title: iFrag: A Protein-Protein Interface Prediction Server Based on Sequence Fragments.
abstract: Protein-protein interactions (PPIs) are crucial in many biological processes. The first step towards the molecular characterisation of PPIs implies the charting of their interfaces, that is, the surfaces mediating the interaction. To this end, we present here iFrag, a sequence-based computational method that infers possible interacting regions between two proteins by searching minimal common sequence fragments of the interacting protein pairs. By utilising the sequences of two interacting proteins (queries), iFrag derives a two-dimensional matrix computing a score for each pair of residues that relates to the presence of similar regions in interolog protein pairs. The scoring matrix is represented as a heat map reflecting the potential interface regions in both query proteins. Unlike existing approaches, iFrag does not require three-dimensional structural information or multiple sequence alignments and can even predict small interaction sites consisting only of few residues. Thus, predicted interfaces range from short fragments composed of few residues to domains of proteins, depending on available information on PPIs, as we demonstrate in several examples. Moreover, as a proof of concept, we include the experimental validation on the successful prediction of a peptide competing with the aggregation of β-amyloid in Alzheimer's disease. iFrag is freely accessible at http://sbi.imim.es/iFrag.
authors.affiliation: Structural Bioinformatics Laboratory, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, C/Doctor Aiguader 88, 08003 Barcelona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Garcia-Garcia
authors.affiliation: Laboratory of Molecular Physiology, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, C/Doctor Aiguader 88, 08003 Barcelona, Spain.
authors.forename: Victòria
authors.initials: V
authors.lastname: Valls-Comamala
authors.affiliation: Center for Complex Network Research and Department of Physics, Northeastern University, Boston, 02115, MA, USA; Joint IRB-BSC-CRG Program in Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), C/Baldiri Reixac 10-12, 08028 Barcelona, Spain.
authors.forename: Emre
authors.initials: E
authors.lastname: Guney
authors.affiliation: Laboratory of Proteomics and Protein Chemistry, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, C/Doctor Aiguader 88, 08003 Barcelona, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Andreu
authors.affiliation: Laboratory of Molecular Physiology, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, C/Doctor Aiguader 88, 08003 Barcelona, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Muñoz
authors.affiliation: Institute of Biological, Environmental and Rural Sciences, Aberystwyth University, Gogerddan Campus, SY23 3EB Aberystwyth, UK.
authors.forename: Narcis
authors.initials: N
authors.lastname: Fernandez-Fuentes
authors.affiliation: Structural Bioinformatics Laboratory, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, C/Doctor Aiguader 88, 08003 Barcelona, Spain. Electronic address: baldo.oliva@upf.edu.
authors.forename: Baldo
authors.initials: B
authors.lastname: Oliva
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry; D019295:Computational Biology; D030562:Databases, Protein; D006801:Humans; D020407:Internet; D011487:Protein Conformation; D025941:Protein Interaction Mapping; D011506:Proteins / Q000737:chemistry; D015203:Reproducibility of Results; D016415:Sequence Alignment; D020539:Sequence Analysis, Protein; D012984:Software
chemical_list: D016229:Amyloid beta-Peptides; D011506:Proteins
keywords: binding site prediction; interface prediction; protein interactions; β-amyloid aggregation