Multiple folding pathways of the SH3 domain.
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.
Borreguero
Jose M
JM
Center for Polymer Studies and Department of Physics, Boston University, Boston, Massachusetts, USA. jmborr@bu.edu
Ding
Feng
F
Buldyrev
Sergey V
SV
Stanley
H Eugene
HE
Dokholyan
Nikolay V
NV
D000818:Animals; D003198:Computer Simulation; D006801:Humans; D008958:Models, Molecular; D017510:Protein Folding; D011518:Proto-Oncogene Proteins / Q000737:chemistry*; D050737:Proto-Oncogene Proteins c-crk; D018909:src Homology Domains
D011518:Proto-Oncogene Proteins; D050737:Proto-Oncogene Proteins c-crk