Journal article
Reparametrization of Protein Force Field Nonbonded Interactions Guided by Osmotic Coefficient Measurements from Molecular Dynamics Simulations
Journal of chemical theory and computation, Vol.13(4), pp.1812-1826
04/11/2017
DOI: 10.1021/acs.jctc.6b01059
PMCID: PMC5543770
PMID: 28296391
Abstract
There is a small, but growing, body of literature describing the use of osmotic coefficient measurements to validate and reparametrize simulation force fields. Here we have investigated the ability of five very commonly used force field and water model combinations to reproduce the osmotic coefficients of seven neutral amino acids and five small molecules. The force fields tested include AMBER ff99SB-ILDN, CHARMM36, GROMOS54a7, and OPLS-AA, with the first of these tested in conjunction with the TIP3P and TIP4P-Ew water models. In general, for both the amino acids and the small molecules, the tested force fields produce computed osmotic coefficients that are lower than experiment; this is indicative of excessively favorable solute-solute interactions. The sole exception to this general trend is provided by GROMOS54a7 when applied to amino acids: in this case, the computed osmotic coefficients are consistently too high. Importantly, we show that all of the force fields tested can be made to accurately reproduce the experimental osmotic coefficients of the amino acids when minor modifications-some previously reported by others and some that are new to this study-are made to the van der Waals interactions of the charged terminal groups. Special care is required, however, when simulating Proline with a number of the force fields, and a hydroxyl-group specific modification is required in order to correct Serine and Threonine when simulated with AMBER ff99SB-ILDN. Interestingly, an alternative parametrization of the van der Waals interactions in the latter force field, proposed by the Nerenberg and Head-Gordon groups, is shown to immediately produce osmotic coefficients that are in excellent agreement with experiment. Overall, this study reinforces the idea that osmotic coefficient measurements can be used to identify general shortcomings in commonly used force fields' descriptions of solute-solute interactions and further demonstrates that modifications to van der Waals parameters provide a simple route to optimizing agreement with experiment.
Details
- Title: Subtitle
- Reparametrization of Protein Force Field Nonbonded Interactions Guided by Osmotic Coefficient Measurements from Molecular Dynamics Simulations
- Creators
- Mark S Miller - Department of Biochemistry, University of Iowa , Iowa City, Iowa 52242, United StatesWesley K Lay - Department of Biochemistry, University of Iowa , Iowa City, Iowa 52242, United StatesShuxiang Li - Department of Biochemistry, University of Iowa , Iowa City, Iowa 52242, United StatesWilliam C Hacker - Department of Biochemistry, University of Iowa , Iowa City, Iowa 52242, United StatesJiadi An - Department of Biochemistry, University of Iowa , Iowa City, Iowa 52242, United StatesJianlan Ren - Department of Biochemistry, University of Iowa , Iowa City, Iowa 52242, United StatesAdrian H Elcock - Department of Biochemistry, University of Iowa , Iowa City, Iowa 52242, United States
- Resource Type
- Journal article
- Publication Details
- Journal of chemical theory and computation, Vol.13(4), pp.1812-1826
- DOI
- 10.1021/acs.jctc.6b01059
- PMID
- 28296391
- PMCID
- PMC5543770
- NLM abbreviation
- J Chem Theory Comput
- ISSN
- 1549-9618
- eISSN
- 1549-9626
- Publisher
- United States
- Grant note
- U54 GM105816 / NIGMS NIH HHS R01 GM087290 / NIGMS NIH HHS R01 GM099865 / NIGMS NIH HHS
- Language
- English
- Date published
- 04/11/2017
- Academic Unit
- Physics and Astronomy; Biochemistry and Molecular Biology
- Record Identifier
- 9984025290202771
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