Extending the MST Model to Large Biomolecular Systems: Parametrization of the ddCOSMO-MST Continuum Solvation Model

Abstract

Continuum solvation models such as the polarizable continuum model and the conductor-like screening model are widely used in quantum chemistry, but their application to large biosystems is hampered by their computational cost. Here, we report the parametrization of the Miertus–Scrocco–Tomasi (MST) model for the prediction of hydration free energies of neutral and ionic molecules based on the domain decomposition formulation of COSMO (ddCOSMO), which allows a drastic reduction of the computational cost by several orders of magnitude. We also introduce several novelties in MST, like a new definition of atom types based on hybridization and an automatic setup of the cavity for charged regions. The model is parametrized at the B3LYP/6-31+G(d) and PM6 levels of theory and compared to the performance of IEFPCM/MST. Then, we demonstrate the robustness of the parametrization on the SAMPL2, SAMPL4, and C10 datasets. The ddCOSMO/MST models provide errors of ~0.8 and ~3.2 kcal/mol for neutrals and ions, respectively, showing a remarkable balanced and accurate description of cations and anions.