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Transition-path sampling of beta-hairpin folding.

ABSTRACT: We examine the dynamical folding pathways of the C-terminal beta-hairpin of protein G-B1 in explicit solvent at room temperature by means of a transition-path sampling algorithm. In agreement with previous free-energy calculations, the resulting path ensembles reveal a folding mechanism in which the hydrophobic residues collapse first followed by backbone hydrogen-bond formation, starting with the hydrogen bonds inside the hydrophobic core. In addition, the path ensembles contain information on the folding kinetics, including solvent motion. Using the recently developed transition interface sampling technique, we calculate the rate constant for unfolding of the protein fragment and find it to be in reasonable agreement with experiments. The results support the validation of using all-atom force fields to study protein folding.

SUBMITTER: Bolhuis PG

PROVIDER: S-EPMC218724 | biostudies-literature | 2003 Oct

REPOSITORIES: biostudies-literature

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Transition-path sampling of beta-hairpin folding.

Bolhuis Peter G PG

Proceedings of the National Academy of Sciences of the United States of America 20031001 21

We examine the dynamical folding pathways of the C-terminal beta-hairpin of protein G-B1 in explicit solvent at room temperature by means of a transition-path sampling algorithm. In agreement with previous free-energy calculations, the resulting path ensembles reveal a folding mechanism in which the hydrophobic residues collapse first followed by backbone hydrogen-bond formation, starting with the hydrogen bonds inside the hydrophobic core. In addition, the path ensembles contain information on ...[more]

PMID: 14523242

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