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Three-body interactions improve the prediction of rate and mechanism in protein folding models.

ABSTRACT: Here we study the effects of many-body interactions on rate and mechanism in protein folding by using the results of molecular dynamics simulations on numerous coarse-grained Calpha-model single-domain proteins. After adding three-body interactions explicitly as a perturbation to a G?-like Hamiltonian with native pairwise interactions only, we have found (i) a significantly increased correlation with experimental phi values and folding rates, (ii) a stronger correlation of folding rate with contact order, matching the experimental range in rates when the fraction of three-body energy in the native state is approximately 20%, and (iii) a considerably larger amount of three-body energy present in chymotripsin inhibitor than in the other proteins studied.

SUBMITTER: Ejtehadi MR

PROVIDER: S-EPMC524050 | biostudies-literature | 2004 Oct

REPOSITORIES: biostudies-literature

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Three-body interactions improve the prediction of rate and mechanism in protein folding models.

Ejtehadi M R MR Avall S P SP Plotkin S S SS

Proceedings of the National Academy of Sciences of the United States of America 20041006 42

Here we study the effects of many-body interactions on rate and mechanism in protein folding by using the results of molecular dynamics simulations on numerous coarse-grained Calpha-model single-domain proteins. After adding three-body interactions explicitly as a perturbation to a Gō-like Hamiltonian with native pairwise interactions only, we have found (i) a significantly increased correlation with experimental phi values and folding rates, (ii) a stronger correlation of folding rate with cont ...[more]

PMID: 15469920

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