Hydration in discrete water (II): from neutral to charged solutes.

Abstract

In our previous work, we introduced a solvation model based on discrete solvent representation and demonstrated its ability to estimate hydration free energies for neutral solutes. Here, we present modifications extending the applicability of the model to charged solutes. They include improvements in the representation of the first hydration shell and systematic treatment of long-range interactions. While sharing computational efficiency of implicit solvent models, our approach avoids some of their important limitations, both in the context of electrostatic and nonpolar hydration effects: it naturally captures hydration asymmetry of opposite charges, it relies on solute description by standard all atom force fields instead of utilizing specialized sets of atomic parameters, it predicts solvent distribution in space without the need to geometrically define solvent accessible surface. By combining discrete solvent representation in vicinity of a solute with continuum description of long-range interactions, the model addresses two distinct aspects of biomolecular hydration: complex, short-range effects arising due to molecular nature of aqueous solvent, and bulk contributions. We demonstrate that the model provides good agreement with experimental results for an extensive set of roughly 700 diverse compounds, including neutral and charged solutes with hydration free energies ranging from +3.4 to -536 kcal/mol.