Homology modeling was used to build 3D models of the N-methyl-d-aspartate (NMDA) receptor glycine binding site on the basis of an X-ray structure of the water-soluble AMPA-sensitive receptor. The docking of agonists and antagonists to these models was used to reveal binding modes of ligands and to explain known structure−activity relationships. Two types of quantitative models, 3D-QSAR/CoMFA and a regression model based on docking energies, were built for antagonists (derivatives of 4-hydroxy-2-quinolone, quinoxaline-2,3-dione, and related compounds). The CoMFA steric and electrostatic maps were superimposed on the homology-based model, and a close correspondence was marked. The derived computational models have permitted the evaluation of the structural features crucial for high glycine binding site affinity and are important for the design of new ligands.
J. Med. Chem., 2003, 46 (9), pp 1609–1616 DOI: 10.1021/jm0210156

Рассмотрена общая методология молекулярного моделирования биологических рецепторов и их взаимодействия с лигандами. Обсуждены методики построения пространственных моделей белков, молекулярного докинга, оценки качества моделей, определения свободной энергии связывания белков с лигандами. Представлены методы молекулярного дизайна новых лекарственных препаратов, основанные на молекулярных моделях биологических мишеней: виртуальный скрининг и модели de novo. Приведены примеры перечисленных выше подходов для моделирования ряда фармакологически значимых рецепторов, анализа взаимодействий рецептор-лиганд и дизайна новых биологически активных органических соединений.
Успехи химии, 2009, Т. 78, № 6, C. 539-557

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.