Impact of rtI233V mutation in hepatitis B virus polymerase protein and adefovir efficacy: Homology modeling and molecular docking studies

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Title	Impact of rtI233V mutation in hepatitis B virus polymerase protein and adefovir efficacy: Homology modeling and molecular docking studies
Authors	Ashrafali Mohamed Ismail¹, Om Prakash Sharma², Muthuvel Suresh Kumar², Rajesh Kannangai¹ & Priya Abraham¹*
Affiliation	¹Departments of Clinical Virology, Christian Medical College, Vellore 632 004, Tamil Nadu, India; ²Centre of excellence in Bioinformatics, Pondicherry University, Puducherry -605 014, India.
Email	priyaabraham@cmcvellore.ac.in; *Corresponding author
Article Type	Hypothesis
Date	Received January 04, 2013; Accepted January 05, 2013; Published February 06, 2013
Abstract	Adefovir is an adenosine analogue approved by the Food and Drug Administration for the treatment of chronic hepatitis B. Mutations occurring in the hepatitis B virus (HBV) reverse transcriptase (rt) domains are shown to confer resistance to antiviral drugs. The role of the rtI233V mutation and adefovir resistance remains contradictory. In this study, it was attempted to evaluate the impact of putative rtI233V substitution on adefovir action by homology modeling and docking studies. The HBVrt nucleotide sequence containing rtI233V mutation was obtained from the treatment-naive chronic hepatitis B subject. The three dimensional model of HBV polymerase/rt was constructed using the HIV-1rt template (PDB code: 1RTD A) and the model was evaluated by the Ramachandran plot. Autodock was employed to dock the HBV polymerase/rt and adefovir. The modelled structure showed the amino acid rtI233 to be located away from the drug interactory site. The substitution of isoleucine to valine did not appear to affect the catalytic sites of the protein. In addition, it does not alter the conformation of bent structure formed by residues 235 to 240 that stabilizes the binding of dNTPs. Therefore, it was predicted that rtI233V substitution may not independently affect the antiviral action of adefovir and incoming dNTP binding.
Keywords	Hepatitis B virus, Adefovir, Mutation, Homology model, Docking, Drug resistance.
Citation	Ismail et al. Bioinformation 9(3): 121-125 (2013)
Edited by	P Kangueane
ISSN	0973-2063
Publisher	Biomedical Informatics
License	This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.