Characterization of Domain–Peptide
Interaction
Interface: Prediction of SH3 Domain-Mediated Protein–Protein
Interaction Network in Yeast by Generic Structure-Based Models
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Abstract
Determination of the binding specificity of SH3 domain,
a peptide
recognition module (PRM), is important to understand their biological
functions and reconstruct the SH3-mediated protein–protein
interaction network. In the present study, the SH3-peptide interactions
for both class I and II SH3 domains were characterized by the intermolecular
residue–residue interaction network. We developed generic MIEC-SVM
models to infer SH3 domain-peptide recognition specificity that achieved
satisfactory prediction accuracy. By investigating the domain–peptide
recognition mechanisms at the residue level, we found that the class-I
and class-II binding peptides have different binding modes even though
they occupy the same binding site of SH3. Furthermore, we predicted
the potential binding partners of SH3 domains in the yeast proteome
and constructed the SH3-mediated protein–protein interaction
network. Comparison with the experimentally determined interactions
confirmed the effectiveness of our approach. This study showed that
our sophisticated computational approach not only provides a powerful
platform to decipher protein recognition code at the molecular level
but also allows identification of peptide-mediated protein interactions
at a proteomic scale. We believe that such an approach is general
to be applicable to other domain–peptide interactions