| dc.description.abstract | The influenza A virus M2 proton channel equilibrates pH across the viral membrane during entry and across the trans-Golgi membrane of infected cells during viral maturation. It is targeted by the antiviral drugs amantadine and rimantadine. In the past two decades, there have been many methods of analyzing the structure of M2 channel protein including recent methods such as crystallography, solution NMR and solid state NMR employed to generate the high resolution of crystal, solution NMR and SSNMR structure of M2 ion channel. Although the structures derived from each of these methods have shown the same overall topology, they were inconsistent with details on the mechanism of channel opening, the drug binding site and drug mechanism. This information is critical for the design of an effective channel inhibitor. In this study we used autodock vina to dock amantadine, rimantadine and 200 compounds from previous studies with 4 models of M2 protein including solution NMR, SSNMR, crystallography with drug bound and unbound structure to calculate the binding affinity between protein and ligands. The binding site of amantadine and rimantadine for each models was also analyzed with autodock tools. Finally, we ranked the previously studied 200 compounds according to their binding affinity and present the top ten for pharmacophore analysis.
Keywords: M2 protein models, binding site, pharmacophore analysis, amantadine, rimantadine | en_US |
