Formation of the folding nucleus of an SH3 domain investigated by loosely coupled molecular dynamics simulations.
The experimentally well-established folding mechanism of the src-SH3 domain, and in particular the phi-value analysis of its transition state, represents a sort of testing table for computational investigations of protein folding. Here, parallel molecular dynamics simulations of the src-SH3 domain have been performed starting from denatured conformations. By rescuing and restarting only trajectories approaching the folding transition state, an ensemble of conformations was obtained with a completely structured central beta-sheet and a native-like packing of residues Ile-110, Ala-121, and Ile-132. An analysis of the trajectories shows that there are several pathways leading to the formation of the central beta-sheet whereas its two hairpins form in a different but consistent way.
Biochemisches Institut, Universität Zürich, Zürich, Switzerland.
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G
Settanni
J
J
Gsponer
A
A
Caflisch
D003198:Computer Simulation; D008956:Models, Chemical; D008958:Models, Molecular; D009038:Motion; D011487:Protein Conformation; D017510:Protein Folding; D018909:src Homology Domains; D019061:src-Family Kinases / Q000737:chemistry*
D019061:src-Family Kinases