高等学校化学学报

高等学校化学学报

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六钼酸盐有机胺杂化衍生物与SARS-CoV 3CLpro相互作用的分子动力学模拟

邵琛1, 王建萍1, 杨国春1, 苏忠民1,2, 胡冬华1, 孙家锺2   

    1. 东北师范大学化学学院功能材料化学研究所, 长春 130024;
    2. 吉林大学理论化学研究所理论化学计算国家重点实验室, 长春 130023
  • 收稿日期:2006-09-06 修回日期:1900-01-01 出版日期:2008-01-10 发布日期:2008-01-10
  • 通讯作者: 苏忠民

Interactions of [Mo6O19]2- and Its Derivatives Substituted with Organic Groups Inhibitor with SARS-CoV 3CLpro by Molecular Modeling

SHAO Chen1, WANG Jian-Ping1, YANG Guo-Chun1, SU Zhong-Min1,2*, HU Dong-Hua1, SUN Chia-Chung2   

    1. Institute of Functional Material Chemistry, Northeast Normal University, Changchun 130024, China;
    2. State Key Laboratory of Theoretical and Computational Chemistry, Jilin University, Changchun 130021, China
  • Received:2006-09-06 Revised:1900-01-01 Online:2008-01-10 Published:2008-01-10
  • Contact: SU Zhong-Min

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摘要： 采用分子动力学模拟方法, 在分子水平上探讨六钼酸盐有机杂化衍生物潜在的抗SARS病毒活性. 3CLpro主蛋白酶是冠状病毒复制和转录过程中起关键作用的功能蛋白, 因此采用SARS-CoV 3CLpro作为靶标进行抗SARS病毒的药物设计. 使用Insight II软件包中的Biopolymer, Discover 3, Profile-3D和Affinity等模块, 研究 POMs/3CLpro相互作用的结合位点和作用性质. 研究其能量变化规律, 探讨了多酸化合物对SARS病毒可能的抑制机理. 研究结果表明, POMs与3CLpro在酶的催化活性位点处有较强的结合力. 形成的复合物主要以静电相互作用相结合, 氢键相互作用对复合物的相对稳定性有一定影响. 对于POMs/3CLpro复合物, 有机胺基团取代的POMs所带负电荷比未取代体系的高, 比3CLpro的结合能更高, 这与POMs的相关量子化学计算结果吻合.

关键词: SARS, 3CLpro, 多金属氧酸盐, 分子动力学, 对接

Abstract: Polyoxometalates(POMs) were proved with the properties of both anti-tumor and anti-HIV. The potential anti-SARS activities of the polyoxometalates [Mo6O19]2- and its derivatives substituted with organic groups were investigated in this paper by molecular modeling method. The 3c like(3CL)protease hydrolyze, namely 3CLpro, is the key protease for virus replication as well as transcription, and thus can be taken as one of the key targets for anti-SARS drug design. InsightII/Dicover 3, affinity, Profile-3D modules were used to explore possible binding locations and properties for POMs/3CLpro interaction. We studied the energy changing tend and investigated the possible inhibiting mechanism of POMs' with SARS-CoV. The results show that POMs bind with 3CLpro in the active site with a high affinity, mainly via electrostatic interactions and H-bond interactions. For the POMs/3CLpro complex, POMs substituted with organic groups with higher negative charge are prefer to bind with 3CLpro than non-substituted ones, and this agrees well with relative quantum chemical calculations. Organic substitutions in ligands have an influence on the stability of complexes by steric hindrance. Our study may provide theoretical reference and illustrations to anti SARS-CoV drug design.

Key words: SARS, 3CLpro, Polyoxometalate, Molecular dynamics, Docking

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