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MCL-1及其BH3 螺旋结合自由能计算研究蛋白-蛋白相互作用原理

  • 刘广 ,
  • 李良 ,
  • 赵润宁 ,
  • 陈杭 ,
  • 李丹 ,
  • 韩聚广
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  • 中国科学技术大学核科学技术学院国家同步辐射实验室, 合肥 230029

收稿日期: 2011-04-22

  修回日期: 2011-06-07

  网络出版日期: 2012-09-15

基金资助

Supported by 973 Fund of Chinese Ministry of Science and Technology(2010CB934504) and NSFC(11179035)

Insights into protein-protein interaction by free energy calculation for human MCL-1 with its BH3 α-helix complex

  • LIU Guang ,
  • LI Liang ,
  • ZHAO Run-Ning ,
  • CHEN Hang ,
  • LI Dan ,
  • HAN Ju-Guang
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  • National Synchrotron Radiation Laboratory, University of Science and Technology of China, Hefei 230029, China

Received date: 2011-04-22

  Revised date: 2011-06-07

  Online published: 2012-09-15

摘要

MCL-1蛋白是细胞增殖和分化的一个关键调控因子. 使用MM-PBSA方法预测MCL-1蛋白与其野生型和碳氢化合物钉子修饰的BH3多肽形成的2个复合物的结合自由能. 结果表明,碳氢化合物钉子对多肽与MCL-1的亲和力影响有限; 并利用自由能分解(BFED)计算部分残基的能量贡献. 疏水效应是稳定复合物结构的主要因素,它同时被额外的静电相互作用强化. 该研究在原子水平上探究蛋白-蛋白相互作用机理,提供了新的癌症治疗候选药物.

本文引用格式

刘广 , 李良 , 赵润宁 , 陈杭 , 李丹 , 韩聚广 . MCL-1及其BH3 螺旋结合自由能计算研究蛋白-蛋白相互作用原理[J]. 中国科学院大学学报, 2012 , 29(5) : 605 -613 . DOI: 10.7523/j.issn.2095-6134.2012.5.005

Abstract

MM-PBSA approach is applied to evaluate the binding affinities for the MCL-1 complexes with the wild-type and hydrocarbon-stapled MCL-1 BH3 peptides. The hydrophobic effect is the main contribution to the stabilization. Moreover, the interactions are reinforced by additional electrostatic interactions. This study gives insight into protein-protein interaction mechanism at the atomic level.

Key words: MCL-1; apoptosis; MD simulation

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