Che, Jianwei, Guo, Zuojun, Li, Bo, Cheng, Li-Tien, Dzubiella, Joachim and McCammon, J. Andrew (2013) Evaluation of Hydration Free Energy by the Level-Set Variational Implicit-Solvent Model with the Coulomb-Field Approximation. Journal of chemical theory and computation. ISSN 1549-9618

Abstract

In this article, we systematically apply a novel implicit solvent model, the variational implicit-solvent model (VISM) together with the Coulomb-Field Approximation (CFA), to calculate the hydration free energy of a large set of small organic molecules. Because these molecules have been studied in detail by molecular dynamics simulations
and other implicit-solvent models, they provide a good benchmark for evaluating the performance of VISM-CFA. With all-atom Amber force field parameters, VISM-CFA is able to reproduce well not only the experimental and MD simulated total hydration free energy but also the polar and nonpolar contributions individually. The correlation between VISM-CFA and experiments is R2 = 0.763 for the total hydration free energy, with a root-mean-square deviation (RMSD) of 1.83 kcal/mol, and the correlation to results from TIP3P explicit water MD simulations is R2 = 0.839 with a RMSD = 1.36 kcal/mol. In addition, we demonstrate that VISM captures dewetting phenomena in the p53/MDM2 complex and hydrophobic characteristics in the system. This work demonstrates that the level-set VISM-CFA can be used to study the energetic behavior of
realistic molecular systems with complicated geometries in solvation, protein−ligand binding, protein−protein association, and protein folding processes.

Item Type:	Article
Date Deposited:	13 Oct 2015 13:13
Last Modified:	13 Oct 2015 13:13
URI:	https://oak.novartis.com/id/eprint/9248