Potential of mean force calculation of solute molecules in water by a modified solvent-accessible surface method

We propose an empirical method for evaluating the potential of mean force (pmf) of solute molecules in water by modifying the solvent-accessible surface (SAS) method described by Eisenberg et al. We re-evaluated the SAS energy for each united atom composing the solute. We took into account the energy required to generate a void between adjacent solute molecules and the Coulombic interactions between atom-centered point charges of solute molecules containing C, O, P, K⁺, Na⁺, and Cl^- atoms in water. The modified SAS method well reproduced the various pmfs given by MD calculations or the integral equation method. The large activation energy of K⁺-18-crown-6 complexation can be explained mostly by the void energy. The computational time required for the modified SAS method is approximately three to four orders of magnitude less than that by MD calculations.