In search of an active alcohol dehydrogenase inhibitor, the structure of which may serve as the basis for a potential drug design, the active site of alcohol dehydrogenase containing NAD and Zn z+ ions was mapped using the method of molecular mechanics. Molecular docking was performed using a number of ligands containing characteristic functional groups: formate ion, ammonia, ammonium ion, methanol, and methylamine. Sites of preferable binding were revealed for each ligand and arranged in order of decreasing energy of binding to the enzyme. A comparison of the predicted ligand-binding sites and the experimental data on the location of water and inhibitor binding sites in the known structures of corresponding alcohol dehydrogenase complexes indicated a coincidence of the complex formation sites, which confirms the validity of the method and provides the requirements for a highly effective inhibitor (the pharmacophore model).
Биоорганическая химия, 2000, 26 (3), 179-186.