Incorporating Nonlinear Solvent Response in Continuum Dielectric Models Using a Two-Sphere Description of the Born Radius

The charging free energy of a model diatomic molecule is studied with free energy simulations and continuum dielectric methods. A comparison of the two methods shows that continuum dielectric theory can successfully encapsulate the nonlinear solvent responses around the solute if the dielectric boundary is defined by 1 / 2 ( R atom, i + R g max, i ), where R atom, i is the atomic radius of solute atom i, and R g max, i is the first peak position of the solute atom−solvent atom radial number/charge density distribution function. Furthermore, continuum dielectric theory in conjunction with the two-sphere description of the dielectric boundary can reproduce simultaneously the electrostatic solvation free energies, as well as the solvent-induced electrostatic potentials and field components at the solute sites derived from simulations in the presence of explicit solvent.