Journal of Biomolecular NMR

, Volume 5, Issue 3, pp 217–225 | Cite as

Chemical shifts and three-dimensional protein structures

  • Eric Oldfield


During the past three years it has become possible to compute ab initio the 13C, 15N and 19F NMR chemical shifts of many sites in native proteins. Chemical shifts are beginning to become a useful supplement to more established methods of solution structure determination, and may find utility in solid-state analysis as well. From 13C NMR, information on ϕ, Ψ and χ torsions can be obtained, permitting both assignment verification, and structure refinement and prediction. For 15N, both torsional and hydrogen-bonding effects are important, while for 19F, chemical shifts are primarily indicators of the local charge field. Chemical shift calculations are still slow, but shielding hypersurfaces — the shift as a function of the dihedral angles that define the molecular conformation — are becoming accessible. Over the next few years, theoretical and computer hardware improvements will enable more routine use of chemical shifts in structural studies, including the study of metal-ligand interactions, the analysis of drug and substrate binding and catalysis, the study of folding/unfolding pathways, as well as the characterization of conformational substates. Rather than simply being a necessary prerequisite for multidimensional NMR, chemical shifts and chemical shift non-equivalence due to folding are now beginning to be useful for structural characterization.


Chemical shifts Chemical shift tensors Ab initio calculations Structure refinement and prediction Electrostatics 


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  1. Augspurger, J.D. and Dykstra, C.E. (1991) J. Phys. Chem., 95, 9230–9238.Google Scholar
  2. Augspurger, J.D., Dykstra, C.E. and Oldfield, E. (1991) J. Am. Chem. Soc., 113, 2447–2451.Google Scholar
  3. Augspurger, J., Pearson, J., Oldfield, E., Dykstra, C.E., Park, K.D. and Schwartz, D. (1992) J. Magn. Reson., 100, 342–357.Google Scholar
  4. Augspurger, J.D., deDios, A.C., Oldfield, E. and Dykstra, C.E. (1993) Chem. Phys. Lett., 213, 211–216.Google Scholar
  5. Brünger, A.T. (1992) X-PLOR, Yale University Press, New Haven, CT.Google Scholar
  6. Buckingham, A.D. (1960) Can. J. Chem., 38, 300–307.Google Scholar
  7. Celda, B., Biamonti, C., Arnau, M.J., Tejero, R. and Montelione, G.T. (1995) J. Biomol. NMR, 5, 161–172.Google Scholar
  8. Cole, H.B.R., Sparks, S.W. and Torchia, D.A. (1988) Proc. Natl. Acad. Sci. USA, 85, 6362–6365.Google Scholar
  9. deDios, A.C. and Oldfield, E. (1993) Chem. Phys. Lett., 205, 108–116.Google Scholar
  10. deDios, A.C., Pearson, J.G. and Oldfield, E. (1993a) J. Am. Chem. Soc., 115, 9768–9773.Google Scholar
  11. deDios, A.C., Pearson, J.G. and Oldfield, E. (1993b) Science, 260, 1491–1496.Google Scholar
  12. deDios, A.C., Laws, D.D. and Oldfield, E. (1994) J. Am. Chem. Soc., 116, 7784–7786.Google Scholar
  13. deDios, A.C. and Oldfield, E. (1994a) J. Am. Chem. Soc., 116, 5307–5314.Google Scholar
  14. deDios, A.C. and Oldfield, E. (1994b) J. Am. Chem. Soc., 116, 11485–11488.Google Scholar
  15. Ditchfield, R. (1972) J. Chem. Phys., 56, 5688–5691.Google Scholar
  16. Fesik, S.W. (1993) J. Biomol. NMR, 3, 261–269.Google Scholar
  17. Frauenfelder, H., Alberding, N.A., Ansari, A., Braunstein, D., Cowen, B.R., Hong, M.K., Iben, I.E.T., Johnson, J.B., Luck, S., Marden, M.C., Mourant, J.R., Ormos, P., Reinisch, L., School, R., Schulte, A., Shyamsunder, E., Sorensen, L.B., Steinback, P.J., Xie, A., Young, R.D. and Yue, K.T. (1990) J. Phys. Chem., 94, 1024–1037.Google Scholar
  18. Gauss, J. (1992) Chem. Phys. Lett., 191, 614–620.Google Scholar
  19. Jiao, D., Barfield, M. and Hruby, J.M. (1993) J. Am. Chem. Soc., 115, 10883–10887.Google Scholar
  20. Kohn, W. and Sham, L.J. (1965) Phys. Rev., 140A, 1133–1138.Google Scholar
  21. Kuszewski, J., Qin, J., Gronenborn, A.M. and Clore, G.M. (1995) J. Magn. Reson. Ser. B, 106, 92–96.Google Scholar
  22. Kutzelnigg, W., VanWullen, C., Fleischer, U., Franke, R. and VanMourik, T. (1993) In Nuclear Magnetic Shieldings and Molecular Structure (Ed., Tossell, J.A.) Kluwer, Dordrecht, pp. 141–162.Google Scholar
  23. Laws, D.D., deDios, A.C. and Oldfield, E. (1993) J. Biomol. NMR, 3, 607–612.Google Scholar
  24. Le, H., Pearson, J.G., de Dios, A.C. and Oldfield, E. (1995) J. Am. Chem. Soc., in press.Google Scholar
  25. London, F. (1937) J. Phys. Radium, 8, 397–409.Google Scholar
  26. Luck, L.A. and Falke, J.J. (1991a) Biochemistry, 30, 4248–4256.Google Scholar
  27. Luck, L.A. and Falke, J.J. (1991b) Biochemistry, 30, 4257–4261.Google Scholar
  28. Malkin, V.G., Malkina, O.L., Casida, M.E. and Salahub, D.R. (1994) J. Am. Chem. Soc., 116, 5898–5908.Google Scholar
  29. Miranker, A., Radford, S.E., Karplus, M. and Dobson, C.M. (1991) Nature, 349, 633–636.Google Scholar
  30. Ösapay, K., Theriault, Y., Wright, P.E. and Case, D.A. (1994) J. Mol. Biol., 244, 183–197.Google Scholar
  31. Pearson, J.G., Oldfield, E., Lee, F.S. and Warshel, A. (1993) J. Am. Chem. Soc., 115, 6851–6862.Google Scholar
  32. Ponder, J.W. and Richards, F.M. (1987) J. Mol. Biol., 193, 775–791.Google Scholar
  33. Ramsey, N.F. (1950) Phys. Rev., 78, 699–703.Google Scholar
  34. Ramsey, N.F. (1952) Phys. Rev., 86, 243–246.Google Scholar
  35. Smith, L.J., Redfield, C., Smith, R.A.G., Dobson, C.M., Clore, G.M., Gronenborn, A.M., Walter, M.R., Naganbushan, T.L. and Wlodawer, A. (1994) Nature Struct. Biol., 1, 301–310.Google Scholar
  36. Spera, S. and Bax, A. (1991) J. Am. Chem. Soc., 113, 5490–5492.Google Scholar
  37. Stephen, M.J. (1957) Mol. Phys., 1, 223–232.Google Scholar
  38. Wagner, G. (1993) J. Biomol. NMR, 3, 375–385.Google Scholar
  39. Warshel, A. (1991) Computer Modeling of Chemical Reactions in Enzymes and Solutions, Wiley, New York, NY.Google Scholar
  40. Wishart, D.S., Sykes, B.D. and Richards, F.M. (1992) Biochemistry, 31, 1647–1651.Google Scholar
  41. Wishart, D.S. and Sykes, B.D. (1994) J. Biomol. NMR, 4, 171–180.Google Scholar
  42. Wolinski, K., Hinton, J.F. and Pulay, P. (1990) J. Am. Chem. Soc., 112, 8251–8260.Google Scholar

Copyright information

© ESCOM Science Publishers B.V. 1995

Authors and Affiliations

  • Eric Oldfield
    • 1
  1. 1.Department of ChemistryUniversity of Illinois at Urbana-ChampaignUrbanaU.S.A.

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