Computational method for relative binding energies of enzyme‐substrate complexes

Abstract
A computational method for estimating the relative binding free energies of enzyme‐substrate complexes is described that combines electrostatic and solvation models and X‐ray crystallographic data. The polar contribution is evaluated by the Poisson‐Boltzman equation. The nonpolar contribution is evaluated by solvent transfer data and surface area calculations. This algorithm was used to calculate the relative binding energies of 63 pairs of nine different mutant proteins with seven different substituted R‐malate substrates of Escherichia coli isocitrate dehydrogenase. Comparison of calculated values with the experimentally observed values shows a high degree of correlation.