新型抗流感病毒药物——三羟基甲氧基黄酮分子对接的研究  

A novel anti-influenza drug:molecular docking of trihydroxymethoxyflavone

作　　者：杨刚[1] 杨志伟[1] 吴晓敏[1] 祖元刚[1] 

机构地区：[1]东北林业大学森林植物生态学教育部重点实验室,黑龙江哈尔滨150040

出　　处：《计算机与应用化学》2008年第4期409-414,共6页Computers and Applied Chemistry

基　　金：国家"十一五"科技支撑计划(2006BAD18B04);东北林业大学引进人才基金(220-602042);中国博士后基金资助(20060400802)

摘　　要：运用柔性分子对接程序Affinity,深入研究了5,7,4′-三羟基-8-甲氧基黄酮(MF)与N1、N9亚型神经氨酸酶之间的结合方式并阐明其作用机制。结果表明MF与N1亚型神经氨酸酶之间有一种作用模式。其结合能为-70.26 kcal·mol^(-1).而与N9亚型之间存在两种竞争性的结合模式,最大结合能为-83.51 kcal·mol^(-1)。进一步分析发现MF与这两种亚型神经氨酸酶相互作用的作用力类型、氢键作用及关键作用的氨基酸残基等有着明显的区别。现行药物奥斯米韦作用模式单一,MF则可以与各种亚型甚至变异的神经氨酸酶发生很好地相互作用。因此,MF是一种极具应用前景的新型抗流感病毒药物。结合前人的研究成果,本研究提出了以MF为底物的流感药物修饰方向。With the aid of flexible molecular docking program Affinity, an in-depth and systemetic investaigation was carried out on the interacting mechanisms between 5,7,4′-trihydroxy-8-methoxyflavone （MF） and N1 and N9 subtype neuraminidases. It was found that there exist one and two binding modes in the cases of N1 and N9 subtype neuraminidases, and their corresponding largest binding energies were calculated to be -70.26 and -83.51 keal · mol^-1, respectively. The further analyses revealed that great distinctions are present in the bindings of MF to N1 and N9 subtype neuraminidases such as the interacting forces, hydrogen bonding and the interacted key amino acid residues. In contrast with the monotonous binding mode of the current oseltamivir drug, MF can be tightly bound with various subtypes of neuraminidases or with the varied ones. Therefore, MF is a novel anti-influenza virus drug with potential applications. Combined with the previous results, we pointed out how to effectively modify the functional groups of MF.

关 键 词：流感病毒 黄酮衍生物 神经氨酸酶 分子对接 植物类天然药物 

分 类 号：O641[理学—物理化学]