A Simple Methodology for Remarkably Fast and Accurate Computation of the Hydration Free Energy, Entropy, and Energy for Multiple Types of Solutes Including Proteins.

Abstract

The hydration free energy (HFE) of a solute in a prescribed structure is the pivotal quantity for elucidating self-assembly processes in aqueous environments. However, the accuracy/speed trade-off in its computation poses a major problem especially when the solute is quite large. To solve this problem, we develop a methodology named ufHybrid wherein several different methods are judiciously combined by utilizing only the merits of each method. Even for a protein, the HFE can be computed in only a few seconds on a workstation, and it is as accurate as the HFE obtained by an efficient version of all-atom molecular dynamics simulation with explicit water. ufHybrid gives not only the HFE but also its energetic and entropic components which are physically insightful. A solute with nonzero total charge can readily be handled. Once the three-dimensional structure of the solute and the force parameters are given, all one has to do is to compute the excluded volume, water-accessible surface area, integrated mean and Gaussian curvatures of the accessible surface, and generalized Born energy. ufHybrid is suited to, for example, studies on protein folding and protein-ligand binding where the HFEs of a protein, ligand, and protein-ligand complex play essential roles.