| 초록 |
Oseltamivir-resistant neuraminidase mutants, His274Tyr, have recently been found from humans, and their crystal structures were also identified. The objective of this research is to elucidate the origin of the resistance at the molecular level via molecular dynamics simulation. For this purpose, the binding free energies of oseltamivir with the wild type neuraminidase and with His274Tyr neuraminidase were calculated using the linear interaction energy method. The nonbonded interaction energies between the oseltamivir and active site residues were also calculated to investigate the contribution of nonbonded interaction to the total biding energy. Remarkable differences have been observed in these two structures during analyses of molecular dynamics trajectories, particularly in the oseltamivir binding modes. These results are expected to be used for the rational design of neuraminidase inhibitors that are more potent against known resistance mutations. |
