The molecular dynamic simulation of zolpidem interaction with gamma aminobutyric acid type A receptor

Our goal was to generate the extracellular domain of gamma-aminobutyric acid type A receptor (GABA(A) receptor) by comparative modeling and to study the interaction of zolpidem with the GABAA receptor. The modeling strategy was verified to provide reasonable 3-dimensional coordinates. These coordinates helped to combine all the subunits well. The benzodiazepine (BZ) binding site was located in a binding pocket between the (x I and gamma 2 subunits of the GABAA receptor. Zolpidem was selected to dock into the binding site. In our study, the residues of the binding pocket were suggested to be alpha His 129, alpha Tyrl 87, alpha Gly228, alpha Thr234, alpha Tyr237, gamma Met96, gamma Phe 116, gamma Ser 130, gamma Gly 143, and gamma Met 169. By the calculation of the docking module, the conformation of zolpidem docking in the BZ binding site was investigated. A hydrogen bond was found at gamma Arg 136 when zolpidem's conformation was in rank 2 of the docking score. The contracted binding pocket showed residues at alpha His 129, alpha Tyrl87, alpha Gly228, alpha Tyr237, gamma Phe 116, and gamma Met 169. Zolpidem docking in a contracted binding pocket might generate a hydrogen bond in alpha His 129.