title: Coverage of protein domain families with structural protein-protein interactions: current progress and future trends.
abstract: Protein interactions have evolved into highly precise and regulated networks adding an immense layer of complexity to cellular systems. The most accurate atomistic description of protein binding sites can be obtained directly from structures of protein complexes. The availability of structurally characterized protein interfaces significantly improves our understanding of interactomes, and the progress in structural characterization of protein-protein interactions (PPIs) can be measured by calculating the structural coverage of protein domain families. We analyze the coverage of protein domain families (defined according to CDD and Pfam databases) by structures, structural protein-protein complexes and unique protein binding sites. Structural PPI coverage of currently available protein families is about 30% without any signs of saturation in coverage growth dynamics. Given the current growth rates of domain databases and structural PPI deposition, complete domain coverage with PPIs is not expected in the near future. As a result of this study we identify families without any protein-protein interaction evidence (listed on a supporting website http://www.ncbi.nlm.nih.gov/Structure/ibis/coverage/) and propose them as potential targets for structural studies with a focus on protein interactions.
authors.affiliation: Computational Biology Branch of the National Center for Biotechnology Information in Bethesda, Maryland, United States.
authors.forename: Alexander
authors.initials: A
authors.lastname: Goncearenco
authors.affiliation: Computational Biology Branch of the National Center for Biotechnology Information in Bethesda, Maryland, United States.
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Shoemaker
authors.affiliation: Computational Biology Branch of the National Center for Biotechnology Information in Bethesda, Maryland, United States.
authors.forename: Dachuan
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Computational Biology Branch of the National Center for Biotechnology Information in Bethesda, Maryland, United States.
authors.forename: Alexey
authors.initials: A
authors.lastname: Sarychev
authors.affiliation: Computational Biology Branch of the National Center for Biotechnology Information in Bethesda, Maryland, United States. Electronic address: panch@ncbi.nlm.nih.gov.
authors.forename: Anna R
authors.initials: AR
authors.lastname: Panchenko
mesh_terms: D001665:Binding Sites; D019295:Computational Biology; D030562:Databases, Protein; D025941:Protein Interaction Mapping / Q000379:methods* / Q000639:trends*; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D011506:Proteins
keywords: Coverage of protein families; PPI; Protein binding sites; Protein–protein interactions; Structural genomics