Citation: ZHANG Chang-Sheng, LAI Lu-Hua. Protein-Protein Interaction: Prediction, Design, and Modulation[J]. Acta Physico-Chimica Sinica, ;2012, 28(10): 2363-2380. doi: 10.3866/PKU.WHXB201209172
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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.
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