HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Faísca, P. F.N. Articles by Plaxco, K. W. Search for Related Content PubMed PubMed Citation Articles by Faísca, P. F.N. Articles by Plaxco, K. W. Social Bookmarking                   What's this?

Cooperativity and the origins of rapid, single-exponential kinetics in protein folding

¹ Centro de Física Teórica e Computacional da Universidade de Lisboa, 1649-003 Lisboa Codex, Portugal
² Department of Chemistry and Biochemistry, University of California, Santa Barbara, Santa Barbara, California 93106, USA

(RECEIVED February 21, 2006; FINAL REVISION April 10, 2006; ACCEPTED April 11, 2006)

The folding of naturally occurring, single-domain proteins is usually well described as a simple, single-exponential process lacking significant trapped states. Here we further explore the hypothesis that the smooth energy landscape this implies, and the rapid kinetics it engenders, arises due to the extraordinary thermodynamic cooperativity of protein folding. Studying Miyazawa-Jernigan lattice polymers, we find that, even under conditions where the folding energy landscape is relatively optimized (designed sequences folding at their temperature of maximum folding rate), the folding of protein-like heteropolymers is accelerated when their thermodynamic cooperativity is enhanced by enhancing the nonadditivity of their energy potentials. At lower temperatures, where kinetic traps presumably play a more significant role in defining folding rates, we observe still greater cooperativity-induced acceleration. Consistent with these observations, we find that the folding kinetics of our computational models more closely approximates single-exponential behavior as their cooperativity approaches optimal levels. These observations suggest that the rapid folding of naturally occurring proteins is, in part, a consequence of their remarkably cooperative folding.

Keywords: Monte Carlo simulation; optimal folding temperature; native topology; contact order; misfolded states; two-state

CiteULike

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				T. O. Street, C. M. Bradley, and D. Barrick Predicting coupling limits from an experimentally determined energy landscape PNAS, March 20, 2007; 104(12): 4907 - 4912. [Abstract] [Full Text] [PDF]