Coupled semiempirical quantum mechanics and molecular mechanics (QM/MM) calculations on the aqueous solvation free energies of ionized molecules

The aqueous solvation free energies of ionized molecules were computed usin g a coupled quantum mechanical and molecular mechanical (QM/MM) model based on the AM1, MNDO, and PM3 semiempirical molecular orbital methods for the solute molecule and the TIP3P molecular mechanics model for Liquid water. T he present work is an extension of our model for neutral solutes where we a ssumed that the total free energy is the sum of components derived from the electrostatic/polarization terms in the Hamiltonian plus an empirical "non polar" term. The electrostatic/polarization contributions to the solvation free energies were computed using molecular dynamics (MD) simulation and th ermodynamic integration techniques, while the nonpolar contributions were t aken from the literature. The contribution to the electrostatic/polarizatio n component of the free energy due to nonbonded interactions outside the cu toff radii used in the MD simulations was approximated by a Born solvation term. The experimental free energies were reproduced satisfactorily using v ariational parameters from the vdW terms as in the original model, in addit ion to a parameter from the one-electron integral terms. The new one-electr on parameter was required to account for the shortrange effects of overlapp ing atomic charge densities. The radial distribution functions obtained fro m the MD simulations showed the expected H-bonded structures between the io nized solute molecule and solvent molecules. We also obtained satisfactory results by neglecting both the empirical nonpolar term and the electronic p olarization of the solute, i.e., by implementing a nonpolarization model. ( C) 1999 John Wiley & Sons, inc.