title: Constructing structural networks of signaling pathways on the proteome scale.
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.
authors.affiliation: Center for Computational Biology and Bioinformatics and College of Engineering, Koc University Rumelifeneri Yolu, 34450 Sariyer Istanbul, Turkey.
authors.forename: Guray
authors.initials: G
authors.lastname: Kuzu
authors.forename: Ozlem
authors.initials: O
authors.lastname: Keskin
authors.forename: Attila
authors.initials: A
authors.lastname: Gursoy
authors.forename: Ruth
authors.initials: R
authors.lastname: Nussinov
mesh_terms: D000818:Animals; D015195:Drug Design; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D011487:Protein Conformation; D025941:Protein Interaction Mapping; D060066:Protein Interaction Maps; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D020543:Proteome / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D011506:Proteins; D020543:Proteome