FREE-ENERGIES OF HYDRATION FOR ORGANIC-MOLECULES FROM MONTE-CARLO SIMULATIONS

Methods for the computation of free energies of solvation are reviewed , with emphasis on aqueous systems and discrete representation of the solvent molecules in Monte Carlo (MC) or molecular dynamics simulation s. Precise results for small organic solutes can now be obtained routi nely by MC/free energy perturbation calculations. The average error fo r computed free energies of hydration is 1.0 kcal/mol with the use of partial charges for the solutes from either OPLS united-atom potential functions or from fitting to the electrostatic potential surface from 6-31G ab initio calculations. A less rigorous, computationally more rapid method based on linear response theory is also found to be valua ble and reduces the average error for the test set of 16 solutes to 0. 6 kcal/mol.