In - Silico Docking of Neuroactive Flavones on Benzodiazepine Binding Site of GABA A Receptor Homology Model

Flavones share structural and mechanistic features of GABAAligands. The mode of binding and interactions of flavones wasinvestigated in a homology model generated in an automated mode. The binding pocket was predicted with Fuzzy oil dropmathematical model. The ligands were docked using PM3 force field method and various ligand-protein docking interactionswere calculated. The ligand poses with maximum negative docking scores were further observed for binding mode and the aminoacid residues lining the 2-phenyl ring and flavone nucleus were noted. Flavones docked inthe predicted binding pocket withenergies comparable to GABAAbenzodiazepine (BZD) site ligands diazepam and zolpidem. Two docking conformers wereobservedFlavones presented two binding conformers which bind head to tail with respect each other with respect to 114TYRresidue. Flavones were classified into two conformers: Conformer A represented by 5’-Bromo-2’-hydroxy-6-methylflavone: inwhich 114 TYR surrounds the 2-phenyl group. Conformer B was represented by apigenin: in which 114 TYR surrounds theflavone nucleus.