Premium
The Molecular Dynamic Simulation of Zolpidem Interaction with Gamma Aminobutyric Acid Type A Receptor
Author(s) -
Chen YuChian
Publication year - 2007
Publication title -
journal of the chinese chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.329
H-Index - 45
eISSN - 2192-6549
pISSN - 0009-4536
DOI - 10.1002/jccs.200700093
Subject(s) - zolpidem , chemistry , docking (animal) , hydrogen bond , gabaa receptor , stereochemistry , binding site , molecular model , receptor , biochemistry , pharmacology , molecule , organic chemistry , medicine , nursing , insomnia
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 GABA A 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 α 1 and γ 2 subunits of the GABA A receptor. Zolpidem was selected to dock into the binding site. In our study, the residues of the binding pocket were suggested to be αHis129, αTyr187, αGly228, αThr234, αTyr237, γMet96, γPhe116, γSer130, γGly143, and γMet169. 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 γArg136 when zolpidem's conformation was in rank 2 of the docking score. The contracted binding pocket showed residues at αHis129, αTyr187, αGly228, αTyr237, γPhe116, and γMet169. Zolpidem docking in a contracted binding pocket might generate a hydrogen bond in α His 129.