蛋白质相互作用预测、设计与调控

Protein-Protein Interaction:Prediction,Design,and Modulation

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.

Protein-protein interactions are the essential events in life at the molecular level Thethree-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.