title: 3DIANA: 3D Domain Interaction Analysis: A Toolbox for Quaternary Structure Modeling.
abstract: Electron microscopy (EM) is experiencing a revolution with the advent of a new generation of Direct Electron Detectors, enabling a broad range of large and flexible structures to be resolved well below 1 nm resolution. Although EM techniques are evolving to the point of directly obtaining structural data at near-atomic resolution, for many molecules the attainable resolution might not be enough to propose high-resolution structural models. However, accessing information on atomic coordinates is a necessary step toward a deeper understanding of the molecular mechanisms that allow proteins to perform specific tasks. For that reason, methods for the integration of EM three-dimensional maps with x-ray and NMR structural data are being developed, a modeling task that is normally referred to as fitting, resulting in the so called hybrid models. In this work, we present a novel application-3DIANA-specially targeted to those cases in which the EM map resolution is medium or low and additional experimental structural information is scarce or even lacking. In this way, 3DIANA statistically evaluates proposed/potential contacts between protein domains, presents a complete catalog of both structurally resolved and predicted interacting regions involving these domains and, finally, suggests structural templates to model the interaction between them. The evaluation of the proposed interactions is computed with DIMERO, a new method that scores physical binding sites based on the topology of protein interaction networks, which has recently shown the capability to increase by 200% the number of domain-domain interactions predicted in interactomes as compared to previous approaches. The new application displays the information at a sequence and structural level and is accessible through a web browser or as a Chimera plugin at http://3diana.cnb.csic.es.
authors.affiliation: GN7, Spanish National Institute for Bioinformatics (INB) and Biocomputing Unit, National Center of Biotechnology (CSIC)/Instruct Image Processing Center, Madrid, Spain. Electronic address: jsegura@cnb.csic.es.
authors.forename: Joan
authors.initials: J
authors.lastname: Segura
authors.affiliation: GN7, Spanish National Institute for Bioinformatics (INB) and Biocomputing Unit, National Center of Biotechnology (CSIC)/Instruct Image Processing Center, Madrid, Spain.
authors.forename: Ruben
authors.initials: R
authors.lastname: Sanchez-Garcia
authors.affiliation: GN7, Spanish National Institute for Bioinformatics (INB) and Biocomputing Unit, National Center of Biotechnology (CSIC)/Instruct Image Processing Center, Madrid, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Tabas-Madrid
authors.affiliation: GN7, Spanish National Institute for Bioinformatics (INB) and Biocomputing Unit, National Center of Biotechnology (CSIC)/Instruct Image Processing Center, Madrid, Spain.
authors.forename: Jesus
authors.initials: J
authors.lastname: Cuenca-Alba
authors.affiliation: GN7, Spanish National Institute for Bioinformatics (INB) and Biocomputing Unit, National Center of Biotechnology (CSIC)/Instruct Image Processing Center, Madrid, Spain.
authors.forename: Carlos Oscar S
authors.initials: CO
authors.lastname: Sorzano
authors.affiliation: GN7, Spanish National Institute for Bioinformatics (INB) and Biocomputing Unit, National Center of Biotechnology (CSIC)/Instruct Image Processing Center, Madrid, Spain.
authors.forename: Jose Maria
authors.initials: JM
authors.lastname: Carazo
mesh_terms: D021621:Imaging, Three-Dimensional; D008854:Microscopy, Electron; D008958:Models, Molecular; D011485:Protein Binding; D000072417:Protein Domains; D020836:Protein Structure, Quaternary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D018167:Receptors, Calcitriol / Q000737:chemistry / Q000378:metabolism; D047488:Retinoid X Receptors / Q000737:chemistry / Q000378:metabolism
chemical_list: D011506:Proteins; D018167:Receptors, Calcitriol; D047488:Retinoid X Receptors