Blog
About

  • Record: found
  • Abstract: found
  • Article: found
Is Open Access

M-ORBIS: Mapping of mOleculaR Binding sItes and Surfaces

1 , 2 , 1 , * , 1

Nucleic Acids Research

Oxford University Press

Read this article at

Bookmark
      There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

      Abstract

      M-ORBIS is a Molecular Cartography approach that performs integrative high-throughput analysis of structural data to localize all types of binding sites and associated partners by homology and to characterize their properties and behaviors in a systemic way. The robustness of our binding site inferences was compared to four curated datasets corresponding to protein heterodimers and homodimers and protein–DNA/RNA assemblies. The Molecular Cartographies of structurally well-detailed proteins shows that 44% of their surfaces interact with non-solvent partners. Residue contact frequencies with water suggest that ∼86% of their surfaces are transiently solvated, whereas only 15% are specifically solvated. Our analysis also reveals the existence of two major binding site families: specific binding sites which can only bind one type of molecule (protein, DNA, RNA, etc.) and polyvalent binding sites that can bind several distinct types of molecule. Specific homodimer binding sites are for instance nearly twice as hydrophobic than previously described and more closely resemble the protein core, while polyvalent binding sites able to form homo and heterodimers more closely resemble the surfaces involved in crystal packing. Similarly, the regions able to bind DNA and to alternatively form homodimers, are more hydrophobic and less polar than previously described DNA binding sites.

      Related collections

      Most cited references 46

      • Record: found
      • Abstract: found
      • Article: not found

      Inference of macromolecular assemblies from crystalline state.

      We discuss basic physical-chemical principles underlying the formation of stable macromolecular complexes, which in many cases are likely to be the biological units performing a certain physiological function. We also consider available theoretical approaches to the calculation of macromolecular affinity and entropy of complexation. The latter is shown to play an important role and make a major effect on complex size and symmetry. We develop a new method, based on chemical thermodynamics, for automatic detection of macromolecular assemblies in the Protein Data Bank (PDB) entries that are the results of X-ray diffraction experiments. As found, biological units may be recovered at 80-90% success rate, which makes X-ray crystallography an important source of experimental data on macromolecular complexes and protein-protein interactions. The method is implemented as a public WWW service.
        Bookmark
        • Record: found
        • Abstract: found
        • Article: not found

        Amino acid substitution matrices from protein blocks.

        Methods for alignment of protein sequences typically measure similarity by using a substitution matrix with scores for all possible exchanges of one amino acid with another. The most widely used matrices are based on the Dayhoff model of evolutionary rates. Using a different approach, we have derived substitution matrices from about 2000 blocks of aligned sequence segments characterizing more than 500 groups of related proteins. This led to marked improvements in alignments and in searches using queries from each of the groups.
          Bookmark
          • Record: found
          • Abstract: found
          • Article: not found

          The Universal Protein Resource (UniProt)

          The Universal Protein Resource (UniProt) provides the scientific community with a single, centralized, authoritative resource for protein sequences and functional information. Formed by uniting the Swiss-Prot, TrEMBL and PIR protein database activities, the UniProt consortium produces three layers of protein sequence databases: the UniProt Archive (UniParc), the UniProt Knowledgebase (UniProt) and the UniProt Reference (UniRef) databases. The UniProt Knowledgebase is a comprehensive, fully classified, richly and accurately annotated protein sequence knowledgebase with extensive cross-references. This centrepiece consists of two sections: UniProt/Swiss-Prot, with fully, manually curated entries; and UniProt/TrEMBL, enriched with automated classification and annotation. During 2004, tens of thousands of Knowledgebase records got manually annotated or updated; we introduced a new comment line topic: TOXIC DOSE to store information on the acute toxicity of a toxin; the UniProt keyword list got augmented by additional keywords; we improved the documentation of the keywords and are continuously overhauling and standardizing the annotation of post-translational modifications. Furthermore, we introduced a new documentation file of the strains and their synonyms. Many new database cross-references were introduced and we started to make use of Digital Object Identifiers. We also achieved in collaboration with the Macromolecular Structure Database group at EBI an improved integration with structural databases by residue level mapping of sequences from the Protein Data Bank entries onto corresponding UniProt entries. For convenient sequence searches we provide the UniRef non-redundant sequence databases. The comprehensive UniParc database stores the complete body of publicly available protein sequence data. The UniProt databases can be accessed online (http://www.uniprot.org) or downloaded in several formats (ftp://ftp.uniprot.org/pub). New releases are published every two weeks.
            Bookmark

            Author and article information

            Affiliations
            1Department of Biology and Structural Genomics, IGBMC, Illkirch, 67404 and 2Department of Structural Bioinformatics, BIONEXT, Boulogne Billancourt, 92100, France
            Author notes
            *To whom correspondence should be addressed. Tel: +33 3 88 65 32 94; Fax: +33 3 88 65 32 76; Email: poch@ 123456igbmc.fr
            Journal
            Nucleic Acids Res
            nar
            nar
            Nucleic Acids Research
            Oxford University Press
            0305-1048
            1362-4962
            January 2011
            January 2011
            2 September 2010
            2 September 2010
            : 39
            : 1
            : 30-43
            3017595
            20813758
            10.1093/nar/gkq736
            gkq736
            © The Author(s) 2010. Published by Oxford University Press.

            This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

            Categories
            Computational Biology

            Genetics

            Comments

            Comment on this article