Direct fitting of structure and chemical shift to NMR spectra

Abstract

The possibility of determining protein structure directly from NMR spectra is investigated. Optimisation of four variables per atom (δ, x, y, z) directly against the nuclear Overhauser effect (NOE) spectrum by simulated annealing is shown to succeed in finding sets of coordinates (i.e. structures) and chemical shifts that match the reference configuration. The procedure is shown to work on both a fully resolved spectrum and when two resonances are overlapping. It is proposed that a direct approach may ultimately replace current methods of structure determination (assignment followed by structure calculation).

References

1. J. Jeener, Ampère International Summer School, Basko Polje, Yugoslavia, 1971.
2. W. P. Aue, E. Bartholdi and R. R. Ernst, J. Chem. Phys., 1976, 64, 2229.
3. R. R. Ernst, G. Bodenhausen and A. Wokaun, Principles of Nuclear Magnetic Resonance in One and Two Dimensions, Oxford University Press, Oxford, 1986.
4. H. Oschkinat, C. Griesinger, P. J. Kraulis, O. W. Sorensen, R. R. Ernst, A. M. Gronenborn and G. M. Clore, Nature (London), 1988, 332, 374.
5. L. Müller, J. Am. Chem. Soc., 1979, 101, 4481.
6. G. Bodenhausen and D. J. Ruben, Chem. Phys. Lett., 1980, 69, 185.
7. A. Bax, R. H. Griffey and B. L. Hawkins, J. Am. Chem. Soc., 1983, 105, 7188.
8. G. M. Clore and A. M. Gronenborn, Methods Enzymol., 1994, 239, 349.
9. K. Wüthrich, NMR of Proteins and Nucleic Acids, Wiley, New York, 1986.
10. G. Wagner, S. G. Hyberts and T. F. Havel, Annu. Rev. Biophys. Biomol. Struct., 1992, 21, 167.
11. D. Neuhaus and M. P. Williamson, The Nuclear Overhauser Effect in Structural and Conformational Analysis, VCH, New York, 1989.
12. M. Karplus, J. Phys. Chem., 1959, 30, 11.
13. A. Pardi, M. Billeter and K. Wüthrich, J. Mol. Biol., 1984, 180, 741.
14. T. F. Havel and K. Wüthrich, J. Mol. Biol., 1985, 182, 281.
15. W. Braun and N. Go, J. Mol. Biol., 1985, 186, 611.
16. A. T. Brünger, G. M. Clore, A. M. Gronenborn and M. Karplus, Proc. Natl. Acad. Sci. USA, 1986, 83, 3801.
17. M. Nilges, G. M. Clore, A. T. Brünger and A. M. Gronenborn, Protein Eng., 1988, 2, 27.
18. T. L. James, Curr. Opin. Struct. Biol., 1994, 4, 275.
19. C. Bartels and K. Wüthrich, J. Biomol. NMR, 1994, 4, 775.
20. M. S. Friedrichs, L. Müller and M. Wittekind, J. Biomol. NMR, 1994, 4, 703.
21. B. J. Hare and J. H. Prestegard, J. Biomol. NMR, 1994, 4, 35.
22. R. P. Meadows, E. T. Olejniczak and S. W. Fesik, J. Biomol. NMR, 1994, 4, 79.
23. J. B. Olson Jr. and J. L. Markley, J. Biomol. NMR, 1994, 4, 385.
24. N. Morelle, B. Brutscher, J.-P. Simorre and D. Marion, J. Biomol. NMR, 1995, 5, 154.
25. D. A. Case, H. J. Dyson and P. E. Wright, Methods Enzymol., 1994, 239, 392.
26. E. Oldfield, J. Biomol. NMR, 1995, 5, 217.
27. T. E. Malliavin, A. Rouh, M. A. Delsuc and J.-Y. Lallemand, C. R. Acad. Sci. Paris II, 1992, 315, 653.
28. C. M. Oshiro and I. D. Kuntz, Biopolymers, 1993, 33, 107.
29. P. J. Kraulis, J. Mol. Biol., 1994, 243, 696.
30. R. A. Atkinson and V. Saudek, in Dynamics and the Problem of Recognition in Biological Macromolecules, ed. O. Jardetzky and J.-F. Lefèvre, Plenum Press, New York, 1996.
31. J. Drenth, Principles of Protein X-Ray Crystallography, Springer-Verlag, New York, 1994.
32. C. Mumenthaler and W. Braun, J. Mol. Biol., 1995, 254, 465.
33. M. Nilges, J. Mol. Biol., 1995, 245, 645.
34. S. Kirkpatrick, C. D. Gelatt Jr. and M. P. Vecchi, Science, 1983, 220, 671.
35. W. L. Goffe, G. D. Ferrier and J. Rogers, J. Econometrics, 1994, 60, 65.
36. A. Wlodawer, J. Nachman, G. L. Gilliland, W. Gallagher and C. Woodward, J. Mol. Biol., 1987, 198, 469.
37. W. L. Goffe, http://www.netlib.no/netlib/opt/simann.f 1994.
38. N. Metropolis, M. Rosenbluth, A. Rosenbluth, A. Teller and E. Teller, J. Chem. Phys., 1953, 21, 1087.
39. A. T. Brünger, X-PLOR version 3.0 User Manual, Yale University, New Haven, USA, 1992.
40. W. H. Press, B. P. Flannery, S. A. Teukolsky and W. T. Vetterling, Numerical Recipes, The Art of Scientific Computing, Cambridge University Press, Cambridge, 1986, pp. 294–3013.
41. P. Yip and D. A. Case, J. Magn. Reson., 1989, 83, 643.
42. P. Koehl and J.-F. Lefèvre, J. Magn. Reson., 1990, 86, 565.
43. M. Nilges, J. Habazettl, A. T. Brünger and T. A. Holak, J. Mol. Biol., 1991, 219, 499.