Multiple folding pathways of the SH3 domain

Biophys J. 2004 Jul;87(1):521-33. doi: 10.1529/biophysj.104.039529.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Computer Simulation*
  • Humans
  • Models, Molecular*
  • Protein Folding*
  • Proto-Oncogene Proteins / chemistry*
  • Proto-Oncogene Proteins c-crk
  • src Homology Domains*

Substances

  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-crk