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Multiple folding pathways of the SH3 domain.

ABSTRACT: Experimental observations suggest that proteins follow different folding pathways under different environmental conditions. We perform molecular dynamics simulations of a model of the c-Crk SH3 domain over a broad range of temperatures, and identify distinct pathways in the folding transition. We determine the kinetic partition temperature-the temperature for which the c-Crk SH3 domain undergoes a rapid folding transition with minimal kinetic barriers-and observe that below this temperature the model protein may undergo a folding transition by multiple folding pathways via only one or two intermediates. Our findings suggest the hypothesis that the SH3 domain, a protein fold for which only two-state folding kinetics was observed in previous experiments, may exhibit intermediate states under conditions that strongly stabilize the native state.

SUBMITTER: Borreguero JM

PROVIDER: S-EPMC1304373 | biostudies-literature | 2004 Jul

REPOSITORIES: biostudies-literature

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Multiple folding pathways of the SH3 domain.

Borreguero Jose M JM Ding Feng F Buldyrev Sergey V SV Stanley H Eugene HE Dokholyan Nikolay V NV

Biophysical journal 20040701 1

Experimental observations suggest that proteins follow different folding pathways under different environmental conditions. We perform molecular dynamics simulations of a model of the c-Crk SH3 domain over a broad range of temperatures, and identify distinct pathways in the folding transition. We determine the kinetic partition temperature-the temperature for which the c-Crk SH3 domain undergoes a rapid folding transition with minimal kinetic barriers-and observe that below this temperature the ...[more]

PMID: 15240485

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