State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences , 345 Lingling Road, Shanghai 200032, People's Republic of China.
J Chem Inf Model. 2013 Sep 23;53(9):2437-47. doi: 10.1021/ci400241s. Epub 2013 Sep 9.
Protein-protein interactions are observed in various biological processes. They are important for understanding the underlying molecular mechanisms and can be potential targets for developing small-molecule regulators of such processes. Previous studies suggest that certain residues on protein-protein binding interfaces are "hot spots". As an extension to this concept, we have developed a residue-based method to identify the characteristic interaction patterns (CIPs) on protein-protein binding interfaces, in which each pattern is a cluster of four contacting residues. Systematic analysis was conducted on a nonredundant set of 1,222 protein-protein binding interfaces selected out of the entire Protein Data Bank. Favored interaction patterns across different protein-protein binding interfaces were retrieved by considering both geometrical and chemical conservations. As demonstrated on two test tests, our method was able to predict hot spot residues on protein-protein binding interfaces with good recall scores and acceptable precision scores. By analyzing the function annotations and the evolutionary tree of the protein-protein complexes in our data set, we also observed that protein-protein interfaces sharing common characteristic interaction patterns are normally associated with identical or similar biological functions.
蛋白质-蛋白质相互作用存在于各种生物过程中。它们对于理解潜在的分子机制非常重要，并且可以成为开发此类过程的小分子调节剂的潜在靶点。先前的研究表明，蛋白质-蛋白质结合界面上的某些残基是“热点”。作为这一概念的延伸，我们开发了一种基于残基的方法来识别蛋白质-蛋白质结合界面上的特征相互作用模式（CIP），其中每个模式都是四个接触残基的簇。对从整个蛋白质数据库中选择的 1222 个非冗余蛋白质-蛋白质结合界面进行了系统分析。通过考虑几何和化学保守性，检索了不同蛋白质-蛋白质结合界面上的有利相互作用模式。通过在两个测试集上的演示，我们的方法能够以良好的召回分数和可接受的精度分数预测蛋白质-蛋白质结合界面上的热点残基。通过分析我们数据集中文库中蛋白质-蛋白质复合物的功能注释和进化树，我们还观察到具有共同特征相互作用模式的蛋白质-蛋白质界面通常与相同或相似的生物学功能相关联。
