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Structure Prediction of Transmembrane Proteins

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Protein Modelling

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Abstract

The roles of transmembrane proteins in living cells are diverse. They are involved in the transport of various solutes and information through membranes, in energy production, in metabolism and more. Despite their biological importance, the number of their structures in Protein Data Base is rather low compared to the number of globular proteins, due to the technical difficulties originating from the fact that these proteins live in a dual environment. Therefore, modeling structures of transmembrane proteins is crucial, as in many cases it is almost the only available technique to get structural information about these proteins. Here we summarize the most important structural aspects of transmembrane proteins and the state-of-the-art methods capable generating their structures in various dimensions: from predicting topography and topology through the 3D structure, oligomer formation to the orientation in the membrane.

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References

  1. Altschul SF, Madden TL, Schäffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ (1997) Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 25(17):3389–3402

    CAS  Google Scholar 

  2. Andreeva A, Howorth D, Chandonia J-M, Brenner SE, Hubbard TJP, Chothia C, Murzin AG (2008) Data growth and its impact on the SCOP database: new developments. Nucleic Acids Res 36:D419–D425

    CAS  Google Scholar 

  3. Arai M, Ikeda M, Shimizu T (2003) Comprehensive analysis of transmembrane topologies in prokaryotic genomes. Gene 304:77–86

    CAS  Google Scholar 

  4. Arnold K, Bordoli L, Kopp J, Schwede T (2006) The SWISS-MODEL workspace: a web-based environment for protein structure homology modelling. Bioinformatics 22(2):195–201

    CAS  Google Scholar 

  5. Atchley WR, Wollenberg KR, Fitch WM, Terhalle W, Dress AW (2000) Correlations among amino acid sites in bHLH protein domains: an information theoretic analysis. Mol Biol Evol 17(1):164–178

    CAS  Google Scholar 

  6. Bagos PG, Liakopoulos TD, Hamodrakas SJ (2006) Algorithms for incorporating prior topological information in HMMs: application to transmembrane proteins. BMC Bioinform 7:189

    Google Scholar 

  7. Barth P, Wallner B, Baker D (2009) Prediction of membrane protein structures with complex topologies using limited constraints. Proc Natl Acad Sci USA 106(5):1409–1414

    CAS  Google Scholar 

  8. Basyn F, Spies B, Bouffioux O, Thomas A, Brasseur R (2003) Insertion of X-ray structures of proteins in membranes. J Mol Graph Model 22(1):11–21

    CAS  Google Scholar 

  9. Bayrhuber M, Meins T, Habeck M, Becker S, Giller K, Villinger S, Vonrhein C, Griesinger C, Zweckstetter M, Zeth K (2008) Structure of the human voltage-dependent anion channel. Proc Natl Acad Sci USA 105(40):15370–15375

    CAS  Google Scholar 

  10. Benkert P, Biasini M, Schwede T (2011) Toward the estimation of the absolute quality of individual protein structure models. Bioinformatics 27(3):343–350

    CAS  Google Scholar 

  11. Bernsel A, Viklund HK, Falk J, Lindahl E, von Heijne G, Elofsson A (2008) Prediction of membrane-protein topology from first principles. Proc Natl Acad Sci USA 105(20):7177–7181

    CAS  Google Scholar 

  12. Berry EA, Guergova-Kuras M, Huang L-S, Crofts AR (2000) Structure and function of Cytochrome bc complexes. Annu Rev Biochem 69(1):1005–1075

    CAS  Google Scholar 

  13. Biller L, Matthiesen J, Kühne V, Lotter H, Handal G, Nozaki T, Saito-Nakano Y, Schümann M, Roeder T, Tannich E, Krause E, Bruchhaus I (2014) The cell surface proteome of Entamoeba histolytica. Mol Cell Proteomics MCP 13(1):132–144

    CAS  Google Scholar 

  14. Bordner AJ (2009) Predicting protein–protein binding sites in membrane proteins. BMC Bioinform 10:312

    Google Scholar 

  15. Bowie JU (1999) Helix-bundle membrane protein fold templates. Protein Sci 8(12):2711–2719

    CAS  Google Scholar 

  16. Bradley P, Misura KMS, Baker D (2005) Toward high-resolution de novo structure prediction for small proteins. Science 309(5742):1868–1871

    CAS  Google Scholar 

  17. Burger L, van Nimwegen E (2010) Disentangling direct from indirect co-evolution of residues in protein alignments. PLoS Comput Biol 6(1):e1000633

    Google Scholar 

  18. Casciari D, Seeber M, Fanelli F (2006) Quaternary structure predictions of transmembrane proteins starting from the monomer: a docking-based approach. BMC Bioinform 7(1):340

    CAS  Google Scholar 

  19. Chen C-M, Chen C-C (2003) Computer simulations of membrane protein folding: structure and dynamics. Biophys J 84(3):1902–1908

    CAS  Google Scholar 

  20. Cheng J, Baldi P (2007) Improved residue contact prediction using support vector machines and a large feature set. BMC Bioinform 8:113

    Google Scholar 

  21. Chetwynd AP, Scott KA, Mokrab Y, Sansom MSP (2008) CGDB: a database of membrane protein/lipid interactions by coarse-grained molecular dynamics simulations. Mol Membr Biol 25(8):662–669

    CAS  Google Scholar 

  22. Choi Y, Deane CM (2010) FREAD revisited: accurate loop structure prediction using a database search algorithm. Proteins 78(6):1431–1440

    CAS  Google Scholar 

  23. Chothia C (1992) Proteins. One thousand families for the molecular biologist. Nature 357(6379):543–544

    CAS  Google Scholar 

  24. Chou K-C, Elrod DW (2002) Bioinformatical analysis of G-protein-coupled receptors. J Proteome Res 1(5):429–433

    CAS  Google Scholar 

  25. Cortes C, Vapnik V (1995) Support-vector networks. Mach Learn 20(3):273–297

    Google Scholar 

  26. Cserzö M, Bernassau JM, Simon I, Maigret B (1994) New alignment strategy for transmembrane proteins. J Mol Biol 243(3):388–396

    Google Scholar 

  27. Cserzö M, Wallin E, Simon I, von Heijne G, Elofsson A (1997) Prediction of transmembrane alpha-helices in prokaryotic membrane proteins: the dense alignment surface method. Protein Eng 10(6):673–676

    Google Scholar 

  28. Daley DO, Rapp M, Granseth E, Melén K, Drew D, von Heijne G (2005) Global topology analysis of the Escherichia coli inner membrane proteome. Science 308(5726):1321–1323

    CAS  Google Scholar 

  29. de Bakker PIW, DePristo MA, Burke DF, Blundell TL (2003) Ab initio construction of polypeptide fragments: accuracy of loop decoy discrimination by an all-atom statistical potential and the AMBER force field with the generalized born solvation model. Proteins 51(1):21–40

    Google Scholar 

  30. Dekker JP, Fodor A, Aldrich RW, Yellen G (2004) A perturbation-based method for calculating explicit likelihood of evolutionary co-variance in multiple sequence alignments. Bioinformatics 20(10):1565–1572

    CAS  Google Scholar 

  31. Drew D, Sjöstrand D, Nilsson J, Urbig T, Chin C-N, de Gier J-W, von Heijne G (2002) Rapid topology mapping of Escherichia coli inner-membrane proteins by prediction and PhoA/GFP fusion analysis. Proc Natl Acad Sci USA 99(5):2690–2695

    CAS  Google Scholar 

  32. Driessen AJ, Rosen BP, Konings WN (2000) Diversity of transport mechanisms: common structural principles. Trends Biochem Sci 25(8):397–401

    CAS  Google Scholar 

  33. Dunn SD, Wahl LM, Gloor GB (2008) Mutual information without the influence of phylogeny or entropy dramatically improves residue contact prediction. Bioinformatics 24(3):333–340

    CAS  Google Scholar 

  34. Ebejer J-P, Hill JR, Kelm S, Shi J, Deane CM (2013) Memoir: template-based structure prediction for membrane proteins. Nucleic Acids Res 41(Web Server issue):W379–W383

    Google Scholar 

  35. Eisenberg D, Schwarz E, Komaromy M, Wall R (1984) Analysis of membrane and surface protein sequences with the hydrophobic moment plot. J Mol Biol 179(1):125–142

    CAS  Google Scholar 

  36. Finn RD, Mistry J, Schuster-Böckler B, Griffiths-Jones S, Hollich V, Lassmann T, Moxon S, Marshall M, Khanna A, Durbin R, Eddy SR, Sonnhammer ELL, Bateman A (2006) Pfam: clans, web tools and services. Nucleic Acids Res 34:D247–D251

    CAS  Google Scholar 

  37. Fleishman SJ, Ben-Tal N (2002) A novel scoring function for predicting the conformations of tightly packed pairs of transmembrane α-helices. J Mol Biol 321(2):363–378

    CAS  Google Scholar 

  38. Forrest LR, Tang CL, Honig B (2006) On the accuracy of homology modeling and sequence alignment methods applied to membrane proteins. Biophys J 91(2):508–517

    CAS  Google Scholar 

  39. Friedrich T, Böttcher B (2004) The gross structure of the respiratory complex I: a Lego system. Biochim Biophys Acta Bioenerg 1608(1):1–9

    CAS  Google Scholar 

  40. Fuchs A, Kirschner A, Frishman D (2009) Prediction of helix–helix contacts and interacting helices in polytopic membrane proteins using neural networks. Proteins 74(4):857–871

    CAS  Google Scholar 

  41. Fuchs A, Martin-Galiano AJ, Kalman M, Fleishman S, Ben-Tal N, Frishman D (2007) Co-evolving residues in membrane proteins. Bioinformatics 23(24):3312–3319

    CAS  Google Scholar 

  42. Göbel U, Sander C, Schneider R, Valencia A (1994) Correlated mutations and residue contacts in proteins. Proteins 18(4):309–317

    Google Scholar 

  43. Gonzalez A, Cordom A, Caltabiano G, Pardo L (2012) Impact of helix irregularities on sequence alignment and homology modeling of G protein-coupled receptors. ChemBioChem 13(10):1393–1399

    CAS  Google Scholar 

  44. Govindarajan S, Recabarren R, Goldstein RA (1999) Estimating the total number of protein folds. Proteins 35(4):408–414

    CAS  Google Scholar 

  45. Granseth E, Daley DO, Rapp M, Melén K, von Heijne G (2005) Experimentally constrained topology models for 51,208 bacterial inner membrane proteins. J Mol Biol 352(3):489–494

    CAS  Google Scholar 

  46. Gu B, Zhang J, Wang W, Mo L, Zhou Y, Chen L, Liu Y, Zhang M (2010) Global expression of cell surface proteins in embryonic stem cells. PLoS One 5(12):e15795

    CAS  Google Scholar 

  47. Gulyás-Kovács A (2012) Integrated analysis of residue coevolution and protein structure in ABC transporters. PLoS One 7(5):e36546

    Google Scholar 

  48. Harte R, Ouzounis CA (2002) Genome-wide detection and family clustering of ion channels. FEBS Lett 514(2–3):129–134

    CAS  Google Scholar 

  49. Hedman M, Deloof H, Von Heijne G, Elofsson A (2002) Improved detection of homologous membrane proteins by inclusion of information from topology predictions. Protein Sci 11(3):652–658

    CAS  Google Scholar 

  50. Heim AJ, Li Z (2012) Developing a high-quality scoring function for membrane protein structures based on specific inter-residue interactions. J Comput Aided Mol Des 26(3):301–309

    CAS  Google Scholar 

  51. Henrick K (1998) PQS: a protein quaternary structure file server. Trends Biochem Sci 23(9):358–361

    CAS  Google Scholar 

  52. Herrero M, de Lorenzo V, Neilands JB (1988) Nucleotide sequence of the iucD gene of the pColV-K30 aerobactin operon and topology of its product studied with phoA and lacZ gene fusions. J Bacteriol 170(1):56–64

    CAS  Google Scholar 

  53. Hill JR, Deane CM (2013) MP-T: improving membrane protein alignment for structure prediction. Bioinformatics 29(1):54–61

    CAS  Google Scholar 

  54. Hopf TA, Colwell LJ, Sheridan R, Rost B, Sander C, Marks DS (2012) Three-dimensional structures of membrane proteins from genomic sequencing. Cell 149(7):1607–1621

    CAS  Google Scholar 

  55. Horner DS, Pirovano W, Pesole G (2008) Correlated substitution analysis and the prediction of amino acid structural contacts. Brief Bioinform 9(1):46–56

    CAS  Google Scholar 

  56. Jackups R, Liang J (2005) Interstrand pairing patterns in beta-barrel membrane proteins: the positive-outside rule, aromatic rescue, and strand registration prediction. J Mol Biol 354(4):979–993

    CAS  Google Scholar 

  57. Jacobson MP, Pincus DL, Rapp CS, Day TJF, Honig B, Shaw DE, Friesner RA (2004) A hierarchical approach to all-atom protein loop prediction. Proteins 55(2):351–367

    CAS  Google Scholar 

  58. John B, Sali A (2003) Comparative protein structure modeling by iterative alignment, model building and model assessment. Nucleic Acids Res 31(14):3982–3992

    CAS  Google Scholar 

  59. Jones DT, Buchan DWA, Cozzetto D, Pontil M (2011) PSICOV: precise structural contact prediction using sparse inverse covariance estimation on large multiple sequence alignments. Bioinformatics 28(2):184–190

    Google Scholar 

  60. Jones DT, Taylor WR, Thornton JM (1994) A model recognition approach to the prediction of all-helical membrane protein structure and topology. Biochemistry 33(10):3038–3049

    CAS  Google Scholar 

  61. Kaczor AA, Selent J, Sanz F, Pastor M (2013) Modeling complexes of transmembrane proteins: systematic analysis of protein–protein docking tools. Mol Inform 32(8):717–733

    CAS  Google Scholar 

  62. Käll L, Krogh A, Sonnhammer ELL (2004) A combined transmembrane topology and signal peptide prediction method. J Mol Biol 338(5):1027–1036

    Google Scholar 

  63. Karakaş M, Woetzel N, Staritzbichler R, Alexander N, Weiner BE, Meiler J (2012) BCL:fold–de novo prediction of complex and large protein topologies by assembly of secondary structure elements. PLoS One 7(11):e49240

    Google Scholar 

  64. Kass I, Horovitz A (2002) Mapping pathways of allosteric communication in GroEL by analysis of correlated mutations. Proteins 48(4):611–617

    CAS  Google Scholar 

  65. Kelm S, Shi J, Deane CM (2009) iMembrane: homology-based membrane-insertion of proteins. Bioinformatics 25(8):1086–1088

    CAS  Google Scholar 

  66. Kelm S, Shi J, Deane CM (2010) MEDELLER: homology-based coordinate generation for membrane proteins. Bioinformatics 26(22):2833–2840

    CAS  Google Scholar 

  67. Kim H, Melén K, Osterberg M, von Heijne G (2006) A global topology map of the Saccharomyces cerevisiae membrane proteome. Proc Natl Acad Sci USA 103(30):11142–11147

    CAS  Google Scholar 

  68. Kim H, Melén K, von Heijne G (2003) Topology models for 37 Saccharomyces cerevisiae membrane proteins based on C-terminal reporter fusions and predictions. J Biol Chem 278(12):10208–10213

    CAS  Google Scholar 

  69. Kim S, Chamberlain AK, Bowie JU (2003) A simple method for modeling transmembrane helix oligomers. J Mol Biol 329(4):831–840

    CAS  Google Scholar 

  70. Koonin EV, Wolf YI, Karev GP (2002) The structure of the protein universe and genome evolution. Nature 420(6912):218–223

    CAS  Google Scholar 

  71. Kozma D, Simon I, Tusnády GE (2012) PDBTM: protein data bank of transmembrane proteins after 8 years. Nucleic Acids Res 41(D1):D524–D529

    Google Scholar 

  72. Krissinel E, Henrick K (2007) Inference of macromolecular assemblies from crystalline state. J Mol Biol 372(3):774–797

    CAS  Google Scholar 

  73. Krogh A, Larsson B, von Heijne G, Sonnhammer EL (2001) Predicting transmembrane protein topology with a hidden Markov model: application to complete genomes. J Mol Biol 305(3):567–580

    CAS  Google Scholar 

  74. Kyte J, Doolittle R (1982) A simple method for displaying the hydropathic character of a protein. J Mol Biol 157(1):105–132

    CAS  Google Scholar 

  75. Lacapère J-J, Pebay-Peyroula E, Neumann J-M, Etchebest C (2007) Determining membrane protein structures: still a challenge! Trends Biochem Sci 32(6):259–270

    Google Scholar 

  76. Langelaan DN, Wieczorek M, Blouin C, Rainey JK (2010) Improved helix and kink characterization in membrane proteins allows evaluation of kink sequence predictors. J Chem Inf Model 50(12):2213–2220

    CAS  Google Scholar 

  77. Lapedes A, Giraud B, Jarzynski C (2012) Using sequence alignments to predict protein structure and stability with high accuracy. arXiv:1207.2484

  78. Laskowski R, Macarthur M, Moss D, Thornton J (1993) PROCHECK: a program to check the stereochemical quality of protein structures. J Appl Cryst 26:283–291

    CAS  Google Scholar 

  79. Latek D, Pasznik P, Carlomagno T, Filipek S (2013) Towards improved quality of GPCR models by usage of multiple templates and profile-profile comparison. PLoS One 8(2):e56742

    CAS  Google Scholar 

  80. Ledesma A, de Lacoba MG, Arechaga I, Rial E (2002) Modeling the transmembrane arrangement of the uncoupling protein UCP1 and topological considerations of the nucleotide-binding site. J Bioenerg Biomembr 34(6):473–486

    CAS  Google Scholar 

  81. Lee J, Lee D, Park H, Coutsias EA, Seok C (2010) Protein loop modeling by using fragment assembly and analytical loop closure. Proteins 78(16):3428–3436

    CAS  Google Scholar 

  82. Lee J, Lee J, Sasaki TN, Sasai M, Seok C, Lee J (2011) De novo protein structure prediction by dynamic fragment assembly and conformational space annealing. Proteins 79(8):2403–2417

    CAS  Google Scholar 

  83. Lehnert U, Xia Y, Royce TE, Goh C-S, Liu Y, Senes A, Yu H, Zhang ZL, Engelman DM, Gerstein M (2004) Computational analysis of membrane proteins: genomic occurrence, structure prediction and helix interactions. Q Rev Biophys 37(2):121–146

    CAS  Google Scholar 

  84. Letunic I, Copley RR, Schmidt S, Ciccarelli FD, Doerks T, Schultz J, Ponting CP, Bork P (2004) SMART 4.0: towards genomic data integration. Nucleic Acids Res 32:D142–D144

    CAS  Google Scholar 

  85. Li Y, Goddard WA (2008) Prediction of structure of G-protein coupled receptors and of bound ligands, with applications for drug design. Pac Symp Biocomput 344–353

    Google Scholar 

  86. Liang J, Naveed H, Jimenez-Morales D, Adamian L, Lin M (2012) Computational studies of membrane proteins: models and predictions for biological understanding. Biochim Biophys Acta 1818(4):927–941

    CAS  Google Scholar 

  87. Liu Y, Gerstein M, Engelman DM (2004) Transmembrane protein domains rarely use covalent domain recombination as an evolutionary mechanism. Proc Natl Acad Sci USA 101(10):3495–3497

    CAS  Google Scholar 

  88. Lockless SW, Ranganathan R (1999) Evolutionarily conserved pathways of energetic connectivity in protein families. Science 286(5438):295–299

    CAS  Google Scholar 

  89. Lomize MA, Lomize AL, Pogozheva ID, Mosberg HI (2006) OPM: orientations of proteins in membranes database. Bioinformatics 22(5):623–625

    CAS  Google Scholar 

  90. Macdonald JT, Kelley LA, Freemont PS (2013) Validating a coarse-grained potential energy function through protein loop modelling. PLoS One 8(6):e65770

    CAS  Google Scholar 

  91. Marks DS, Colwell LJ, Sheridan R, Hopf TA, Pagnani A, Zecchina R, Sander C (2011) Protein 3D structure computed from evolutionary sequence variation. PLoS One 6(12):e28766

    CAS  Google Scholar 

  92. Miller CS, Eisenberg D (2008) Using inferred residue contacts to distinguish between correct and incorrect protein models. Bioinformatics 24(14):1575–1582

    CAS  Google Scholar 

  93. Mindaye ST, Ra M, Lo Surdo J, Bauer SR, Alterman MA (2013) Improved proteomic profiling of the cell surface of culture-expanded human bone marrow multipotent stromal cells. J Proteomics 78:1–14

    CAS  Google Scholar 

  94. Minsky M, Seymour P (1969) Perceptrons. MIT Press, Oxford

    Google Scholar 

  95. Monastyrskyy B, D’Andrea D, Fidelis K, Tramontano A, Kryshtafovych A (2014) Evaluation of residue-residue contact prediction in CASP10. Proteins 82(Suppl 2):138–153

    CAS  Google Scholar 

  96. Morcos F, Jana B, Hwa T, Onuchic JN (2013) Coevolutionary signals across protein lineages help capture multiple protein conformations. Proc Natl Acad Sci USA 110(51):20533–20538

    CAS  Google Scholar 

  97. Morcos F, Pagnani A, Lunt B, Bertolino A, Marks DS, Sander C, Zecchina R, Onuchic JN, Hwa T, Weigt M (2011) Direct-coupling analysis of residue coevolution captures native contacts across many protein families. Proc Natl Acad Sci USA 108(49):E1293–E1301

    CAS  Google Scholar 

  98. Naveed H, Jackups R, Liang J (2009) Predicting weakly stable regions, oligomerization state, and protein–protein interfaces in transmembrane domains of outer membrane proteins. Proc Natl Acad Sci USA 106(31):12735–12740

    CAS  Google Scholar 

  99. Naveed H, Xu Y, Jackups R, Liang J (2012) Predicting three-dimensional structures of transmembrane domains of β-barrel membrane proteins. J Am Chem Soc 134(3):1775–1781

    CAS  Google Scholar 

  100. Neumann S, Fuchs A, Hummel B, Frishman D (2013) Classification of α-helical membrane proteins using predicted helix architectures. PLoS One 8(10):e77491

    CAS  Google Scholar 

  101. Niehage C, Steenblock C, Pursche T, Bornhäuser M, Corbeil D, Hoflack B (2011) The cell surface proteome of human mesenchymal stromal cells. PLoS One 6(5):e20399

    CAS  Google Scholar 

  102. Noivirt O, Eisenstein M, Horovitz A (2005) Detection and reduction of evolutionary noise in correlated mutation analysis. Protein Eng Des Sel 18(5):247–253

    CAS  Google Scholar 

  103. Nugent T, Jones DT (2010) Predicting transmembrane helix packing arrangements using residue contacts and a force-directed algorithm. PLoS Comput Biol 6(3):e1000714

    Google Scholar 

  104. Nugent T, Jones DT (2011) Membrane protein structural bioinformatics. J Struct Biol 179(3):327–337

    Google Scholar 

  105. Nugent T, Jones DT (2013) Membrane protein orientation and refinement using a knowledge-based statistical potential. BMC Bioinform 14(1):276

    Google Scholar 

  106. Nugent T, Ward S, Jones DT (2011) The MEMPACK alpha-helical transmembrane protein structure prediction server. Bioinformatics 27(10):1438–1439

    CAS  Google Scholar 

  107. Oberai A, Ihm Y, Kim S, Bowie JU (2006) A limited universe of membrane protein families and folds. Protein Sci 15(7):1723–1734

    CAS  Google Scholar 

  108. Olivella M, Gonzalez A, Pardo L, Deupi X (2013) Relation between sequence and structure in membrane proteins. Bioinformatics 29(13):1589–1592

    CAS  Google Scholar 

  109. Olmea O, Rost B, Valencia A (1999) Effective use of sequence correlation and conservation in fold recognition. J Mol Biol 293(5):1221–1239

    CAS  Google Scholar 

  110. Ortiz AR, Kolinski A, Rotkiewicz P, Ilkowski B, Skolnick J (1999) Ab initio folding of proteins using restraints derived from evolutionary information. Proteins Struct Funct Genet 37(S3):177–185

    Google Scholar 

  111. Park SH, Opella SJ (2005) Tilt angle of a trans-membrane helix is determined by hydrophobic mismatch. J Mol Biol 350(2):310–318

    CAS  Google Scholar 

  112. Pellegrini-Calace M, Carotti A, Jones DT (2003) Folding in lipid membranes (FILM): a novel method for the prediction of small membrane protein 3D structures. Proteins 50(4):537–545

    CAS  Google Scholar 

  113. Phan G, Remaut H, Wang T, Allen WJ, Pirker KF, Lebedev A, Henderson NS, Geibel S, Volkan E, Yan J, Kunze MBA, Pinkner JS, Ford B, Kay CWM, Li H, Hultgren SJ, Thanassi DG, Waksman G (2011) Crystal structure of the FimD usher bound to its cognate FimC-FimH substrate. Nature 474(7349):49–53

    CAS  Google Scholar 

  114. Phatak M, Adamczak R, Cao B, Wagner M, Meller J (2011) Solvent and lipid accessibility prediction as a basis for model quality assessment in soluble and membrane proteins. Curr Protein Pept Sci 12(6):563–573

    CAS  Google Scholar 

  115. Pieper U, Schlessinger A, Kloppmann E, Chang GA, Chou JJ, Dumont ME, Fox BG, Fromme P, Hendrickson WA, Malkowski MG, Rees DC, Stokes DL, Stowell MHB, Wiener MC, Rost B, Stroud RM, Stevens RC, Sali A (2013) Coordinating the impact of structural genomics on the human α-helical transmembrane proteome. Nat Struct Mol Biol 20(2):135–138

    CAS  Google Scholar 

  116. Pilpel Y, Ben-Tal N, Lancet D (1999) kPROT: a knowledge-based scale for the propensity of residue orientation in transmembrane segments. Application to membrane protein structure prediction. J Mol Biol 294(4):921–935

    CAS  Google Scholar 

  117. Punta M, Forrest LR, Bigelow H, Kernytsky A, Liu J, Rost B (2007) Membrane protein prediction methods. Methods 41(4):460–474

    CAS  Google Scholar 

  118. Punta M, Rost B (2005) PROFcon: novel prediction of long-range contacts. Bioinformatics 21(13):2960–2968

    CAS  Google Scholar 

  119. Rabiner L (1989) A tutorial on hidden Markov models and selected applications in speech recognition. Proc IEEE 77(2):257–286

    Google Scholar 

  120. Rapp M, Drew D, Daley DO, Nilsson J, Carvalho T, Melén K, De Gier J-W, Von Heijne G (2004) Experimentally based topology models for E. coli inner membrane proteins. Protein Sci 13(4):937–945

    CAS  Google Scholar 

  121. Ray A, Lindahl E, Wallner B (2010) Model quality assessment for membrane proteins. Bioinformatics 26(24):3067–3074

    CAS  Google Scholar 

  122. Reddy CS, Vijayasarathy K, Srinivas E, Sastry GM, Sastry GN (2006) Homology modeling of membrane proteins: a critical assessment. Comput Biol Chem 30(2):120–126

    CAS  Google Scholar 

  123. Remm M, Sonnhammer E (2000) Classification of transmembrane protein families in the Caenorhabditis elegans genome and identification of human orthologs. Genome Res 10(11):1679–1689

    CAS  Google Scholar 

  124. Rohl CA, Strauss CEM, Misura KMS, Baker D (2004) Protein structure prediction using Rosetta. Methods Enzymol 383:66–93

    CAS  Google Scholar 

  125. Rost B (1999) Twilight zone of protein sequence alignments. Protein Eng Des Sel 12(2):85–94

    CAS  Google Scholar 

  126. Rost B, Fariselli P, Casadio R (1996) Topology prediction for helical transmembrane proteins at 86 % accuracy. Protein Sci 5(8):1704–1718

    CAS  Google Scholar 

  127. Sadowski MI, Maksimiak K, Taylor WR (2011) Direct correlation analysis improves fold recognition. Comput Biol Chem 35(5):323–332

    CAS  Google Scholar 

  128. Saier MJ, Beatty J, Goffeau A, Harley K, Heijne W, Huang S, Jack D, Jähn P, Lew K, Liu J, Pao S, Paulsen I, Tseng T, Virk P (1999) The major facilitator superfamily. J Mol Microbiol Biotechnol 1(2):257–279

    CAS  Google Scholar 

  129. Sansom MS, Shrivastava IH, Bright JN, Tate J, Capener CE, Biggin PC (2002) Potassium channels: structures, models, simulations. Biochim Biophys Acta Biomembr 1565(2):294–307

    CAS  Google Scholar 

  130. Sathyapriya R, Duarte JM, Stehr H, Filippis I, Lappe M (2009) Defining an essence of structure determining residue contacts in proteins. PLoS Comput Biol 5(12):e1000584

    CAS  Google Scholar 

  131. Schäffer AA, Aravind L, Madden TL, Shavirin S, Spouge JL, Wolf YI, Koonin EV, Altschul SF (2001) Improving the accuracy of PSI-BLAST protein database searches with composition-based statistics and other refinements. Nucleic Acids Res 29(14):2994–3005

    Google Scholar 

  132. Schmitt L (2002) Structure and mechanism of ABC transporters. Curr Opin Struct Biol 12(6):754–760

    CAS  Google Scholar 

  133. Schramm CA, Hannigan BT, Donald JE, Keasar C, Saven JG, Degrado WF, Samish I (2012) Knowledge-based potential for positioning membrane-associated structures and assessing residue-specific energetic contributions. Structure 20(5):924–935

    CAS  Google Scholar 

  134. Senes A, Chadi DC, Law PB, Walters RFS, Nanda V, Degrado WF (2007) E(z), a depth-dependent potential for assessing the energies of insertion of amino acid side-chains into membranes: derivation and applications to determining the orientation of transmembrane and interfacial helices. J Mol Biol 366(2):436–448

    CAS  Google Scholar 

  135. Shacham S, Marantz Y, Bar-Haim S, Kalid O, Warshaviak D, Avisar N, Inbal B, Heifetz A, Fichman M, Topf M, Naor Z, Noiman S, Becker OM (2004) PREDICT modeling and in-silico screening for G-protein coupled receptors. Proteins 57(1):51–86

    CAS  Google Scholar 

  136. Sigrist CJA, de Castro E, Cerutti L, Cuche BA, Hulo N, Bridge A, Bougueleret L, Xenarios I (2013) New and continuing developments at PROSITE. Nucleic Acids Res 41:D344–D347

    CAS  Google Scholar 

  137. Sipos L, von Heijne G (1993) Predicting the topology of eukaryotic membrane proteins. Eur J Biochem/FEBS 213(3):1333–1340

    CAS  Google Scholar 

  138. Söding J (2005) Protein homology detection by HMM-HMM comparison. Bioinformatics 21(7):951–960

    Google Scholar 

  139. Sonnhammer EL, von Heijne G, Krogh A (1998) A hidden Markov model for predicting transmembrane helices in protein sequences. Proc Int Conf Intell Syst Mol Biol 6:175–182

    CAS  Google Scholar 

  140. Stamm M, Staritzbichler R, Khafizov K, Forrest LR (2013) Alignment of helical membrane protein sequences using AlignMe. PLoS One 8(3):e57731

    CAS  Google Scholar 

  141. Tusnády GE, Dosztányi Z, Simon I (2004) Transmembrane proteins in the protein data bank: identification and classification. Bioinformatics 20(17):2964–2972

    Google Scholar 

  142. Tusnády GE, Dosztányi Z, Simon I (2005) PDB_TM: selection and membrane localization of transmembrane proteins in the protein data bank. Nucleic Acids Res 33:D275–D278

    Google Scholar 

  143. Tusnády GE, Dosztányi Z, Simon I (2005) TMDET: web server for detecting transmembrane regions of proteins by using their 3D coordinates. Bioinformatics 21(7):1276–1277

    Google Scholar 

  144. Tusnády GE, Kalmár L, Hegyi H, Tompa P, Simon I (2008) TOPDOM: database of domains and motifs with conservative location in transmembrane proteins. Bioinformatics 24(12):1469–1470

    Google Scholar 

  145. Tusnády GE, Simon I (2001) The HMMTOP transmembrane topology prediction server. Bioinformatics 17(9):849–850

    Google Scholar 

  146. Tusnády GE, Simon I (2010) Topology prediction of helical transmembrane proteins: how far have we reached? Curr Protein Pept Sci 11(7):550–561

    Google Scholar 

  147. Vaidehi N, Floriano WB, Trabanino R, Hall SE, Freddolino P, Choi EJ, Zamanakos G, Goddard WA (2002) Prediction of structure and function of G protein-coupled receptors. Proc Natl Acad Sci USA 99(20):12622–12627

    CAS  Google Scholar 

  148. van Geest M, Lolkema JS (2000) Membrane topology and insertion of membrane proteins: search for topogenic signals. Microbiol Mol Biol Rev 64(1):13–33

    Google Scholar 

  149. Viklund HK, Elofsson A (2008) OCTOPUS: improving topology prediction by two-track ANN-based preference scores and an extended topological grammar. Bioinformatics 24(15):1662–1668

    CAS  Google Scholar 

  150. Volkan E, Kalas V, Pinkner JS, Dodson KW, Henderson NS, Pham T, Waksman G, Delcour AH, Thanassi DG, Hultgren SJ (2013) Molecular basis of usher pore gating in Escherichia coli pilus biogenesis. Proc Natl Acad Sci USA 110(51):20741–20746

    CAS  Google Scholar 

  151. von Heijne G (1986) The distribution of positively charged residues in bacterial inner membrane proteins correlates with the trans-membrane topology. EMBO J 5(11):3021–3027

    CAS  Google Scholar 

  152. von Heijne G (1991) Proline kinks in transmembrane alpha-helices. J Mol Biol 218(3):499–503

    Google Scholar 

  153. von Heijne G (1992) Membrane protein structure prediction. Hydrophobicity analysis and the positive-inside rule. J Mol Biol 225(2):487–494

    Google Scholar 

  154. Šali A, Blundell TL (1993) Comparative protein modelling by satisfaction of spatial restraints. J Mol Biol 234(3):779–815

    Google Scholar 

  155. Waldispühl J, Berger B, Clote P, Steyaert J-M (2006) Predicting transmembrane beta-barrels and interstrand residue interactions from sequence. Proteins 65(1):61–74

    Google Scholar 

  156. Waldispühl J, Steyaert J-M (2005) Modeling and predicting all-α transmembrane proteins including helix–helix pairing. Theor Comput Sci 335(1):67–92

    Google Scholar 

  157. Wallin E, von Heijne G (1998) Genome-wide analysis of integral membrane proteins from eubacterial, archaean, and eukaryotic organisms. Protein Sci 7(4):1029–1038

    CAS  Google Scholar 

  158. Wang H, He Z, Zhang C, Zhang L, Xu D (2013) Transmembrane protein alignment and fold recognition based on predicted topology. PLoS One 8(7):e69744

    CAS  Google Scholar 

  159. Wang Z, Xu J (2013) Predicting protein contact map using evolutionary and physical constraints by integer programming. Bioinformatics 29(13):i266–i273

    CAS  Google Scholar 

  160. Weiner BE, Woetzel N, Karakaş M, Alexander N, Meiler J (2013) BCL:MP-fold: folding membrane proteins through assembly of transmembrane helices. Structure 21(7):1107–1117

    CAS  Google Scholar 

  161. White SH (2009) Biophysical dissection of membrane proteins. Nature 459(7245):344–346

    CAS  Google Scholar 

  162. Wolf YI, Grishin NV, Koonin EV (2000) Estimating the number of protein folds and families from complete genome data. J Mol Biol 299(4):897–905

    CAS  Google Scholar 

  163. Xiang Z, Soto CS, Honig B (2002) Evaluating conformational free energies: the colony energy and its application to the problem of loop prediction. Proc Natl Acad Sci USA 99(11):7432–7437

    CAS  Google Scholar 

  164. Yarov-Yarovoy V, Schonbrun J, Baker D (2006) Multipass membrane protein structure prediction using Rosetta. Proteins 62(4):1010–1025

    CAS  Google Scholar 

  165. Zhang Y, Devries ME, Skolnick J (2006) Structure modeling of all identified G protein-coupled receptors in the human genome. PLoS Comput Biol 2(3):e13

    Google Scholar 

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  1. Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, P.O. Box 7, Budapest, 1518, Hungary

    Gábor E. Tusnády & Dániel Kozma

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  1. Gábor E. Tusnády
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Correspondence to Gábor E. Tusnády .

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  1. Chemistry Department, Eotvos Lorand University, Budapest, Hungary

    Gábor Náray-Szabó

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Tusnády, G.E., Kozma, D. (2014). Structure Prediction of Transmembrane Proteins. In: Náray-Szabó, G. (eds) Protein Modelling. Springer, Cham. https://doi.org/10.1007/978-3-319-09976-7_9

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