TY - JOUR
T1 - Genome-Wide Prediction of SH2 Domain Targets Using Structural Information and the FoldX Algorithm
AU - Sanchez, Ignacio E.
AU - Beltrao, Pedro
AU - Stricher, Francois
AU - Schymkowitz, Joost
AU - Ferkinghoff-Borg, Jesper
AU - Rousseau, Frederic
AU - Serrano, Luis
PY - 2008
Y1 - 2008
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
AB - 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
U2 - 10.1371/journal.pcbi.1000052
DO - 10.1371/journal.pcbi.1000052
M3 - Journal article
C2 - 18389064
VL - 4
SP - e1000052
JO - P L o S Computational Biology (Online)
JF - P L o S Computational Biology (Online)
SN - 1553-7358
IS - 4
ER -