Molecular docking studies of 1, 3, 4 oxadiazoles Derivatives as anti-convulsive agents

Abstract

Molecular docking is a computational technique that places a small molecule (ligand) in the binding site of its macromolecular target (receptor) and estimates its binding affinity. The present study attempted the high throughput in-silico screening of 65 compounds docked with the GABAA receptor (PDB ID: 4COF) using Molegro virtual docker (6.0). Out of these 65 compounds, 17 compounds showed very good mol dock score in ranging between -66.344 & -102.653. Ethosuximide and Carbamazepine drugs was used as a standard drug which showed mol dock score -50.6357 & -58.5047 respectively. Most of test compounds demonstrated excellent number of hydrogen bond interactions viz compounds 33, 38, 39, 45, 47, 53, 54, 59, 61, 62, 63, 64 & 65 which showed 7 to 11 number of hydrogen bond interactions as compared to standard drug interactions values 6 & 5 respectively and also showed the interaction with same amino acids Glu52, Ser51and Val53 and some other amino acids Asn54, Thr58 and Thr133 also showed very acceptable bond length less than 3.91Å. The obtained results indicated that all studied ligands have similar position and orientation inside the putative binding site of GABAA receptor (PDB ID: 4COF) which reveals a large space bounded by a membrane-binding domain which serves as an entry channel for substrate to the active site. In addition, the affinity of any small molecule can be considered as a unique tool in the field of drug design and offer prospective in future research to develop a potent anticonvulsant agent.