Abstract—The H274Y mutant neuraminidase, known as oseltamivir-resistant, can be inhibited by zanamivir and laninamivir. The inhibition of oseltamivir-resistant neuraminidase has been experimented in vivo and in vitro in several experiments. To complete the usage of zanamivir and laninamivir inhibition experiments, we investigate the structural and dynamics of neuraminidase-inhibitors complexes using heating dynamics simulation. All processes which support the simulation also reported to produce a vast review of the subject. Through homology modeling method and models assessments, the best model (model number 3) was selected to proceed to the attachment of the substrate via CDOCKER molecular docking. The best docked pose was continued to energy minimization and heating dynamics simulation. The simulation results have been observed using root mean square deviation (RMSD), the percentage of hydrogen bonds occupancy, and the binding free energies comparison. From these results, we have concluded that the high value of the binding free energies, the value and the fluctuation of neuraminidase-oseltamivir RMSD, and the percentage of hydrogen bonds occupancy may be related with the resistance of H274Y mutant neuraminidase to oseltamivir. The simulation results were also correlated to the success of laninamivir and zanamivir to bind H274Y mutant neuraminidase compared with peramivir and oseltamivir. Both laninamivir and zanamivir are preferable to treat H274Y mutant neuraminidase that could resist oseltamivir carboxylate.

Index Terms—Influenza, neuraminidase, mutant, simulation

The authors are with the Departemen Fisika, Fmipa, Universitas Indonesia, P.O. Box 16424 Indonesia (e-mail: sigit.jaya.herlambang@gmail.com, sigit.jaya.herlambang@r103a.com).

Cite: Sigit J. Herlambang and Rosari Saleh, "Heating Dynamics Simulation of H274Y Mutant Neuraminidase-Inhibitors Complexes," International Journal of Bioscience, Biochemistry and Bioinformatics vol. 2, no. 3, pp. 192-199, 2012.