Comparative modeling of sodium- and chloride-dependent GABA transporter 1 and docking studies with natural compounds

ABSTRACT

Epilepsy is a chronic neurological disorder that causes uncontrolled seizures which can affect the bodyphysically and psychologically. When a person experiences seizure, it is very difficult for them to breathe andthey bite their tongue as a reflex. Glutamatergic and gamma-aminobutyric acid ergic (GABAergic) transmissionin the brain causes seizures. The immature brain is more prone to seizures than the adult brain. Gene SLC6A1produces GABA1 protein which helps in reuptake of GABA from the synapse. Presently in this study, proteinmodeling and molecular docking were performed on protein sequence sodium- and chloride-dependent GABAtransporter 1 that was retrieved from uniport. MODELLER 9.21 versions were used to develop a homologymodel. X-ray structure of Drosophila dopamine transporter in complex with cocaine (4XP4) from speciesDrosophila melanogaster was used as a template. Autodock4.2, a docking software, was used for moleculardocking studies. Against the modeled protein, 22 natural compounds were docked. According to the results,natural compounds like Morusin showed high binding energy against modeled protein than standard drugs.