Effective Charges for Macromolecules in Solvent

Abstract

In order to study protein−protein and protein−DNA association, the electrostatic forces and interaction free energies for two macromolecules at different mutual orientations and separations need to be evaluated. Realistic systems typically consist of thousands of atomic charges in an environment with a nonuniform dielectric permittivity and a solvent of nonzero ionic strength. Consequently, accurate evaluations of electrostatic forces and energies for such systems are only computationally feasible for a limited number of macromolecule positions. Here, we show that, by representing each molecule by a small number of effective charges in a uniform dielectric, intermolecular electrostatic interactions can be calculated simply and with high accuracy. The effective charges are derived by fitting them to reproduce the molecular electrostatic potential calculated by numerical solution of the finite-difference linearized Poisson−Boltzmann equation. The derived charges are expected to be useful in applications such as the simulation of the diffusional encounter of proteins where they will provide improved accuracy over the commonly-used test charge approximation.