计算生物学

Vol.2 No.3 (September 2012)

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

 

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PMIMDMX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PMI5个残基能与MDMX产生强烈的相互作用,而且也表明CH-CHCH-ππ-π相互作用主导了PMIMDMX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。

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 (2012) 肿瘤蛋白MDMX与抑制剂PMI作用机制的分子动力学研究。 计算生物学, 2, 27-33. doi: 10.12677/hjcb.2012.23003

 

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