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Article

A Hybrid Hamiltonian for the Accelerated Sampling along Experimental Restraints

Institute of Biotechnology of the Czech Academy of Sciences, BIOCEV, Průmyslová 595, 252 50 Vestec, Prague West, Czech Republic
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Int. J. Mol. Sci. 2019, 20(2), 370; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20020370
Received: 17 December 2018 / Revised: 7 January 2019 / Accepted: 10 January 2019 / Published: 16 January 2019
(This article belongs to the Collection Protein Folding)
In this article, we present an enhanced sampling method based on a hybrid Hamiltonian which combines experimental distance restraints with a bias dependent from multiple path-dependent variables. This simulation method determines the bias-coordinates on the fly and does not require a priori knowledge about reaction coordinates. The hybrid Hamiltonian accelerates the sampling of proteins, and, combined with experimental distance information, the technique considers the restraints adaptively and in dependency of the system’s intrinsic dynamics. We validate the methodology on the dipole relaxation of two water models and the conformational landscape of dialanine. Using experimental NMR-restraint data, we explore the folding landscape of the TrpCage mini-protein and in a second example apply distance restraints from chemical crosslinking/mass spectrometry experiments for the sampling of the conformation space of the Killer Cell Lectin-like Receptor Subfamily B Member 1A (NKR-P1A). The new methodology has the potential to adaptively introduce experimental restraints without affecting the conformational space of the system along an ergodic trajectory. Since only a limited number of input- and no-order parameters are required for the setup of the simulation, the method is broadly applicable and has the potential to be combined with coarse-graining methods. View Full-Text
Keywords: enhanced molecular dynamics simulations; protein folding enhanced molecular dynamics simulations; protein folding
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MDPI and ACS Style

Peter, E.K.; Černý, J. A Hybrid Hamiltonian for the Accelerated Sampling along Experimental Restraints. Int. J. Mol. Sci. 2019, 20, 370. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20020370

AMA Style

Peter EK, Černý J. A Hybrid Hamiltonian for the Accelerated Sampling along Experimental Restraints. International Journal of Molecular Sciences. 2019; 20(2):370. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20020370

Chicago/Turabian Style

Peter, Emanuel K., and Jiří Černý. 2019. "A Hybrid Hamiltonian for the Accelerated Sampling along Experimental Restraints" International Journal of Molecular Sciences 20, no. 2: 370. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20020370

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