Hydration in Discrete Water. A Mean Field, Cellular Automata Based Approach to Calculating Hydration Free Energies

A simple, semiheuristic solvation model based on a discrete, BCC grid of solvent cells has been presented. The model utilizes a mean field approach for the calculation of solute-solvent and solvent-solvent interaction energies and a cellular automata based algorithm for the prediction of solvent distribution in the presence of solute. The construction of the effective Hamiltonian for a solvent cell provides an explicit coupling between orientation-dependent water-solute electrostatic interactions and water-water hydrogen bonding. The water-solute dispersion interaction is also explicitly taken into account. The model does not depend on any arbitrary definition of the solute-solvent interface nor does it use a microscopic surface tension for the calculation of nonpolar contributions to the hydration free energies. It is demonstrated that the model provides satisfactory predictions of hydration free energies for drug-like molecules and is able to reproduce the distribution of buried water molecules within protein structures. The model is computationally efficient and is applicable to arbitrary molecules described by atomistic force field.