SH3-SPOT: An algorithm to predict preferred ligands to different members of the SH3 gene family

Barbara Brannetti, Allegra Via, Gianluca Cestra, Gianni Cesareni, Manuela Helmer Citterich

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

We have developed a procedure to predict the peptide binding specificity of an SH3 domain from its sequence. The procedure utilizes information extracted from position-specific contacts derived from six SH3/peptide or SH3/protein complexes of known structure. The framework of SH3/peptide contacts defined on the structure of the complexes is used to build a residue-residue interaction database derived from ligands obtained by panning peptide libraries displayed on filamentous phage. The SH3-specific interaction database is a multidimensional array containing frequencies of position-specific contacts. As input, SH3-SPOT requires the sequence of an SH3 domain and of a query decapeptide ligand. The array, that we call the SH3-specific matrix, is then used to evaluate the probability that the peptide would bind the given SH3 domain. This procedure is fast enough to be applied to the entire protein sequence database. Panning experiments were performed to search putative specific ligands of different SH3 domains in a database of decapeptides, or in a database of protein sequences. The procedure ranked some of the natural partners of interaction of a number of SH3 domains among the best ligands of the ~5.6 x 109 different decapeptides in the SWISSPROT database. We expect the predictive power of the method to increase with the enrichment of the SH3-specific matrix by interaction data derived from new complex structures or from the characterization of new ligands. The procedure was developed using the SH3 domain family as test case but its application can easily be extended to other families of protein domains (such as, SH2, MHC, EH, PDZ, etc.). (C) 2000 Academic Press.

Original languageEnglish
Pages (from-to)313-328
Number of pages16
JournalJournal of Molecular Biology
Volume298
Issue number2
DOIs
Publication statusPublished - Apr 28 2000

Fingerprint

src Homology Domains
Ligands
Databases
Genes
Protein Databases
Peptides
Peptide Library
Bacteriophages
Proteins

Keywords

  • Bioinformatics
  • Prediction
  • Protein/peptide interaction
  • SH3 domain
  • Specificity

ASJC Scopus subject areas

  • Virology

Cite this

SH3-SPOT : An algorithm to predict preferred ligands to different members of the SH3 gene family. / Brannetti, Barbara; Via, Allegra; Cestra, Gianluca; Cesareni, Gianni; Citterich, Manuela Helmer.

In: Journal of Molecular Biology, Vol. 298, No. 2, 28.04.2000, p. 313-328.

Research output: Contribution to journalArticle

Brannetti, Barbara ; Via, Allegra ; Cestra, Gianluca ; Cesareni, Gianni ; Citterich, Manuela Helmer. / SH3-SPOT : An algorithm to predict preferred ligands to different members of the SH3 gene family. In: Journal of Molecular Biology. 2000 ; Vol. 298, No. 2. pp. 313-328.
@article{b62468921a2e4c9fa76528af94890b1f,
title = "SH3-SPOT: An algorithm to predict preferred ligands to different members of the SH3 gene family",
abstract = "We have developed a procedure to predict the peptide binding specificity of an SH3 domain from its sequence. The procedure utilizes information extracted from position-specific contacts derived from six SH3/peptide or SH3/protein complexes of known structure. The framework of SH3/peptide contacts defined on the structure of the complexes is used to build a residue-residue interaction database derived from ligands obtained by panning peptide libraries displayed on filamentous phage. The SH3-specific interaction database is a multidimensional array containing frequencies of position-specific contacts. As input, SH3-SPOT requires the sequence of an SH3 domain and of a query decapeptide ligand. The array, that we call the SH3-specific matrix, is then used to evaluate the probability that the peptide would bind the given SH3 domain. This procedure is fast enough to be applied to the entire protein sequence database. Panning experiments were performed to search putative specific ligands of different SH3 domains in a database of decapeptides, or in a database of protein sequences. The procedure ranked some of the natural partners of interaction of a number of SH3 domains among the best ligands of the ~5.6 x 109 different decapeptides in the SWISSPROT database. We expect the predictive power of the method to increase with the enrichment of the SH3-specific matrix by interaction data derived from new complex structures or from the characterization of new ligands. The procedure was developed using the SH3 domain family as test case but its application can easily be extended to other families of protein domains (such as, SH2, MHC, EH, PDZ, etc.). (C) 2000 Academic Press.",
keywords = "Bioinformatics, Prediction, Protein/peptide interaction, SH3 domain, Specificity",
author = "Barbara Brannetti and Allegra Via and Gianluca Cestra and Gianni Cesareni and Citterich, {Manuela Helmer}",
year = "2000",
month = "4",
day = "28",
doi = "10.1006/jmbi.2000.3670",
language = "English",
volume = "298",
pages = "313--328",
journal = "Journal of Molecular Biology",
issn = "0022-2836",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - SH3-SPOT

T2 - An algorithm to predict preferred ligands to different members of the SH3 gene family

AU - Brannetti, Barbara

AU - Via, Allegra

AU - Cestra, Gianluca

AU - Cesareni, Gianni

AU - Citterich, Manuela Helmer

PY - 2000/4/28

Y1 - 2000/4/28

N2 - We have developed a procedure to predict the peptide binding specificity of an SH3 domain from its sequence. The procedure utilizes information extracted from position-specific contacts derived from six SH3/peptide or SH3/protein complexes of known structure. The framework of SH3/peptide contacts defined on the structure of the complexes is used to build a residue-residue interaction database derived from ligands obtained by panning peptide libraries displayed on filamentous phage. The SH3-specific interaction database is a multidimensional array containing frequencies of position-specific contacts. As input, SH3-SPOT requires the sequence of an SH3 domain and of a query decapeptide ligand. The array, that we call the SH3-specific matrix, is then used to evaluate the probability that the peptide would bind the given SH3 domain. This procedure is fast enough to be applied to the entire protein sequence database. Panning experiments were performed to search putative specific ligands of different SH3 domains in a database of decapeptides, or in a database of protein sequences. The procedure ranked some of the natural partners of interaction of a number of SH3 domains among the best ligands of the ~5.6 x 109 different decapeptides in the SWISSPROT database. We expect the predictive power of the method to increase with the enrichment of the SH3-specific matrix by interaction data derived from new complex structures or from the characterization of new ligands. The procedure was developed using the SH3 domain family as test case but its application can easily be extended to other families of protein domains (such as, SH2, MHC, EH, PDZ, etc.). (C) 2000 Academic Press.

AB - We have developed a procedure to predict the peptide binding specificity of an SH3 domain from its sequence. The procedure utilizes information extracted from position-specific contacts derived from six SH3/peptide or SH3/protein complexes of known structure. The framework of SH3/peptide contacts defined on the structure of the complexes is used to build a residue-residue interaction database derived from ligands obtained by panning peptide libraries displayed on filamentous phage. The SH3-specific interaction database is a multidimensional array containing frequencies of position-specific contacts. As input, SH3-SPOT requires the sequence of an SH3 domain and of a query decapeptide ligand. The array, that we call the SH3-specific matrix, is then used to evaluate the probability that the peptide would bind the given SH3 domain. This procedure is fast enough to be applied to the entire protein sequence database. Panning experiments were performed to search putative specific ligands of different SH3 domains in a database of decapeptides, or in a database of protein sequences. The procedure ranked some of the natural partners of interaction of a number of SH3 domains among the best ligands of the ~5.6 x 109 different decapeptides in the SWISSPROT database. We expect the predictive power of the method to increase with the enrichment of the SH3-specific matrix by interaction data derived from new complex structures or from the characterization of new ligands. The procedure was developed using the SH3 domain family as test case but its application can easily be extended to other families of protein domains (such as, SH2, MHC, EH, PDZ, etc.). (C) 2000 Academic Press.

KW - Bioinformatics

KW - Prediction

KW - Protein/peptide interaction

KW - SH3 domain

KW - Specificity

UR - http://www.scopus.com/inward/record.url?scp=0034724569&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034724569&partnerID=8YFLogxK

U2 - 10.1006/jmbi.2000.3670

DO - 10.1006/jmbi.2000.3670

M3 - Article

C2 - 10764600

AN - SCOPUS:0034724569

VL - 298

SP - 313

EP - 328

JO - Journal of Molecular Biology

JF - Journal of Molecular Biology

SN - 0022-2836

IS - 2

ER -