CALCULATION OF BINDING-ENERGY DIFFERENCES FOR RECEPTOR-LIGAND SYSTEMS USING THE POISSON-BOLTZMANN METHOD

An approach using the finite difference solution of the Poisson-Boltzmann equation to estimate binding free energy changes for two receptor-ligand systems, arabinose binding protein and sulfate binding protein, is presented. The eight calculated binding free energy changes agree with experiment, showing a correlation coefficient of 0.92 and energy deviations of 1 kcal/mol or less. More importantly, the decomposition of solvation and assembly energies in this approach provides an understanding of binding mechanisms and therefore could suggest directions to alter binding affinities. The method is demonstrated to be useful in analyzing experimental binding structures and predicting binding effects of mutants or modified ligands for macromolecular systems, in which the electrostatic forces dominate the overall interaction and the structural perturbations upon modifications are small. (C) 1995 by John Wiley and Sons, Inc.