Molecular Simulation of Interaction Mechanisms of Neuraminidase and Trihydroxy-methoxyflavone Derivatives

doi:10.7503/cjcu20120725

Abstract

Abstract:

A series of trihydroxy-methoxyflavone(MF) analogues was designed starting from MF, contracts that reference structural characters of the existing neuraminidase inhibitors. The docking and molecular dyna-mics simulations were carried out, aiming to discover the novel antiviral agents and contribute to the understanding on the interacting mechanisms. It is found that the binding locations of derivatives at the neuraminidase active site will not be influenced much with the addition of functional groups(carboxyl and guanidino/N-acetylamino), and there are some connections between the structures of derivatives and their interaction energies. Compound 9, with the replacements of carboxyl and guanidino groups at C7 and C5 of MF, demonstrates the highest interaction energy among the covered derivatives, equals-1172.52 kJ/mol, and is larger than the values of available lead drugs BA and MF(-672.12 and-347.44 kJ/mol). The space orientations of carboxyl and guanidino groups within the compound 9 at the neuraminidase active site are in good agreement with the current drugs. In addition, compound 9 has strong interactions with the conserved active-site residues Asp151 and Glu227, which is similar to the situation of MF. Therefore, compound 9 is a novel neuraminidase inhibitor with potential applications. We hope that these results will arouse the interest of experimental aspects to design novel anti-influenza drugs.

Key words: Influenza, Neuraminidase, Trihydroxy-methoxyflavone, Molecular docking, Rational drug design

CLC Number:

O641
O629

TrendMD:

WU Fei, YANG Zhi-Wei, YUAN Xiao-Hui. Molecular Simulation of Interaction Mechanisms of Neuraminidase and Trihydroxy-methoxyflavone Derivatives[J]. Chem. J. Chinese Universities, 2013, 34(4): 931.

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