Improving Implicit Solvent Models with Differential Geometry

Abstract

Implicit solvent models are popular for their high computational efficiency and simplicity over explicit solvent models. Hence, there has been significant interest in testing and improving these models for their ability to accurately compute the thermodynamic properties of a wide range of chemicals and macromolecules. One such model is a differential geometry-based solvation model where a generalized geometric flow (GF) equation and a generalized Poisson-Boltzmann (PB) equation are self-consistently solved to compute a smooth dielectric profile, and the polar and non-polar solvation free energies. The GF equation contains the polar energetic terms defined by the PB equation, and non-polar energetic terms describing the pressure-volume work to create a cavity in the solvent, energy to create a solute-solvent interface, and solute-solvent attractive dispersion interactions. The solution to the GF equation is a characteristic function that describes a smooth solute-solvent boundary. This function defines the smooth dielectric profile used in the PB equation to compute the electrostatic potential. Therefore, the main parameters of the model are the solute/solvent dielectric, solvent pressure, surface tension, solvent density, and molecular force-field parameters. As for other solvation models, these parameters have to be determined by experimental conditions or optimized against experimental solvation energy data before the model can be applied for new molecules. However, it is not clearly understood how different choices of the model parameters are coupled with force field choice to affect the computed results. In this work, we have performed a parametric study on the GF-based solvation model to investigate how changes in the pressure, surface tension and use of different force fields affect the optimal solutions to the solvation free energies of small organic molecules. Results of this model will be presented for a set of 17 small organic molecules using three different force fields.