Constructing structural networks of signaling pathways on the proteome scale

Guray Kuzu, Ozlem Keskin, Attila Gursoy, Ruth Nussinov

Research output: Contribution to journalReview articlepeer-review

Abstract

Proteins function through their interactions, and the availability of protein interaction networks could help in understanding cellular processes. However, the known structural data are limited and the classical network node-and-edge representation, where proteins are nodes and interactions are edges, shows only which proteins interact; not how they interact. Structural networks provide this information. Protein-protein interface structures can also indicate which binding partners can interact simultaneously and which are competitive, and can help forecasting potentially harmful drug side effects. Here, we use a powerful protein-protein interactions prediction tool which is able to carry out accurate predictions on the proteome scale to construct the structural network of the extracellular signal-regulated kinases (ERK) in the mitogen-activated protein kinase (MAPK) signaling pathway. This knowledge-based method, PRISM, is motif-based, and is combined with flexible refinement and energy scoring. PRISM predicts protein interactions based on structural and evolutionary similarity to known protein interfaces.

Original languageEnglish
Pages (from-to)367-377
Number of pages11
JournalCurrent Opinion in Structural Biology
Volume22
Issue number3
DOIs
StatePublished - Jun 2012

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