Automatic parametrization of non-polar implicit solvent models for the blind prediction of solvation free energies

In this work, a systematic protocol is proposed to automatically parametrize the non-polar part of implicit solvent models with polar and non-polar components. The proposed protocol utilizes either the classical Poisson model or the Kohn-Sham density functional theory based polarizable Poisson model for modeling polar solvation free energies. Four sets of radius parameters are combined with four sets of charge force fields to arrive at a total of 16 different parametrizations for the polar component. For the non-polar component, either the standard model of surface area, molecular volume, and van der Waals interactions or a model with atomic surface areas and molecular volume is employed. To automatically parametrize a non-polar model, we develop scoring and ranking algorithms to classify solute molecules. The their non-polar parametrization is obtained based on the assumption that similar molecules have similar parametrizations. A large database with 668 experimental data is collected and employed to validate the proposed protocol. The lowest leave-one-out root mean square (RMS) error for the database is 1.33 kcal/mol. Additionally, five subsets of the database, i.e., SAMPL0-SAMPL4, are employed to further demonstrate that the proposed protocol. The optimal RMS errors are 0.93, 2.82, 1.90, 0.78, and 1.03 kcal/mol, respectively, for SAMPL0, SAMPL1, SAMPL2, SAMPL3, and SAMPL4 test sets. The corresponding RMS errors for the polarizable Poisson model with the Amber Bondi radii are 0.93, 2.89, 1.90, 1.16, and 1.07 kcal/mol, respectively.