EFFECTIVE CHARGES FOR MACROMOLECULES IN SOLVENT

In order to study protein-protein and protein-DNA association, the ele ctrostatic 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 i n an environment with a nonuniform dielectric permittivity and a solve nt of nonzero ionic strength. Consequently, accurate evaluations of el ectrostatic forces and energies for such systems are only computationa lly feasible for a limited number of macromolecule positions. Here, we show that, by representing each molecule by a small number of effecti ve charges in a uniform dielectric, intermolecular electrostatic inter actions can be calculated simply and with high accuracy, The effective charges are derived by fitting them to reproduce the molecular electr ostatic potential calculated by numerical solution of the finite-diffe rence linearized Poisson-Boltzmann equation. The derived charges are e xpected to be useful in applications such as the simulation of the dif fusional encounter of proteins where they will provide improved accura cy over the commonly-used test charge approximation.