Combining the polarizable Drude force field with a continuum electrostatic Poisson-Boltzmann implicit solvation model.

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TitleCombining the polarizable Drude force field with a continuum electrostatic Poisson-Boltzmann implicit solvation model.
Publication TypeJournal Article
Year of Publication2018
AuthorsAleksandrov, A, Lin, F-Y, Roux, B, Mackerell, AD
JournalJ Comput Chem
Date Published2018 May 08
ISSN1096-987X
Abstract

In this work, we have combined the polarizable force field based on the classical Drude oscillator with a continuum Poisson-Boltzmann/solvent-accessible surface area (PB/SASA) model. In practice, the positions of the Drude particles experiencing the solvent reaction field arising from the fixed charges and induced polarization of the solute must be optimized in a self-consistent manner. Here, we parameterized the model to reproduce experimental solvation free energies of a set of small molecules. The model reproduces well-experimental solvation free energies of 70 molecules, yielding a root mean square difference of 0.8 kcal/mol versus 2.5 kcal/mol for the CHARMM36 additive force field. The polarization work associated with the solute transfer from the gas-phase to the polar solvent, a term neglected in the framework of additive force fields, was found to make a large contribution to the total solvation free energy, comparable to the polar solute-solvent solvation contribution. The Drude PB/SASA also reproduces well the electronic polarization from the explicit solvent simulations of a small protein, BPTI. Model validation was based on comparisons with the experimental relative binding free energies of 371 single alanine mutations. With the Drude PB/SASA model the root mean square deviation between the predicted and experimental relative binding free energies is 3.35 kcal/mol, lower than 5.11 kcal/mol computed with the CHARMM36 additive force field. Overall, the results indicate that the main limitation of the Drude PB/SASA model is the inability of the SASA term to accurately capture non-polar solvation effects. © 2018 Wiley Periodicals, Inc.

DOI10.1002/jcc.25345
Alternate JournalJ Comput Chem
PubMed ID29737546
Grant ListR01 GM051501 / GM / NIGMS NIH HHS / United States
R01 GM070855 / GM / NIGMS NIH HHS / United States
R01 GM072558 / GM / NIGMS NIH HHS / United States