Genome-Wide Prediction of SH2 Domain Targets Using Structural Information and the FoldX Algorithm

@article{10.1371/journal.pcbi.1000052, abstract = {Current experiments likely cover only a fraction of all protein-protein interactions. Here, we developed a method to predict SH2-mediated protein-protein interactions using the structure of SH2-phosphopeptide complexes and the FoldX algorithm. We show that our approach performs similarly to experimentally derived consensus sequences and substitution matrices at predicting known in vitro and in vivo targets of SH2 domains. We use our method to provide a set of high-confidence interactions for human SH2 domains with known structure filtered on secondary structure and phosphorylation state. We validated the predictions using literature-derived SH2 interactions and a probabilistic score obtained from a naive Bayes integration of information on coexpression, conservation of the interaction in other species, shared interaction partners, and functions. We show how our predictions lead to a new hypothesis for the role of SH2 domains in signaling.}, author = {S\'{a}nchez, Ignacio E. and Beltrao, Pedro and Stricher, Francois and Schymkowitz, Joost and Borg, Jesper F. and Rousseau, Frederic and Serrano, Luis }, citeulike-article-id = {2643283}, doi = {http://dx.doi.org/10.1371/journal.pcbi.1000052}, journal = {PLoS Comput Biol}, keywords = {bioinformatics, interaction, protein-protein, sh2, specificity}, month = {Apr}, number = {4}, posted-at = {2008-04-09 02:23:44}, priority = {2}, publisher = {Public Library of Science}, title = {Genome-Wide Prediction of SH2 Domain Targets Using Structural Information and the FoldX Algorithm}, url = {http://dx.doi.org/10.1371/journal.pcbi.1000052}, volume = {4}, year = {2008} }

TY - JOUR ID - 10.1371/journal.pcbi.1000052 L3 - citeulike-article-id:2643283 TI - Genome-Wide Prediction of SH2 Domain Targets Using Structural Information and the FoldX Algorithm JF - PLoS Comput Biol VL - 4 IS - 4 PB - Public Library of Science N2 - Current experiments likely cover only a fraction of all protein-protein interactions. Here, we developed a method to predict SH2-mediated protein-protein interactions using the structure of SH2-phosphopeptide complexes and the FoldX algorithm. We show that our approach performs similarly to experimentally derived consensus sequences and substitution matrices at predicting known in vitro and in vivo targets of SH2 domains. We use our method to provide a set of high-confidence interactions for human SH2 domains with known structure filtered on secondary structure and phosphorylation state. We validated the predictions using literature-derived SH2 interactions and a probabilistic score obtained from a naive Bayes integration of information on coexpression, conservation of the interaction in other species, shared interaction partners, and functions. We show how our predictions lead to a new hypothesis for the role of SH2 domains in signaling. KW - bioinformatics KW - interaction KW - protein-protein KW - sh2 KW - specificity AU - Sánchez, Ignacio AU - Beltrao, Pedro AU - Stricher, Francois AU - Schymkowitz, Joost AU - Borg, Jesper AU - Rousseau, Frederic AU - Serrano, Luis PY - 2008/Apr// UR - http://dx.doi.org/10.1371/journal.pcbi.1000052 ER -