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

Ignacio E. Sanchez, Pedro Beltrao, Francois Stricher, Joost Schymkowitz, Jesper Ferkinghoff-Borg, Frederic Rousseau, Luis Serrano

Research output: Contribution to journalJournal articleResearchpeer-review

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
Original languageEnglish
JournalP L o S Computational Biology (Online)
Volume4
Issue number4
Pages (from-to)e1000052
ISSN1553-7358
DOIs
Publication statusPublished - 2008

Cite this

Sanchez, I. E., Beltrao, P., Stricher, F., Schymkowitz, J., Ferkinghoff-Borg, J., Rousseau, F., & Serrano, L. (2008). Genome-Wide Prediction of SH2 Domain Targets Using Structural Information and the FoldX Algorithm. P L o S Computational Biology (Online), 4(4), e1000052. https://doi.org/10.1371/journal.pcbi.1000052
Sanchez, Ignacio E. ; Beltrao, Pedro ; Stricher, Francois ; Schymkowitz, Joost ; Ferkinghoff-Borg, Jesper ; Rousseau, Frederic ; Serrano, Luis. / Genome-Wide Prediction of SH2 Domain Targets Using Structural Information and the FoldX Algorithm. In: P L o S Computational Biology (Online). 2008 ; Vol. 4, No. 4. pp. e1000052.
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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",
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Sanchez, IE, Beltrao, P, Stricher, F, Schymkowitz, J, Ferkinghoff-Borg, J, Rousseau, F & Serrano, L 2008, 'Genome-Wide Prediction of SH2 Domain Targets Using Structural Information and the FoldX Algorithm', P L o S Computational Biology (Online), vol. 4, no. 4, pp. e1000052. https://doi.org/10.1371/journal.pcbi.1000052

Genome-Wide Prediction of SH2 Domain Targets Using Structural Information and the FoldX Algorithm. / Sanchez, Ignacio E.; Beltrao, Pedro; Stricher, Francois; Schymkowitz, Joost; Ferkinghoff-Borg, Jesper; Rousseau, Frederic; Serrano, Luis.

In: P L o S Computational Biology (Online), Vol. 4, No. 4, 2008, p. e1000052.

Research output: Contribution to journalJournal articleResearchpeer-review

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AU - Sanchez, Ignacio E.

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AU - Ferkinghoff-Borg, Jesper

AU - Rousseau, Frederic

AU - Serrano, Luis

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