DEPENDENCE OF THE SOLVATION FREE-ENERGIES ON ATOMIC CHARGE-DISTRIBUTION

The dependency of hydration free energies on the atomic charge distrib ution has been studied using the free energy perturbation method and m olecular dynamics simulations. Several hypothetical sets of atomic cha rges far methanal molecule have been constructed, yielding the same to tal molecular dipole moment of 2.14 D. Each of the sets has been pertu rbed into another one and the electrostatic contributions to the hydra tion free energy differences associated with such changes have been de termined. The magnitude of calculated electrostatic contribution to th e solvation free energies crucially depends an the position of the cen ter of charge and orientation of the total dipole moment within molecu lar van der Waals envelope. It depends less on higher molecular multip ole moments. The issue of convergence of the electrostatic contributio n to the free energies obtained from molecular dynamics simulations wi ll be also addressed.