| dc.description.abstract | The 2009 pandemic Influenza A H1N1 (09pdm-H1N1) Neuraminidase (NA) resistant to Oseltamivir (OTV) has been a critical issue in clinical flu treatment. In this study, dual resistant 09pdm-H1N1 NA mutants (4 single mutants: I223V, I223R, H275Y, S247N; H275Y/I223V and H275Y/S247N) two dual mutants in complex with Oseltamivir/Sialic Acid were used to investigate the mechanisms of drug resistance using molecular dynamics simulations. Our results were incomparable to experimental data due to expected error that the binding energies of the complexes were positive instead of negative values. We had inspected the error using different approaches including ligand optimization, protein structure refinement, forcefield selection. Surprisingly, after careful considerations, we found no observable flaws in our experimental design but rather we assumed that the error may be due to CHARMM forcefield- GROMACS simulation software incompatibility. Our proposed solution is to reduce the version of GROMACS to previous stable version for another set of simulations. Nevertheless, the computational resource and time consumption have already reached the expectation for the project. Thus, in this thesis, we reported our findings involving the mentioned error.
Keywords:
Influenza A H1N1, 2009 pandemics, Neuraminidase, Oseltamivir, Resistant mutants. | en_US |
