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 language | English |
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Pages (from-to) | 521-533 |
Number of pages | 13 |
Journal | Biophysical Journal |
Volume | 87 |
Issue number | 1 |
DOIs | |
State | Published - Jul 2004 |
Externally published | Yes |
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.