Modeling Water, the Hydrophobic Effect, and Ion Solvation

Abstract

▪ Abstract  Water plays a central role in the structures and properties of biomolecules—proteins, nucleic acids, and membranes—and in their interactions with ligands and drugs. Over the past half century, our understanding of water has been advanced significantly owing to theoretical and computational modeling. However, like the blind men and the elephant, different models describe different aspects of water's behavior. The trend in water modeling has been toward finer-scale properties and increasing structural detail, at increasing computational expense. Recently, our labs and others have moved in the opposite direction, toward simpler physical models, focusing on more global properties—water's thermodynamics, phase diagram, and solvation properties, for example—and toward less computational expense. Simplified models can guide a better understanding of water in ways that complement what we learn from more complex models. One ultimate goal is more tractable models for computer simulations of biomolecules. This review gives a perspective from simple models on how the physical properties of water—as a pure liquid and as a solvent—derive from the geometric and hydrogen bonding properties of water.