Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
443715 | Journal of Molecular Graphics and Modelling | 2007 | 9 Pages |
The three-dimensional models of the αk/γ2 (k = 1, 2, 3 and 5) interface of GABAA receptors, which included the agonist-binding site, were constructed and validated by molecular modeling technology. To investigate the mechanism of α subunit selectivity of zolpidem, docking calculations were used to illustrate the potential binding modes of zolpidem with different α subtypes. The results revealed that there were three reasons resulting in the distinct binding affinity of zolpidem to different α subtype. Firstly, the number of hydrogen bonds of agonist–receptor complex would determine the magnitude of binding affinity. Secondly, the His residue in loop A of α subunit was indicated as a key role of benzodiazepine binding. Thirdly, the side chain of Glu in loop C reduced the affinity of zolpidem to those receptors containing α2, α3 or α5 subunits.