Demystifying the Molecular Basis of Pyrazoloquinolinones Recognition at the Extracellular α1+/β3- Interface of the GABA_A Receptor by Molecular Modeling.

ABSTRACT: GABA_A receptors are pentameric ligand-gated ion channels that serve as major inhibitory neurotransmitter receptors in the mammalian brain and the target of numerous clinically relevant drugs interacting with different ligand binding sites. Here, we report an in silico approach to investigate the binding of pyrazoloquinolinones (PQs) that mediate allosteric effects through the extracellular α+/β- interface of GABA_A receptors. First, we docked a potent prototype of PQs into the α1+/β3- site of a homology model of the human α1β3γ2 subtype of the GABA_A receptor. Next, for each docking pose, we computationally derived protein-ligand complexes for 18 PQ analogs with known experimental potency. Subsequently, binding energy was calculated for all complexes using th

SUBMITTER: Singh N 

PROVIDER: S-EPMC7518038 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature