iWRAP: An Interface Threading Approach with Application to Prediction of Cancer-Related Protein–Protein Interactions
Author(s)Hosur, Raghavendra; Xu, Jinbo; Berger, Bonnie; Bienkowska, Jadwiga R.
MetadataShow full item record
Current homology modeling methods for predicting protein–protein interactions (PPIs) have difficulty in the “twilight zone” (< 40%) of sequence identities. Threading methods extend coverage further into the twilight zone by aligning primary sequences for a pair of proteins to a best-fit template complex to predict an entire three-dimensional structure. We introduce a threading approach, iWRAP, which focuses only on the protein interface. Our approach combines a novel linear programming formulation for interface alignment with a boosting classifier for interaction prediction. We demonstrate its efficacy on SCOPPI, a classification of PPIs in the Protein Databank, and on the entire yeast genome. iWRAP provides significantly improved prediction of PPIs and their interfaces in stringent cross-validation on SCOPPI. Furthermore, by combining our predictions with a full-complex threader, we achieve a coverage of 13% for the yeast PPIs, which is close to a 50% increase over previous methods at a higher sensitivity. As an application, we effectively combine iWRAP with genomic data to identify novel cancer-related genes involved in chromatin remodeling, nucleosome organization, and ribonuclear complex assembly. iWRAP is available at http://iwrap.csail.mit.edu.
DepartmentMassachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory; Massachusetts Institute of Technology. Department of Materials Science and Engineering; Massachusetts Institute of Technology. Department of Mathematics
Journal of Molecular Biology
Hosur, Raghavendra, Jinbo Xu, Jadwiga Bienkowska, and Bonnie Berger. “iWRAP: An Interface Threading Approach with Application to Prediction of Cancer-Related Protein–Protein Interactions.” Journal of Molecular Biology 405, no. 5 (February 2011): 1295–1310.
Author's final manuscript