Evaluation of the performances of different atomic charge and nonelectrostatic models in the finite‐difference Poisson–Boltzmann approach

Abstract

AbstractIn this work, we investigate the effects of different atomic charge and nonelectrostatic models on the hydration energies of neutral molecules, using an implicit solvation model. The solvation free energy is divided into two main components, the first resulting from a self‐consistent reaction field treatment of the bulk electrostatics obtained by solving the Poisson equation in a finite‐difference (FD) approach where the solute charge density is approximated by atomic charges, the second corresponding to short‐range interactions between the solute and the solvent in the first solvation shell. Five different atomic charge models (Mulliken, Hirshfeld, Hirshfeld‐I, CM5 and its iterative version, CM5‐I) have been considered, both at the Hartree–Fock (HF) and B3LYP levels, with three different basis sets, alongside two nonelectrostatic models including the cavity, dispersion, and solvent structural effects (CDS) model. Averaging over the three considered basis sets, Hirshfeld charges combined to the CDS model led to the lowest mean unsigned error (MUE), with a value of 0.92 kcal/mol with respect to the experimental data. On the other hand, a MUE of 2.02 kcal/mol was obtained with CM5 charges combined to the CDS model, highlighting the low transferability of the original CDS parameters developed for the generalized Born electrostatics to a different electrostatics model. By scaling down the CM5 charges to better balance with the original CDS model, a MUE of 0.68 kcal/mol was however obtained, outlining the delicate balance existing between the electrostatic and nonelectrostatic contributions to the solvation free energy in implicit solvation models.