Journal article
COFFDROP: A Coarse-Grained Nonbonded Force Field for Proteins Derived from All-Atom Explicit-Solvent Molecular Dynamics Simulations of Amino Acids
Journal of chemical theory and computation, Vol.10(11), pp.5178-5194
11/11/2014
DOI: 10.1021/ct5006328
PMCID: PMC4230375
PMID: 25400526
Abstract
We describe the derivation of a set of bonded and nonbonded coarse-grained (CG) potential functions for use in implicit-solvent Brownian dynamics (BD) simulations of proteins derived from all-atom explicit-solvent molecular dynamics (MD) simulations of amino acids. Bonded potential functions were derived from 1 μs MD simulations of each of the 20 canonical amino acids, with histidine modeled in both its protonated and neutral forms; nonbonded potential functions were derived from 1 μs MD simulations of every possible pairing of the amino acids (231 different systems). The angle and dihedral probability distributions and radial distribution functions sampled during MD were used to optimize a set of CG potential functions through use of the iterative Boltzmann inversion (IBI) method. The optimized set of potential functions-which we term COFFDROP (COarse-grained Force Field for Dynamic Representation Of Proteins)-quantitatively reproduced all of the "target" MD distributions. In a first test of the force field, it was used to predict the clustering behavior of concentrated amino acid solutions; the predictions were directly compared with the results of corresponding all-atom explicit-solvent MD simulations and found to be in excellent agreement. In a second test, BD simulations of the small protein villin headpiece were carried out at concentrations that have recently been studied in all-atom explicit-solvent MD simulations by Petrov and Zagrovic (
,
, e1003638). The anomalously strong intermolecular interactions seen in the MD study were reproduced in the COFFDROP simulations; a simple scaling of COFFDROP's nonbonded parameters, however, produced results in better accordance with experiment. Overall, our results suggest that potential functions derived from simulations of pairwise amino acid interactions might be of quite broad applicability, with COFFDROP likely to be especially useful for modeling unfolded or intrinsically disordered proteins.
Details
- Title: Subtitle
- COFFDROP: A Coarse-Grained Nonbonded Force Field for Proteins Derived from All-Atom Explicit-Solvent Molecular Dynamics Simulations of Amino Acids
- Creators
- Casey T Andrews - 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.10(11), pp.5178-5194
- Publisher
- United States
- DOI
- 10.1021/ct5006328
- PMID
- 25400526
- PMCID
- PMC4230375
- ISSN
- 1549-9618
- eISSN
- 1549-9626
- Grant note
- R01 GM087290 / NIGMS NIH HHS R01 GM099865 / NIGMS NIH HHS
- Language
- English
- Date published
- 11/11/2014
- Academic Unit
- Physics and Astronomy; Biochemistry and Molecular Biology
- Record Identifier
- 9984024543902771
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