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

Unlabelled: In this paper, a data set of [H] 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 receptor αβγ 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/αβγ 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.