D.S. Zolotykh, E.T. Oganesian, I.P. Kodonidi

Using quantum mechanic method AM1 (calculation of atomic charges in ligands) the study was carried out to detect complementarity centers in binding sites of GABAA-receptor for γ-amino butyric acid and benzodiazepines. We used molecular docking (full evaluation version of Molegro Virtual Docker) with accounting of ligands and receptor conformational flexibility. We established the correlation between known IC50 values and molecular descriptor, which characterizes ligand-GABAA-receptor interaction. The coefficient of correlation is 0.9572. During analysis of benzodiazepine binding site, we established the most informative and reliable binding energy with His 102. Several groups of variables were used: 1) atomic charges of benzodiazepine fragment - N[O]-CH(R)-N=, 2) binding energies for the same atomic benzodiazepine fragment, 3) molecular descriptor, which characterize agonist interaction with benzodiazepine binding site. Mentioned groups of variables were used in statistical models (linear, partial square, vector regression and ANN). Maximal coefficient of correlation was obtained for ANN (R2=0.9967).