title: Development of a novel bioinformatics tool for in silico validation of protein interactions.
abstract: Protein interactions are crucial in most biological processes. Several in silico methods have been recently developed to predict them. This paper describes a bioinformatics method that combines sequence similarity and structural information to support experimental studies on protein interactions. Given a target protein, the approach selects the most likely interactors among the candidates revealed by experimental techniques, but not yet in vivo validated. The sequence and the structural information of the in vivo confirmed proteins and complexes are exploited to evaluate the candidate interactors. Finally, a score is calculated to suggest the most likely interactors of the target protein. As an example, we searched for GRB2 interactors. We ranked a set of 46 candidate interactors by the presented method. These candidates were then reduced to 21, through a score threshold chosen by means of a cross-validation strategy. Among them, the isoform 1 of MAPK14 was in silico confirmed as a GRB2 interactor. Finally, given a set of already confirmed interactors of GRB2, the accuracy and the precision of the approach were 75% and 86%, respectively. In conclusion, the proposed method can be conveniently exploited to select the proteins to be experimentally investigated within a set of potential interactors.
authors.affiliation: Laboratory of Biomedical Informatics, Department of Computer Science and Systems, University of Pavia, Pavia, Italy. nicola.barbarini@unipv.it
authors.forename: Nicola
authors.initials: N
authors.lastname: Barbarini
authors.forename: Luca
authors.initials: L
authors.lastname: Simonelli
authors.forename: Alberto
authors.initials: A
authors.lastname: Azzalin
authors.forename: Sergio
authors.initials: S
authors.lastname: Comincini
authors.forename: Riccardo
authors.initials: R
authors.lastname: Bellazzi
mesh_terms: D020816:Amino Acid Motifs; D019295:Computational Biology / Q000379:methods*; D030562:Databases, Protein; D051380:GRB2 Adaptor Protein / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006860:Hydrogen Bonding; D019950:Mitogen-Activated Protein Kinase 1 / Q000737:chemistry / Q000378:metabolism; D048308:Mitogen-Activated Protein Kinase 14 / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D025941:Protein Interaction Mapping / Q000379:methods*; D015203:Reproducibility of Results; D016415:Sequence Alignment
chemical_list: D051380:GRB2 Adaptor Protein; D046912:Multiprotein Complexes; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048308:Mitogen-Activated Protein Kinase 14