物理化学学报 >> 2012, Vol. 28 >> Issue (10): 2363-2380.doi: 10.3866/PKU.WHXB201209172

生物物理化学 上一篇    下一篇

蛋白质相互作用预测、设计与调控

张长胜1,2,3, 来鲁华1,2,3   

  1. 1 北京大学化学与分子工程学院, 物理化学研究所, 分子动态与稳态结构国家重点实验室, 北京分子科学国家实验室, 北京 100871;
    2 北京大学定量生物学中心, 北京 100871;
    3 北京大学-清华大学生命科学联合中心, 北京 100871
  • 收稿日期:2012-09-09 修回日期:2012-09-17 发布日期:2012-09-26
  • 通讯作者: 来鲁华 E-mail:lhlai@pku.edu.cn
  • 基金资助:

    国家自然科学基金(11021463, 90913021)和国家科技部(2009CB9185000)资助项目

Protein-Protein Interaction: Prediction, Design, and Modulation

ZHANG Chang-Sheng1,2,3, LAI Lu-Hua1,2,3   

  1. 1 Beijing National Laboratory for Molecular Science, State Key Laboratory of Structural Chemistry for Stable and Unstable Species, Institute of Physical Chemistry, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, P. R. China;
    2 Center for Quantitative Biology, Peking University, Beijing 100871, P. R. China;
    3 Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, P. R. China
  • Received:2012-09-09 Revised:2012-09-17 Published:2012-09-26
  • Supported by:

    The project was supported in part by the National Natural Science Foundation of China (11021463, 90913021) and the Ministry of Science and Technology of China (2009CB9185000). ZC was supported by the postdoc fellowship Peking‐Tsinghua Center for Life Scieneces.

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摘要：

蛋白质相互作用是生命活动在分子水平上的基本事件. 蛋白质相互作用的三维图像可以给出关键生命活动过程的分子细节. 了解蛋白质相互作用的原理有助于揭示生命活动的机制, 并在此基础上开展有重要价值的蛋白质设计. 本文对于蛋白质相互作用预测、设计和调控研究的近期进展进行了总结归纳, 介绍了作者实验室在相关领域的研究进展, 并对今后的研究方向进行了展望. 主要包括: (1) 蛋白质相互作用网络、蛋白质相互作用机制和蛋白质复合物结构计算分析; (2) 基于序列、结合位点以及复合物结构的蛋白质相互作用预测; (3)蛋白质相互作用设计方法; (4) 利用化学分子调控蛋白质相互作用的方法; (5) 针对蛋白质相互作用的蛋白质药物设计方法.

关键词: 蛋白质相互作用, 相互作用预测, 蛋白质-蛋白质对接, 蛋白质相互作用设计, 蛋白质药物, 药物设计

Abstract:

Protein-protein interactions are the essential events in life at the molecular level. The three-dimensional structures of protein-protein interactions provide clear pictures for the molecular details of various cellular processes. Understanding the basics of protein-protein interaction provides clues for revealing the secret of life, and useful information for designing proteins for various application purposes. The present review summarizes recent progresses of protein-protein interaction prediction, design, and modulation study, briefly introduces the progresses in the authors' group, and discusses future directions of the field. Protein-protein interaction network analysis, protein-protein interaction principles, and computational analysis of interfaces are briefly reviewed first. Methods and progress for predicting protein-protein interaction at sequence level, interaction-site level, and complex-structure level are given. Based on the knowledge about the nature of protein-protein interactions, protein-protein interaction design and modulation can be done on purpose. We give a summary of three kinds of protein-protein interaction design methods: redesign, grafting, and de novo, and three kinds of protein-protein interaction modulation methods using small molecules: direct competition, allosteric modulation, and stabilization. Protein design approaches for potential therapeutic applications targeting protein-protein interactions are also discussed.

Key words: Protein-protein interaction, Interaction prediction, Protein-protein docking, Protein-protein interaction design, Protein drug, Drug design