Journal of Biomolecular NMR

, Volume 13, Issue 3, pp 289–302 | Cite as

Protein backbone angle restraints from searching a database for chemical shift and sequence homology

  • Gabriel Cornilescu
  • Frank Delaglio
  • Ad Bax


Chemical shifts of backbone atoms in proteins are exquisitely sensitive to local conformation, and homologous proteins show quite similar patterns of secondary chemical shifts. The inverse of this relation is used to search a database for triplets of adjacent residues with secondary chemical shifts and sequence similarity which provide the best match to the query triplet of interest. The database contains 13Cα, 13Cβ, 13C′, 1Hα and 15N chemical shifts for 20 proteins for which a high resolution X-ray structure is available. The computer program TALOS was developed to search this database for strings of residues with chemical shift and residue type homology. The relative importance of the weighting factors attached to the secondary chemical shifts of the five types of resonances relative to that of sequence similarity was optimized empirically. TALOS yields the 10 triplets which have the closest similarity in secondary chemical shift and amino acid sequence to those of the query sequence. If the central residues in these 10 triplets exhibit similar φ and Ψ backbone angles, their averages can reliably be used as angular restraints for the protein whose structure is being studied. Tests carried out for proteins of known structure indicate that the root-mean-square difference (rmsd) between the output of TALOS and the X-ray derived backbone angles is about 15°. Approximately 3% of the predictions made by TALOS are found to be in error.

φ angle Ψ angle backbone angles chemical shift homology of chemical shift protein structure sequence homology TALOS 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Supplementary material

10858_2004_Article_205504_MOESM1_ESM.pdf (23 kb)
Supplementary Figure (PDF 24 KB)


  1. Ando, I., Saito, H., Tabeta, R., Shoji, A. and Ozaki, T. (1984) Macromolecules, 17, 457–461.CrossRefADSGoogle Scholar
  2. Archer, S.J., Vinson, V.K., Pollard, T.D. and Torchia, D.A. (1994) FEBS Lett., 337, 145–151.CrossRefGoogle Scholar
  3. Bax, A. and Tjandra, N. (1997) J. Biomol. NMR, 10, 289–292.CrossRefGoogle Scholar
  4. Beger, D.B. and Bolton, P.H. (1997) J. Biomol. NMR, 10, 129–142.CrossRefGoogle Scholar
  5. Berndt, K.D., Guntert, P., Orbons, L.P. and Wüthrich, K. (1992) J. Mol. Biol., 227, 757–775.CrossRefGoogle Scholar
  6. Betzel, C., Klupsch, S., Papendorf, G., Hastrup, S., Branner, S. and Wilson, K.S. (1992) J. Mol. Biol., 223, 427–445.CrossRefGoogle Scholar
  7. Bewley, C.A., Gustafson, K.R., Boyd, M.R., Covell, D.G., Bax, A., Clore, G.M. and Gronenborn, A.M. (1998) Nat. Struct. Biol., 5, 571–578.CrossRefGoogle Scholar
  8. Brünger, A.T. (1993) XPLOR Manual, Version 3.1, Yale University, New Haven, CT.Google Scholar
  9. Celda, B., Biamonti, C., Arnau, M.J., Tejero, R. and Montelione, G.T. (1995) J. Biomol. NMR, 5, 161–172.CrossRefGoogle Scholar
  10. Chattopadhyaya, R., Meador, W.E., Means, A.R. and Quiocho, F.A. (1992) J. Mol. Biol., 228, 1177–1192.CrossRefGoogle Scholar
  11. Clore, G.M., Bax, A., Driscoll, P.C., Wingfield, P. and Gronenborn, A. (1990) Biochemistry, 29, 8172–8184.CrossRefGoogle Scholar
  12. Clore, G.M., Starich, M.R. and Gronenborn, A.M. (1998) J. Am. Chem. Soc., 120, 10571–10572.CrossRefGoogle Scholar
  13. Concha, N.O., Rasmussen, B.A., Bush, K. and Herzberg, O. (1996) Structure, 4, 823–836.CrossRefGoogle Scholar
  14. Copie, V., Battles, J.A., Schwab, J.M. and Torchia, D.A. (1996) J. Biomol. NMR, 7, 335–340.CrossRefGoogle Scholar
  15. Davis, J.H., Agard, D.A., Handel, T.M. and Basus, V.J. (1997) J. Biomol. NMR, 10, 21–27.CrossRefGoogle Scholar
  16. de Dios, A.C. and Oldfield, E. (1993) J. Am. Chem. Soc., 116, 5307–5314.CrossRefGoogle Scholar
  17. de Dios, A.C., Pearson, J.G. and Oldfield, E. (1993) Science, 260, 1491–1495.CrossRefADSGoogle Scholar
  18. Delaglio, F., Grzesiek, S., Vuister, G., Zhu, G., Pfeifer, J. and Bax, A. (1995) J. Biomol. NMR, 6, 277–293.CrossRefGoogle Scholar
  19. Drakenberg, T., Hofman, T. and Chazin, W.J. (1989) Biochemistry, 28, 5946–5954.CrossRefGoogle Scholar
  20. Fedorov, A.A., Magnus, K.A., Graupe, M.H., Lattman, E.E., Pollard, T.D. and Almo, S.C. (1994) Proc. Natl. Acad. Sci. USA, 30, 8636–8640.CrossRefADSGoogle Scholar
  21. Fogh, R.H., Schipper, D., Boelens, R. and Kaptein, R. (1995) J. Biomol. NMR, 5, 259–270.CrossRefGoogle Scholar
  22. Fujinaga, M., Delbaere, L.T.J., Brayer, G.D. and James, M.N.G. (1985) J. Mol. Biol., 184, 479–502.CrossRefGoogle Scholar
  23. Gardner, K.H., Zhang, X., Gehring, K. and Kay, L.E. (1998) J. Am. Chem. Soc., 120, 11738–11748.CrossRefGoogle Scholar
  24. Gronenborn, A.M. and Clore, G.M. (1994) J. Biomol. NMR, 4, 455–458.CrossRefGoogle Scholar
  25. Gronwald, W., Boyko, R.F., Sönnichsen, F.D., Wishart, D.S. and Sykes, B.D. (1997) J. Biomol. NMR, 10, 165–179.CrossRefGoogle Scholar
  26. Hansen, P.E. (1991) Biochemistry, 30, 10457–10466.CrossRefGoogle Scholar
  27. Hansen, M.R., Rance, M. and Pardi, A. (1998) J. Am. Chem. Soc., 120, 11210–11211.CrossRefGoogle Scholar
  28. Ikura, M., Kay, L.E. and Bax, A. (1990) Biochemistry, 29, 4659–4667.CrossRefGoogle Scholar
  29. Ikura, M., Kay, L.E., Krinks, M. and Bax, A. (1991) Biochemistry, 30, 5498–5504.CrossRefGoogle Scholar
  30. Ke, H.M., Zydowsky, L.D., Liu, J. and Walsh, C.T. (1991) Proc. Natl. Acad. Sci. USA, 88, 9483–9487.CrossRefADSGoogle Scholar
  31. Kricheldorf, H.R. and Muller, D. (1983) Macromolecules, 16, 615–623.CrossRefADSGoogle Scholar
  32. Kumar, V. and Kannan, K.K. (1994) J. Mol. Biol., 241, 226–232.CrossRefGoogle Scholar
  33. Kuntz, I.D., Kosen, P.A. and Craig, E.C. (1991) J. Am. Chem. Soc., 113, 1406–1408.CrossRefGoogle Scholar
  34. Kuszewski, J., Qin, J., Gronenborn A.M. and Clore, G.M. (1995) J. Magn. Reson., B106, 92–96.Google Scholar
  35. Kuszewski, J., Gronenborn, A.M. and Clore, G.M. (1997) J. Magn. Reson., 125, 171–177.CrossRefADSGoogle Scholar
  36. Lam, P.Y.S., Jadhav, P.K., Eyerman, C.J., Hodge, C.N., Ru, Y., Bacheler, L.T., Meek, J.L., Otto, M.J., Rayner, M.M., Wong, Y.N., Chang, C.-H., Weber, P.C., Jackson, D.A., Sharpe, T.R. and Erickson-Viitanen, S. (1994) Science, 263, 380–384.CrossRefADSGoogle Scholar
  37. Leesong, M., Henderson, B.S., Gillig, J.R., Schwab, J.M. and Smith, J.L. (1996) Structure, 4, 253–256.CrossRefGoogle Scholar
  38. Loll, P.J. and Lattman, E.E. (1989) Proteins Struct. Funct. Genet., 5, 183–201.CrossRefGoogle Scholar
  39. Longhi, S., Czjzek, M., Lamzin, V., Nicolas, A. and Cambillau, C. (1997) J. Mol. Biol., 268, 779–799.CrossRefGoogle Scholar
  40. Luginbühl, P., Szyperski T. and Wüthrich, K. (1995) J. Magn. Reson., 109, 229–233.CrossRefGoogle Scholar
  41. Markley, J.L., Bax, A., Arata, Y., Hilbers, C.W., Kaptein, R., Sykes, B.D., Wright, P.E. and Wüthrich, K. (1998) J. Biomol. NMR, 12, 1–23.CrossRefGoogle Scholar
  42. Meador, W.E., Means, A.R. and Quiocho, F.A. (1992) Science, 257, 1251–1255.CrossRefADSGoogle Scholar
  43. Nilges, M., Gronenborn, A.M., Brünger, A.T. and Clore, G.M. (1988) Protein Eng., 2, 27–38.CrossRefGoogle Scholar
  44. Ösapay, K. and Case, D.A. (1994) J. Biomol. NMR, 4, 215–230.CrossRefGoogle Scholar
  45. Ottiger, M., Zerbe, O., Güntert, P. and Wüthrich, K. (1997) J. Mol. Biol., 272, 64–81.CrossRefGoogle Scholar
  46. Ousterhout, J.K. (1994) Tcl and the Tk Toolkit, Addison-Wesley, Reading, MA.zbMATHGoogle Scholar
  47. Pardi, A., Wagner, G. and Wüthrich, K. (1983) Eur. J. Biochem., 137, 445–454.CrossRefGoogle Scholar
  48. Pastore, A. and Saudek, V. (1990) J. Magn. Reson., 90, 165–176.Google Scholar
  49. Pearson, J.G., Wang, J., Markley, J.L., Le, H. and Oldfield, E. (1995) J. Am. Chem. Soc., 117, 8823–8829.CrossRefGoogle Scholar
  50. Pelton, J.G., Torchia, D.A., Meadow, N.D., Wong, C. and Roseman, S. (1991) Biochemistry, 30, 10043–10057.CrossRefGoogle Scholar
  51. Prompers, J.J., Groenewegen, A., van Schaik, R.C., Pepermans, H.A.M. and Hilbers, C.W. (1997) Protein Sci., 6, 2375–2384.CrossRefGoogle Scholar
  52. Qin, J., Clore, G.C. and Gronenborn, A.M. (1996) Biochemistry, 35, 7–13.CrossRefGoogle Scholar
  53. Redfield, C. and Robertson, J. (1991) Proceedings of a NATO Advanced Research Workshop on Computational Aspects of the Study of Biological Macromolecules by NMR, Plenum Press, New York, NY.Google Scholar
  54. Saito, H. (1986) Magn. Reson. Chem., 24, 835–852.CrossRefGoogle Scholar
  55. Scrofani, S.D.B., Wright, P.E. and Dyson, J.H. (1998) J. Biomol. NMR, 12, 201–202.CrossRefGoogle Scholar
  56. Seavey, B.R., Farr, E.A., Westler, W.M. and Markley, L. (1991) J. Biomol. NMR, 1, 217–236.CrossRefGoogle Scholar
  57. Sethson, I., Edlund, U., Holak, T.A., Ross, A. and Johnson, B.-H. (1996) J. Biomol. NMR, 8, 417–428.CrossRefGoogle Scholar
  58. Sharff, A.J., Rodseth, L.E. and Quiocho, F.A. (1993) Biochemistry, 32, 10553–10559.CrossRefGoogle Scholar
  59. Spera, S. and Bax, A. (1991) J. Am. Chem. Soc., 113, 5491–5492.CrossRefGoogle Scholar
  60. Svensson, L.A., Thulin, E. and Forsen, S. (1992) J. Mol. Biol., 223, 601–606.CrossRefGoogle Scholar
  61. Veerapandian, B., Gilliland, G.L., Raag, R., Svensson, L.A., Masui, Y., Hirai, Y. and Poulos, T.L. (1992) Proteins Struct. Funct. Genet., 12, 10–23.CrossRefGoogle Scholar
  62. Vijay-Kumar, S., Bugg, C.E. and Cook, W.J. (1987) J. Mol. Biol., 194, 531–544.CrossRefGoogle Scholar
  63. Vuister, G.W., Delaglio, F. and Bax, A. (1992) J. Am. Chem. Soc., 114, 9674–9675.CrossRefGoogle Scholar
  64. Vuister, G.W., Delaglio, F. and Bax, A. (1993) J. Biomol. NMR, 3, 67–80.Google Scholar
  65. Wang, A.C., Grzesiek, S., Tschudin, R., Lodi, P.J. and Bax, A. (1995) J. Biomol. NMR, 5, 376–382.Google Scholar
  66. Wang, Y.-X., Marquardt, J.L., Wingfield, P., Stahl, S.J., Lee-Huang, S., Torchia, D.A. and Bax, A. (1998) J. Am. Chem. Soc., 120, 7385–7386.CrossRefGoogle Scholar
  67. Weichsel, A., Gasdaska, J.R., Powis, G. and Montfort, W.R. (1996) Structure, 15, 735–751.CrossRefGoogle Scholar
  68. Williamson, M. (1990) Biopolymers, 29, 1423–1431.CrossRefGoogle Scholar
  69. Wishart, D.S., Sykes, B.D. and Richards, F.M. (1991) J. Mol. Biol., 222, 311–333.CrossRefGoogle Scholar
  70. Wishart, D.S. and Sykes, B.D. (1994) J. Biomol. NMR, 4, 171–180.CrossRefGoogle Scholar
  71. Wishart, D.S., Colin, G.B., Holm, A., Hodges, R.S. and Sykes, B.D. (1995a) J. Biomol. NMR, 5, 67–81.CrossRefGoogle Scholar
  72. Wishart, D.S., Colin, G.B., Yao, J., Abildgaard, F., Dyson, H.J., Oldfield, E., Markley, J.L. and Sykes, B.D. (1995b) J. Biomol. NMR, 6, 135–140.CrossRefGoogle Scholar
  73. Wishart, D.S., Watson, M.S., Boyko, R.F. and Sykes, B.D. (1997) J. Biomol. NMR, 10, 329–336.CrossRefGoogle Scholar
  74. Wlodawer, A., Walter, J., Huber, R. and Sjolin, L. (1984) J. Mol. Biol., 198, 469–480.CrossRefGoogle Scholar
  75. Worthylake, D., Meadow, N.D., Roseman, S., Liao, D.-I., Herzberg, O. and Remington, S.J. (1991) Proc. Natl. Acad. Sci. USA, 88, 10382–10386.CrossRefADSGoogle Scholar
  76. Yamazaki, T., Hinck, A.P., Wang, Y.-X., Nicholson, L.K., Torchia, D.A., Wingfield, P.T., Stahl, S.J., Kaufman, J.D., Chang, C.-H., Domaille, P.J. and Lam, P.Y.S. (1996) Protein Sci., 5, 495–506.CrossRefGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1999

Authors and Affiliations

  • Gabriel Cornilescu
    • 1
  • Frank Delaglio
    • 1
  • Ad Bax
    • 1
  1. 1.Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney DiseasesNational Institutes of HealthBethesdaU.S.A.

Personalised recommendations