The surface constraint all atom model provides size independent results in calculations of hydration free energies

Abstract

Consistent approaches for calculations of solvation free energies should provide results which are independent of the size of the simulation region. Simulations that use periodic boundary conditions and a standard Ewald treatment yield size dependent results. Corrections that can overcome this problem have been formulated, but have not yet been fully validated for solutes with general charge distributions. Furthermore, Ewald treatments of proteins may involve size dependent problems whose nature has not been explored by systematic studies. Here we demonstrate that our surface constraint all-atom solvent (SCAAS) model with its spherical boundary conditions (that include special polarization constraints) provides proper size independent results. It is also pointed out that this approach lends itself to an effective treatment of long-range interactions and offers a useful way of obtaining size independent free energies in studies of electrostatic effects in proteins.