Physical Modeling of Aqueous Solvation

摘要

We consider the free energies of solvating molecules in water. Computational modeling usually involves either detailed explicit-solvent simulations, or faster computations, which are based on implicit continuum approximations or additivity assumptions. These simpler approaches often miss microscopic physical details and non-additivities present in experimental data. We review explicit-solvent modeling that identifies the physical bases for the errors in the simpler approaches. One problem is that water molecules that are shared between two substituent groups often behave differently than waters around each substituent individually. One manifestation of non-additivities is that solvation free energies in water can depend not only on surface area or volume, but on other properties, such as the surface curvature. We also describe a new computational approach, called Semi-Explicit Assembly, that aims to repair these flaws and capture more of the physics of explicit water models, but with computational efficiencies approaching those of implicit-solvent models.