title: Membrane protein orientation and refinement using a knowledge-based statistical potential.
abstract: BACKGROUND
  Recent increases in the number of deposited membrane protein crystal structures necessitate the use of automated computational tools to position them within the lipid bilayer. Identifying the correct orientation allows us to study the complex relationship between sequence, structure and the lipid environment, which is otherwise challenging to investigate using experimental techniques due to the difficulty in crystallising membrane proteins embedded within intact membranes.
  
  
  RESULTS
  We have developed a knowledge-based membrane potential, calculated by the statistical analysis of transmembrane protein structures, coupled with a combination of genetic and direct search algorithms, and demonstrate its use in positioning proteins in membranes, refinement of membrane protein models and in decoy discrimination.
  
  
  CONCLUSIONS
  Our method is able to quickly and accurately orientate both alpha-helical and beta-barrel membrane proteins within the lipid bilayer, showing closer agreement with experimentally determined values than existing approaches. We also demonstrate both consistent and significant refinement of membrane protein models and the effective discrimination between native and decoy structures. Source code is available under an open source license from http://bioinf.cs.ucl.ac.uk/downloads/memembed/.
authors.affiliation: Bioinformatics Group, Department of Computer Science, University College London, Gower Street, London WC1E 6BT, UK. d.jones@cs.ucl.ac.uk.
authors.forename: Timothy
authors.initials: T
authors.lastname: Nugent
authors.forename: David T
authors.initials: DT
authors.lastname: Jones
mesh_terms: D000465:Algorithms; D019295:Computational Biology / Q000379:methods*; D051188:Knowledge Bases; D008051:Lipid Bilayers / Q000737:chemistry; D008564:Membrane Potentials / Q000502:physiology*; D008565:Membrane Proteins / Q000737:chemistry*; D008958:Models, Molecular; D015203:Reproducibility of Results
chemical_list: D008051:Lipid Bilayers; D008565:Membrane Proteins
references.citation: Bioinformatics. 2005 Apr 1;21(7):1276-7
references.pmid: 15539454
references.citation: Protein Sci. 2012 Jan;21(1):50-62
references.pmid: 22031179
references.citation: Bioinformatics. 2006 Mar 1;22(5):623-5
references.pmid: 16397007
references.citation: Nature. 2013 Jan 10;493(7431):255-8
references.pmid: 23222544
references.citation: PLoS Comput Biol. 2010 Mar 19;6(3):e1000714
references.pmid: 20333233
references.citation: Proteins. 2005 May 1;59(2):252-65
references.pmid: 15723347
references.citation: Cell. 2012 Jun 22;149(7):1607-21
references.pmid: 22579045
references.citation: Bioinformatics. 2010 Nov 15;26(22):2833-40
references.pmid: 20926421
references.citation: Nat Struct Biol. 1994 Dec;1(12):858-62
references.pmid: 7773774
references.citation: Bioinformatics. 2010 Apr 1;26(7):889-95
references.pmid: 20164152
references.citation: Nature. 2010 Oct 21;467(7318):991-4
references.pmid: 20861838
references.citation: Structure. 2012 May 9;20(5):924-35
references.pmid: 22579257
references.citation: Proteins. 2003 Mar 1;50(4):537-45
references.pmid: 12577259
references.citation: Protein Sci. 2006 Jun;15(6):1318-33
references.pmid: 16731967
references.citation: Bioinformatics. 2012 Jan 15;28(2):184-90
references.pmid: 22101153
references.citation: Biochem Soc Trans. 2008 Feb;36(Pt 1):27-32
references.pmid: 18208379
references.citation: BMC Struct Biol. 2004 Jun 18;4:8
references.pmid: 15207004
references.citation: Annu Rev Biophys Biomol Struct. 2000;29:291-325
references.pmid: 10940251
references.citation: Nucleic Acids Res. 2000 Jan 1;28(1):235-42
references.pmid: 10592235
references.citation: Proteins. 2006 Mar 1;62(4):1010-25
references.pmid: 16372357
references.citation: J Struct Biol. 2007 Mar;157(3):593-605
references.pmid: 17116404
references.citation: Proc Natl Acad Sci U S A. 2012 Jun 12;109(24):E1540-7
references.pmid: 22645369
references.citation: BMC Bioinformatics. 2012 Jul 17;13:169
references.pmid: 22805427
references.citation: Proteins. 2011;79 Suppl 10:74-90
references.pmid: 22069034
references.citation: J Mol Med (Berl). 1997 May;75(5):312-6
references.pmid: 9181472
references.citation: J Mol Biol. 2005 Feb 11;346(1):377-85
references.pmid: 15663952
references.citation: J Mol Biol. 2007 Feb 16;366(2):436-48
references.pmid: 17174324
references.citation: Science. 2007 Sep 21;317(5845):1746-8
references.pmid: 17717154
references.citation: BMC Bioinformatics. 2009 May 26;10:159
references.pmid: 19470175
references.citation: Nature. 2007 Dec 13;450(7172):1026-30
references.pmid: 18075582
references.citation: Nucleic Acids Res. 2013 Jan;41(Database issue):D524-9
references.pmid: 23203988
references.citation: Curr Opin Struct Biol. 2011 Aug;21(4):460-6
references.pmid: 21763125
references.citation: Philos Trans R Soc Lond B Biol Sci. 2006 Mar 29;361(1467):465-75
references.pmid: 16524835
references.citation: Nat Struct Biol. 2000 Feb;7(2):91-4
references.pmid: 10655604
references.citation: J Chem Theory Comput. 2011 Apr 12;7(4):1157-66
references.pmid: 26606363
references.citation: Nucleic Acids Res. 2012 Jan;40(Database issue):D370-6
references.pmid: 21890895
references.citation: Proteins. 2009;77 Suppl 9:66-80
references.pmid: 19714776
references.citation: Science. 2010 Jun 25;328(5986):1698-700
references.pmid: 20508091
references.citation: Bioinformatics. 2003 Aug 12;19(12):1589-91
references.pmid: 12912846
references.citation: Proc Natl Acad Sci U S A. 2008 May 20;105(20):7177-81
references.pmid: 18477697
references.citation: Trends Biochem Sci. 2005 Jul;30(7):355-7
references.pmid: 15935679
references.citation: Nucleic Acids Res. 2005 Jan 1;33(Database issue):D275-8
references.pmid: 15608195
references.citation: Proc Natl Acad Sci U S A. 2009 Feb 3;106(5):1409-14
references.pmid: 19190187
references.citation: Proteomics. 2010 Mar;10(6):1141-9
references.pmid: 20175080
references.citation: Nucleic Acids Res. 2005 Jul 1;33(Web Server issue):W94-8
references.pmid: 15980589
references.citation: Proteins. 2003;53 Suppl 6:480-5
references.pmid: 14579336
references.citation: Proteins. 2010 May 1;78(6):1431-40
references.pmid: 20034110
references.citation: Bioinformatics. 2006 Jul 15;22(14):e191-6
references.pmid: 16873471
references.citation: Bioinformatics. 2008 Dec 15;24(24):2928-9
references.pmid: 18945683
references.citation: Proc Natl Acad Sci U S A. 2007 Oct 2;104(40):15682-7
references.pmid: 17905872
references.citation: Bioinformatics. 2008 Aug 1;24(15):1662-8
references.pmid: 18474507
references.citation: Biochim Biophys Acta. 2003 May 2;1612(1):1-40
references.pmid: 12729927
references.citation: Bioengineered. 2013 Sep-Oct;4(5):266-78
references.pmid: 23222169