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运用柔性分子对接和分子动力学方法,深入研究了4-(氮乙酰氨基)-5-胍基-3-(3-戊氧基)安息香酸(BA)与各类型神经氨酸酶(N1,N2,N9亚型和B型)间的作用机制.结果显示,BA与各类型神经氨酸酶结合模式存在差异,但作用机制比较相似:与它们的活性腔均匹配良好,并形成稳定的复合体系,最大结合能分别等于-1233.62,-1385.72,-663.11,-1058.87kJ·mol-1.这表明BA对各类型神经氨酸酶均有良好的抑制效果.进一步分析发现,BA与各类型神经氨酸酶活性腔内保守关键氨基酸残基发生较强的静电和氢键作用,而与易突变氨基酸残基作用较弱,表明了活性腔内易突变氨基酸残基发生突变也不会对抑制效果造成明显影响.因此,BA是一种极具应用前景的新型抗流感病毒药物.结合以前的研究结果,我们提出了以BA为底物的抗流感病毒药物的修饰方向.
Using flexible molecular docking and molecular dynamics methods, the effects of 4- (N-acetylamino) -5-guanidino-3- (3-pentyloxy) benzoic acid (BA) and various types of neuraminidase (N1, N2, N9 subtype and B type) .The results showed that the binding modes of BA with different types of neuraminidase were different, but the mechanism of action was similar: they all matched well with their active cavities and formed a stable complex System, the maximum binding energy is equal to -1233.62, -1385.72, -663.11, -1058.87kJ · mol-1, respectively, indicating that BA has a good inhibitory effect on all kinds of neuraminidase.According to further analysis, BA and various types of nerve Enzyme activity of the cavity-conserved key amino acid residues occur strong electrostatic and hydrogen bonding, and easy to mutate amino acid residues weak, indicating that the active cavity mutated amino acid mutations do not have the effect of inhibition Therefore, BA is a new promising anti-influenza virus drug.With the previous research results, we propose BA-based anti-influenza virus drug modification direction.