PNNL

Abstract

Implicit solvent models are popular for their high computational efficiency and simplicity over explicit solvent models, and are therefore, extensively used for computing solvation properties of molecules. The accuracy of implicit solvent models depends on the geometric description of the solute-solvent interface and the solvent dielectric profile that is defined near the surface of the solute molecule. Typically, it is assumed that the dielectric profile is spatially homogeneous in the bulk solvent medium and varies sharply across the solute-solvent interface. However, the specific form of this profile is often described by ad hoc geometric models rather than physical solute-solvent interactions. Hence, it is of significant interest to improve the accuracy of these implicit solvent models by more realistically defining the solute-solvent boundary within a continuum setting. Recently, a differential geometry-based geometric flow solvation model was developed, in which the polar and nonpolar free energies are coupled through a characteristic function that describes a smooth dielectric interface profile across the solvent–solute boundary in a thermodynamically self-consistent fashion. The main parameters of the model are the solute/solvent dielectric constants, solvent pressure on the solute, microscopic surface tension, solvent density, and molecular force-field parameters. This model, however, has not been systematically parameterized and tested for its predictive power, thus limiting the use of this model. In this work, we investigate how changes in the pressure, surface tension, and choice of different force-field charge and radii parameters (namely, AM1-BCCv1/ZAP-9, AM1-BCCv1/Bondi, and OPLS-AA) affect the prediction accuracy for hydration free energies of 17 small organic molecules based on the geometric flow solvation model. The results of our study provide useful insights on the parameterization of this new implicit solvation model for improving the accuracy and predictive power of the model.