Acta Phys. -Chim. Sin. ›› 2012, Vol. 28 ›› Issue (10): 2363-2380.doi: 10.3866/PKU.WHXB201209172

• BIOPHYSICAL CHEMISTRY • Previous Articles     Next Articles

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.


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