A Hybrid Monte Carlo Scheme for Multibackbone Protein Design

Abstract : Multistate protein design explores side chain mutations, with the backbone allowed to sample a small, predetermined library of conformations. To achieve Boltzmann sampling of sequences and conformations, we use a hybrid Monte Carlo (MC) scheme: a trial hop between backbone models is followed by a short MC segment where side chain rotamers adjust to the new backbone, before applying a Metropolis-like acceptance test. The theoretical form and a practical approximation for the acceptance test are derived. We then compute backbone conformational free energies for two SH2 and SH3 proteins using different routes and protocols, and verify that for simple test problems, the free energy behaves like a state function, a hallmark of Boltzmann sampling.
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Article dans une revue
Journal of Chemical Theory and Computation, American Chemical Society, 2016, 〈10.1021/acs.jctc.6b00421〉
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https://hal-cea.archives-ouvertes.fr/cea-01412185
Contributeur : Julien Bigot <>
Soumis le : jeudi 8 décembre 2016 - 10:09:19
Dernière modification le : jeudi 11 janvier 2018 - 06:25:26

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Julien Bigot, Karen Druart, Edouard Audit, Thomas Simonson. A Hybrid Monte Carlo Scheme for Multibackbone Protein Design. Journal of Chemical Theory and Computation, American Chemical Society, 2016, 〈10.1021/acs.jctc.6b00421〉. 〈cea-01412185〉

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