肿瘤蛋白MDMX与抑制剂PMI作用机制的分子动力学研究.docVIP

Hans Journal of Computational Biology 计算生物学, 2012, 2, 27-33 /10.12677/hjcb.2012.23003 Published Online September 2012 (/journal/hjcb.html) Molecular Dynamics Insight into the Interaction Mechanism of Inhibitor PMI with MDMX* Weiyuan Cheng , Zhiqiang Liang , Wei Wang , Changhong Yi , Keyan Wang , Hongyun Li , Jianzhong Chen 1 2 2 2 2 2 2# 1 Affair Office, Shandong Jiaotong University, Jinan 2 School of Science, Shandong Jiaotong University, Jinan # Email: chenjianzhong1970@163.com Received: Aug. 23 , 2012; revised: Aug. 27 , 2012; accepted: Sep. 3 , 2012 rd th rd 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. Keywords: p53-MDMX Interaction; Molecular Dynamics; MM-PBSA; Binding Free Energy 肿瘤蛋白 MDMX与抑制剂 PMI作用机制的 分子动力学研究* 程伟渊，梁志强，王伟，伊长虹，王克彦，李洪云，陈建中 2# 1 2 2 2 2 2 1 2 山东交通学院办公室，济南 山东交通学院理学院，济南 Email: chenjianzhong1970@163.com # 收稿日期：2