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Dominant folding pathways of a WW domain.

ABSTRACT: We investigate the folding mechanism of the WW domain Fip35 using a realistic atomistic force field by applying the Dominant Reaction Pathways approach. We find evidence for the existence of two folding pathways, which differ by the order of formation of the two hairpins. This result is consistent with the analysis of the experimental data on the folding kinetics of WW domains and with the results obtained from large-scale molecular dynamics simulations of this system. Free-energy calculations performed in two coarse-grained models support the robustness of our results and suggest that the qualitative structure of the dominant paths are mostly shaped by the native interactions. Computing a folding trajectory in atomistic detail only required about one hour on 48 Central Processing Units. The gain in computational efficiency opens the door to a systematic investigation of the folding pathways of a large number of globular proteins.

SUBMITTER: A Beccara S

PROVIDER: S-EPMC3289289 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

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Dominant folding pathways of a WW domain.

A Beccara Silvio S Škrbić Tatjana T Covino Roberto R Faccioli Pietro P

Proceedings of the National Academy of Sciences of the United States of America 20120126 7

We investigate the folding mechanism of the WW domain Fip35 using a realistic atomistic force field by applying the Dominant Reaction Pathways approach. We find evidence for the existence of two folding pathways, which differ by the order of formation of the two hairpins. This result is consistent with the analysis of the experimental data on the folding kinetics of WW domains and with the results obtained from large-scale molecular dynamics simulations of this system. Free-energy calculations p ...[more]

PMID: 22308345

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