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秦艳,谢能中,杜奇石,黄日波.流感病毒M2质子通道抑制机理的计算化学模拟和理论分析[J].广西科学院学报,2014,30(4):289-293. [点击复制]
- QIN Yan,XIE Neng-zhong,DU Qi-shi,HUANG Ri-bo.Theoretical Study and Computational Chemistry Modeling for the Inhibition Mechanism of M2 Proton Channel in Influenza A Virus[J].Journal of Guangxi Academy of Sciences,2014,30(4):289-293. [点击复制]
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| 流感病毒M2质子通道抑制机理的计算化学模拟和理论分析 |
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秦艳1, 谢能中1, 杜奇石1,2, 黄日波1
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| (1.广西科学院, 非粮生物质酶解国家重点实验室, 国家非粮生物质能源工程技术研究中心, 广西南宁 530007;2.美国戈登生命科学研究所, MA 02478, USA) |
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| 摘要: |
| [背景]A型流感病毒的M2质子通道蛋白的X-ray和NMR结构已于2008年测定,并成为发展抗流感的重要药物靶标,但学术界对于抑制剂的作用机理尚有争论。[方法]用SYBYL软件作M2通道蛋白与金刚烷胺抑制剂的对接计算,在可能的对接位点(Asp-44,Trp-41,His-37)上用精确的量子化学方法计算对接能,并根据结构化学和物理化学的原理分析抑制剂的作用机理。[结果]计算了金刚烷胺与M2质子通道的多个可能的结合位点的结合能,包括His-37,Trp-41和Asp-44。[结论]金刚烷胺对M2的抑制是一个动态过程,可能有多个位点结合。金刚烷胺穿透细胞膜后在通道出口与Asp-44形成盐桥,质子流使盐桥解离,金刚烷胺再进入通道与芳香氨基酸Trp-41(或His-37)形成阳离子-π键。 |
| 关键词: 流感病毒 金刚烷 M2质子通道 抑制机理 |
| DOI： |
| 投稿时间：2014-10-10 |
| 基金项目:国家自然科学基金项目(31370716和31360207)资助。 |
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| Theoretical Study and Computational Chemistry Modeling for the Inhibition Mechanism of M2 Proton Channel in Influenza A Virus |
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QIN Yan1, XIE Neng-zhong1, DU Qi-shi1,2, HUANG Ri-bo1
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| (1.State Key Laboratory of Non-food Biomass and Enzyme Technology, National Engineering Research Center for Non-food Biorefinery, Guangxi Academy of Sciences, Nanning, Guangxi, 530007, China;2.Gordon Life Science Institute, 53 South Cottage Road, Belmont, MA, 02478, USA) |
| Abstract: |
| [Background] The structure of M2 proton channel in influenza A virus has been solved in 2008 by using X-ray and NMR,which is a drug-target for inhibitor design. However,so far the inhibition mechanism is not very clear.[Methods] The possible binding sites of amantadine in M2 channel are determined by using docking calculations. Then the binding energies are calculated by using higher level quantum cheical calculations.[Results] The accurate binding energies at the sites His-37,Trp-41,and Asp-44 are calculated.[Conclusion] This inhibition of amantadine to M2 channel is a dynamic procedure. After the amantadine penetrates the cell membrane it binds at the Asp-44 through salt-bridge interaction. The salt-bridge may be broken in the proton flow,then amantadine comes in the channel,and binds at the aromatic amino acid Trp-41 (or His-37) with the cation-π interaction. |
| Key words: influenza A virus amantadine M2 proton channel inhibition mechanism |
