where E MM is the molecular mechanical energy in the gasphase consisting of contributions for electrostatic, van der Waals and internal energies, E GB is the polar solvation free energy based on the Generalized-Born implicit solvent model, E SASA is the non-polar solvation term calculated using the solvent accessible surface area (SASA) and T S solute is the product of the absolute temperature T and the solute entropy S solute . The solute entropy term can either be ignored (often done for congeneric series) or approximated. The quasiharmonic approximation and normal mode analysis of the vibration frequencies are most commonly used for estimating the solute entropy term.