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Localization of Millisecond Dynamics: Dihedral Entropy from Accelerated MD.

ABSTRACT: Here, we demonstrate a method to capture local dynamics on a time scale 3 orders of magnitude beyond state-of-the-art simulation approaches. We apply accelerated molecular dynamics simulations for conformational sampling and extract reweighted backbone dihedral distributions. Local dynamics are characterized by torsional probabilities, resulting in residue-wise dihedral entropies. Our approach is successfully validated for three different protein systems of increasing size: alanine dipeptide, bovine pancreatic trypsin inhibitor (BPTI), and the major birch pollen allergen Bet v 1a. We demonstrate excellent agreement of flexibility profiles with both large-scale computer simulations and NMR experiments. Thus, our method provides efficient access to local protein dynamics on extended time scales of high biological relevance.

SUBMITTER: Kamenik AS

PROVIDER: S-EPMC4980685 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Localization of Millisecond Dynamics: Dihedral Entropy from Accelerated MD.

Kamenik Anna S AS Kahler Ursula U Fuchs Julian E JE Liedl Klaus R KR

Journal of chemical theory and computation 20160711 8

Here, we demonstrate a method to capture local dynamics on a time scale 3 orders of magnitude beyond state-of-the-art simulation approaches. We apply accelerated molecular dynamics simulations for conformational sampling and extract reweighted backbone dihedral distributions. Local dynamics are characterized by torsional probabilities, resulting in residue-wise dihedral entropies. Our approach is successfully validated for three different protein systems of increasing size: alanine dipeptide, bo ...[more]

PMID: 27322931

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