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Letter

Multimeric Threading-Based Prediction of Protein–Protein Interactions on a Genomic Scale: Application to the Saccharomyces cerevisiae Proteome

¹ Center of Excellence in Bioinformatics, University at Buffalo, Buffalo, New York 14203, USA ² Department of Biochemistry and Molecular Biophysics, Washington University Medical School, St. Louis, Missouri 63110, USA ³ Department of Bioengineering, University of Illinois at Chicago, Chicago, Illinois 60612, USA

MULTIPROSPECTOR, a multimeric threading algorithm for the prediction of protein–protein interactions, is applied to the genome of Saccharomyces cerevisiae. Each possible pairwise interaction among more than 6000 encoded proteins is evaluated against a dimer database of 768 complex structures by using a confidence estimate of the fold assignment and the magnitude of the statistical interfacial potentials. In total, 7321 interactions between pairs of different proteins are predicted, based on 304 complex structures. Quality estimation based on the coincidence of subcellular localizations and biological functions of the predicted interactors shows that our approach ranks third when compared with all other large-scale methods. Unlike other in silico methods, MULTIPROSPECTOR is able to identify the residues that participate directly in the interaction. Three hundred seventy-four of our predictions can be found by at least one of the other studies, which is compatible with the overlap between two different other methods. From the analysis of the mRNA abundance data, our method does not bias towards proteins with high abundance. Finally, several relevant predictions involved in various functions are presented. In summary, we provide a novel approach to predict protein–protein interactions on a genomic scale that is a useful complement to experimental methods.

⁴ Corresponding author.
E-MAIL skolnick{at}buffalo.edu; FAX (716) 849-6747.

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