title: Elucidating Molecular Interactions of Natural Inhibitors with HPV-16 E6 Oncoprotein through Docking Analysis.
abstract: Human papillomavirus (HPV) infection is the leading cause of cancer mortality among women worldwide. The life-threatening infection caused by HPV demands the need for designing anticancerous drugs. In the recent years, different compounds from natural origins, such as carrageenan, curcumin, epigallocatechin gallate, indole-3-carbinol, jaceosidin, and withaferin, have been used as a hopeful source of anticancer therapy. These compounds have been shown to suppress HPV infection by different researchers. In the present study, we explored these natural inhibitors against E6 oncoprotein of high-risk HPV-16, which is known to inactivate the p53 tumor suppressor protein. A robust homology model of HPV-16 E6 was built to anticipate the interaction mechanism of E6 oncoprotein with natural inhibitory molecules using a structure-based drug designing approach. Docking analysis showed the interaction of these natural compounds with the p53-binding site of E6 protein residues 113-122 (CQKPLCPEEK) and helped the restoration of p53 functioning. Docking analysis, besides helping in silico validation of natural compounds, also helps understand molecular mechanisms of protein-ligand interactions.
authors.affiliation: Bioinformatics Centre & Biochemistry, Mahatma Gandhi Institute of Medical Sciences, Sevagram 442-102, India.
authors.forename: Satish
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Bioinformatics Centre & Biochemistry, Mahatma Gandhi Institute of Medical Sciences, Sevagram 442-102, India.
authors.forename: Lingaraja
authors.initials: L
authors.lastname: Jena
authors.affiliation: Bioinformatics Centre & Biochemistry, Mahatma Gandhi Institute of Medical Sciences, Sevagram 442-102, India.
authors.forename: Sneha
authors.initials: S
authors.lastname: Galande
authors.affiliation: Datta Meghe Institute of Medical Sciences (Deemed University), Nagpur 440-022, India.
authors.forename: Sangeeta
authors.initials: S
authors.lastname: Daf
authors.affiliation: Bioinformatics Centre & Biochemistry, Mahatma Gandhi Institute of Medical Sciences, Sevagram 442-102, India.
authors.forename: Kanchan
authors.initials: K
authors.lastname: Mohod
authors.affiliation: Advanced Centre for Treatment, Research & Education in Cancer, Khargar, Navi Mumbai 410-210, India.
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Varma
keywords: DNA probes HPV; molecular docking; neoplasms; plant products