Molecular Docking and Molecular Dynamics Simulation-Based Identification of Natural Inhibitors against Druggable Human Papilloma Virus Type 16 Target

Abstract

The E5 protein is the smallest known oncoprotein linked to HPV 16 cancer development. In this study, we determined the potential of asarinin and thiazolo as an inhibitor of the E5 protein through molecular dynamics. The results showed that the binding site is unstable because of its hydrophobic nature and small size, causing considerable changes in the binding site for each of the 3 drugs examined. Except for asarinin, which still interacts with the first hydrophobic domain, they preserved their capacity to prevent endosomal acidification, hyper amplification of the EGFR pathway and contact with BAP31. It may inhibit E5-MHC I interaction. Thiazolo[3,2-a]benzymidazole-3(2H)-one,2-(2-fluorobenzylideno)-7,8-dimethyl (thiazolo) is expected to form more stable protein-ligand complexes than the other 2. However, the SASA, hydrogen bond and DCCM plots show that both compounds are equivalent to HPV 16 E5 protein.