A Comparison of Perturbation Methods and Poisson-Boltzmann Electrostatics Calculations for Estimation of Relative Solvation Free Energies

We have utilized two different computational techniques, free energy perturbation and finite difference Poisson-Boltzmann calculations, to estimate relative free energies of hydration for a series of organophosphorus molecules. The two methods are shown to give comparable results for small molecules with the general structure CH 3 -PO 2 -X-CH 3 (where X=O, NH, or CH 2 ). For larger organophosphorus molecules, free energy perturbation techniques failed to give consistent results, but the Poisson-Boltzmann method gave results that agreed qualitatively with those obtained for the smaller molecules and with experimental measurements of hydration energies for similar compounds