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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\u2010Jernigan 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\u2010like 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\u2010induced acceleration. Consistent with these observations, we find that the folding kinetics of our computational models more closely approximates single\u2010exponential 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.<\/jats:p>","DOI":"10.1110\/ps.062180806","type":"journal-article","created":{"date-parts":[[2006,6,30]],"date-time":"2006-06-30T20:28:51Z","timestamp":1151699331000},"page":"1608-1618","source":"Crossref","is-referenced-by-count":26,"title":["Cooperativity and the origins of rapid, single\u2010exponential kinetics in protein folding"],"prefix":"10.1002","volume":"15","author":[{"given":"Patr\u00edcia F.N.","family":"Fa\u00edsca","sequence":"first","affiliation":[]},{"given":"Kevin W.","family":"Plaxco","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2009,1]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1995.0511"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1359-0278(96)00033-8"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.21.7524"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/j100356a007"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/prot.340210302"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.480893"},{"key":"e_1_2_6_8_1","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1038\/nsb0197-10","article-title":"From Levinthal to pathways to funnels","volume":"4","author":"Chan H.S.","year":"1997","journal-title":"Nat. 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