OnLine Journal of Biological Sciences

IN SILICO DESIGN OF THE M2 PROTON CHANNEL INHIBITORS OF H1N1 VIRUS

Usman Sumo Friend Tambunan, Mochamad Reza Rahdiansyah and Arli Aditya Parikesit

DOI : 10.3844/ojbsci.2013.1.12

OnLine Journal of Biological Sciences

Volume 13, Issue 1

Pages 1-12

Abstract

M2 proton channel of H1N1 Influenza A virus is the target protein anti-flu drugs amantadine and rimantadine. However, the two once powerful adamantane-based drugs lost their 90% bioactivity because of mutations of virus in recent twenty years. The resistance of influenza A virus to amantadine need to develop more effective adamantane-based drugs. Several research by molecular docking method have been conducted to design and discover ligands which become potential inhibitors for the M2 channel protein of influenza virus in order to inhibit the replication of influenza virus. In this research are studied and evaluated the interaction of ligands towards the protein in the hydrated state using molecular dynamics simulations at two different temperatures. Analysis of ligand interaction yields that AM-L6-R6 ligand has best affinity towards the protein than the T-R6-L6, T-L6-R12 and the standard ligand. It is shown by the ligand interaction on the enzyme active site which remains to be formed during the simulation performed. At the end of simulation temperature of 300 K, AM-L6-R6 ligand has a residue contact with the Arg45 and formed hydrogen bond with Asp44. Then at the end of simulation temperature of 312 K, AM-L6-R6 ligands also could form a hydrogen bond with Asp44. Conformational changes of protein which occur during simulation showed the dynamicization of an protein in the presence of solvent and inhibitor.

Copyright

© 2013 Usman Sumo Friend Tambunan, Mochamad Reza Rahdiansyah and Arli Aditya Parikesit. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.