Determining the Molecular Interactions of Natural Inhibitors with the HPV-16 E6 Oncoprotein by Docking and Dynamics Simulation Studies

Abstract

The oncoprotein E6, a pivotal player in HPV-16-induced cancer, has long been the focus of extensive research. Building upon our previous study, we identified asarinin and thiazolo[3,2-a] benzimidazole-3(2H)-one-(2-fluorobenzylideno)-7,8-dimethyl (thiazolo) as potential potent anti-HPV-16 E6 oncoprotein agents. Utilizing the UniProt-derived E6 sequence, we employed I-TASSER to model the protein's three-dimensional structure. Subsequent molecular docking via AutoDock Vina, coupled with a 1,000 ps dynamic analysis under physiological parameters, revealed that both asarinin and thiazolo have a high chance of forming stable protein-ligand complexes with HPV-16 E6, displaying distinct molecular dynamic properties. Thiazolo exhibited superior stability in simulation, evident in ligand conformation and movement graphs, while asarinin excelled in terms of contact residues. Furthermore, SASA, hydrogen bond graphs, and the DCCM graph collectively underscore the comparable potential of both drugs as robust inhibitors of the HPV-16 E6 oncoprotein.

Keywords:
Anti-viral; Cervical cancer; E6 protein; HPV16; Molecular dynamic

HIGHLIGHTS

The E6 protein is a major oncoprotein linked to the development of cancer caused by HPV-16 infections.

Asarinin and thiazolo are expected to form stable protein-ligand complexes with the HPV-16 E6 protein.

Asarinin is more stable than the other compounds in terms of contact residues, while the ligand conformation and movement graph indicate that thiazolo is more stable in simulation.

The SASA, hydrogen bond, and DCCM graphs support both compounds being equally effective against HPV-16 E6 protein.