Investigation of [³H]diazepam derivatives as allosteric modulators of GABAA receptor α₁β₂γ₂ subtypes: combination of molecular docking/dynamic simulations, pharmacokinetics/drug-likeness prediction, and QSAR analysis.

ABSTRACT: In this paper, a data set of [³H] diazepam derivatives was analyzed using various computational methods: molecular docking/dynamic simulations, and QSAR analysis. The main aims of these studies are to understand the binding mechanisms by which benzodiazepines allosterically modulate GABA_A receptor α₁β₂γ₂ subtypes, from inducing neuronal inhibition at lower doses to the anesthetic effect at higher doses, and also, to define the structural requirements that contribute to improving the response of GABA_A/α₁β₂γ₂ receptor to benzodiazepine drugs. The results of the molecular docking study allowed selecting Ro12-6377 and proflazepam as the best modulators for the four binding sites simultaneously. S

SUBMITTER: Djebaili R 

PROVIDER: S-EPMC9365687 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature