title: Modeling Complexes of Transmembrane Proteins: Systematic Analysis of ProteinProtein Docking Tools.
abstract: Proteinprotein docking methodology is frequently used to model complexes of transmembrane proteins, in particular oligomers of G protein-coupled receptors (GPCRs), even if its applicability for these systems has never been fully validated. The aim of this work is to perform a systematic study on the suitability of some widely-used proteinprotein docking software for modeling complexes of transmembrane proteins. In this study we tested the programs ZDOCK, ClusPro, HEX, GRAMM-X, PatchDock, SymmDock, and HADDOCK, using a set of membrane protein oligomers for which the 3D structure has been obtained experimentally, including opsin dimer, the recently published chemokine CXCR4 and kappa opioid receptor dimers. The results show that the docking success depends on the applied docking algorithm and scoring functions, but also on inherent structural features of the transmembrane proteins. Thus, proteins with large interface surfaces, rich in surface cavities, high-order symmetry, and small conformational change upon complex formation are well predicted more often than proteins without these features. The results of this systematic analysis provide guidelines that can be used for obtaining reliable models of transmembrane proteins, including GPCRs. Therefore they can be useful for the application of structure-based methods in drug discovery projects involving these targets.
authors.affiliation: Research Programme on Biomedical Informatics (GRIB), Department of Experimental and Health Sciences, Universitat Pompeu Fabra, IMIM (Hospital del Mar Medical Research Institute). Dr. Aiguader 88, Barcelona, Spain phone: +48 815357365, fax: +48 815357355; phone: +34 933160515, fax: +34 93 316 0550. agnieszka.kaczor@umlub.pl.|Department of Synthesis and Chemical Technology of Pharmaceutical Substances with Computer Modelling Lab, Faculty of Pharmacy with Division for Medical Analytics, Medical University of Lublin 4A Chodźki St., PL-20059 Lublin, Poland. agnieszka.kaczor@umlub.pl.
authors.forename: Agnieszka A
authors.initials: AA
authors.lastname: Kaczor
authors.affiliation: Research Programme on Biomedical Informatics (GRIB), Department of Experimental and Health Sciences, Universitat Pompeu Fabra, IMIM (Hospital del Mar Medical Research Institute). Dr. Aiguader 88, Barcelona, Spain phone: +48 815357365, fax: +48 815357355; phone: +34 933160515, fax: +34 93 316 0550. jana.selent@upf.edu.
authors.forename: Jana
authors.initials: J
authors.lastname: Selent
authors.affiliation: Research Programme on Biomedical Informatics (GRIB), Department of Experimental and Health Sciences, Universitat Pompeu Fabra, IMIM (Hospital del Mar Medical Research Institute). Dr. Aiguader 88, Barcelona, Spain phone: +48 815357365, fax: +48 815357355; phone: +34 933160515, fax: +34 93 316 0550.
authors.forename: Ferran
authors.initials: F
authors.lastname: Sanz
authors.affiliation: Research Programme on Biomedical Informatics (GRIB), Department of Experimental and Health Sciences, Universitat Pompeu Fabra, IMIM (Hospital del Mar Medical Research Institute). Dr. Aiguader 88, Barcelona, Spain phone: +48 815357365, fax: +48 815357355; phone: +34 933160515, fax: +34 93 316 0550.
authors.forename: Manuel
authors.initials: M
authors.lastname: Pastor
keywords: Docking algorithms; G protein-coupled receptor dimers; Protein complexes; Proteinprotein docking; Transmembrane proteins