title: An estimated 5% of new protein structures solved today represent a new Pfam family.
abstract: High-resolution structural knowledge is key to understanding how proteins function at the molecular level. The number of entries in the Protein Data Bank (PDB), the repository of all publicly available protein structures, continues to increase, with more than 8000 structures released in 2012 alone. The authors of this article have studied how structural coverage of the protein-sequence space has changed over time by monitoring the number of Pfam families that acquired their first representative structure each year from 1976 to 2012. Twenty years ago, for every 100 new PDB entries released, an estimated 20 Pfam families acquired their first structure. By 2012, this decreased to only about five families per 100 structures. The reasons behind the slower pace at which previously uncharacterized families are being structurally covered were investigated. It was found that although more than 50% of current Pfam families are still without a structural representative, this set is enriched in families that are small, functionally uncharacterized or rich in problem features such as intrinsically disordered and transmembrane regions. While these are important constraints, the reasons why it may not yet be time to give up the pursuit of a targeted but more comprehensive structural coverage of the protein-sequence space are discussed.
authors.affiliation: European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, England.
authors.forename: Jaina
authors.initials: J
authors.lastname: Mistry
authors.forename: Edda
authors.initials: E
authors.lastname: Kloppmann
authors.forename: Burkhard
authors.initials: B
authors.lastname: Rost
authors.forename: Marco
authors.initials: M
authors.lastname: Punta
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics; D018360:Crystallography, X-Ray; D030562:Databases, Protein / Q000592:standards / Q000639:trends; D006801:Humans; D008958:Models, Molecular; D005810:Multigene Family; D046912:Multiprotein Complexes / Q000737:chemistry* / Q000235:genetics; D055503:Protein Multimerization / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D046912:Multiprotein Complexes; D043562:Receptors, G-Protein-Coupled
keywords: Pfam families; protein-sequence space; structural coverage