title: GPCR-SSFE: a comprehensive database of G-protein-coupled receptor template predictions and homology models.
abstract: BACKGROUND
  G protein-coupled receptors (GPCRs) transduce a wide variety of extracellular signals to within the cell and therefore have a key role in regulating cell activity and physiological function. GPCR malfunction is responsible for a wide range of diseases including cancer, diabetes and hyperthyroidism and a large proportion of drugs on the market target these receptors. The three dimensional structure of GPCRs is important for elucidating the molecular mechanisms underlying these diseases and for performing structure-based drug design. Although structural data are restricted to only a handful of GPCRs, homology models can be used as a proxy for those receptors not having crystal structures. However, many researchers working on GPCRs are not experienced homology modellers and are therefore unable to benefit from the information that can be gleaned from such three-dimensional models. Here, we present a comprehensive database called the GPCR-SSFE, which provides initial homology models of the transmembrane helices for a large variety of family A GPCRs.
  
  
  METHODS
  Extending on our previous theoretical work, we have developed an automated pipeline for GPCR homology modelling and applied it to a large set of family A GPCR sequences. Our pipeline is a fragment-based approach that exploits available family A crystal structures. The GPCR-SSFE database stores the template predictions, sequence alignments, identified sequence and structure motifs and homology models for 5025 family A GPCRs. Users are able to browse the GPCR dataset according to their pharmacological classification or search for results using a UniProt entry name. It is also possible for a user to submit a GPCR sequence that is not contained in the database for analysis and homology model building. The models can be viewed using a Jmol applet and are also available for download along with the alignments.
  
  
  CONCLUSIONS
  The data provided by GPCR-SSFE are useful for investigating general and detailed sequence-structure-function relationships of GPCRs, performing structure-based drug design and for better understanding the molecular mechanisms underlying disease-associated mutations in GPCRs. The effectiveness of our multiple template and fragment approach is demonstrated by the accuracy of our predicted homology models compared to recently published crystal structures.
authors: Leibniz-Institut für Molekulare Pharmakologie, 13125 Berlin, Germany.
authors: Catherine L
authors: CL
authors: Worth
authors: Annika
authors: A
authors: Kreuchwig
authors: Gunnar
authors: G
authors: Kleinau
authors: Gerd
authors: G
authors: Krause
references: J Med Chem. 2009 Aug 27;52(16):5207-16
references: 19627087
references: J Mol Model. 2011 May;17(5):1207-21
references: 20661609
references: Nat Rev Drug Discov. 2009 Jun;8(6):455-63
references: 19461661
references: Science. 2008 Nov 21;322(5905):1211-7
references: 18832607
references: Hum Mutat. 2010 Jun;31(6):E1519-25
references: 20513138
references: J Biol Chem. 2008 Jun 27;283(26):17753-6
references: 18463093
references: Nucleic Acids Res. 2010 Jan;38(Database issue):D142-8
references: 19843607
references: Proteins. 2010 Aug 1;78(10):2189-201
references: 20544957
references: Nucleic Acids Res. 2009 Jul;37(Web Server issue):W571-4
references: 19429894
references: Bioinformatics. 2010 Jul 15;26(14):1804-5
references: 20501551
references: J Mol Biol. 1993 Dec 5;234(3):779-815
references: 8254673
references: Mol Pharmacol. 2005 May;67(5):1414-25
references: 15687224
references: Science. 2010 Nov 19;330(6007):1066-71
references: 20929726
references: Nature. 2007 Nov 15;450(7168):383-7
references: 17952055
references: Protein Sci. 2006 Nov;15(11):2507-24
references: 17075131
references: PLoS Comput Biol. 2006 Feb;2(2):e13
references: 16485037
references: Nucleic Acids Res. 2000 Jan 1;28(1):235-42
references: 10592235
references: Nature. 2008 May 15;453(7193):363-7
references: 18480818
references: BMC Bioinformatics. 2008 Jan 23;9:40
references: 18215316
references: Mol Endocrinol. 2006 Sep;20(9):2247-55
references: 16543405
references: Database (Oxford). 2010 Aug 05;2010:baq019
references: 20689020
references: Biochem Pharmacol. 2009 Jul 1;78(1):11-20
references: 19447219
references: Science. 2000 Aug 4;289(5480):739-45
references: 10926528
references: Science. 2007 Nov 23;318(5854):1258-65
references: 17962520
references: Science. 2010 Nov 19;330(6007):1091-5
references: 21097933
references: Curr Opin Drug Discov Devel. 2010 May;13(3):317-25
references: 20443165
references: Proteins. 2009;77 Suppl 9:100-13
references: 19768687
references: PLoS One. 2009 Sep 16;4(9):e7011
references: 19756152
references: Nature. 2008 Jul 24;454(7203):486-91
references: 18594507
references: Nucleic Acids Res. 2009 Jan;37(Database issue):D680-5
references: 18948278
references: Mol Pharmacol. 2003 Jun;63(6):1256-72
references: 12761335
references: J Med Chem. 2009 May 28;52(10):3166-73
references: 19397376
references: Nucleic Acids Res. 1998 Jan 1;26(1):275-9
references: 9399852