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Multiscale enhanced sampling of intrinsically disordered protein conformations
Author(s) -
Lee Kuo Hao,
Chen Jianhan
Publication year - 2016
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/jcc.23957
Subject(s) - intrinsically disordered proteins , replica , molecular dynamics , conformational ensembles , statistical physics , sampling (signal processing) , force field (fiction) , computer science , biological system , hamiltonian (control theory) , chemical physics , chemistry , physics , computational chemistry , mathematics , artificial intelligence , mathematical optimization , nuclear magnetic resonance , biology , art , filter (signal processing) , visual arts , computer vision
In a recently developed multiscale enhanced sampling (MSES) technique, topology‐based coarse‐grained (CG) models are coupled to atomistic force fields to enhance the sampling of atomistic protein conformations. Here, the MSES protocol is refined by designing more sophisticated Hamiltonian/temperature replica exchange schemes that involve additional parameters in the MSES coupling restraint potential, to more carefully control how conformations are coupled between the atomistic and CG models. A specific focus is to derive an optimal MSES protocol for simulating conformational ensembles of intrinsically disordered proteins (IDPs). The efficacy of the refined protocols, referred to as MSES‐soft asymptote (SA), was evaluated using two model peptides with various levels of residual helicities. The results show that MSES‐SA generates more reversible helix‐coil transitions and leads to improved convergence on various ensemble conformational properties. This study further suggests that more detailed CG models are likely necessary for more effective sampling of local conformational transition of IDPs. © 2015 Wiley Periodicals, Inc.