Exploring the parameter space of the coarse-grained UNRES force field by random search: selecting a transferable medium-resolution force field.

Full Abstract

We explored the energy-parameter space of our coarse-grained UNRES force field for large-scale ab initio simulations of protein folding, to obtain good initial approximations for hierarchical optimization of the force field with new virtual-bond-angle bending and side-chain-rotamer potentials which we recently introduced to replace the statistical potentials. 100 sets of energy-term weights were generated randomly, and good sets were selected by carrying out replica-exchange molecular dynamics simulations of two peptides with a minimal alpha-helical and a minimal beta-hairpin fold, respectively: the tryptophan cage (PDB code: 1L2Y) and tryptophan zipper (PDB code: 1LE1). Eight sets of parameters produced native-like structures of these two peptides. These eight sets were tested on two larger proteins: the engrailed homeodomain (PDB code: 1ENH) and FBP WW domain (PDB code: 1E0L); two sets were found to produce native-like conformations of these proteins. These two sets were tested further on a larger set of nine proteins with alpha or alpha + beta structure and found to locate native-like structures of most of them. These results demonstrate that, in addition to finding reasonable initial starting points for optimization, an extensive search of parameter space is a powerful method to produce a transferable force field. Copyright 2009 Wiley Periodicals, Inc.

Author information

Author/s: He, Yi (Y); Xiao, Yi (Y); Liwo, Adam (A); Scheraga, Harold A (HA);

Affiliation: Biomolecular Physics and Modeling Group, School of Physics, Huazhong University of Science and Technology, Wuhan 430074, China.

Grants: GM-14312 (Agency:NIGMS NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.

Journal: Journal of computational chemistry (J Comput Chem), published in United States. (Language: eng)

Reference: 2009-Oct; vol 30 (issue 13) : pp 2127-35

Dates: Created 2009/08/03; Completed 2009/10/09; Revised 2009/10/13;

PMID: 19242966, status: MEDLINE (last retrieval date: 10/14/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

External Links for this article
(including full text providers, if available):

Click Electronic Full-text Provider Links to see options for finding the electronic full text links to this article. Note there may be a subscription or fee required for access to the full text. See our FAQ for information on finding FREE full text articles.

This article may also be located in paper journal collections available in many libraries. Use the Journal and Publication Information above to find the full article.