Parametrization of Backbone Flexibility in a Coarse-Grained Force Field for Proteins (COFFDROP) Derived from All-Atom Explicit-Solvent Molecular Dynamics Simulations of All Possible Two-Residue Peptides

Tamara Frembgen-Kesner; Casey T Andrews; Shuxiang Li; Nguyet Anh Ngo; Scott A Shubert; Aakash Jain; Oluwatoni J Olayiwola; Mitch R Weishaar; Adrian H Elcock

doi:10.1021/acs.jctc.5b00038

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Parametrization of Backbone Flexibility in a Coarse-Grained Force Field for Proteins (COFFDROP) Derived from All-Atom Explicit-Solvent Molecular Dynamics Simulations of All Possible Two-Residue Peptides

Tamara Frembgen-Kesner, Casey T Andrews, Shuxiang Li, Nguyet Anh Ngo, Scott A Shubert, Aakash Jain, Oluwatoni J Olayiwola, Mitch R Weishaar and Adrian H Elcock

Journal of chemical theory and computation, Vol.11(5), pp.2341-2354

05/12/2015

DOI: 10.1021/acs.jctc.5b00038

PMCID: PMC4658516

PMID: 26574429

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Abstract

Recently, we reported the parametrization of a set of coarse-grained (CG) nonbonded potential functions, derived from all-atom explicit-solvent molecular dynamics (MD) simulations of amino acid pairs and designed for use in (implicit-solvent) Brownian dynamics (BD) simulations of proteins; this force field was named COFFDROP (COarse-grained Force Field for Dynamic Representations Of Proteins). Here, we describe the extension of COFFDROP to include bonded backbone terms derived from fitting to results of explicit-solvent MD simulations of all possible two-residue peptides containing the 20 standard amino acids, with histidine modeled in both its protonated and neutral forms. The iterative Boltzmann inversion (IBI) method was used to optimize new CG potential functions for backbone-related terms by attempting to reproduce angle, dihedral, and distance probability distributions generated by the MD simulations. In a simple test of the transferability of the extended force field, the angle, dihedral, and distance probability distributions obtained from BD simulations of 56 three-residue peptides were compared to results from corresponding explicit-solvent MD simulations. In a more challenging test of the COFFDROP force field, it was used to simulate eight intrinsically disordered proteins and was shown to quite accurately reproduce the experimental hydrodynamic radii (Rhydro), provided that the favorable nonbonded interactions of the force field were uniformly scaled downward in magnitude. Overall, the results indicate that the COFFDROP force field is likely to find use in modeling the conformational behavior of intrinsically disordered proteins and multidomain proteins connected by flexible linkers.

Thermodynamics

Peptides - metabolism

Proteins - metabolism

Peptides - chemistry

Solvents - chemistry

Proteins - chemistry

Molecular Dynamics Simulation

Details

Title: Subtitle: Parametrization of Backbone Flexibility in a Coarse-Grained Force Field for Proteins (COFFDROP) Derived from All-Atom Explicit-Solvent Molecular Dynamics Simulations of All Possible Two-Residue Peptides
Creators: Tamara Frembgen-Kesner - Department of Biochemistry, University of Iowa , Iowa City, Iowa 52242, United States
Casey T Andrews - Department of Biochemistry, University of Iowa , Iowa City, Iowa 52242, United States
Shuxiang Li - Department of Biochemistry, University of Iowa , Iowa City, Iowa 52242, United States
Nguyet Anh Ngo - Department of Biochemistry, University of Iowa , Iowa City, Iowa 52242, United States
Scott A Shubert - Department of Biochemistry, University of Iowa , Iowa City, Iowa 52242, United States
Aakash Jain - Department of Biochemistry, University of Iowa , Iowa City, Iowa 52242, United States
Oluwatoni J Olayiwola - Department of Biochemistry, University of Iowa , Iowa City, Iowa 52242, United States
Mitch R Weishaar - Department of Biochemistry, University of Iowa , Iowa City, Iowa 52242, United States
Adrian 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.11(5), pp.2341-2354
DOI: 10.1021/acs.jctc.5b00038
PMID: 26574429
PMCID: PMC4658516
NLM abbreviation: J Chem Theory Comput
ISSN: 1549-9618
eISSN: 1549-9626
Publisher: American Chemical Society (ACS); United States
Grant note: R01 GM087290 / NIGMS NIH HHS R01 GM099865 / NIGMS NIH HHS
Language: English
Date published: 05/12/2015
Academic Unit: Physics and Astronomy; Biochemistry and Molecular Biology
Record Identifier: 9984024516802771

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