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

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 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.

SUBMITTER: Settanni G

PROVIDER: S-EPMC1304005 | biostudies-literature | 2004 Mar

REPOSITORIES: biostudies-literature

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

Settanni G G Gsponer J J Caflisch A A

Biophysical journal 20040301 3

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 comple ...[more]

PMID: 14990497

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