THE SURFACE CONSTRAINT ALL ATOM MODEL PROVIDES SIZE INDEPENDENT RESULTS IN CALCULATIONS OF HYDRATION FREE-ENERGIES

Consistent approaches for calculations of solvation free energies shou ld provide results which are independent of the size of the simulation region. Simulations that use periodic boundary conditions and a stand ard Ewald treatment yield size dependent results. Corrections that can overcome this problem have been formulated, but have not yet been ful ly validated for solutes with general charge distributions. Furthermor e, Ewald treatments of proteins may involve size dependent problems wh ose nature has not been explored by systematic studies. Here we demons trate that our surface constraint all-atom solvent (SCAAS) model with its spherical boundary conditions (that include special polarization c onstraints) provides proper size independent results. It is also point ed out that this approach lends itself to an effective treatment of lo ng-range interactions and offers a useful way of obtaining size indepe ndent free energies in studies of electrostatic effects in proteins. ( C) 1998 American Institute of Physics. [S0021-9606(98)51842-9]