Struct2Net: a web service to predict protein–protein interactions using a structure-based approach

Struct2Net is a web server for predicting interactions between arbitrary protein pairs using a structure-based approach. Prediction of protein–protein interactions (PPIs) is a central area of interest and successful prediction would provide leads for experiments and drug design; however, the experimental coverage of the PPI interactome remains inadequate. We believe that Struct2Net is the first community-wide resource to provide structure-based PPI predictions that go beyond homology modeling. Also, most web-resources for predicting PPIs currently rely on functional genomic data (e.g. GO annotation, gene expression, cellular localization, etc.). Our structure-based approach is independent of such methods and only requires the sequence information of the proteins being queried. The web service allows multiple querying options, aimed at maximizing flexibility. For the most commonly studied organisms (fly, human and yeast), predictions have been pre-computed and can be retrieved almost instantaneously. For proteins from other species, users have the option of getting a quick-but-approximate result (using orthology over pre-computed results) or having a full-blown computation performed. The web service is freely available at http://struct2net.csail.mit.edu.

[1]  K. Gunsalus,et al.  Empirically controlled mapping of the Caenorhabditis elegans protein-protein interactome network , 2009, Nature Methods.

[2]  Ting Chen,et al.  An integrated approach to the prediction of domain-domain interactions , 2006, BMC Bioinformatics.

[3]  José A. Encinar,et al.  ADAN: a database for prediction of protein-protein interaction of modular domains mediated by linear motifs , 2009, Bioinform..

[4]  T. Ideker,et al.  Modeling cellular machinery through biological network comparison , 2006, Nature Biotechnology.

[5]  Hui Lu,et al.  Development of unified statistical potentials describing protein-protein interactions. , 2003, Biophysical journal.

[6]  Geoffrey J. Barton,et al.  SNAPPI-DB: a database and API of Structures, iNterfaces and Alignments for Protein–Protein Interactions , 2007, Nucleic Acids Res..

[7]  B. Berger,et al.  Herpesviral Protein Networks and Their Interaction with the Human Proteome , 2006, Science.

[8]  T. N. Bhat,et al.  The Protein Data Bank , 2000, Nucleic Acids Res..

[9]  Serafim Batzoglou,et al.  Integrated Protein Interaction Networks for 11 Microbes , 2006, RECOMB.

[10]  Carlos Prieto,et al.  APID: Agile Protein Interaction DataAnalyzer , 2006, Nucleic Acids Res..

[11]  Ziv Bar-Joseph,et al.  Evaluation of different biological data and computational classification methods for use in protein interaction prediction , 2006, Proteins.

[12]  Bonnie Berger,et al.  Global alignment of multiple protein interaction networks with application to functional orthology detection , 2008, Proceedings of the National Academy of Sciences.

[13]  Bonnie Berger,et al.  LTHREADER: Prediction of extracellular ligand–receptor interactions in cytokines using localized threading , 2008, Protein science : a publication of the Protein Society.

[14]  Robert B. Russell,et al.  3did: interacting protein domains of known three-dimensional structure , 2004, Nucleic Acids Res..

[15]  I. Jurisica,et al.  Unequal evolutionary conservation of human protein interactions in interologous networks , 2007, Genome Biology.

[16]  Robert B. Russell,et al.  InterPreTS: protein Interaction Prediction through Tertiary Structure , 2003, Bioinform..

[17]  Ming Li,et al.  Assessment of RAPTOR's linear programming approach in CAFASP3 , 2003, Proteins.

[18]  Y. Zhang,et al.  IntAct—open source resource for molecular interaction data , 2006, Nucleic Acids Res..

[19]  A. Barabasi,et al.  An empirical framework for binary interactome mapping , 2008, Nature Methods.

[20]  Robert D. Finn,et al.  iPfam: visualization of protein?Cprotein interactions in PDB at domain and amino acid resolutions , 2005, Bioinform..

[21]  Jinbo Xu,et al.  Template‐based and free modeling by RAPTOR++ in CASP8 , 2009, Proteins.

[22]  See-Kiong Ng,et al.  InterDom: a database of putative interacting protein domains for validating predicted protein interactions and complexes , 2003, Nucleic Acids Res..

[23]  Gabriele Ausiello,et al.  MINT: the Molecular INTeraction database , 2006, Nucleic Acids Res..

[24]  Kyungsook Han,et al.  PSIbase: a database of Protein Structural Interactome map (PSIMAP) , 2005, Bioinform..

[25]  Patrick Aloy,et al.  Interrogating protein interaction networks through structural biology , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[26]  Huan-Xiang Zhou,et al.  Nonadditive effects of mixed crowding on protein stability , 2009, Proteins.

[27]  Bonnie Berger,et al.  Optimal contact map alignment of protein–protein interfaces , 2008, Bioinform..

[28]  D. Koller,et al.  InSite: a computational method for identifying protein-protein interaction binding sites on a proteome-wide scale , 2007, Genome Biology.

[29]  Andrew Chatr-aryamontri,et al.  DOMINO: a database of domain–peptide interactions , 2006, Nucleic Acids Res..

[30]  Christian von Mering,et al.  STRING 8—a global view on proteins and their functional interactions in 630 organisms , 2008, Nucleic Acids Res..

[31]  Arne Elofsson,et al.  Quantitative assessment of the structural bias in protein–protein interaction assays , 2008, Proteomics.

[32]  C. Prieto,et al.  Structural domain–domain interactions: Assessment and comparison with protein–protein interaction data to improve the interactome , 2010, Proteins.

[33]  Takeshi Kawabata,et al.  Prediction of interacting proteins from homology-modeled complex structures using sequence and structure scores , 2007, Biophysics.

[34]  Bonnie Berger,et al.  Struct2Net: Integrating Structure into Protein-Protein Interaction Prediction , 2005, Pacific Symposium on Biocomputing.

[35]  Takeshi Kawabata,et al.  HOMCOS: a server to predict interacting protein pairs and interacting sites by homology modeling of complex structures , 2008, Nucleic Acids Res..

[36]  Fred P. Davis,et al.  PIBASE: a comprehensive database of structurally defined protein interfaces , 2005, Bioinform..

[37]  Hui Lu,et al.  Multimeric threading-based prediction of protein-protein interactions on a genomic scale: application to the Saccharomyces cerevisiae proteome. , 2003, Genome research.

[38]  Kara Dolinski,et al.  The BioGRID Interaction Database: 2008 update , 2008, Nucleic Acids Res..

[39]  M. Gerstein,et al.  Annotation transfer between genomes: protein-protein interologs and protein-DNA regulogs. , 2004, Genome research.

[40]  Marc A. Martí-Renom,et al.  MODBASE: a database of annotated comparative protein structure models and associated resources , 2005, Nucleic Acids Res..