Multimeric threading-based prediction of protein-protein interactions on a genomic scale: application to the Saccharomyces cerevisiae proteome.
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.
Lu
Long
L
Center of Excellence in Bioinformatics, University at Buffalo, Buffalo, New York 14203, USA.
Arakaki
Adrian K
AK
Lu
Hui
H
Skolnick
Jeffrey
J
D004271:DNA, Fungal / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D005656:Fungal Proteins / Q000235:genetics / Q000502:physiology; D016681:Genome, Fungal; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000502:physiology; D011495:Histone-Lysine N-Methyltransferase; D046911:Macromolecular Substances; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology; D011237:Predictive Value of Tests; D011485:Protein Binding / Q000235:genetics / Q000502:physiology; D017510:Protein Folding; D025941:Protein Interaction Mapping / Q000379:methods*; D011494:Protein Kinases / Q000235:genetics / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000235:genetics / Q000502:physiology; D011484:Protein-Arginine N-Methyltransferases; D020543:Proteome; D012331:RNA, Fungal / Q000378:metabolism; D011995:Recombination, Genetic / Q000502:physiology; D012261:Ribonucleoproteins / Q000235:genetics / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000502:physiology; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins / Q000235:genetics / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology; D018631:ras Proteins / Q000235:genetics / Q000502:physiology
D004271:DNA, Fungal; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C076227:GCR1 protein, S cerevisiae; D020662:Guanine Nucleotide Exchange Factors; C115602:Lcp5 protein, S cerevisiae; C111098:MPP10 protein, S cerevisiae; C094801:MSH5 protein, S cerevisiae; D046911:Macromolecular Substances; D009687:Nuclear Proteins; D010750:Phosphoproteins; D020543:Proteome; C440829:RAP1 protein, S cerevisiae; D012331:RNA, Fungal; D012261:Ribonucleoproteins; C115954:SDC25 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins; D014157:Transcription Factors; C081647:high affinity DNA-binding factor, S cerevisiae; D011484:Protein-Arginine N-Methyltransferases; C120666:HSL7 protein, S cerevisiae; C416235:Dot1 protein, S cerevisiae; D011495:Histone-Lysine N-Methyltransferase; D011494:Protein Kinases; D018631:ras Proteins