Journal
JOURNAL OF MOLECULAR BIOLOGY
Volume 326, Issue 1, Pages 247-253Publisher
ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD
DOI: 10.1016/S0022-2836(02)01356-6
Keywords
contact order; non-additivity; topological frustration
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Funding
- NIGMS NIH HHS [R01GM62868-01A2] Funding Source: Medline
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The relative folding rates of simple, single-domain proteins, proteins whose folding energy landscapes are smooth, are highly dispersed and strongly correlated with native-state topology. In contrast, the relative folding rates of small, G (o) over bar -potential lattice polymers, which also exhibit smooth energy landscapes, are poorly dispersed and insignificantly correlated with native-state topology. Here, we investigate this discrepancy in light of a recent, quantitative theory of two-state folding kinetics, the topo, mer search model. This model stipulates that the topology-dependence of two-state folding rates is a direct consequence of the extraordinarily cooperative equilibrium folding of simple proteins. We demonstrate that traditional G (o) over bar polymers lack the extreme cooperativity that characterizes the folding of naturally occurring, two-state proteins and confirm that the folding rates of a diverse set of G (o) over bar 27-mers are poorly dispersed and effectively uncorrelated with native state topology. Upon modestly increasing the cooperativity of the G (o) over bar -potential, however, significantly increased dispersion and strongly topology-dependent kinetics are observed. These results support previous arguments that the cooperative folding of simple, single-domain proteins gives rise to their topology-dependent folding rates. We speculate that this cooperativity, and thus, indirectly, the topology-rate relationship, may have arisen in order to generate the smooth energetic landscapes upon which rapid folding can occur. (C) 2003 Elsevier Science Ltd. All rights reserved.
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