肿瘤蛋白MDMX与抑制剂PMI作用机制的分子动力学研究
Molecular Dynamics Insight into the Interaction Mechanism of Inhibitor PMI with MDMX
DOI: 10.12677/hjcb.2012.23003, PDF, HTML, 下载: 3,851  浏览: 15,131  国家自然科学基金支持
作者: 程伟渊：山东交通学院办公室；梁志强, 王 伟, 伊长虹, 王克彦, 李洪云, 陈建中*：山东交通学院理学院
关键词: p53-MDMX相互作用；分子动力学；MM-PBSA；结合自由能；p53-MDMX Interaction; Molecular Dynamics; MM-PBSA; Binding Free Energy
摘要: 恢复抑癌蛋白p53的功能已经成为一种治疗癌症的新途径。本文采用分子动力学模拟和MM-PBSA方法计算了抑制剂PMI与肿瘤蛋白MDMX的结合自由能。结果表明范德华相互作用驱动了PMI与MDMX的结合。同时也使用基于残基对的自由能分解方法计算了残基–残基相互作用，结果不仅表明PMI的5个残基能与MDMX产生强烈的相互作用，而且也表明CH-CH，CH-π，π-π相互作用主导了PMI在MDMX疏水性裂缝中的结合。我们期望这个研究能为抑制p53-MDMX相互作用药物的研发提供理论上的启示。
Abstract: Restoration of p53 function is considered to be a new therapeutic strategy for anti-cancers. Molecular Dynamics (MD) simulations coupled with Molecular Mechanics/Possion-Boltzman Surface Area (MM-PBSA) method were used to study the mechanism of the PMI-MDMX interaction. The results show that van der walls energy drives the PMI-MDMX interaction. Calculations based on residue-residue interaction were also performed, and the results not only suggest that five residues of PMI can produce strong interaction with MDMX, but also the CH-CH, CH-π, π-π interactions predominate the binding of PMI in the hydrophobic cleft of MDMX. We expect that this study can contribute significantly to the designs of the potent inhibitors inhibiting the PMI-MDMX interaction.
文章引用：程伟渊, 梁志强, 王伟, 伊长虹, 王克彦, 李洪云, 陈建中. 肿瘤蛋白MDMX与抑制剂PMI作用机制的分子动力学研究[J]. 计算生物学, 2012, 2(3): 27-33. http://dx.doi.org/10.12677/hjcb.2012.23003

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