A lock-and-key model for protein-protein interactions
A lock-and-key model for protein-protein interactions
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DOI：
10.1093/bioinformatics/btl338
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发表时间：
2006-08-15
期刊：
影响因子：
5.8
通讯作者：
Gilbert, David R.
中科院分区：
文献类型：
--
作者：
Morrison, Julie L.;Breitling, Rainer;Gilbert, David R.
动机：蛋白质-蛋白质相互作用网络是分子生物学家可用的主要后基因组数据来源之一。它们提供了生物体蛋白质组整体相互作用结构的全面视图，以及特定相互作用的详细信息。在这里，我们提出了一种蛋白质相互作用的物理模型，可用于在中间水平上提取附加信息：它使我们能够识别共享生物相互作用基序的蛋白质，并识别潜在缺失或虚假的相互作用。结果：我们的新图模型通过互补结合域的潜在相互作用（锁和钥匙模型）解释了观察到的蛋白质之间的相互作用。这导致了一种新颖的图论算法来识别蛋白质-蛋白质相互作用网络中的二分子图，其中基础数据取自酵母双杂交实验结果。通过对合成数据进行测试，我们证明在某些建模假设下，该算法将返回有关网络中每个蛋白质的正确域信息。对各种模型生物数据的测试表明，模型预测的局部和全局模式确实在实验数据中找到了。使用功能和蛋白质结构注释，我们表明可以识别与生物学相关的相互作用基序相对应的二分子网络。其中一些是新颖的，我们讨论一个涉及来自酿酒酵母相互作用组的 SH3 结构域的例子。
Motivation: Protein-protein interaction networks are one of the major post-genomic data sources available to molecular biologists. They provide a comprehensive view of the global interaction structure of an organism's proteome, as well as detailed information on specific interactions. Here we suggest a physical model of protein interactions that can be used to extract additional information at an intermediate level: It enables us to identify proteins which share biological interaction motifs, and also to identify potentially missing or spurious interactions.Results: Our new graph model explains observed interactions between proteins by an underlying interaction of complementary binding domains (lock-and-key model). This leads to a novel graph-theoretical algorithm to identify bipartite subgraphs within protein-protein interaction networks where the underlying data are taken from yeast two-hybrid experimental results. By testing on synthetic data, we demonstrate that under certain modelling assumptions, the algorithm will return correct domain information about each protein in the network. Tests on data from various model organisms show that the local and global patterns predicted by the model are indeed found in experimental data. Using functional and protein structure annotations, we show that bipartite subnetworks can be identified that correspond to biologically relevant interaction motifs. Some of these are novel and we discuss an example involving SH3 domains from the Saccharomyces cerevisiae interactome.