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

Authors

Tomohiko Hayashi, Shunsuke Miyamoto, Masato Kawamura, Kouki Hattori, Satoshi Yasuda, Takeshi Murata, Masahiro Kinoshita

Published in

The journal of physical chemistry. B. Jul 13, 2026. Epub Jul 13, 2026.

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.

PMID:
42439072
Bibliographic data and abstract were imported from PubMed on 13 Jul 2026.

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