title: Quaternary structure predictions of transmembrane proteins starting from the monomer: a docking-based approach.
abstract: BACKGROUND
  We introduce a computational protocol for effective predictions of the supramolecular organization of integral transmembrane proteins, starting from the monomer. Despite the demonstrated constitutive and functional importance of supramolecular assemblies of transmembrane subunits or proteins, effective tools for structure predictions of such assemblies are still lacking. Our computational approach consists in rigid-body docking samplings, starting from the docking of two identical copies of a given monomer. Each docking run is followed by membrane topology filtering and cluster analysis. Prediction of the native oligomer is therefore accomplished by a number of progressive growing steps, each made of one docking run, filtering and cluster analysis. With this approach, knowledge about the oligomerization status of the protein is required neither for improving sampling nor for the filtering step. Furthermore, there are no size-limitations in the systems under study, which are not limited to the transmembrane domains but include also the water-soluble portions.
  
  
  RESULTS
  Benchmarks of the approach were done on ten homo-oligomeric membrane proteins with known quaternary structure. For all these systems, predictions led to native-like quaternary structures, i.e. with Calpha-RMSDs lower than 2.5 A from the native oligomer, regardless of the resolution of the structural models.
  
  
  CONCLUSIONS
  Collectively, the results of this study emphasize the effectiveness of the prediction protocol that will be extensively challenged in quaternary structure predictions of other integral membrane proteins.
authors.affiliation: Department of Chemistry, Dulbecco Telethon Institute, University of Modena e Reggio Emilia, Via Campi 183, 41100 Modena, Italy. casciari.daniele@unimo.it
authors.forename: D
authors.initials: D
authors.lastname: Casciari
authors.forename: M
authors.initials: M
authors.lastname: Seeber
authors.forename: F
authors.initials: F
authors.lastname: Fanelli
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D003198:Computer Simulation; D019281:Dimerization; D008565:Membrane Proteins / Q000737:chemistry* / Q000648:ultrastructure*; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000737:chemistry* / Q000648:ultrastructure*; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D016415:Sequence Alignment / Q000379:methods; D020539:Sequence Analysis, Protein / Q000379:methods*
chemical_list: D008565:Membrane Proteins; D046912:Multiprotein Complexes