Effects of forcefield and sampling method in all-atom simulations of inherently disordered proteins: Application to conformational preferences of human amylin

Peng, E, Todorova, N and Yarovsky, I 2017, 'Effects of forcefield and sampling method in all-atom simulations of inherently disordered proteins: Application to conformational preferences of human amylin', PLoS ONE, vol. 12, no. 10, e0186219, pp. 1-15.


Document type: Journal Article
Collection: Journal Articles

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Title Effects of forcefield and sampling method in all-atom simulations of inherently disordered proteins: Application to conformational preferences of human amylin
Author(s) Peng, E
Todorova, N
Yarovsky, I
Year 2017
Journal name PLoS ONE
Volume number 12
Issue number 10
Article Number e0186219
Start page 1
End page 15
Total pages 15
Publisher Public Library of Science
Abstract Although several computational modelling studies have investigated the conformational behaviour of inherently disordered protein (IDP) amylin, discrepancies in identifying its preferred solution conformations still exist between various forcefields and sampling methods used. Human islet amyloid polypeptide has long been a subject of research, both experimentally and theoretically, as the aggregation of this protein is believed to be the lead cause of type-II diabetes. In this work, we present a systematic forcefield assessment using one of the most advanced non-biased sampling techniques, Replica Exchange with Solute Tempering (REST2), by comparing the secondary structure preferences of monomeric amylin in solution. This study also aims to determine the ability of common forcefields to sample a transition of the protein from a helical membrane bound conformation into the disordered solution state of amylin. Our results demonstrated that the CHARMM22* forcefield showed the best ability to sample multiple conformational states inherent for amylin. It is revealed that REST2 yielded results qualitatively consistent with experiments and in quantitative agreement with other sampling methods, however far more computationally efficiently and without any bias. Therefore, combining an unbiased sampling technique such as REST2 with a vigorous forcefield testing could be suggested as an important step in developing an efficient and robust strategy for simulating IDPs.
Subject Theory and Design of Materials
Theoretical and Computational Chemistry not elsewhere classified
Proteins and Peptides
DOI - identifier 10.1371/journal.pone.0186219
Copyright notice © 2017 Peng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
ISSN 1932-6203
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