title: Evaluation of Hydration Free Energy by Level-Set Variational Implicit-Solvent Model with Coulomb-Field Approximation.
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 isR2= 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 isR2= 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.
authors.affiliation: Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, California 92121, United States.
authors.forename: Zuojun
authors.initials: Z
authors.lastname: Guo
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.forename: Joachim
authors.initials: J
authors.lastname: Dzubiella
authors.forename: Li-Tien
authors.initials: LT
authors.lastname: Cheng
authors.forename: J Andrew
authors.initials: JA
authors.lastname: McCammon
authors.forename: Jianwei
authors.initials: J
authors.lastname: Che