Finite-size effect on the charging free energy of protein in explicit solvent.

Abstract

The finite-size effect in periodic system is examined for the charging free energy of protein in explicit solvent over a variety of charged states. The key to the finite-size correction is the self-energy, which is defined as the interaction energy of the solute with its own periodic images and the neutralizing background. By employing the thermodynamic-integration method with systematically varied sizes of the unit cell of molecular dynamics (MD) simulations, we show for ubiquitin that the self-energy corrects the finite-size effect on the charging free energy within 1 kcal/mol at total charges of -5e, -1e, neutral, and +1e and within 5 kcal/mol even for a highly charged state with +8e. We then sought the additional correction from the solvation effect using the numerical solution to the Poisson equation of the protein with implicit solvent. This correction reduces the cell-size dependence of the charging free energy at +8e to 3 kcal/mol and is well expressed as the self-energy divided by the dielectric constant of solvent water.