Structure-based prediction of protein–protein interactions on a genome-wide scale
添加于 2012/10/30 15:43:29 2283次阅读 | 0次推荐 | 3个评论
The genome-wide identification of pairs of interacting proteins is an important step in the elucidation of cell regulatory mechanisms1, 2. Much of our present knowledge derives from high-throughput techniques such as the yeast two-hybrid assay and affinity purification3, as well as from manual curation of experiments on individual systems4. A variety of computational approaches based, for example, on sequence homology, gene co-expression and phylogenetic profiles, have also been developed for the genome-wide inference of protein–protein interactions (PPIs)5, 6. Yet comparative studies suggest that the development of accurate and complete repertoires of PPIs is still in its early stages7, 8, 9. Here we show that three-dimensional structural information can be used to predict PPIs with an accuracy and coverage that are superior to predictions based on non-structural evidence. Moreover, an algorithm, termed PrePPI, which combines structural information with other functional clues, is comparable in accuracy to high-throughput experiments, yielding over 30,000 high-confidence interactions for yeast and over 300,000 for human. Experimental tests of a number of predictions demonstrate the ability of the PrePPI algorithm to identify unexpected PPIs of considerable biological interest. The surprising effectiveness of three-dimensional structural information can be attributed to the use of homology models combined with the exploitation of both close and remote geometric relationships between proteins.
Qiangfeng Cliff Zhang, Donald Petrey, Lei Deng, Li Qiang, Yu Shi, Chan Aye Thu, Brygida Bisikirska, Celine Lefebvre, Domenico Accili, Tony Hunter, Tom Maniatis, Andrea Califano & Barry Honig
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生命科学 » 生物物理、生物化学与分子生物学 » 蛋白质组学