Predicting protein-protein interactions on a proteome scale by matching evolutionary and structural similarities at interfaces using PRISM

Gursoy, Attila
Tunçbağ, Nurcan
Keskin, Ozlem
Prediction of protein-protein interactions at the structural level on the proteome scale is important because it allows prediction of protein function, helps drug discovery and takes steps toward genome-wide structural systems biology. We provide a protocol (termed PRISM, protein interactions by structural matching) for large-scale prediction of protein-protein interactions and assembly of protein complex structures. The method consists of two components: rigid-body structural comparisons of target proteins to known template protein-protein interfaces and flexible refinement using a docking energy function. The PRISM rationale follows our observation that globally different protein structures can interact via similar architectural motifs. PRISM predicts binding residues by using structural similarity and evolutionary conservation of putative binding residue 'hot spots'. Ultimately, PRISM could help to construct cellular pathways and functional, proteome-scale annotation. PRISM is implemented in Python and runs in a UNIX environment. The program accepts Protein Data Bank-formatted protein structures and is available at


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Keskin, Ozlem; Tunçbağ, Nurcan; Gursoy, Attila (2016-04-27)
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Prediction of Protein Interactions by Structural Matching: Prediction of PPI Networks and the Effects of Mutations on PPIs that Combines Sequence and Structural Information
Tunçbağ, Nurcan; Nussinov, Ruth; Gursoy, Attila (Humana Press Inc., 2017)
Structural details of protein interactions are invaluable to the understanding of cellular processes. However, the identification of interactions at atomic resolution is a continuing challenge in the systems biology era. Although the number of structurally resolved complexes in the Protein Databank increases exponentially, the complexes only cover a small portion of the known structural interactome. In this chapter, we review the PRISM system that is a protein–protein interaction (PPI) prediction tool—its r...
Citation Formats
A. Gursoy, N. Tunçbağ, R. NUSSINOV, and O. Keskin, “Predicting protein-protein interactions on a proteome scale by matching evolutionary and structural similarities at interfaces using PRISM,” NATURE PROTOCOLS, pp. 1341–1354, 2011, Accessed: 00, 2020. [Online]. Available: