Using Genome-Wide Measurements for Computational Prediction of SH2–Peptide Interactions

DSpace/Manakin Repository

Using Genome-Wide Measurements for Computational Prediction of SH2–Peptide Interactions

Citable link to this page


Title: Using Genome-Wide Measurements for Computational Prediction of SH2–Peptide Interactions
Author: Wunderlich, Zeba Batool; Mirny, Leonid Alex

Note: Order does not necessarily reflect citation order of authors.

Citation: Wunderlich, Zeba, and Leonid A. Mirny. 2009. Using genome-wide measurements for computational prediction of SH2–peptide interactions. Nucleic Acids Research 37(14): 4629-4641.
Full Text & Related Files:
Abstract: Peptide-recognition modules (PRMs) are used throughout biology to mediate protein–protein interactions, and many PRMs are members of large protein domain families. Recent genome-wide measurements describe networks of peptide–PRM interactions. In these networks, very similar PRMs recognize distinct sets of peptides, raising the question of how peptide-recognition specificity is achieved using similar protein domains. The analysis of individual protein complex structures often gives answers that are not easily applicable to other members of the same PRM family. Bioinformatics-based approaches, one the other hand, may be difficult to interpret physically. Here we integrate structural information with a large, quantitative data set of SH2 domain–peptide interactions to study the physical origin of domain–peptide specificity. We develop an energy model, inspired by protein folding, based on interactions between the amino-acid positions in the domain and peptide. We use this model to successfully predict which SH2 domains and peptides interact and uncover the positions in each that are important for specificity. The energy model is general enough that it can be applied to other members of the SH2 family or to new peptides, and the cross-validation results suggest that these energy calculations will be useful for predicting binding interactions. It can also be adapted to study other PRM families, predict optimal peptides for a given SH2 domain, or study other biological interactions, e.g. protein–DNA interactions.
Published Version: doi: 10.1093/nar/gkp394
Other Sources:
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at
Citable link to this page:
Downloads of this work:

Show full Dublin Core record

This item appears in the following Collection(s)


Search DASH

Advanced Search