ATOMIC RADII FOR CONTINUUM ELECTROSTATICS CALCULATIONS BASED ON MOLECULAR-DYNAMICS FREE-ENERGY SIMULATIONS

The electrostatic contribution to the solvation free energy of the 20 naturally occurring amino acids is examined using atomic models. The a mino acids are modeled by N-acetyl-X-N'-methylamide. Free energy pertu rbation techniques with explicit water molecules are used to evaluate the contribution of solute-solvent electrostatic interactions to the s olvation flee energies. An analysis based on the radial solvent charge distribution yields a basic rule to determine a set of atomic Born ra dii defining the dielectric boundary between the solute and the solven t in continuum electrostatic models. Minor adjustments are made to ref ine the atomic Born radii in order to reproduce quantitatively the ele ctrostatic contribution to the solvation free energy calculated by fre e energy perturbation techniques. The good agreement of continuum elec trostatic and molecular dynamics free energy perturbations suggests th at the new set of atomic Born radii may be used as a computationally i nexpensive alternative to the microscopic treatment of solvent with ex plicit water molecules.