Home LiteratureArticle Details
PMID: 17868464 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

InSite: a computational method for identifying protein-protein interaction binding sites on a proteome-wide scale.

Genome biology ·Vol. 8 ·No. 9 ·2007-00-00 ·Pages R192

Wang H, Segal E, Ben-Hur A, Li QR, Vidal M, Koller D

Abstract

We propose InSite, a computational method that integrates high-throughput protein and sequence data to infer the specific binding regions of interacting protein pairs. We compared our predictions with binding sites in Protein Data Bank and found significantly more binding events occur at sites we predicted. Several regions containing disease-causing mutations or cancer polymorphisms in human are predicted to be binding for protein pairs related to the disease, which suggests novel mechanistic hypotheses for several diseases.

MeSH Terms
Algorithms Computational Biology/methods Databases, Protein Electronic Data Processing Gene Expression Profiling Humans Polymorphism, Genetic Protein Binding Protein Interaction Mapping/methods Proteome Proteomics Saccharomyces cerevisiae/metabolism Software Two-Hybrid System Techniques
Chemicals
Proteome
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Wang Haidong
Computer Science Department, Stanford University, Serra Mall, Stanford, CA 94305, USA. haidong@cs.stanford.edu
Segal Eran
Ben-Hur Asa
Li Qian-Ru
Vidal Marc
Koller Daphne
References (76)
76 references, click to expand
  1. The Pfam protein families database.
    Nucleic Acids Res. 2004 Jan 1;32(Database issue):D138-41 PMID: 14681378
  2. Are protein-protein interfaces more conserved in sequence than the rest of the protein surface?
    Protein Sci. 2004 Jan;13(1):190-202 PMID: 14691234
  3. Prediction of protein-protein interaction sites using support vector machines.
    Protein Eng Des Sel. 2004 Feb;17(2):165-73 PMID: 15047913
  4. Predicting co-complexed protein pairs using genomic and proteomic data integration.
    BMC Bioinformatics. 2004 Apr 16;5:38 PMID: 15090078
  5. Protein interaction maps for complete genomes based on gene fusion events.
    Nature. 1999 Nov 4;402(6757):86-90 PMID: 10573422
  6. The Protein Data Bank.
    Nucleic Acids Res. 2000 Jan 1;28(1):235-42 PMID: 10592235
  7. Towards a proteome-scale map of the human protein-protein interaction network.
    Nature. 2005 Oct 20;437(7062):1173-8 PMID: 16189514
  8. A haploid-specific transcriptional response to irradiation in Saccharomyces cerevisiae.
    Nucleic Acids Res. 2005;33(20):6635-43 PMID: 16321968
  9. Effects of iodine on global gene expression in Saccharomyces cerevisiae.
    Biosci Biotechnol Biochem. 2005 Dec;69(12):2285-93 PMID: 16377885
  10. Pfam: clans, web tools and services.
    Nucleic Acids Res. 2006 Jan 1;34(Database issue):D247-51 PMID: 16381856
  11. Discovery of biological networks from diverse functional genomic data.
    Genome Biol. 2005;6(13):R114 PMID: 16420673
  12. Proteome survey reveals modularity of the yeast cell machinery.
    Nature. 2006 Mar 30;440(7084):631-6 PMID: 16429126
  13. Global landscape of protein complexes in the yeast Saccharomyces cerevisiae.
    Nature. 2006 Mar 30;440(7084):637-43 PMID: 16554755
  14. Choosing negative examples for the prediction of protein-protein interactions.
    BMC Bioinformatics. 2006;7 Suppl 1:S2 PMID: 16723005
  15. An integrated approach to the prediction of domain-domain interactions.
    BMC Bioinformatics. 2006;7:269 PMID: 16725050
  16. CONTRAfold: RNA secondary structure prediction without physics-based models.
    Bioinformatics. 2006 Jul 15;22(14):e90-8 PMID: 16873527
  17. Co-evolutionary analysis of domains in interacting proteins reveals insights into domain-domain interactions mediating protein-protein interactions.
    J Mol Biol. 2006 Sep 29;362(4):861-75 PMID: 16949097
  18. Relating three-dimensional structures to protein networks provides evolutionary insights.
    Science. 2006 Dec 22;314(5807):1938-41 PMID: 17185604
  19. Protein interaction mapping in C. elegans using proteins involved in vulval development.
    Science. 2000 Jan 7;287(5450):116-22 PMID: 10615043
  20. A comprehensive analysis of protein-protein interactions in Saccharomyces cerevisiae.
    Nature. 2000 Feb 10;403(6770):623-7 PMID: 10688190
  21. Gene ontology: tool for the unification of biology. The Gene Ontology Consortium.
    Nat Genet. 2000 May;25(1):25-9 PMID: 10802651
  22. Genome-wide protein interaction maps using two-hybrid systems.
    FEBS Lett. 2000 Aug 25;480(1):32-6 PMID: 10967325
  23. Genomic expression programs in the response of yeast cells to environmental changes.
    Mol Biol Cell. 2000 Dec;11(12):4241-57 PMID: 11102521
  24. Brevican is degraded by matrix metalloproteinases and aggrecanase-1 (ADAMTS4) at different sites.
    J Biol Chem. 2000 Dec 8;275(49):38885-90 PMID: 10986281
  25. The EMOTIF database.
    Nucleic Acids Res. 2001 Jan 1;29(1):202-4 PMID: 11125091
  26. Remodeling of yeast genome expression in response to environmental changes.
    Mol Biol Cell. 2001 Feb;12(2):323-37 PMID: 11179418
  27. A comprehensive two-hybrid analysis to explore the yeast protein interactome.
    Proc Natl Acad Sci U S A. 2001 Apr 10;98(8):4569-74 PMID: 11283351
  28. Structural basis of transcription: RNA polymerase II at 2.8 angstrom resolution.
    Science. 2001 Jun 8;292(5523):1863-76 PMID: 11313498
  29. Correlated sequence-signatures as markers of protein-protein interaction.
    J Mol Biol. 2001 Aug 24;311(4):681-92 PMID: 11518523
  30. Genomic expression responses to DNA-damaging agents and the regulatory role of the yeast ATR homolog Mec1p.
    Mol Biol Cell. 2001 Oct;12(10):2987-3003 PMID: 11598186
  31. MIPS: a database for genomes and protein sequences.
    Nucleic Acids Res. 2002 Jan 1;30(1):31-4 PMID: 11752246
  32. The PROSITE database, its status in 2002.
    Nucleic Acids Res. 2002 Jan 1;30(1):235-8 PMID: 11752303
  33. DIP, the Database of Interacting Proteins: a research tool for studying cellular networks of protein interactions.
    Nucleic Acids Res. 2002 Jan 1;30(1):303-5 PMID: 11752321
  34. Functional organization of the yeast proteome by systematic analysis of protein complexes.
    Nature. 2002 Jan 10;415(6868):141-7 PMID: 11805826
  35. Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry.
    Nature. 2002 Jan 10;415(6868):180-3 PMID: 11805837
  36. Rosetta in CASP4: progress in ab initio protein structure prediction.
    Proteins. 2001;Suppl 5:119-26 PMID: 11835488
  37. Dissecting protein-protein recognition sites.
    Proteins. 2002 May 15;47(3):334-43 PMID: 11948787
  38. Interrogating protein interaction networks through structural biology.
    Proc Natl Acad Sci U S A. 2002 Apr 30;99(9):5896-901 PMID: 11972061
  39. Comparative assessment of large-scale data sets of protein-protein interactions.
    Nature. 2002 May 23;417(6887):399-403 PMID: 12000970
  40. A third osmosensing branch in Saccharomyces cerevisiae requires the Msb2 protein and functions in parallel with the Sho1 branch.
    Mol Cell Biol. 2002 Jul;22(13):4739-49 PMID: 12052881
  41. Inferring domain-domain interactions from protein-protein interactions.
    Genome Res. 2002 Oct;12(10):1540-8 PMID: 12368246
  42. The Usher syndrome proteins cadherin 23 and harmonin form a complex by means of PDZ-domain interactions.
    Proc Natl Acad Sci U S A. 2002 Nov 12;99(23):14946-51 PMID: 12407180
  43. Beta-hydroxyaspartic acid in the first epidermal growth factor-like domain of protein C. Its role in Ca2+ binding and biological activity.
    J Biol Chem. 1988 Dec 15;263(35):19240-8 PMID: 2461936
  44. Proapoptotic protein Bax heterodimerizes with Bcl-2 and homodimerizes with Bax via a novel domain (BH3) distinct from BH1 and BH2.
    J Biol Chem. 1996 Mar 29;271(13):7440-4 PMID: 8631771
  45. Structure-function analysis of Bcl-2 family proteins. Regulators of programmed cell death.
    Adv Exp Med Biol. 1996;406:99-112 PMID: 8910675
  46. harakiri, a novel regulator of cell death, encodes a protein that activates apoptosis and interacts selectively with survival-promoting proteins Bcl-2 and Bcl-X(L).
    EMBO J. 1997 Apr 1;16(7):1686-94 PMID: 9130713
  47. Exploring the metabolic and genetic control of gene expression on a genomic scale.
    Science. 1997 Oct 24;278(5338):680-6 PMID: 9381177
  48. Hematopoietic malignancies demonstrate loss-of-function mutations of BAX.
    Blood. 1998 Apr 15;91(8):2991-7 PMID: 9531611
  49. Fyn and ZAP-70 are required for Vav phosphorylation in T cells stimulated by antigen-presenting cells.
    J Biol Chem. 1998 Nov 27;273(48):31932-8 PMID: 9822663
  50. A dynamic programming algorithm for RNA structure prediction including pseudoknots.
    J Mol Biol. 1999 Feb 5;285(5):2053-68 PMID: 9925784
  51. Detecting protein function and protein-protein interactions from genome sequences.
    Science. 1999 Jul 30;285(5428):751-3 PMID: 10427000
  52. A probabilistic functional network of yeast genes.
    Science. 2004 Nov 26;306(5701):1555-8 PMID: 15567862
  53. eBLOCKs: enumerating conserved protein blocks to achieve maximal sensitivity and specificity.
    Nucleic Acids Res. 2005 Jan 1;33(Database issue):D178-82 PMID: 15608172
  54. Online Mendelian Inheritance in Man (OMIM), a knowledgebase of human genes and genetic disorders.
    Nucleic Acids Res. 2005 Jan 1;33(Database issue):D514-7 PMID: 15608251
  55. Winchester syndrome caused by a homozygous mutation affecting the active site of matrix metalloproteinase 2.
    Clin Genet. 2005 Mar;67(3):261-6 PMID: 15691365
  56. Statistical analysis of domains in interacting protein pairs.
    Bioinformatics. 2005 Apr 1;21(7):993-1001 PMID: 15509600
  57. Transcriptional response of Saccharomyces cerevisiae to the plasma membrane-perturbing compound chitosan.
    Eukaryot Cell. 2005 Apr;4(4):703-15 PMID: 15821130
  58. Dynamical remodeling of the transcriptome during short-term anaerobiosis in Saccharomyces cerevisiae: differential response and role of Msn2 and/or Msn4 and other factors in galactose and glucose media.
    Mol Cell Biol. 2005 May;25(10):4075-91 PMID: 15870279
  59. Inferring protein-protein interactions through high-throughput interaction data from diverse organisms.
    Bioinformatics. 2005 Aug 1;21(15):3279-85 PMID: 15905281
  60. Probabilistic model of the human protein-protein interaction network.
    Nat Biotechnol. 2005 Aug;23(8):951-9 PMID: 16082366
  61. A human protein-protein interaction network: a resource for annotating the proteome.
    Cell. 2005 Sep 23;122(6):957-68 PMID: 16169070
  62. Inferring protein domain interactions from databases of interacting proteins.
    Genome Biol. 2005;6(10):R89 PMID: 16207360
  63. Predicting domain-domain interactions using a parsimony approach.
    Genome Biol. 2006;7(11):R104 PMID: 17094802
  64. Patterns of somatic mutation in human cancer genomes.
    Nature. 2007 Mar 8;446(7132):153-8 PMID: 17344846
  65. Large-scale mapping of human protein-protein interactions by mass spectrometry.
    Mol Syst Biol. 2007;3:89 PMID: 17353931
  66. The AnnoLite and AnnoLyze programs for comparative annotation of protein structures.
    BMC Bioinformatics. 2007;8 Suppl 4:S4 PMID: 17570147
  67. A three-helix homo-oligomerization domain containing BH3 and BH1 is responsible for the apoptotic activity of Bax.
    Genes Dev. 2007 Aug 1;21(15):1937-48 PMID: 17671092
  68. Protein interactions and disease: computational approaches to uncover the etiology of diseases.
    Brief Bioinform. 2007 Sep;8(5):333-46 PMID: 17638813
  69. Integrative approach for computationally inferring protein domain interactions.
    Bioinformatics. 2003 May 22;19(8):923-9 PMID: 12761053
  70. Predicted protein-protein interaction sites from local sequence information.
    FEBS Lett. 2003 Jun 5;544(1-3):236-9 PMID: 12782323
  71. Multimeric threading-based prediction of protein-protein interactions on a genomic scale: application to the Saccharomyces cerevisiae proteome.
    Genome Res. 2003 Jun;13(6A):1146-54 PMID: 12799350
  72. Protein-protein docking with simultaneous optimization of rigid-body displacement and side-chain conformations.
    J Mol Biol. 2003 Aug 1;331(1):281-99 PMID: 12875852
  73. Development of human protein reference database as an initial platform for approaching systems biology in humans.
    Genome Res. 2003 Oct;13(10):2363-71 PMID: 14525934
  74. Learning to predict protein-protein interactions from protein sequences.
    Bioinformatics. 2003 Oct 12;19(15):1875-81 PMID: 14555619
  75. A Bayesian networks approach for predicting protein-protein interactions from genomic data.
    Science. 2003 Oct 17;302(5644):449-53 PMID: 14564010
  76. A protein interaction map of Drosophila melanogaster.
    Science. 2003 Dec 5;302(5651):1727-36 PMID: 14605208
Article Info
Journal
Genome biology
Abbr.
Genome Biol
ISSN
1474-760X
DOI
10.1186/gb-2007-8-9-r192
Email
haidong@cs.stanford.edu
Published
2007-00-00
Pages
R192
Language
English
Region
England
NLM ID
100960660
PMCID
PMC2375030
Subset
IM
External Links
PubMed source DOI: 10.1186/gb-2007-8-9-r192 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2