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 @entity74 ( @entity74 ) simulations of @entity1522 . Bonded potential functions were derived from 1  s @entity74 simulations of each of the 20 canonical @entity1522 , with @entity3793 modeled in both its protonated and neutral forms; nonbonded potential functions were derived from 1  s @entity74 simulations of every possible pairing of the @entity1522 (231 different systems). The angle and dihedral probability distributions and radial distribution functions sampled during @entity74 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" @entity74 distributions. In a first test of the force field, it was used to predict the clustering behavior of concentrated @entity3689 solutions; the predictions were directly compared with the results of corresponding all-atom explicit-solvent @entity74 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 @entity74 simulations by Petrov and Zagrovic (PLoS Comput. Biol. 2014, 5, e1003638). The anomalously strong intermolecular interactions seen in the @entity74 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 @entity3689 interactions might be of quite broad applicability, with COFFDROP likely to be especially useful for modeling unfolded or intrinsically disordered proteins.

COFFDROP: A Coarse-Grained Nonbonded Force Field for Proteins Derived from All-Atom Explicit-Solvent Molecular Dynamics Simulations of XXXX .

@entity3793 :: ('CHEBI:27570', 'Chemical') :: ['histidine'] @entity1522 :: ('CHEBI:33709', 'Chemical') :: ['amino acids'] @entity3689 :: ('D000596', 'Chemical') :: ['amino acid'] @entity74 :: ('MESH:D030342', 'Disease') :: ['molecular dynamics', 'MD']
@entity1522 :: (CHEBI:33709,Chemical) :: ['Amino Acids']
