Drug Discovery Screening by Combination of X-ray Crystal Structure Analysis and FMO Calculation

Quantum chemistry calculations are the best way to understand the specific interactions between drug targets and ligands in the process of drug discovery lead optimization, using the crystal structures of these complexes. The present ab initio FMO calculations elucidate the reason why a slight structural difference of VD3 derivatives could cause a large difference in their binding affinities, although it could not be understood by just looking at their complex structures. We are confident that the combination of X-ray analysis and FMO calculations is a powerful tool to understand why the biological activities of the ligands are drastically changed by the slight differences in the ligand structures. Based on the results of FMO calculations, we would like to use for the novel potent ligand which can bind specifically to the ligand binding domain of human vitamin D receptor and inhibit the pathogenesis of immune diseases.