Absolute Solvation Free Energies from Quasi-Chemical Theory

Quasi-chemical theory, as introduced by Lawrence Pratt and colleagues, provides an exact separation of the excess chemical potential into local, chemical interactions and long-ranged packing and dispersion and/or electrostatic contributions due to the solution environment. The local contribution can be obtained from ab-initio, quantum mechanical calculations or estimated from classical dynamics simulations. The packing contribution is the excess chemical potential of a hard-core solute and can be estimated from simulations of pure water using a 2-moment Gaussian “information theory” model. A general method is presented for obtaining upper and lower bounds for the long-ranged contribution in this formalism. This separation is applied to estimate the solvation free energies of several small molecule solutes. The advantages and limitations of the method are discussed.