Predicting hydration free energies of polychlorinated aromatic compounds from the SAMPL-3 data set with FiSH and LIE models

Abstract

Next-generation solvation models are devised to mimic the accuracy and generality of explicit solvation models at the speed of current popular implicit solvation models. One such method is the first-shell of hydration (FiSH) continuum model that was trained on hydration energetics from LIE calculations and molecular dynamics simulations in explicit solvent. Here we tested prospectively the FiSH model on the SAMPL-3 hydration data set that zooms in the effect of chlorination on solvation. We compare these FiSH predictions with those from retrospective LIE calculations. We find that neither FiSH nor LIE can reproduce well the absolute values and the trend of hydration free energies in the biphenyl and dioxin aromatic chlorination series. Some of the hypotheses behind this performance are discussed and tested. The LIE explicit-solvent model shows some improvement relative to the FiSH continuum model, and we correct a systematic deviation in the continuum van der Waals term of FiSH associated with aromatic Cl atom type.