Journal of Biomolecular NMR

, Volume 28, Issue 3, pp 273–287 | Cite as

Application of Correlated Residual Dipolar Couplings to the Determination of the Molecular Alignment Tensor Magnitude of Oriented Proteins and Nucleic Acids

  • David L. Bryce
  • Ad Bax


Residual dipolar couplings (RDC) between nuclear spins in partially aligned samples offer unique insights into biomacromolecular structure and dynamics. To fully benefit from the RDC data, accurate knowledge of the magnitude (D a) and rhombicity (R) of the molecular alignment tensor, A, is important. An extended histogram method (EHM) is presented which extracts these parameters more effectively from dipolar coupling data. The method exploits the correlated nature of RDCs for structural elements of planar geometry, such as the one-bond 13C′i13Ci α, 13C′i15Ni+1, and 15Ni+11HN i+1 couplings in peptide bonds of proteins, or suitably chosen combinations of 1 D C1′H1′, 1 D C2′H2′, 1 D C1′C2′, 2 D C2′H1′, 2 D C1′H2′, and 3 D H1′H2′ couplings in nucleic acids, to generate an arbitrarily large number of synthetic RDCs. These synthetic couplings result in substantially improved histograms and resulting values of D a and R, compared with histograms generated solely from the original sets of correlated RDCs, particularly when the number of planar fragments for which couplings are available is small. An alternative method, complementary to the EHM, is also described, which uses a systematic grid search procedure, based on least-squares fitting of sets of correlated RDCs to structural elements of known geometry, and provides an unambiguous lower limit for the degree of molecular alignment.

alignment tensor dipolar coupling histogram liquid crystal molecular alignment powder pattern residual dipolar couplings RNA 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Supplementary material

10858_2004_Article_5253167_MOESM1_ESM.pdf (133 kb)
Supplementary Figures (PDF 133 KB)


  1. Alderman, D.W., Solum, M.S. and Grant, D.M. (1986) J. Chem. Phys., 84, 3717–3725.CrossRefADSGoogle Scholar
  2. Al-Hashimi, H.M., Pitt, S.W., Majumdar, A., Xu, W.J. and Patel, D.J. (2003) J. Mol. Biol, 329, 867–873.CrossRefGoogle Scholar
  3. Andrew, E.R. and Wynn, V.T. (1966) Proc. Roy. Soc. London Ser. A, 291, 257–266.CrossRefADSGoogle Scholar
  4. Bak, M., Rasmussen, J.T. and Nielsen, N.C. (2000) J. Magn. Reson., 147, 296–330.CrossRefADSGoogle Scholar
  5. Bax, A. (2003) Prot. Sci., 12, 1–16.CrossRefGoogle Scholar
  6. Bax, A. and Tjandra, N. (1997) J. Biomol. NMR, 10, 289–292.CrossRefGoogle Scholar
  7. Bothner-By, A.A. (1996) In Encyclopedia of Nuclear Magnetic Resonance (Grant, D.M., and Harris, R.K. (Eds.), Wiley, Chichester, pp. 2932–2938.Google Scholar
  8. Brunner, E. (2001) Concepts Magn. Res. 13, 238–259.CrossRefGoogle Scholar
  9. Bryce, D.L. and Wasylishen, R.E. (2003) J. Biomol. NMR, 25, 73–78.CrossRefGoogle Scholar
  10. Case, D.A. (1999) J. Biomol. NMR, 15, 95–102.CrossRefGoogle Scholar
  11. Chou, J.J., Gaemers, S., Howder, B., Louis, J.M. and Bax, A. (2001) J. Biomol. NMR, 21, 377–382.CrossRefGoogle Scholar
  12. Choy, W.Y., Tollinger, M., Mueller, G.A. and Kay, L.E. (2001) J. Biomol. NMR, 21, 31–40.CrossRefGoogle Scholar
  13. Clore, G.M. (2000) Proc. Natl. Acad. Sci. USA 97, 9021–9025.CrossRefADSGoogle Scholar
  14. Clore, G.M., Gronenborn, A.M. and Bax, A. (1998a) J. Magn. Reson., 133, 216–221.CrossRefADSGoogle Scholar
  15. Clore, G.M., Gronenborn, A.M. and Tjandra, N. (1998b) J. Magn. Reson., 131, 159–162.CrossRefADSGoogle Scholar
  16. Clore, G.M., Starich, M.R. and Gronenborn, A.M. (1998c) J. Am. Chem. Soc., 120, 10571–10572.CrossRefGoogle Scholar
  17. Cornilescu, G. and Bax, A. (2000) J. Am. Chem. Soc., 122, 10143–10154.CrossRefGoogle Scholar
  18. Cornilescu, G., Marquardt, J.L., Ottiger, M. and Bax, A. (1998) J. Am. Chem. Soc., 120, 6836–6837.CrossRefGoogle Scholar
  19. de Alba, E. and Tjandra, N. (2002) Prog. Nucl. Magn. Reson. Spectrosc., 40, 175–197.CrossRefGoogle Scholar
  20. Delaglio, F., Grzesiek, S., Vuister, G.W., Zhu, G., Pfeifer, J. and Bax, A. (1995) J. Biomol. NMR, 6, 277–293.CrossRefGoogle Scholar
  21. Derrick, J.P. and Wigley, D.B. (1994) J. Mol. Biol., 243, 906–918.CrossRefGoogle Scholar
  22. Eichele, K. and Wasylishen, R.E. (2001) University of Tubingen ( Scholar
  23. Fushman, D., Ghose, R. and Cowburn, D. (2000) J. Am. Chem. Soc., 122, 10640–10649.CrossRefGoogle Scholar
  24. Gayathri, C., Bothnerby, A.A., Vanzijl, P.C.M. and Maclean, C. (1982) Chem. Phys. Lett., 87, 192–196.CrossRefADSGoogle Scholar
  25. Grant, D.M. (1996) In Encyclopedia of Nuclear Magnetic Resonance (Grant, D.M. and Harris, R.K. (Eds.), Wiley, Chichester, pp. 1298–1321.Google Scholar
  26. Griffin, R.G., Ellett, J.D., Mehring, M., Bullitt, J.G. and Waugh, J.S. (1972) J. Chem. Phys., 57, 2147–2155.CrossRefADSGoogle Scholar
  27. Hansen, M.R., Mueller, L. and Pardi, A. (1998) Nat. Struct. Biol., 5, 1065–1074.CrossRefGoogle Scholar
  28. Hu, J.S. and Bax, A. (1997) J. Am. Chem. Soc., 119, 6360–6368.CrossRefGoogle Scholar
  29. Klosterman, P.S., Shah, S.A. and Steitz, T.A. (1999) Biochemistry, 38, 14784–14792.CrossRefGoogle Scholar
  30. Kuhn, P., Knapp, M., Soltis, S.M., Ganshaw, G., Thoene, M. and Bott, R. (1998) Biochemistry, 37, 13446–13452.CrossRefGoogle Scholar
  31. Kung, H.C., Wang, K.Y., Goljer, I. and Bolton, P.H. (1995) J. Magn. Reson. Ser. B, 109, 323–325.CrossRefGoogle Scholar
  32. Lee, L.K., Rance, M., Chazin, W.I. and Palmer, A.G. (1997) J. Biomol. NMR, 9, 287–298.CrossRefGoogle Scholar
  33. Lipsitz, R.S. and Tjandra, N. (2001) J. Am. Chem. Soc., 123, 11065–11066.CrossRefGoogle Scholar
  34. Losonczi, J.A., Andrec, M., Fischer, M.W.F. and Prestegard, J.H. (1999) J. Magn. Reson., 138, 334–342.CrossRefADSGoogle Scholar
  35. Lukin, J.A., Kontaxis, G., Simplaceanu, V., Yuan, Y., Bax, A. and Ho, C. (2003) Proc. Natl. Acad. Sci. USA 100, 517–520.CrossRefADSGoogle Scholar
  36. MacArthur, M.W. and Thornton, J.M. (1996) J. Mol. Biol., 264, 1180–1195.CrossRefGoogle Scholar
  37. Maricq, M.M. and Waugh, J.S. (1979) J. Chem. Phys., 70, 3300–3316.CrossRefADSGoogle Scholar
  38. Mehring, M. (1983) High resolution NMR in Solids, 2nd edn., Springer Verlag, Berlin.Google Scholar
  39. Meiler, J., Blomberg, N., Nilges, M. and Griesinger, C. (2000) J. Biomol. NMR, 16, 245–252.CrossRefGoogle Scholar
  40. Meiler, J., Peti, W. and Griesinger, C. (2003) J. Am. Chem. Soc., 125, 8072–8073.CrossRefGoogle Scholar
  41. Mueller, G.A., Choy, W.Y., Yang, D.W., Forman-Kay, J.D., Venters, R.A. and Kay, L.E. (2000) J. Mol. Biol., 300, 197–212.CrossRefGoogle Scholar
  42. Olejniczak, E.T., Vega, S. and Griffin, R.G. (1984) J. Chem. Phys., 81, 4804–4817.CrossRefADSGoogle Scholar
  43. Ottiger, M. and Bax, A. (1998) J. Am. Chem. Soc., 120, 12334–12341.CrossRefGoogle Scholar
  44. Prestegard, J.H., Al-Hashimi, H.M. and Tolman, J.R. (2000) Q. Rev. Biophys., 33, 371–424.CrossRefGoogle Scholar
  45. Ruckert, M. and Otting, G. (2000) J. Am. Chem. Soc., 122, 7793–7797.CrossRefGoogle Scholar
  46. Sass, J., Cordier, F., Hoffmann, A., Rogowski, M., Cousin, A., Omichinski, J.G., Lowen, H. and Grzesiek, S. (1999) J. Am. Chem. Soc., 121, 2047–2055.CrossRefGoogle Scholar
  47. Sass, H.J., Musco, G., Stahl, S.J., Wingfield, P.T. and Grzesiek, S. (2000) J. Biomol. NMR, 18, 303–309.CrossRefGoogle Scholar
  48. Sass, H.J., Musco, G., Stahl, S.J., Wingfield, P.T. and Grzesiek, S. (2001) J. Biomol. NMR, 21, 275–280.CrossRefGoogle Scholar
  49. Skrynnikov, N.R. and Kay, L.E. (2000) J. Biomol. NMR, 18, 239–252.CrossRefGoogle Scholar
  50. Skrynnikov, N.R., Goto, N.K., Yang, D.W., Choy, W.Y., Tolman, J.R., Mueller, G.A. and Kay, L.E. (2000) J. Mol. Biol., 295, 1265–1273.CrossRefGoogle Scholar
  51. Tjandra, N. and Bax, A. (1997) Science, 278, 1111–1114.CrossRefADSGoogle Scholar
  52. Tjandra, N., Omichinski, J.G., Gronenborn, A.M., Clore, G.M. and Bax, A. (1997) Nat. Struct. Biol., 4, 732–738.CrossRefGoogle Scholar
  53. Tolman, J.R., Flanagan, J.M., Kennedy, M.A. and Prestegard, J.H. (1995) Proc. Natl. Acad. Sci. USA, 92, 9279–9283.CrossRefADSGoogle Scholar
  54. Tugarinov, V. and Kay, L.E. (2003) J. Mol. Biol., 327, 1121–1133.CrossRefGoogle Scholar
  55. Tycko, R., Blanco, F.J. and Ishii, Y. (2000) J. Am. Chem. Soc., 122, 9340–9341.CrossRefGoogle Scholar
  56. Ulmer, T.S., Ramirez, B.E., Delaglio, F. and Bax, A. (2003) J. Am. Chem. Soc., 125, 9179–9191.CrossRefGoogle Scholar
  57. Vijay-Kumar, S., Bugg, C.E. and Cook, W.J. (1987) J. Mol. Biol., 194, 531–544.CrossRefGoogle Scholar
  58. Warren, J.J. and Moore, P.B. (2001) J. Magn. Reson., 149, 271–275.CrossRefADSGoogle Scholar
  59. Wu, Z.R., Tjandra, N. and Bax, A. (2001) J. Am. Chem. Soc., 123, 3617–3618.CrossRefGoogle Scholar
  60. Zidek, L., Padrta, P., Chmelik, J. and Sklenar, V. (2003) J. Magn. Reson., 162, 385–395.CrossRefADSGoogle Scholar
  61. Zweckstetter, M. and Bax, A. (2002) J. Biomol. NMR, 23, 127–137.CrossRefGoogle Scholar

Copyright information

© Kluwer Academic Publishers 2004

Authors and Affiliations

  • David L. Bryce
    • 1
  • Ad Bax
    • 1
  1. 1.Laboratory of Chemical PhysicsNational Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of HealthBethesdaU.S.A.

Personalised recommendations