90:
and on short timescales. He suggested that the paradox can be resolved if "protein folding is sped up and guided by the rapid formation of local interactions which then determine the further folding of the peptide; this suggests local amino acid sequences which form stable interactions and serve as
70:
bond angles. If each of these bond angles can be in one of three stable conformations, the protein may misfold into a maximum of 3 different conformations (including any possible folding redundancy). Therefore, if a protein were to attain its correctly folded configuration by sequentially sampling
38:) would take an immense duration, however, in reality, protein folding happens very quickly, even in the case of the most complex structures, suggesting that the transitions are guided into a stable state through an uneven energy landscape.
114:
Levinthal also suggested that the native structure might have a higher energy, if the lowest energy was not kinetically accessible. An analogy is a rock tumbling down a hillside that lodges in a gully rather than reaching the base.
79:) rates. The "paradox" is that most small proteins fold spontaneously on a millisecond or even microsecond time scale. The solution to this paradox has been established by computational approaches to
58:, the molecule has an astronomical number of possible conformations. An estimate of 10 was made in one of his papers (often incorrectly cited as the 1968 paper). For example, a polypeptide of 100
71:
all the possible conformations, it would require a time longer than the age of the universe to arrive at its correct native conformation. This is true even if conformations are sampled at rapid (
51:
225:
34:
seeks a stable energy configuration. An algorithmic search through all possible conformations to identify the minimum energy configuration (the
177:
111:. Some computational approaches to protein structure prediction have sought to identify and simulate the mechanism of protein folding.
202:
601:
172:(7th ed.). New York, NY : Houndmills, Basingstoke: W.H. Freeman and Company ; Macmillan Higher Education.
707:
692:
80:
27:
702:
677:
697:
207:
Mossbauer
Spectroscopy in Biological Systems: Proceedings of a Meeting Held at Allerton House, Monticello, Illinois
166:
Nelson, David L.; Cox, Michael M.; Lehninger, Albert L. (2017). "Polypeptides Fold
Rapidly by a Stepwise Process".
333:
256:
96:
468:
286:
240:
332:
Rooman, Marianne Rooman; Yves
Dehouck; Jean Marc Kwasigroch; Christophe Biot; Dimitri Gilis (2002).
147:
136:
87:
640:
492:
407:
364:
23:
667:
127:
and Igor
Berezovsky, the proteins fold by subunits (modules) of the size of 25β30 amino acids.
632:
624:
582:
533:
484:
399:
356:
314:
183:
173:
616:
572:
564:
523:
476:
434:
391:
348:
304:
294:
248:
100:
210:
124:
104:
47:
31:
672:
472:
290:
244:
577:
552:
142:
108:
67:
648:
528:
511:
438:
686:
309:
274:
644:
411:
678:
https://web.archive.org/web/20041011182039/http://www.sdsc.edu/~nair/levinthal.html
620:
496:
368:
352:
63:
35:
453:
425:
Durup, Jean (1998). "On "Levinthal paradox" and the theory of protein folding".
139: – proteins that assist other proteins in folding or unfolding
92:
76:
72:
59:
628:
568:
252:
187:
636:
586:
360:
167:
537:
488:
403:
318:
299:
395:
55:
480:
602:"Loop fold structure of proteins: Resolution of Levinthal's paradox"
382:
Dill K; H.S. Chan (1997). "From
Levinthal to pathways to funnels".
668:
http://www-wales.ch.cam.ac.uk/~mark/levinthal/levinthal.html
452:
sΛAli, Andrej; Shakhnovich, Eugene; Karplus, Martin (1994).
107:. This is also described as protein folding directed within
95:
points in the folding process". Indeed, the protein folding
233:
Journal de Chimie
Physique et de Physico-Chimie Biologique
103:
were experimentally detected, which explains the fast
673:
https://www.wired.com/wired/archive/9.07/blue_pr.html
600:Berezovsky, Igor N.; Trifonov, Edward N. (2002).
609:Journal of Biomolecular Structure & Dynamics
50:noted that, because of the very large number of
341:Journal of Biomolecular Structure and Dynamics
334:"What is paradoxical about Levinthal Paradox?"
8:
512:"The Levinthal paradox: yesterday and today"
273:Zwanzig R, Szabo A, Bagchi B (1992-01-01).
28:computational protein structure prediction
576:
527:
308:
298:
226:"Are there pathways for protein folding?"
158:
16:Thought experiment of protein folding
7:
169:Lehninger principles of biochemistry
14:
86:Levinthal himself was aware that
621:10.1080/07391102.2002.10506817
427:Journal of Molecular Structure
353:10.1080/07391102.2002.10506850
66:, and therefore 198 different
1:
529:10.1016/S1359-0278(97)00067-9
439:10.1016/S0166-1280(97)00238-8
109:funnel-like energy landscapes
81:protein structure prediction
88:proteins fold spontaneously
724:
454:"How does a protein fold?"
224:Levinthal, Cyrus (1968).
201:Levinthal, Cyrus (1969).
99:and the partially folded
569:10.1038/sj.embor.7400655
510:Karplus, Martin (1997).
203:"How to Fold Graciously"
551:Hunter, Philip (2006).
209:: 22β24. Archived from
279:Proc Natl Acad Sci USA
253:10.1051/jcp/1968650044
119:Suggested explanations
275:"Levinthal's paradox"
516:Folding & Design
300:10.1073/pnas.89.1.20
708:Thought experiments
693:Eponymous paradoxes
473:1994Natur.369..248S
291:1992PNAS...89...20Z
245:1968JCP....65...44L
20:Levinthal's paradox
703:Physical paradoxes
396:10.1038/nsb0197-10
52:degrees of freedom
24:thought experiment
698:Protein structure
467:(6477): 248β251.
384:Nat. Struct. Biol
179:978-1-4641-2611-6
101:transition states
56:polypeptide chain
715:
656:
655:
653:
647:. Archived from
606:
597:
591:
590:
580:
548:
542:
541:
531:
507:
501:
500:
481:10.1038/369248a0
458:
449:
443:
442:
433:(1β2): 157β169.
422:
416:
415:
379:
373:
372:
338:
329:
323:
322:
312:
302:
270:
264:
263:
261:
255:. Archived from
230:
221:
215:
214:
198:
192:
191:
163:
148:Anfinsen's dogma
26:in the field of
723:
722:
718:
717:
716:
714:
713:
712:
683:
682:
664:
659:
651:
604:
599:
598:
594:
553:"Into the fold"
550:
549:
545:
509:
508:
504:
456:
451:
450:
446:
424:
423:
419:
381:
380:
376:
336:
331:
330:
326:
272:
271:
267:
259:
228:
223:
222:
218:
200:
199:
195:
180:
165:
164:
160:
156:
133:
125:Edward Trifonov
121:
105:protein folding
54:in an unfolded
48:Cyrus Levinthal
44:
32:protein folding
17:
12:
11:
5:
721:
719:
711:
710:
705:
700:
695:
685:
684:
681:
680:
675:
670:
663:
662:External links
660:
658:
657:
654:on 2005-02-12.
592:
563:(3): 249β252.
543:
522:(4): S69βS75.
502:
444:
417:
374:
347:(3): 327β329.
324:
265:
262:on 2009-09-02.
216:
213:on 2010-10-07.
193:
178:
157:
155:
152:
151:
150:
145:
143:Folding funnel
140:
132:
129:
120:
117:
43:
40:
15:
13:
10:
9:
6:
4:
3:
2:
720:
709:
706:
704:
701:
699:
696:
694:
691:
690:
688:
679:
676:
674:
671:
669:
666:
665:
661:
650:
646:
642:
638:
634:
630:
626:
622:
618:
614:
610:
603:
596:
593:
588:
584:
579:
574:
570:
566:
562:
558:
554:
547:
544:
539:
535:
530:
525:
521:
517:
513:
506:
503:
498:
494:
490:
486:
482:
478:
474:
470:
466:
462:
455:
448:
445:
440:
436:
432:
428:
421:
418:
413:
409:
405:
401:
397:
393:
389:
385:
378:
375:
370:
366:
362:
358:
354:
350:
346:
342:
335:
328:
325:
320:
316:
311:
306:
301:
296:
292:
288:
284:
280:
276:
269:
266:
258:
254:
250:
246:
242:
238:
234:
227:
220:
217:
212:
208:
204:
197:
194:
189:
185:
181:
175:
171:
170:
162:
159:
153:
149:
146:
144:
141:
138:
135:
134:
130:
128:
126:
123:According to
118:
116:
112:
110:
106:
102:
98:
97:intermediates
94:
89:
84:
82:
78:
74:
69:
65:
64:peptide bonds
62:will have 99
61:
57:
53:
49:
41:
39:
37:
33:
29:
25:
21:
649:the original
612:
608:
595:
560:
556:
546:
519:
515:
505:
464:
460:
447:
430:
426:
420:
390:(1): 10β19.
387:
383:
377:
344:
340:
327:
285:(1): 20β22.
282:
278:
268:
257:the original
236:
232:
219:
211:the original
206:
196:
168:
161:
122:
113:
85:
45:
36:native state
19:
18:
68:phi and psi
687:Categories
615:(1): 5β6.
154:References
93:nucleation
77:picosecond
73:nanosecond
629:0739-1102
239:: 44β45.
188:986827885
137:Chaperone
46:In 1969,
645:33174198
637:12144347
587:16607393
557:EMBO Rep
412:11557990
361:12437370
131:See also
60:residues
578:1456894
538:9269572
497:4281915
489:7710478
469:Bibcode
404:8989315
369:6839744
319:1729690
287:Bibcode
241:Bibcode
42:History
643:
635:
627:
585:
575:
536:
495:
487:
461:Nature
410:
402:
367:
359:
317:
307:
186:
176:
652:(PDF)
641:S2CID
605:(PDF)
493:S2CID
457:(PDF)
408:S2CID
365:S2CID
337:(PDF)
310:48166
260:(PDF)
229:(PDF)
22:is a
633:PMID
625:ISSN
583:PMID
534:PMID
485:PMID
400:PMID
357:PMID
315:PMID
184:OCLC
174:ISBN
617:doi
573:PMC
565:doi
524:doi
477:doi
465:369
435:doi
431:424
392:doi
349:doi
305:PMC
295:doi
249:doi
75:or
689::
639:.
631:.
623:.
613:20
611:.
607:.
581:.
571:.
559:.
555:.
532:.
518:.
514:.
491:.
483:.
475:.
463:.
459:.
429:.
406:.
398:.
386:.
363:.
355:.
345:20
343:.
339:.
313:.
303:.
293:.
283:89
281:.
277:.
247:.
237:65
235:.
231:.
205:.
182:.
83:.
30:;
619::
589:.
567::
561:7
540:.
526::
520:2
499:.
479::
471::
441:.
437::
414:.
394::
388:4
371:.
351::
321:.
297::
289::
251::
243::
190:.
Text is available under the Creative Commons Attribution-ShareAlike License. Additional terms may apply.