A computational scheme of pKa values based on the three-dimensional reference interaction site model self-consistent field theory coupled with the linear fitting correction scheme

Abstract

A scheme for quantitatively computing the acid dissociation constant, pK_a, of hydrated molecules is proposed. It is based on the three-dimensional reference interaction site model self-consistent field (3D-RISM-SCF) theory coupled with the linear fitting correction (LFC) scheme. In LFC/3D-RISM-SCF, pK_a values of target molecules are evaluated using the Gibbs energy difference between the protonated and unprotonated states calculated by 3D-RISM-SCF and the parameters fitted by the LFC scheme to the experimental values of training set systems. The pK_a values computed by LFC/3D-RISM-SCF show quantitative agreement with the experimental data.