Multiple folding pathways of the SH3 domain

Jose M. Borreguero, Feng Ding, Sergey V. Buldyrev, H. Eugene Stanley, Nikolay V. Dokholyan

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

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.

Original languageEnglish
Pages (from-to)521-533
Number of pages13
JournalBiophysical Journal
Volume87
Issue number1
DOIs
StatePublished - Jul 2004
Externally publishedYes

Funding

We acknowledge E. I. Shakhnovich for insightful discussions, R. Badzey for careful reading of the manuscript, and the Petroleum Research Fund for support. N.V.D. acknowledges support of the University of North Carolina at Chapel Hill Research Council Grant.

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