 abstract = "ATP, the main biological energy currency, is synthesized
9532 from ADP and inorganic phosphate by ATP synthase in an
9533 energy-requiring reaction. The F1 portion of ATP synthase, also
9534 known as F1-ATPase, functions as a rotary molecular motor: in
9535 vitro its gamma-subunit rotates against the surrounding
9536 alpha3beta3 subunits, hydrolysing ATP in three separate catalytic
9537 sites on the beta-subunits. It is widely believed that reverse
9538 rotation of the gamma-subunit, driven by proton flow through the
9539 associated F(o) portion of ATP synthase, leads to ATP synthesis in
9540 biological systems. Here we present direct evidence for the
9541 chemical synthesis of ATP driven by mechanical energy. We attached
9542 a magnetic bead to the gamma-subunit of isolated F1 on a glass
9543 surface, and rotated the bead using electrical magnets. Rotation
9544 in the appropriate direction resulted in the appearance of ATP in
9545 the medium as detected by the luciferase-luciferin reaction. This
9546 shows that a vectorial force (torque) working at one particular
9547 point on a protein machine can influence a chemical reaction
9548 occurring in physically remote catalytic sites, driving the
9549 reaction far from equilibrium.",
9551 doi = "10.1038/nature02212",
9552 URL = "http://www.ncbi.nlm.nih.gov/pubmed/14749837",
9557 author = NSakaki #" and "# RShimoKon #" and "# KAdachi
9558 #" and "# HItoh #" and "# SFuruike #" and "# EMuneyuki
9559 #" and "# MYoshida #" and "# KKinosita,
9560 title = "One rotary mechanism for {F1}-{ATP}ase over {ATP}
9561 concentrations from millimolar down to nanomolar.",
9566 address = "Department of Functional Molecular Science, The Graduate
9567 University for Advanced Studies, Nishigonaka 38, Myodaiji, Okazaki
9571 pages = "2047--2056",
9572 keywords = "Adenosine Triphosphate",
9573 keywords = "Hydrolysis",
9574 keywords = "Kinetics",
9575 keywords = "Microchemistry",
9576 keywords = "Molecular Motor Proteins",
9577 keywords = "Nanostructures",
9578 keywords = "Protein Binding",
9579 keywords = "Protein Conformation",
9580 keywords = "Proton-Translocating ATPases",
9581 keywords = "Rotation",
9582 keywords = "Torque",
9583 abstract = "F(1)-ATPase is a rotary molecular motor in which the
9584 central gamma-subunit rotates inside a cylinder made of
9585 alpha(3)beta(3)-subunits. The rotation is driven by ATP hydrolysis
9586 in three catalytic sites on the beta-subunits. How many of the
9587 three catalytic sites are filled with a nucleotide during the
9588 course of rotation is an important yet unsettled question. Here we
9589 inquire whether F(1) rotates at extremely low ATP concentrations
9590 where the site occupancy is expected to be low. We observed under
9591 an optical microscope rotation of individual F(1) molecules that
9592 carried a bead duplex on the gamma-subunit. Time-averaged rotation
9593 rate was proportional to the ATP concentration down to 200 pM,
9594 giving an apparent rate constant for ATP binding of 2 x 10(7)
9595 M(-1)s(-1). A similar rate constant characterized bulk ATP
9596 hydrolysis in solution, which obeyed a simple Michaelis-Menten
9597 scheme between 6 mM and 60 nM ATP. F(1) produced the same torque
9598 of approximately 40 pN.nm at 2 mM, 60 nM, and 2 nM ATP. These
9599 results point to one rotary mechanism governing the entire range
9600 of nanomolar to millimolar ATP, although a switchover between two
9601 mechanisms cannot be dismissed. Below 1 nM ATP, we observed less
9602 regular rotations, indicative of the appearance of another
9605 doi = "10.1529/biophysj.104.054668",
9606 URL = "http://www.ncbi.nlm.nih.gov/pubmed/15626703",
9610 @article{ schmidt02,
9611 author = JSchmidt #" and "# XJiang #" and "# CMontemagno,
9612 title = "Force Tolerances of Hybrid Nanodevices",
9616 pages = "1229--1233",
9618 doi = "10.1021/nl025773v",
9619 URL = "http://pubs.acs.org/doi/abs/10.1021/nl025773v",
9620 eprint = "http://pubs.acs.org/doi/pdf/10.1021/nl025773v",
9621 abstract = "We have created hybrid devices consisting of nanoscale
9622 fabricated inorganic components integrated with and powered by a
9623 genetically engineered motor protein. We wish to increase the
9624 assembly yield and lifetime of these devices through
9625 identification, measurement, and improvement of weak internal
9626 bonds. Using dynamic force spectroscopy, we have measured the bond
9627 rupture force of (histidine)\textsubscript{6} on a number of
9628 different surfaces as a function of loading rate. The bond sizes,
9629 lifetimes, and energy barrier heights were derived from these
9630 measurements. We compare the (His)\textsubscript{6}--nickel bonds
9631 to other bonds composing the hybrid device and describe
9632 preliminary measurements of the force tolerances of the protein
9633 itself. Pathways for improvement of device longevity and
9634 robustness are discussed.",
9638 author = YSLo #" and "# YJZhu #" and "# TBeebe,
9639 title = "Loading-Rate Dependence of Individual Ligand−Receptor
9640 Bond-Rupture Forces Studied by Atomic Force Microscopy",
9644 pages = "3741--3748",
9646 doi = "10.1021/la001569g",
9647 URL = "http://pubs.acs.org/doi/abs/10.1021/la001569g",
9648 eprint = "http://pubs.acs.org/doi/pdf/10.1021/la001569g",
9649 abstract = "It is known that bond strength is a dynamic property
9650 that is dependent upon the force loading rate applied during the
9651 rupturing of a bond. For biotin--avidin and biotin--streptavidin
9652 systems, dynamic force spectra, which are plots of bond strength
9653 vs loge(loading rate), have been acquired in a recent biomembrane
9654 force probe (BFP) study at force loading rates in the range
9655 0.05--60 000 pN/s. In the present study, the dynamic force spectrum
9656 of the biotin--streptavidin bond strength in solution was extended
9657 from loading rates of ∼104 to ∼107 pN/s with the atomic force
9658 microscope (AFM). A Poisson statistical analysis method was
9659 applied to extract the magnitude of individual bond-rupture forces
9660 and nonspecific interactions from the AFM force--distance curve
9661 measurements. The bond strengths were found to scale linearly with
9662 the logarithm of the loading rate. The nonspecific interactions
9663 also exhibited a linear dependence on the logarithm of loading
9664 rate, although not increasing as rapidly as the specific
9665 interactions. The dynamic force spectra acquired here with the AFM
9666 combined well with BFP measurements by Merkel et al. The combined
9667 spectrum exhibited two linear regimes, consistent with the view
9668 that multiple energy barriers are present along the unbinding
9669 coordinate of the biotin--streptavidin complex. This study
9670 demonstrated that unbinding forces measured by different
9671 techniques are in agreement and can be used together to obtain a
9672 dynamic force spectrum covering 9 orders of magnitude in loading
9674 note = "These guys seem to be pretty thorough, give this one another read.",
9678 author = ABaljon #" and "# MRobbins,
9679 title = "Energy Dissipation During Rupture of Adhesive Bonds",
9686 doi = "10.1126/science.271.5248.482",
9687 URL = "http://www.sciencemag.org/content/271/5248/482.abstract",
9688 eprint = "http://www.sciencemag.org/content/271/5248/482.full.pdf",
9689 abstract = "Molecular dynamics simulations were used to study
9690 energy-dissipation mechanisms during the rupture of a thin
9691 adhesive bond formed by short chain molecules. The degree of
9692 dissipation and its velocity dependence varied with the state of
9693 the film. When the adhesive was in a liquid phase, dissipation was
9694 caused by viscous loss. In glassy films, dissipation occurred
9695 during a sequence of rapid structural rearrangements. Roughly
9696 equal amounts of energy were dissipated in each of three types of
9697 rapid motion: cavitation, plastic yield, and bridge rupture. These
9698 mechanisms have similarities to nucleation, plastic flow, and
9699 crazing in commercial polymeric adhesives.",
9702 @article{ fisher99a,
9703 author = TEFisher #" and "# PMarszalek #" and "# AOberhauser
9704 #" and "# MCarrionVazquez #" and "# JFernandez,
9705 title = "The micro-mechanics of single molecules studied with
9706 atomic force microscopy.",
9711 address = "Department of Physiology and Biophysics, Mayo Foundation,
9712 1-117 Medical Sciences Building, Rochester, MN 55905, USA.",
9713 volume = "520 Pt 1",
9715 keywords = "Animals",
9716 keywords = "Extracellular Matrix",
9717 keywords = "Extracellular Matrix Proteins",
9718 keywords = "Humans",
9719 keywords = "Microscopy, Atomic Force",
9720 keywords = "Polysaccharides",
9721 abstract = "The atomic force microscope (AFM) in its force-measuring
9722 mode is capable of effecting displacements on an angstrom scale
9723 (10 A = 1 nm) and measuring forces of a few piconewtons. Recent
9724 experiments have applied AFM techniques to study the mechanical
9725 properties of single biological polymers. These properties
9726 contribute to the function of many proteins exposed to mechanical
9727 strain, including components of the extracellular matrix
9728 (ECM). The force-bearing proteins of the ECM typically contain
9729 multiple tandem repeats of independently folded domains, a common
9730 feature of proteins with structural and mechanical
9731 roles. Polysaccharide moieties of adhesion glycoproteins such as
9732 the selectins are also subject to strain. Force-induced extension
9733 of both types of molecules with the AFM results in conformational
9734 changes that could contribute to their mechanical function. The
9735 force-extension curve for amylose exhibits a transition in
9736 elasticity caused by the conversion of its glucopyranose rings
9737 from the chair to the boat conformation. Extension of multi-domain
9738 proteins causes sequential unraveling of domains, resulting in a
9739 force-extension curve displaying a saw tooth pattern of peaks. The
9740 engineering of multimeric proteins consisting of repeats of
9741 identical domains has allowed detailed analysis of the mechanical
9742 properties of single protein domains. Repetitive extension and
9743 relaxation has enabled direct measurement of rates of domain
9744 unfolding and refolding. The combination of site-directed
9745 mutagenesis with AFM can be used to elucidate the amino acid
9746 sequences that determine mechanical stability. The AFM thus offers
9747 a novel way to explore the mechanical functions of proteins and
9748 will be a useful tool for studying the micro-mechanics of
9751 URL = "http://www.ncbi.nlm.nih.gov/pubmed/10517795",
9755 @article{ fisher99b,
9756 author = TEFisher #" and "# AOberhauser #" and "# MCarrionVazquez
9757 #" and "# PMarszalek #" and "# JFernandez,
9758 title = "The study of protein mechanics with the atomic force microscope.",
9759 journal = "Trends in biochemical sciences",
9762 address = "Dept of Physiology and Biophysics, Mayo Foundation, 1-117
9763 Medical Sciences Building, Rochester, MN 55905, USA.",
9767 keywords = "Entropy",
9768 keywords = "Kinetics",
9769 keywords = "Microscopy, Atomic Force",
9770 keywords = "Protein Binding",
9771 keywords = "Protein Folding",
9772 keywords = "Proteins",
9773 abstract = "The unfolding and folding of single protein molecules
9774 can be studied with an atomic force microscope (AFM). Many
9775 proteins with mechanical functions contain multiple, individually
9776 folded domains with similar structures. Protein engineering
9777 techniques have enabled the construction and expression of
9778 recombinant proteins that contain multiple copies of identical
9779 domains. Thus, the AFM in combination with protein engineering
9780 has enabled the kinetic analysis of the force-induced unfolding
9781 and refolding of individual domains as well as the study of the
9782 determinants of mechanical stability.",
9784 URL = "http://www.ncbi.nlm.nih.gov/pubmed/10500301",
9788 @article{ zlatanova00,
9789 author = JZlatanova #" and "# SLindsay #" and "# SLeuba,
9790 title = "Single molecule force spectroscopy in biology using the
9791 atomic force microscope.",
9794 address = "Biochip Technology Center, Argonne National Laboratory,
9795 9700 South Cass Avenue, Bldg. 202-A253, Argonne, IL 60439,
9796 USA. jzlatano@duke.poly.edu",
9800 keywords = "Biophysics",
9801 keywords = "Cell Adhesion",
9803 keywords = "Elasticity",
9804 keywords = "Microscopy, Atomic Force",
9805 keywords = "Polysaccharides",
9806 keywords = "Proteins",
9807 keywords = "Signal Processing, Computer-Assisted",
9808 keywords = "Viscosity",
9809 abstract = "The importance of forces in biology has been recognized
9810 for quite a while but only in the past decade have we acquired
9811 instrumentation and methodology to directly measure interactive
9812 forces at the level of single biological macromolecules and/or
9813 their complexes. This review focuses on force measurements
9814 performed with the atomic force microscope. A general introduction
9815 to the principle of action is followed by review of the types of
9816 interactions being studied, describing the main results and
9817 discussing the biological implications.",
9819 URL = "http://www.ncbi.nlm.nih.gov/pubmed/11106806",
9821 note = "Lots of great force-clamp cartoons explaining different
9822 approach/retract features.",
9826 author = MViani #" and "# TESchafer #" and "# AChand #" and "# MRief
9827 #" and "# HEGaub #" and "# HHansma,
9828 title = "Small cantilevers for force spectroscopy of single molecules",
9833 pages = "2258--2262",
9834 abstract = "We have used a simple process to fabricate small
9835 rectangular cantilevers out of silicon nitride. They have lengths
9836 of 9--50 $\mu$m, widths of 3--5 $\mu$m, and thicknesses of 86 and
9837 102 nm. We have added metallic reflector pads to some of the
9838 cantilever ends to maximize reflectivity while minimizing
9839 sensitivity to temperature changes. We have characterized small
9840 cantilevers through their thermal spectra and show that they can
9841 measure smaller forces than larger cantilevers with the same
9842 spring constant because they have lower coefficients of viscous
9843 damping. Finally, we show that small cantilevers can be used for
9844 experiments requiring large measurement bandwidths, and have used
9845 them to unfold single titin molecules over an order of magnitude
9846 faster than previously reported with conventional cantilevers.",
9848 issn_online = "1089-7550",
9849 doi = "10.1063/1.371039",
9850 URL = "http://jap.aip.org/resource/1/japiau/v86/i4/p2258_s1",
9854 @article{ capitanio02,
9855 author = MCapitanio #" and "# GRomano #" and "# RBallerini #" and "#
9856 MGiuntini #" and "# FPavone #" and "# DDunlap #" and "# LFinzi,
9857 title = "Calibration of optical tweezers with differential
9858 interference contrast signals",
9863 pages = "1687--1696",
9864 abstract = "A comparison of different calibration methods for
9865 optical tweezers with the differential interference contrast (DIC)
9866 technique was performed to establish the uses and the advantages
9867 of each method. A detailed experimental and theoretical analysis
9868 of each method was performed with emphasis on the anisotropy
9869 involved in the DIC technique and the noise components in the
9870 detection. Finally, a time of flight method that permits the
9871 reconstruction of the optical potential well was demonstrated.",
9873 issn_online = "1089-7623",
9874 doi = "10.1063/1.1460929",
9875 URL = "http://rsi.aip.org/resource/1/rsinak/v73/i4/p1687_s1",
9880 author = GBinnig #" and "# CQuate #" and "# CGerber,
9881 title = "Atomic force microscope",
9889 abstract = "The scanning tunneling microscope is proposed as a
9890 method to measure forces as small as $10^{-18}$ N. As one
9891 application for this concept, we introduce a new type of
9892 microscope capable of investigating surfaces of insulators on an
9893 atomic scale. The atomic force microscope is a combination of the
9894 principles of the scanning tunneling microscope and the stylus
9895 profilometer. It incorporates a probe that does not damage the
9896 surface. Our preliminary results in air demonstrate a lateral
9897 resolution of 30 \AA and a vertical resolution less than 1 \AA.",
9899 doi = "10.1103/PhysRevLett.56.930",
9900 URL = "http://www.ncbi.nlm.nih.gov/pubmed/10033323",
9901 eprint = {http://prl.aps.org/pdf/PRL/v56/i9/p930_1},
9903 note = "Original AFM paper.",
9907 author = BDrake #" and "# CBPrater #" and "# ALWeisenhorn #" and "#
9908 SAGould #" and "# TRAlbrecht #" and "# CQuate #" and "#
9909 DSCannell #" and "# HHansma #" and "# PHansma,
9910 title = {Imaging crystals, polymers, and processes in water with the
9911 atomic force microscope},
9918 pages = {1586--1589},
9919 doi = {10.1126/science.2928794},
9920 url = {http://www.sciencemag.org/content/243/4898/1586.abstract},
9921 eprint = {http://www.sciencemag.org/content/243/4898/1586.full.pdf},
9922 abstract ={The atomic force microscope (AFM) can be used to image
9923 the surface of both conductors and nonconductors even if they are
9924 covered with water or aqueous solutions. An AFM was used that
9925 combines microfabricated cantilevers with a previously described
9926 optical lever system to monitor deflection. Images of mica
9927 demonstrate that atomic resolution is possible on rigid materials,
9928 thus opening the possibility of atomic-scale corrosion experiments
9929 on nonconductors. Images of polyalanine, an amino acid polymer,
9930 show the potential of the AFM for revealing the structure of
9931 molecules important in biology and medicine. Finally, a series of
9932 ten images of the polymerization of fibrin, the basic component of
9933 blood clots, illustrate the potential of the AFM for revealing
9934 subtle details of biological processes as they occur in real
9938 @article{ radmacher92,
9939 author = MRadmacher #" and "# RWTillmann #" and "# MFritz #" and "# HEGaub,
9940 title = {From molecules to cells: imaging soft samples with the
9941 atomic force microscope},
9948 pages = {1900--1905},
9949 doi = {10.1126/science.1411505},
9950 url = {http://www.sciencemag.org/content/257/5078/1900.abstract},
9951 eprint = {http://www.sciencemag.org/content/257/5078/1900.full.pdf},
9952 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.},
9955 @article{ williams86,
9956 author = CCWilliams #" and "# HKWickramasinghe,
9957 title = "Scanning thermal profiler",
9964 pages = "1587--1589",
9965 abstract = "A new high-resolution profilometer has been demonstrated
9966 based upon a noncontacting near-field thermal probe. The thermal
9967 probe consists of a thermocouple sensor with dimensions
9968 approaching 100 nm. Profiling is achieved by scanning the heated
9969 sensor above but close to the surface of a solid. The conduction
9970 of heat between tip and sample via the air provides a means for
9971 maintaining the sample spacing constant during the lateral
9972 scan. The large difference in thermal properties between air and
9973 solids makes the profiling technique essentially independent of
9974 the material properties of the solid. Noncontact profiling of
9975 resist and metal films has shown a lateral resolution of 100 nm
9976 and a depth solution of 3 nm. The basic theory of the new probe is
9977 described and the results presented.",
9979 issn_online = "1077-3118",
9980 doi = "10.1063/1.97288",
9981 URL = "http://apl.aip.org/resource/1/applab/v49/i23/p1587_s1",
9986 author = GMeyer #" and "# NMAmer,
9987 title = "Novel optical approach to atomic force microscopy",
9994 pages = "1045--1047",
9995 abstract = "A sensitive and simple optical method for detecting the
9996 cantilever deflection in atomic force microscopy is described. The
9997 method was incorporated in an atomic force microscope, and imaging
9998 and force measurements, in ultrahigh vacuum, were successfully
10000 issn = "0003-6951",
10001 issn_online = "1077-3118",
10002 doi = "10.1063/1.100061",
10003 URL = "http://apl.aip.org/resource/1/applab/v53/i12/p1045_s1",
10008 author = EDijkstra,
10009 title = {Notes on Structured Programming},
10012 url = {http://www.cs.utexas.edu/users/EWD/ewd02xx/EWD249.PDF},
10013 publisher = THEMath,
10014 note = {T.H. Report 70-WSK-03},
10019 title = {On the Composition of Well-Structured Programs},
10020 journal = ACM:CSur,
10025 pages = {247--259},
10027 issn = {0360-0300},
10028 doi = {10.1145/356635.356639},
10029 url = {http://doi.acm.org/10.1145/356635.356639},
10031 address = {New York, NY, USA},
10034 @article{ shneiderman79,
10035 author = BShneiderman #" and "# RMayer,
10036 title = {Syntactic/semantic interactions in programmer behavior: A
10037 model and experimental results},
10042 pages = {219--238},
10043 issn = {0091-7036},
10044 doi = {10.1007/BF00977789},
10045 url = {http://dx.doi.org/10.1007/BF00977789},
10047 keywords = {Programming; programming languages; cognitive models;
10048 program composition; program comprehension; debugging;
10049 modification; learning; education; information processing},
10050 language = {English},
10053 @article{ hughes89,
10055 title = {Why Functional Programming Matters},
10061 doi = {10.1093/comjnl/32.2.98},
10062 URL = {http://comjnl.oxfordjournals.org/content/32/2/98.abstract},
10063 eprint = {http://comjnl.oxfordjournals.org/content/32/2/98.full.pdf+html},
10064 abstract ={As software becomes more and more complex, it is more and
10065 more important to structure it well. Well-structured software is
10066 easy to write, easy to debug, and provides a collection of modules
10067 that can be re-used to reduce future programming
10068 costs. Conventional languages place conceptual limits on the way
10069 problems can be modularised. Functional languages push those
10070 limits back. In this paper we show that two features of functional
10071 languages in particular, higher-order functions and lazy
10072 evaluation, can contribute greatly to modularity. As examples, we
10073 manipulate lists and trees, program several numerical algorithms,
10074 and implement the alpha-beta heuristics (an Artificial
10075 Intelligence algorithm used in game-playing programs). Since
10076 modularity is the key to successful programming, functional
10077 languages are vitally important to the real world.},
10080 @article{ hilburn93,
10082 title = {A top-down approach to teaching an introductory computer science course},
10083 journal = ACM:SIGCSE,
10088 issn = {0097-8418},
10091 doi = {10.1145/169073.169349},
10092 url = {http://doi.acm.org/10.1145/169073.169349},
10095 address = {New York, NY, USA},
10100 title = {The mythical man-month},
10101 edition = {20$^\text{th}$ anniversary},
10103 isbn = {0-201-83595-9},
10105 address = {Boston, MA, USA},
10106 url = {http://dl.acm.org/citation.cfm?id=207583},
10107 note = {First published in 1975},
10110 @inproceedings{ claerbout92,
10111 author = JClaerbout #" and "# MKarrenbach,
10112 title = {Electronic documents give reproducible research a new meaning},
10113 booktitle = {SEG Technical Program Expanded Abstracts 1992},
10116 pages = {601--604},
10117 doi = {10.1190/1.1822162},
10118 issn = {1052-3812},
10120 url = {http://library.seg.org/doi/abs/10.1190/1.1822162},
10121 eprint = {http://sepwww.stanford.edu/doku.php?id=sep:research:reproducible:seg92},
10124 @incollection{ buckheit95,
10125 author = JBuckheit #" and "# DDonoho,
10126 title = {WaveLab and Reproducible Research},
10127 booktitle = {Wavelets and Statistics},
10128 series = {Lecture Notes in Statistics},
10129 editor = AAntoniadis #" and "# GOppenheim,
10133 isbn = {978-0-387-94564-4},
10134 doi = {10.1007/978-1-4612-2544-7_5},
10135 url = {http://dx.doi.org/10.1007/978-1-4612-2544-7_5},
10136 eprint = {http://www-stat.stanford.edu/~wavelab/Wavelab_850/wavelab.pdf},
10137 publisher = SPRINGER,
10138 language = {English},
10141 @article{ schwab00,
10142 author = MSchwab #" and "# MKarrenbach #" and "# JClaerbout,
10143 title = {Making scientific computations reproducible},
10146 month = {November--December},
10150 doi = {10.1109/5992.881708},
10151 ISSN = {1521-9615},
10152 keywords = {document handling;file organisation;natural sciences
10153 computing;research and development
10154 management;ReDoc;authors;computational results;reproducible
10155 scientific computations;research paper;software filing
10156 system;standardized rules;Computer
10157 interfaces;Documentation;Electronic
10158 publishing;Laboratories;Organizing;Reproducibility of
10159 results;Software maintenance;Software systems;Software
10160 testing;Technological innovation},
10161 abstract = {To verify a research paper's computational results,
10162 readers typically have to recreate them from scratch. ReDoc is a
10163 simple software filing system for authors that lets readers easily
10164 reproduce computational results using standardized rules and
10168 @article{ wilson06a,
10170 title = {Where's the Real Bottleneck in Scientific Computing?},
10173 month = {January--February},
10176 @article{ wilson06b,
10178 title = {Software Carpentry: Getting Scientists to Write Better
10179 Code by Making Them More Productive},
10182 month = {November--December},
10185 @article{ vandewalle09,
10186 author = PVandewalle #" and "# JKovacevic #" and "# MVetterli ,
10187 title = {Reproducible Research in Signal Processing - What, why, and how},
10188 journal = IEEE:SPM,
10194 doi = {10.1109/MSP.2009.932122},
10195 issn = {1053-5888},
10196 url = {http://rr.epfl.ch/17/},
10197 eprint = {http://rr.epfl.ch/17/1/VandewalleKV09.pdf},
10198 keywords={research and development;signal processing;high-quality
10199 reviewing process;large data set;reproducible research;signal
10200 processing;win-win situation;Advertising;Digital signal
10201 processing;Education;Programming;Reproducibility of
10202 results;Scholarships;Signal processing;Signal processing
10203 algorithms;Testing;Wikipedia},
10204 abstract = {Have you ever tried to reproduce the results presented
10205 in a research paper? For many of our current publications, this
10206 would unfortunately be a challenging task. For a computational
10207 algorithm, details such as the exact data set, initialization or
10208 termination procedures, and precise parameter values are often
10209 omitted in the publication for various reasons, such as a lack of
10210 space, a lack of self-discipline, or an apparent lack of interest
10211 to the readers, to name a few. This makes it difficult, if not
10212 impossible, for someone else to obtain the same results. In our
10213 experience, it is often even worse as even we are not always able
10214 to reproduce our own experiments, making it difficult to answer
10215 questions from colleagues about details. Following are some
10216 examples of e-mails we have received: ``I just read your paper
10217 X. It is very completely described, however I am confused by
10218 Y. Could you provide the implementation code to me for reference
10219 if possible?'' ``Hi! I am also working on a project related to
10220 X. I have implemented your algorithm but cannot get the same
10221 results as described in your paper. Which values should I use for
10222 parameters Y and Z?''},
10225 @article{ aruliah12,
10226 author = DAruliah #" and "# CTBrown #" and "# NPCHong #" and "#
10227 MDavis #" and "# RTGuy #" and "# SHaddock #" and "# KHuff #" and "#
10228 IMitchell #" and "# MPlumbley #" and "# BWaugh #" and "#
10229 EPWhite #" and "# GWilson #" and "# PWilson,
10230 title = {Best Practices for Scientific Computing},
10232 volume = {abs/1210.0530},
10237 url = {http://arxiv.org/abs/1210.0530},
10238 eprint = {http://arxiv.org/pdf/1210.0530v3},
10239 note = {v3: Thu, 29 Nov 2012 19:28:27 GMT},
10242 @article{ ziegler42,
10243 author = JZiegler #" and "# NNichols,
10244 title = {Optimum Settings for Automatic Controllers},
10249 pages = {759--765},
10250 url = {http://www.driedger.ca/Z-N/Z-N.html},
10251 eprint = {http://www.driedger.ca/Z-N/Z-n.pdf},
10255 author = GHCohen #" and "# GACoon,
10256 title = {Theoretical considerations of retarded control},
10260 pages = {827--834},
10264 author = FSWang #" and "# WSJuang #" and "# CTChan,
10265 title = {Optimal tuning of {PID} controllers for single and
10266 cascade control loops},
10272 publisher = GordonBreach,
10273 issn = {0098-6445},
10274 doi = {10.1080/00986449508936294},
10275 url = {http://www.tandfonline.com/doi/abs/10.1080/00986449508936294},
10276 keywords = {process control; cascade control; controller tuning},
10277 abstract = {Design of one parameter tuning of three-mode PID
10278 controller was developed in this present study. The integral time
10279 and the derivative time of the controller were expressed in terms
10280 of the time constant and dead time of the process. Only the
10281 proportional gain was observed to be dependent on the implemented
10282 tunable parameter in which the stable region could be
10283 predetermined by the Routh test. Extension of the concept towards
10284 designing cascade PID controllers was straightforward such that
10285 only two parameters for the inner and outer PID controllers
10286 required to be tuned, respectively. The optimal tuning correlative
10287 formulas of the proportional gain for single and cascade control
10288 systems were obtained by the least square regression method.},
10291 @article{ astrom93,
10292 author = KAstrom #" and "# THagglund #" and "# CCHang #" and "# WKHo,
10293 title = {Automatic tuning and adaptation for {PID} controllers---a survey},
10298 pages = {699--714},
10299 issn = "0967-0661",
10300 doi = "10.1016/0967-0661(93)91394-C",
10301 url = "http://dx.doi.org/10.1016/0967-0661(93)91394-C",
10302 keywords = {Adaptive control},
10303 keywords = {automatic tuning},
10304 keywords = {gain scheduling},
10305 keywords = {{PID} control},
10306 abstract = {Adaptive techniques such as gain scheduling, automatic
10307 tuning and continuous adaptation have been used in industrial
10308 single-loop controllers for about ten years. This paper gives a
10309 survey of the different adaptive techniques, the underlying
10310 process models and control designs. An overview of industrial
10311 products is also presented, which includes a fairly detailed
10312 investigation of four different adaptive single-loop
10318 title = {Notes on the use of propagation of error formulas},
10324 pages = {263--273},
10326 issn = {0022-4316},
10327 url = {http://nistdigitalarchives.contentdm.oclc.org/cdm/compoundobject/collection/p13011coll6/id/78003/rec/5},
10328 eprint = {http://nistdigitalarchives.contentdm.oclc.org/utils/getfile/collection/p13011coll6/id/78003/filename/print/page/download},
10329 keywords = {Approximation; error; formula; imprecision; law of
10330 error; products; propagation of error; random; ratio; systematic;
10332 abstract = {The ``law of propagation of error'' is a tool that
10333 physical scientists have conveniently and frequently used in their
10334 work for many years, yet an adequate reference is difficult to
10335 find. In this paper an expository review of this topic is
10336 presented, particularly in the light of current practices and
10337 interpretations. Examples on the accuracy of the approximations
10338 are given. The reporting of the uncertainties of final results is
10342 @article{ livadaru03,
10343 author = LLivadaru #" and "# RRNetz #" and "# HJKreuzer,
10344 title = {Stretching Response of Discrete Semiflexible Polymers},
10348 journal = Macromol,
10351 pages = {3732--3744},
10352 doi = {10.1021/ma020751g},
10353 URL = {http://pubs.acs.org/doi/abs/10.1021/ma020751g},
10354 eprint = {http://pubs.acs.org/doi/pdf/10.1021/ma020751g},
10355 abstract = {We demonstrate that semiflexible polymer chains
10356 (characterized by a persistence length $l$) made up of discrete
10357 segments or bonds of length $b$ show at large stretching forces a
10358 crossover from the standard wormlike chain (WLC) behavior to a
10359 discrete-chain (DC) behavior. In the DC regime, the stretching
10360 response is independent of the persistence length and shows a
10361 different force dependence than in the WLC regime. We perform
10362 extensive transfer-matrix calculations for the force-response of a
10363 freely rotating chain (FRC) model as a function of varying bond
10364 angle $\gamma$ (and thus varying persistence length) and chain
10365 length. The FRC model is a first step toward the understanding of
10366 the stretching behavior of synthetic polymers, denatured proteins,
10367 and single-stranded DNA under large tensile forces. We also
10368 present scaling results for the force response of the elastically
10369 jointed chain (EJC) model, that is, a chain made up of freely
10370 jointed bonds that are connected by joints with some bending
10371 stiffness; this is the discretized version of the continuum WLC
10372 model. The EJC model might be applicable to stiff biopolymers such
10373 as double-stranded DNA or Actin. Both models show a similar
10374 crossover from the WLC to the DC behavior, which occurs at a force
10375 $f/k_BT\sim l/b^2$ and is thus (for polymers with a moderately
10376 large persistence length) in the piconewton range probed in many
10377 AFM experiments. We also give a heuristic simple function for the
10378 force--distance relation of a FRC, valid in the global force
10379 range, which can be used to fit experimental data. Our findings
10380 might help to resolve the discrepancies encountered when trying to
10381 fit experimental data for the stretching response of polymers in a
10382 broad force range with a single effective persistence length.},
10383 note = {There are two typos in \fref{equation}{46}.
10384 \citet{livadaru03} have
10386 \frac{R_z}{L} = \begin{cases}
10387 \frac{fa}{3k_BT} & \frac{fb}{k_BT} < \frac{b}{l} \\
10388 1 - \p({\frac{fl}{4k_BT}})^{-0.5}
10389 & \frac{b}{l} < \frac{fb}{k_BT} < \frac{l}{b} \\
10390 1 - \p({\frac{fb}{ck_BT}})^{-1} & \frac{1}{b} < \frac{fb}{k_BT} \;,
10393 but the correct formula is
10395 \frac{R_z}{L} = \begin{cases}
10396 \frac{fa}{3k_BT} & \frac{fb}{k_BT} < \frac{b}{l} \\
10397 1 - \p({\frac{4fl}{k_BT}})^{-0.5}
10398 & \frac{b}{l} < \frac{fb}{k_BT} < \frac{l}{b} \\
10399 1 - \p({\frac{cfb}{k_BT}})^{-1} & \frac{1}{b} < \frac{fb}{k_BT} \;,
10402 with both the $4$ and the $c$ moved into their respective
10403 numerators. I pointed these errors out to Roland Netz in 2012,
10404 along with the fact that even with the corrected formula there is
10405 a discontinuity between the low- and moderate-force regimes. Netz
10406 confirmed the errors, and pointed out that the discontinuity is
10407 because \fref{equation}{46} only accounts for the scaling (without
10408 prefactors). Unfortunately, there does not seem to be a published
10409 erratum pointing out the error and at least \citet{puchner08} have
10410 quoted the incorrect form.},
10414 author = PCarl #" and "# PDalhaimer,
10415 title = {{PUNIAS}: Protein Unfolding and Nano-indentation Analysis
10420 note = {4 Int. Workshop, Scanning Probe Microscopy in Life Sciences},
10421 address = {Berlin},
10422 url = {http://punias.voila.net/},
10426 author = PCarl #" and "# HSchillers,
10427 title = {Elasticity measurement of living cells with an atomic force
10428 microscope: data acquisition and processing.},
10432 address = {Institute of Physiology II, University of M{\"u}nster,
10433 Robert-Koch-Str. 27b, 48149, M{\"u}nster, Germany.},
10437 pages = {551--559},
10438 issn = {0031-6768},
10439 doi = {10.1007/s00424-008-0524-3},
10440 url = {http://www.ncbi.nlm.nih.gov/pubmed/18481081},
10442 keywords = {Animals},
10443 keywords = {Biomechanics},
10444 keywords = {CHO Cells},
10445 keywords = {Cricetinae},
10446 keywords = {Cricetulus},
10447 keywords = {Cystic Fibrosis Transmembrane Conductance Regulator},
10448 keywords = {Elastic Modulus},
10449 keywords = {Equipment Design},
10450 keywords = {Microscopy, Atomic Force},
10451 keywords = {Models, Biological},
10452 keywords = {Reproducibility of Results},
10453 keywords = {Signal Processing, Computer-Assisted},
10454 keywords = {Transfection},
10455 abstract = {Elasticity of living cells is a parameter of increasing
10456 importance in cellular physiology, and the atomic force microscope
10457 is a suitable instrument to quantitatively measure it. The
10458 principle of an elasticity measurement is to physically indent a
10459 cell with a probe, to measure the applied force, and to process
10460 this force-indentation data using an appropriate model. It is
10461 crucial to know what extent the geometry of the indenting probe
10462 influences the result. Therefore, we indented living Chinese
10463 hamster ovary cells at 37 degrees C with sharp tips and colloidal
10464 probes (spherical particle tips) of different sizes and
10465 materials. We furthermore developed an implementation of the Hertz
10466 model, which simplifies the data processing. Our results show (a)
10467 that the size of the colloidal probe does not influence the result
10468 over a wide range (radii $0.5$-$26\U{$\mu$m}$) and (b) indenting
10469 cells with sharp tips results in higher Young's moduli
10470 (approximately $1,300\U{Pa}$) than using colloidal probes
10471 (approximately $400\U{Pa}$).},
10472 note = {Mentions \citetalias{punias} as if it was in-house software,
10473 which makes sense because Philippe Carl seems to be a major author.},
10476 @article{ struckmeier08,
10477 author = JStruckmeier #" and "# RWahl #" and "# MLeuschner #" and "#
10478 JNunes #" and "# HJanovjak #" and "# UGeisler #" and "#
10479 GHofmann #" and "# TJahnke #" and "# DJMuller,
10480 title = {Fully automated single-molecule force spectroscopy for
10481 screening applications},
10485 address = {Cellular Machines, Biotechnology Center,
10486 Technische Universit{\"a}t Dresden, Tatzberg 47, D-01307
10492 issn = {0957-4484},
10493 doi = {10.1088/0957-4484/19/38/384020},
10494 url = {http://www.ncbi.nlm.nih.gov/pubmed/21832579},
10496 abstract = {With the introduction of single-molecule force
10497 spectroscopy (SMFS) it has become possible to directly access the
10498 interactions of various molecular systems. A bottleneck in
10499 conventional SMFS is collecting the large amount of data required
10500 for statistically meaningful analysis. Currently, atomic force
10501 microscopy (AFM)-based SMFS requires the user to tediously `fish'
10502 for single molecules. In addition, most experimental and
10503 environmental conditions must be manually adjusted. Here, we
10504 developed a fully automated single-molecule force
10505 spectroscope. The instrument is able to perform SMFS while
10506 monitoring and regulating experimental conditions such as buffer
10507 composition and temperature. Cantilever alignment and calibration
10508 can also be automatically performed during experiments. This,
10509 combined with in-line data analysis, enables the instrument, once
10510 set up, to perform complete SMFS experiments autonomously.},
10511 note = {An advertisement for JPK's \citetalias{force-robot}.},
10514 @article{ andreopoulos11,
10515 author = BAndreopoulos #" and "# DLabudde,
10516 title = {Efficient unfolding pattern recognition in single molecule
10517 force spectroscopy data},
10521 address = {Department of Bioinformatics, Biotechnological Center,
10522 University of Technology Dresden, Dresden, Germany.
10523 williama@biotec.tu-dresden.de},
10528 issn = {1748-7188},
10529 doi = {10.1186/1748-7188-6-16},
10530 url = {http://www.ncbi.nlm.nih.gov/pubmed/21645400},
10532 abstract = {Single-molecule force spectroscopy (SMFS) is a technique
10533 that measures the force necessary to unfold a protein. SMFS
10534 experiments generate Force-Distance (F-D) curves. A statistical
10535 analysis of a set of F-D curves reveals different unfolding
10536 pathways. Information on protein structure, conformation,
10537 functional states, and inter- and intra-molecular interactions can
10542 editor = HWTurnbull,
10544 title = {The correspondence of Isaac Newton},
10549 url = {http://books.google.com/books?id=pr8WAQAAMAAJ},
10550 note = {The ``Giants'' quote is on page 416, in a letter to Robert
10551 Hooke dated February 5, 1676.},
10554 @book{ whitehead11,
10555 author = ANWhitehead,
10556 title = {An introduction to mathematics},
10560 address = {London},
10561 url = {http://archive.org/details/introductiontoma00whitiala},
10562 note = {The ``civilization'' quote is on page 61.},
10566 author = NJMlot #" and "# CATovey #" and "# DLHu,
10567 title = {Fire ants self-assemble into waterproof rafts to survive floods},
10571 address = {Schools of Mechanical Engineering, Industrial and
10572 Systems Engineering, and Biology,
10573 Georgia Institute of Technology, Atlanta, GA 30318, USA.},
10577 pages = {7669--7673},
10578 issn = {1091-6490},
10579 doi = {10.1073/pnas.1016658108},
10580 url = {http://www.ncbi.nlm.nih.gov/pubmed/21518911},
10582 keywords = {Animals},
10584 keywords = {Behavior, Animal},
10585 keywords = {Biophysical Phenomena},
10586 keywords = {Floods},
10587 keywords = {Hydrophobic and Hydrophilic Interactions},
10588 keywords = {Microscopy, Electron, Scanning},
10589 keywords = {Models, Biological},
10590 keywords = {Social Behavior},
10591 keywords = {Surface Properties},
10592 keywords = {Time-Lapse Imaging},
10593 keywords = {Video Recording},
10594 keywords = {Water},
10595 abstract = {Why does a single fire ant \species{Solenopsis invicta}
10596 struggle in water, whereas a group can float effortlessly for
10597 days? We use time-lapse photography to investigate how fire ants
10598 \species{S.~invicta} link their bodies together to build
10599 waterproof rafts. Although water repellency in nature has been
10600 previously viewed as a static material property of plant leaves
10601 and insect cuticles, we here demonstrate a self-assembled
10602 hydrophobic surface. We find that ants can considerably enhance
10603 their water repellency by linking their bodies together, a process
10604 analogous to the weaving of a waterproof fabric. We present a
10605 model for the rate of raft construction based on observations of
10606 ant trajectories atop the raft. Central to the construction
10607 process is the trapping of ants at the raft edge by their
10608 neighbors, suggesting that some ``cooperative'' behaviors may rely
10610 note = {Higher resolution pictures are available at
10611 \url{http://antlab.gatech.edu/antlab/The_Ant_Raft.html}.},
10614 @article{ hofmeister88,
10615 author = FHofmeister,
10616 title = {Zur Lehre von der Wirkung der Salze.},
10619 address = {Prague},
10624 doi = {10.1007/BF01838161},
10625 url = {http://link.springer.com/article/10.1007/BF01838161},
10626 eprint = {http://link.springer.com/content/pdf/10.1007%2FBF01838161.pdf},
10630 @article{ chauhan97,
10631 author = VPChauhan #" and "# IRay #" and "# AChauhan #" and "#
10632 JWegiel #" and "# HMWisniewski,
10633 title = {Metal cations defibrillize the amyloid beta-protein fibrils.},
10636 address = {New York State Institute for Basic Research in
10637 Developmental Disabilities, Staten Island 10314-6399,
10642 pages = {805--809},
10643 issn = {0364-3190},
10644 url = {http://www.ncbi.nlm.nih.gov/pubmed/9232632},
10645 doi = {10.1023/A:1022079709085},
10647 keywords = {Alzheimer Disease},
10648 keywords = {Amyloid beta-Peptides},
10649 keywords = {Drug Evaluation, Preclinical},
10650 keywords = {Humans},
10651 keywords = {Metals},
10652 keywords = {Peptide Fragments},
10653 keywords = {Solubility},
10654 abstract = {Amyloid beta-protein (A beta) is the major constituent
10655 of amyloid fibrils composing beta-amyloid plaques and
10656 cerebrovascular amyloid in Alzheimer's disease (AD). We studied
10657 the effect of metal cations on preformed fibrils of synthetic A
10658 beta by Thioflavin T (ThT) fluorescence spectroscopy and
10659 electronmicroscopy (EM) in negative staining. The amount of cross
10660 beta-pleated sheet structure of A beta 1-40 fibrils was found to
10661 decrease by metal cations in a concentration-dependent manner as
10662 measured by ThT fluorescence spectroscopy. The order of
10663 defibrillization of A beta 1-40 fibrils by metal cations was: Ca2+
10664 and Zn2+ (IC50 = 100 microM) > Mg3+ (IC50 = 300 microM) > Al3+
10665 (IC50 = 1.1 mM). EM analysis in negative staining showed that A
10666 beta 1-40 fibrils in the absence of cations were organized in a
10667 fine network with a little or no amorphous material. The addition
10668 of Ca2+, Mg2+, and Zn2+ to preformed A beta 1-40 fibrils
10669 defibrillized the fibrils or converted them into short rods or to
10670 amorphous material. Al3+ was less effective, and reduced the
10671 fibril network by about 80\% of that in the absence of any metal
10672 cation. Studies with A beta 1-42 showed that this peptide forms
10673 more dense network of fibrils as compared to A beta 1-40. Both ThT
10674 fluorescence spectroscopy and EM showed that similar to A beta
10675 1-40, A beta 1-42 fibrils are also defibrillized in the presence
10676 of millimolar concentrations of Ca2+. These studies suggest that
10677 metal cations can defibrillize the fibrils of synthetic A beta.},
10678 note = {From page 806, ``The exact mechanism by which these metal
10679 ions affect the fibrillization of A$\beta$ is not known.''},
10682 @article{ friedman05,
10683 author = RFriedman #" and "# ENachliel #" and "# MGutman,
10684 title = {Molecular dynamics of a protein surface: ion-residues
10689 address = {Laser Laboratory for Fast Reactions in Biology,
10690 Department of Biochemistry, The George S. Wise Faculty
10691 for Life Sciences, Tel Aviv University, Israel.},
10695 pages = {768--781},
10696 issn = {0006-3495},
10697 doi = {10.1529/biophysj.105.058917},
10698 url = {http://www.ncbi.nlm.nih.gov/pubmed/15894639},
10700 keywords = {Amino Acids},
10701 keywords = {Binding Sites},
10702 keywords = {Chlorine},
10703 keywords = {Computer Simulation},
10705 keywords = {Models, Chemical},
10706 keywords = {Models, Molecular},
10707 keywords = {Motion},
10708 keywords = {Protein Binding},
10709 keywords = {Protein Conformation},
10710 keywords = {Ribosomal Protein S6},
10711 keywords = {Sodium},
10712 keywords = {Solutions},
10713 keywords = {Static Electricity},
10714 keywords = {Surface Properties},
10715 keywords = {Water},
10716 abstract = {Time-resolved measurements indicated that protons could
10717 propagate on the surface of a protein or a membrane by a special
10718 mechanism that enhanced the shuttle of the proton toward a
10719 specific site. It was proposed that a suitable location of
10720 residues on the surface contributes to the proton shuttling
10721 function. In this study, this notion was further investigated by
10722 the use of molecular dynamics simulations, where Na(+) and Cl(-)
10723 are the ions under study, thus avoiding the necessity for quantum
10724 mechanical calculations. Molecular dynamics simulations were
10725 carried out using as a model a few Na(+) and Cl(-) ions enclosed
10726 in a fully hydrated simulation box with a small globular protein
10727 (the S6 of the bacterial ribosome). Three independent 10-ns-long
10728 simulations indicated that the ions and the protein's surface were
10729 in equilibrium, with rapid passage of the ions between the
10730 protein's surface and the bulk. However, it was noted that close
10731 to some domains the ions extended their duration near the surface,
10732 thus suggesting that the local electrostatic potential hindered
10733 their diffusion to the bulk. During the time frame in which the
10734 ions were detained next to the surface, they could rapidly shuttle
10735 between various attractor sites located under the electrostatic
10736 umbrella. Statistical analysis of the molecular dynamics and
10737 electrostatic potential/entropy consideration indicated that the
10738 detainment state is an energetic compromise between attractive
10739 forces and entropy of dilution. The similarity between the motion
10740 of free ions next to a protein and the proton transfer on the
10741 protein's surface are discussed.},
10744 @article{ friedman11,
10745 author = RFriedman,
10746 title = {Ions and the protein surface revisited: extensive molecular
10747 dynamics simulations and analysis of protein structures in
10748 alkali-chloride solutions.},
10752 address = {School of Natural Sciences, Linn{\ae}us University,
10753 391 82 Kalmar, Sweden. ran.friedman@lnu.se},
10757 pages = {9213--9223},
10758 issn = {1520-5207},
10759 doi = {10.1021/jp112155m},
10760 URL = {http://www.ncbi.nlm.nih.gov/pubmed/21688775},
10762 keywords = {Alkalies},
10763 keywords = {Amyloid},
10764 keywords = {Chlorides},
10765 keywords = {Databases, Protein},
10766 keywords = {Fungal Proteins},
10767 keywords = {HIV Protease},
10768 keywords = {Humans},
10769 keywords = {Molecular Dynamics Simulation},
10770 keywords = {Protein Multimerization},
10771 keywords = {Protein Structure, Secondary},
10772 keywords = {Proteins},
10773 keywords = {Ribosomal Protein S6},
10774 keywords = {Solutions},
10775 keywords = {Solvents},
10776 keywords = {Surface Properties},
10777 abstract = {Proteins interact with ions in various ways. The surface
10778 of proteins has an innate capability to bind ions, and it is also
10779 influenced by the screening of the electrostatic potential owing
10780 to the presence of salts in the bulk solution. Alkali metal ions
10781 and chlorides interact with the protein surface, but such
10782 interactions are relatively weak and often transient. In this
10783 paper, computer simulations and analysis of protein structures are
10784 used to characterize the interactions between ions and the protein
10785 surface. The results show that the ion-binding properties of
10786 protein residues are highly variable. For example, alkali metal
10787 ions are more often associated with aspartate residues than with
10788 glutamates, whereas chlorides are most likely to be located near
10789 arginines. When comparing NaCl and KCl solutions, it was found
10790 that certain surface residues attract the anion more strongly in
10791 NaCl. This study demonstrates that protein-salt interactions
10792 should be accounted for in the planning and execution of
10793 experiments and simulations involving proteins, particularly if
10794 subtle structural details are sought after.},
10798 author = YZhang #" and "# PSCremer,
10799 title = {Interactions between macromolecules and ions: The
10800 {H}ofmeister series.},
10804 address = {Department of Chemistry, Texas A\&M University,
10805 College Station, TX 77843, USA.},
10809 pages = {658--663},
10810 issn = {1367-5931},
10811 doi = {10.1016/j.cbpa.2006.09.020},
10812 url = {http://www.ncbi.nlm.nih.gov/pubmed/17035073},
10814 keywords = {Acrylamides},
10815 keywords = {Biopolymers},
10816 keywords = {Solubility},
10817 keywords = {Thermodynamics},
10818 keywords = {Water},
10819 abstract = {The Hofmeister series, first noted in 1888, ranks the
10820 relative influence of ions on the physical behavior of a wide
10821 variety of aqueous processes ranging from colloidal assembly to
10822 protein folding. Originally, it was thought that an ion's
10823 influence on macromolecular properties was caused at least in part
10824 by `making' or `breaking' bulk water structure. Recent
10825 time-resolved and thermodynamic studies of water molecules in salt
10826 solutions, however, demonstrate that bulk water structure is not
10827 central to the Hofmeister effect. Instead, models are being
10828 developed that depend upon direct ion-macromolecule interactions
10829 as well as interactions with water molecules in the first
10830 hydration shell of the macromolecule.},
10831 note = {A quick pass through Hofmeister history, but no discussion
10832 of cations (``A complete picture will inevitably involve an
10833 integrated understanding of the role of cations (including
10834 guanidinium ions) and osmolytes (such as urea and tri-methylamine
10835 N-oxide) as well. There has been some progress in these fields,
10836 although such subjects are generally beyond the scope of this
10837 short review.'').},
10840 @article{ isaacs06,
10841 author = AMIsaacs #" and "# DBSenn #" and "# MYuan #" and "#
10842 JPShine #" and "# BAYankner,
10843 title = {Acceleration of Amyloid $\beta$-Peptide Aggregation by
10844 Physiological Concentrations of Calcium.},
10848 address = {Department of Neurology and Division of Neuroscience,
10849 The Children's Hospital, Harvard Medical School,
10850 Boston, Massachusetts 02115, USA.},
10854 pages = {27916--27923},
10855 issn = {0021-9258},
10856 doi = {10.1074/jbc.M602061200},
10857 url = {http://www.ncbi.nlm.nih.gov/pubmed/16870617},
10859 keywords = {Alzheimer Disease},
10860 keywords = {Amyloid},
10861 keywords = {Amyloid beta-Peptides},
10862 keywords = {Animals},
10863 keywords = {Calcium},
10864 keywords = {Cells, Cultured},
10865 keywords = {Copper},
10866 keywords = {Neurons},
10869 abstract = {Alzheimer disease is characterized by the accumulation
10870 of aggregated amyloid beta-peptide (Abeta) in the brain. The
10871 physiological mechanisms and factors that predispose to Abeta
10872 aggregation and deposition are not well understood. In this
10873 report, we show that calcium can predispose to Abeta aggregation
10874 and fibril formation. Calcium increased the aggregation of early
10875 forming protofibrillar structures and markedly increased
10876 conversion of protofibrils to mature amyloid fibrils. This
10877 occurred at levels 20-fold below the calcium concentration in the
10878 extracellular space of the brain, the site at which amyloid plaque
10879 deposition occurs. In the absence of calcium, protofibrils can
10880 remain stable in vitro for several days. Using this approach, we
10881 directly compared the neurotoxicity of protofibrils and mature
10882 amyloid fibrils and demonstrate that both species are inherently
10883 toxic to neurons in culture. Thus, calcium may be an important
10884 predisposing factor for Abeta aggregation and toxicity. The high
10885 extracellular concentration of calcium in the brain, together with
10886 impaired intraneuronal calcium regulation in the aging brain and
10887 Alzheimer disease, may play an important role in the onset of
10888 amyloid-related pathology.},
10889 note = {Physiological levels of \NaCl\ are $\sim 150\U{mM}$. \Ca\
10890 is $\sim 2\U{mM}$.},
10894 author = AItkin #" and "# VDupres #" and "# YFDufrene #" and "#
10895 BBechinger #" and "# JMRuysschaert #" and "# VRaussens,
10896 title = {Calcium ions promote formation of amyloid $\beta$-peptide
10897 (1-40) oligomers causally implicated in neuronal toxicity of
10898 {A}lzheimer's disease.},
10902 address = {Laboratory of Structure and Function of Biological
10903 Membranes, Center for Structural Biology and
10904 Bioinformatics, Universit{\'e} Libre de Bruxelles,
10905 Brussels, Belgium.},
10906 journal = PLOS:ONE,
10910 keywords = {Alzheimer Disease},
10911 keywords = {Amyloid beta-Peptides},
10912 keywords = {Blotting, Western},
10913 keywords = {Calcium},
10914 keywords = {Fluorescence},
10915 keywords = {Humans},
10917 keywords = {Models, Biological},
10918 keywords = {Mutant Proteins},
10919 keywords = {Neurons},
10920 keywords = {Protein Structure, Quaternary},
10921 keywords = {Protein Structure, Secondary},
10922 keywords = {Spectroscopy, Fourier Transform Infrared},
10923 keywords = {Thiazoles},
10924 ISSN = {1932-6203},
10925 doi = {10.1371/journal.pone.0018250},
10926 URL = {http://www.ncbi.nlm.nih.gov/pubmed/21464905},
10928 abstract = {Amyloid $\beta$-peptide (A$\beta$) is directly linked to
10929 Alzheimer's disease (AD). In its monomeric form, A$\beta$
10930 aggregates to produce fibrils and a range of oligomers, the latter
10931 being the most neurotoxic. Dysregulation of Ca(2+) homeostasis in
10932 aging brains and in neurodegenerative disorders plays a crucial
10933 role in numerous processes and contributes to cell dysfunction and
10934 death. Here we postulated that calcium may enable or accelerate
10935 the aggregation of A$\beta$. We compared the aggregation pattern
10936 of A$\beta$(1-40) and that of A$\beta$(1-40)E22G, an amyloid
10937 peptide carrying the Arctic mutation that causes early onset of
10938 the disease. We found that in the presence of Ca(2+),
10939 A$\beta$(1-40) preferentially formed oligomers similar to those
10940 formed by A$\beta$(1-40)E22G with or without added Ca(2+), whereas
10941 in the absence of added Ca(2+) the A$\beta$(1-40) aggregated to
10942 form fibrils. Morphological similarities of the oligomers were
10943 confirmed by contact mode atomic force microscopy imaging. The
10944 distribution of oligomeric and fibrillar species in different
10945 samples was detected by gel electrophoresis and Western blot
10946 analysis, the results of which were further supported by
10947 thioflavin T fluorescence experiments. In the samples without
10948 Ca(2+), Fourier transform infrared spectroscopy revealed
10949 conversion of oligomers from an anti-parallel $\beta$-sheet to the
10950 parallel $\beta$-sheet conformation characteristic of
10951 fibrils. Overall, these results led us to conclude that calcium
10952 ions stimulate the formation of oligomers of A$\beta$(1-40), that
10953 have been implicated in the pathogenesis of AD.},
10954 note = {$2\U{mM}$ of \Ca\ is the \emph{extracellular} concentration.
10955 Cytosol concetrations are in the $\mu$M range.},
10959 author = JZidar #" and "# FMerzel,
10960 title = {Probing amyloid-beta fibril stability by increasing ionic
10965 address = {National Institute of Chemistry, Hajdrihova 19,
10966 SI-1000 Ljubljana, Slovenia.},
10970 pages = {2075--2081},
10971 issn = {1520-5207},
10972 doi = {10.1021/jp109025b},
10973 URL = {http://www.ncbi.nlm.nih.gov/pubmed/21329333},
10975 keywords = {Amyloid beta-Peptides},
10976 keywords = {Entropy},
10977 keywords = {Hydrogen Bonding},
10978 keywords = {Molecular Dynamics Simulation},
10979 keywords = {Osmolar Concentration},
10980 keywords = {Protein Multimerization},
10981 keywords = {Protein Stability},
10982 keywords = {Protein Structure, Secondary},
10983 keywords = {Solvents},
10984 keywords = {Vibration},
10985 abstract = {Previous experimental studies have demonstrated changing
10986 the ionic strength of the solvent to have a great impact on the
10987 mechanism of aggregation of amyloid-beta (A$\beta$) protein
10988 leading to distinct fibril morphology at high and low ionic
10989 strength. Here, we use molecular dynamics simulations to elucidate
10990 the ionic strength-dependent effects on the structure and dynamics
10991 of the model A$\beta$ fibril. The change in ionic strength was
10992 brought forth by varying the NaCl concentration in the environment
10993 surrounding the A$\beta$ fibril. Comparison of the calculated
10994 vibrational spectra of A$\beta$ derived from 40 ns all-atom
10995 molecular dynamics simulations at different ionic strength reveals
10996 the fibril structure to be stiffer with increasing ionic
10997 strength. This finding is further corroborated by the calculation
10998 of the stretching force constants. Decomposition of binding and
10999 dynamical properties into contributions from different structural
11000 segments indicates the elongation of the fibril at low ionic
11001 strength is most likely promoted by hydrogen bonding between
11002 N-terminal parts of the fibril, whereas aggregation at higher
11003 ionic strength is suggested to be driven by the hydrophobic
11005 note = {Only study \NaCl\ over the range to $308\U{mM}$, but show a
11006 general decreased hydrogen bonding as concentration increases.},
11010 author = LMiao #" and "# HQin #" and "# PKoehl #" and "# JSong,
11011 title = {Selective and specific ion binding on proteins at
11012 physiologically-relevant concentrations.},
11016 address = {Department of Biological Sciences, Faculty of Science,
11017 National University of Singapore, Singapore.},
11021 pages = {3126--3132},
11022 issn = {1873-3468},
11023 doi = {10.1016/j.febslet.2011.08.048},
11024 url = {http://www.ncbi.nlm.nih.gov/pubmed/21907714},
11026 keywords = {Amino Acid Sequence},
11027 keywords = {Ephrin-B2},
11029 keywords = {Models, Molecular},
11030 keywords = {Molecular Sequence Data},
11031 keywords = {Nuclear Magnetic Resonance, Biomolecular},
11032 keywords = {Protein Binding},
11033 keywords = {Protein Folding},
11034 keywords = {Protein Structure, Tertiary},
11035 keywords = {Salts},
11036 keywords = {Solutions},
11037 keywords = {Thermodynamics},
11038 keywords = {Water},
11039 abstract = {Insoluble proteins dissolved in unsalted water appear to
11040 have no well-folded tertiary structures. This raises a fundamental
11041 question as to whether being unstructured is due to the absence of
11042 salt ions. To address this issue, we solubilized the insoluble
11043 ephrin-B2 cytoplasmic domain in unsalted water and first confirmed
11044 using NMR spectroscopy that it is only partially folded. Using NMR
11045 HSQC titrations with 14 different salts, we further demonstrate
11046 that the addition of salt triggers no significant folding of the
11047 protein within physiologically relevant ion concentrations. We
11048 reveal however that their 8 anions bind to the ephrin-B2 protein
11049 with high affinity and specificity at biologically-relevant
11050 concentrations. Interestingly, the binding is found to be both
11051 salt- and residue-specific.},
11052 note = {They suggest that for low concentrations ($<100\U{mM}$),
11053 protein-ion interactions are mostly electrostatic. The Hofmeister
11054 effects only kick in at higher consentrations.},
11058 author = MDSmith #" and "# LCCruz,
11059 title = {Effect of Ionic Aqueous Environments on the Structure and
11060 Dynamics of the A$\beta_{21-30}$ Fragment: a Molecular-Dynamics
11065 address = {Department of Physics, 3141 Chestnut Street,
11066 Drexel University, Philadelphia, Pennsylvania 19104,
11071 pages = {6614--6624},
11072 issn = {1520-5207},
11073 doi = {10.1021/jp312653h},
11074 url = {http://www.ncbi.nlm.nih.gov/pubmed/23675877},
11076 abstract = {The amyloid $\beta$-protein (A$\beta$) has been
11077 implicated in the pathogenesis of Alzheimer's disease. The role
11078 of the structure and dynamics of the central A$\beta_{21-30}$
11079 decapeptide region of the full-length A$\beta$ is considered
11080 crucial in the aggregation pathway of A$\beta$. Here we report
11081 results of isobaric--isothermal (NPT) all-atom explicit water
11082 molecular dynamics simulations of the monomeric form of the
11083 wild-type A$\beta_{21-30}$ fragment in aqueous salt environments
11084 formed by neurobiologically important group IA (\NaCl, \KCl) and
11085 group IIA (\CaCl, \MgCl) salts. Our simulations reveal the
11086 existence of salt-specific changes to secondary structure
11087 propensities, lifetimes, hydrogen bonding, salt-bridge formation,
11088 and decapeptide--ion contacts of this decapeptide. These results
11089 suggest that aqueous environments with the \CaCl\ salt, and to a
11090 much lesser extent the \MgCl\ salt, have profound effects by
11091 increasing random coil structure propensities and lifetimes and
11092 diminishing intrapeptide hydrogen bonding. These effects are
11093 rationalized in terms of direct cation--decapeptide contacts and
11094 changes to the hydration-shell water molecules. On the other side
11095 of the spectrum, environments with the \NaCl\ and \KCl\ salts have
11096 little influence on the decapeptide's secondary structure despite
11097 increasing hydrogen bonding, salt-bridge formation, and lifetime
11098 of turn structures. The observed enhancement of open structures
11099 by group IIA may be of importance in the folding and aggregation
11100 pathway of the full-length A$\beta$.},
11104 author = HJDyson #" and "# PEWright,
11105 title = {Intrinsically unstructured proteins and their functions.},
11109 address = {Department of Molecular Biology and Skaggs Institute
11110 for Chemical Biology, The Scripps Research Institute,
11111 10550 North Torrey Pines Road, La Jolla, California
11112 92037, USA. dyson@scripps.edu},
11115 pages = {197--208},
11116 issn = {1471-0072},
11117 doi = {10.1038/nrm1589},
11118 url = {http://www.ncbi.nlm.nih.gov/pubmed/15738986},
11120 keywords = {CREB-Binding Protein},
11121 keywords = {Humans},
11122 keywords = {Nuclear Proteins},
11123 keywords = {Nucleic Acids},
11124 keywords = {Protein Binding},
11125 keywords = {Protein Processing, Post-Translational},
11126 keywords = {Protein Structure, Tertiary},
11127 keywords = {Proteins},
11128 keywords = {Trans-Activators},
11129 keywords = {Tumor Suppressor Protein p53},
11130 abstract = {Many gene sequences in eukaryotic genomes encode entire
11131 proteins or large segments of proteins that lack a well-structured
11132 three-dimensional fold. Disordered regions can be highly conserved
11133 between species in both composition and sequence and, contrary to
11134 the traditional view that protein function equates with a stable
11135 three-dimensional structure, disordered regions are often
11136 functional, in ways that we are only beginning to discover. Many
11137 disordered segments fold on binding to their biological targets
11138 (coupled folding and binding), whereas others constitute flexible
11139 linkers that have a role in the assembly of macromolecular
11143 @article{ cleland64,
11144 author = WWCleland,
11145 title = {Dithiothreitol, a New Protective Reagent for SH Groups},
11151 pages = {480--482},
11152 keywords = {Alcohols},
11153 keywords = {Chromatography},
11154 keywords = {Coenzyme A},
11155 keywords = {Oxidation-Reduction},
11156 keywords = {Research},
11157 keywords = {Sulfhydryl Compounds},
11158 keywords = {Sulfides},
11159 keywords = {Ultraviolet Rays},
11160 issn = {0006-2960},
11161 doi = {10.1021/bi00892a002},
11162 url = {http://www.ncbi.nlm.nih.gov/pubmed/14192894},
11163 eprint = {http://pubs.acs.org/doi/pdf/10.1021/bi00892a002},