Prediction of Ligand Binding Affinity to Target Proteins by Molecular Mechanics Theoretical Calculation

Accurate estimation of ligand-receptor binding affinity is indispensable for computer-assisted drug discovery and structure-based drug design. Many computational scoring functions for estimating binding affinity have been proposed. Every scoring function reported so far, however, has strengths and weaknesses depending on the chemical properties of ligands and the feature of the binding site of the receptor. Hence, potential functions that can be used for many kinds of target proteins are required. In this work, we developed a software program based on Morse-type potential functions that enables evaluation of binding affinity and geometry optimization. Eight different kinds of proteins were used as test data, and ligand chemicals for which the binding pose to the protein and inhibitory constant are known were selected for evaluation. The calculated binding score and the experimentally measured inhibitory constant showed good compatibilities for six target proteins but poor correlation for one target. These compatibilities were compared with the results obtained by using two other software programs. The comparison suggested that the performance of the software developed in this work is good. Since the software can be handled in a computer facility with a many-core system, the software will be effective for search for an active compound from a chemical database and for assistance in chemical modification of the active compound in the pharmaceutical research field.