Abstract
The effects of electronic polarization in biomolecular interactions will differ depending on the local dielectric constant of the environment, such as in solvent, DNA, proteins, and membranes. Here the performance of the AMOEBA polarizable force field is evaluated under nonaqueous conditions by calculating the solvation free energies of small molecules in four common organic solvents. Results are compared with experimental data and equivalent simulations performed with the GAFF pairwise‐additive force field. Although AMOEBA results give mean errors close to “chemical accuracy,” GAFF performs surprisingly well, with statistically significantly more accurate results than AMOEBA in some solvents. However, for both models, free energies calculated in chloroform show worst agreement to experiment and individual solutes are consistently poor performers, suggesting non‐potential‐specific errors also contribute to inaccuracy. Scope for the improvement of both potentials remains limited by the lack of high quality experimental data across multiple solvents, particularly those of high dielectric constant. © 2016 The Authors. Journal of Computational Chemistry Published by Wiley Periodicals, Inc.
Highlights
IntroductionMuch effort has been devoted to advancing computational techniques to predict free energies in biomolecular systems, ranging from more theoretically rigorous (e.g. alchemical free energy calculations) to less rigorous (e.g. continuum solvation, docking and scoring) methods.[1]
Much effort has been devoted to advancing computational techniques to predict free energies in biomolecular systems, ranging from more theoretically rigorous to less rigorous methods.[1]
To determine whether the explicit inclusion of polarization in a potential energy function is able to improve the accuracy of its free energy calculations over a much simpler and cheaper energy function, here we evaluate the performance of the AMOEBA model
Summary
Much effort has been devoted to advancing computational techniques to predict free energies in biomolecular systems, ranging from more theoretically rigorous (e.g. alchemical free energy calculations) to less rigorous (e.g. continuum solvation, docking and scoring) methods.[1]. Within the range of fixed-point-charge, pairwise additive MM force fields available for molecular simulation,[8,10,11,12,13,14,15,16,17] a number of philosophies exist for the derivation of atomic partial charges and calculation of electrostatic interactions. These models often take account of polarization implicitly in the derivation of charges, and are mainly parameterized to recreate interactions in the aqueous phase. The ability of the AMOEBA force field to capture these effects may be expected to result in parameters with greater transferability than standard fixed-point-charge models, and thereby give accurate predictions of interaction energetics across a variety of systems
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