Formation of the folding nucleus of an SH3 domain investigated by loosely coupled molecular dynamics simulations

TitleFormation of the folding nucleus of an SH3 domain investigated by loosely coupled molecular dynamics simulations
Publication TypeJournal Article
Year of Publication2004
AuthorsSettanni G., Gsponer J., Caflisch A.
JournalBiophysical Journal
Volume86
Issue3
Pagination1691-1701
Date Published2004 Mar
Type of ArticleResearch Article
ISSN0006-3495
KeywordsComputer Simulation, Models, Chemical, Models, Molecular, Motion, Protein Conformation, Protein Folding, src Homology Domains, src-Family Kinases
Abstract

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 β-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 β-sheet whereas its two hairpins form in a different but consistent way.

DOI10.1016/S0006-3495(04)74238-1
pubindex

0055

Alternate JournalBiophys. J.
PubMed ID14990497
PubMed Central IDPMC1304005
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