Journal of the American Society for Mass Spectrometry

, Volume 12, Issue 11, pp 1153–1162

Automatic analysis of hydrogen/deuterium exchange mass spectra of peptides and proteins using calculations of isotopic distributions

Article

Abstract

High mass-resolving power has been shown to be useful for studying the conformational dynamics of proteins by hydrogen/deuterium (H/D) exchange. A computer algorithm was developed that automatically identifies peptides and their extent of deuterium incorporation from H/D exchange mass spectra of enzymatic digests or fragment ions produced by collisionally induced dissociation (CID) or electron capture dissociation (ECD). The computer algorithm compares measured and calculated isotopic distributions and uses a fast calculation of isotopic distributions using the fast Fourier transform (FFT). The algorithm facilitates rapid and automated analysis of H/D exchange mass spectra suitable for high-throughput approaches to the study of peptide and protein structures. The algorithm also makes the identification independent on comparisons with undeuterated control samples. The applicability of the algorithm was demonstrated on simulated isotopic distributions as well as on experimental data, such as Fourier transform ion cyclotron resonance (FTICR) mass spectra of myoglobin peptic digests, and CID and ECD spectra of substance P.

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References

  1. 1.
    Pandey, A.; Mann, M. Nature 2000, 405, 837–846.CrossRefGoogle Scholar
  2. 2.
    McLafferty, F. W.; Fridriksson, E. K.; Horn, D. M.; Zubarev, R. A.; Lewis, M. A. Science 1999, 284, 1289–1290.CrossRefGoogle Scholar
  3. 3.
    Rostom, A. A.; Robinson, C. V. Curr. Opin. Struct. Biol. 1999, 9, 135–141.CrossRefGoogle Scholar
  4. 4.
    Henderson, S. C.; Valentine, S. J.; Counterman, A. E.; Clemmer, D. E. Anal. Chem. 1999, 71, 291–301.CrossRefGoogle Scholar
  5. 5.
    Last, A. M.; Robinson, C. V. Curr. Opin. Chem. Biol. 1999, 3, 564–570.CrossRefGoogle Scholar
  6. 6.
    Marshall, A. G.; Hendrickson, C. L.; Jackson, G. S. Mass Spectrom. Rev. 1998, 17, 1–35.CrossRefGoogle Scholar
  7. 7.
    Conrads, T. P.; Anderson, G. A.; Veenstra, T. D.; Pasa-Tolic, L.; Smith, R. D. Anal. Chem. 2000, 72, 3349–3354.CrossRefGoogle Scholar
  8. 8.
    Yergey, J.; Heller, H.; Hansen, G.; Cotter, R. J.; Fenselau, C. Anal. Chem. 1983, 55, 353–356.CrossRefGoogle Scholar
  9. 9.
    Senko, M. W.; Beu, S. C.; McLafferty, F. W. J. Am. Soc. Mass Spectrom. 1995, 6, 229–233.CrossRefGoogle Scholar
  10. 10.
    He, F.; Hendrickson, C. L.; Marshall, A. G. J. Am. Soc. Mass Spectrom. 2000, 11, 120–126.CrossRefGoogle Scholar
  11. 11.
    Shi, S. D. H.; Hendrickson, C. L.; Marshall, A. G. Proc. Natl. Acad. Sci. U.S.A. 1998, 95, 11532–11537.CrossRefGoogle Scholar
  12. 12.
    Englander, S. W.; Sosnick, T. R.; Englander, J. J.; Mayne, L. Curr. Opin. Struct. Biol. 1996, 6, 18–23.CrossRefGoogle Scholar
  13. 13.
    Smith, D. L.; Deng, Y.; Zhang, Z. J. Mass Spec. 1997, 32, 135–146.CrossRefGoogle Scholar
  14. 14.
    Woodward, C. J. Am. Soc. Mass Spectrom. 1999, 10, 672–674.CrossRefGoogle Scholar
  15. 15.
    Roder, H.; Elove, G. A.; Englander, S. W. Nature 1988, 335, 700–704.CrossRefGoogle Scholar
  16. 16.
    Miranker, A.; Robinson, C. V.; Radford, S. E.; Aplin, R. T.; Dobson, C. M. Science 1993, 262, 896–900.CrossRefGoogle Scholar
  17. 17.
    Katta, V.; Chait, B. T. J. Am. Chem. Soc. 1993, 115, 6317–6321.CrossRefGoogle Scholar
  18. 18.
    Dharmasiri, K.; Smith, D. L. J. Am. Soc. Mass Spectrom. 1997, 8, 1039–1045.CrossRefGoogle Scholar
  19. 19.
    Zhang, Z.; Post, C. B.; Smith, D. L. Biochemistry 1996, 35, 779–791.CrossRefGoogle Scholar
  20. 20.
    Johnson, R. S. J. Am. Soc. Mass. Spectrom. 1996, 7, 515–521.CrossRefGoogle Scholar
  21. 21.
    Maier, C. S.; Kim, O. H.; Deinzer, M. L. Anal. Biochem. 1997, 252, 127–135.CrossRefGoogle Scholar
  22. 22.
    Mandell, J. G.; Falick, A. M.; Komives, E. A. Proc. Natl. Acad. Sci. U.S.A. 1998, 95, 14705–14710.CrossRefGoogle Scholar
  23. 23.
    Chung, E. W.; Nettleton, E. J.; Morgan, C. J.; Gross, M.; Miranker, A.; Radford, S. E.; Dobson, C. M.; Robinson, C. V. Protein Sci. 1997, 6, 1316–1324.CrossRefGoogle Scholar
  24. 24.
    Horn, D. M.; Zubarev, R. A.; McLafferty, F. W. J. Am. Soc. Mass. Spectrom. 2000, 11, 320–332.CrossRefGoogle Scholar
  25. 25.
    Zhang, Z.; Smith, D. L. Protein Sci. 1993, 2, 522–531.CrossRefGoogle Scholar
  26. 26.
    Deng, Y.; Smith, D. L. J. Mol. Biol. 1999, 294, 247–258.CrossRefGoogle Scholar
  27. 27.
    Waring, A. J.; Mobley, P. W.; Gordon, L. M.; Proteins 1998, Suppl., 38–49.Google Scholar
  28. 28.
    Anderegg, R. J.; Wagner, D. S.; Stevenson, C. L.; Borchardt, R. T. J. Am. Soc. Mass Spectrom. 1994, 5, 425–433.CrossRefGoogle Scholar
  29. 29.
    Hayes, R. N.; Gross, M. L. Methods Enzymol. 1990, 193, 237–263.CrossRefGoogle Scholar
  30. 30.
    Cody, R. B.; Freiser, B. S. Int. J. Mass Spectrom. Ion Phys. 1982, 41, 199–204.CrossRefGoogle Scholar
  31. 31.
    Deng, Y.; Pan, H.; Smith, D. L. J. Am. Chem. Soc. 1999, 121, 1966–1967.CrossRefGoogle Scholar
  32. 32.
    Zubarev, R. A.; Kelleher, N. L.; McLafferty, F. W. J. Am. Chem. Soc. 1998, 120, 3265–3266.CrossRefGoogle Scholar
  33. 33.
    Axelsson, J.; Palmblad, M.; Håkansson, K.; Håkansson, P. Rapid Commun. Mass Spectrom. 1999, 13, 474–477.CrossRefGoogle Scholar
  34. 34.
    Zhang, Z.; Li, W.; Logan, T. M.; Li, M.; Marshall, A. G. Protein Sci. 1997, 6, 2203–2217.CrossRefGoogle Scholar
  35. 35.
    Bai, Y.; Milne, J. S.; Mayne, L.; Englander, S. W. Proteins 1993, 17, 75–86.CrossRefGoogle Scholar
  36. 36.
    Buijs, J.; Håkansson, K.; Hagman, C.; Håkansson, P.; Oscarsson, S. Rapid Commun. Mass Spectrom. 2000, 14, 1751–1756.CrossRefGoogle Scholar
  37. 37.
    Palmblad, M.; Håkansson, K.; Håkansson, P.; Feng, X.; Cooper, H. J.; Giannakopulos, A. E.; Green, P. S.; Derrick, P. J. Eur. Mass. Spectrom. 2000, 6, 267–275.CrossRefGoogle Scholar
  38. 38.
    Rockwood, A. L. Rapid Commun. Mass Spectrom. 1995, 9, 103–105.CrossRefGoogle Scholar
  39. 39.
    Cooley, J. W.; Tukey, J. W. Math. Comp. 1965, 19, 297–301.CrossRefGoogle Scholar
  40. 40.
    http://prospector.ucsf.edu/ ProteinProspector Home Page.Google Scholar
  41. 41.
    Palmblad, M.; Wetterhall, M.; Markides, M.; Håkansson, P.; Bergquist, J. Rapid Commun. Mass Spectrom. 2000, 14, 1029–1034.CrossRefGoogle Scholar
  42. 42.
    Suckau, D.; Shi, Y.; Beu, S. C.; Senko, M. W.; Quinn, J. P.; Wampler, F. M. D.; McLafferty, F. W. Proc. Natl. Acad. Sci. U.S.A. 1993, 90, 790–793.CrossRefGoogle Scholar
  43. 43.
    Chowdhury, S. K.; Katta, V.; Chait, B. T. J. Am. Chem. Soc. 1990, 112, 9012.CrossRefGoogle Scholar
  44. 44.
    Brent, R. P. Algorithms for Minimization without Derivatives; Prentice-Hall: New York, 1973; p 78.Google Scholar
  45. 45.
    Press, W. H.; Teukolsky, S. A.; Vetterling, W. T.; Flannery, B. P. Numerical Recipes in C, the Art of Scientific Computing, 2nd ed.; Cambridge, UK: Cambridge University Press, pp 402–405.Google Scholar
  46. 46.
    Frigo, M.; Johnson, S. G. Proceedings of the IEEE International Conference on Acoustics, Speech and Signal Processing. FFTW: An Adaptive Software Architecture for the FFT Vol. 3; Piscataway, NJ: IEEE, 1998 pp 1381–1384.Google Scholar
  47. 47.
    http://caml.inria.fr The Caml Language Home Page.Google Scholar
  48. 48.
    http://gcc.gnu.org GCC Home Page.Google Scholar
  49. 49.
    http://www.cygwin.com Cygwin Home Page.Google Scholar
  50. 50.
    Zubarev, R. A.; Håkansson, P.; Sundqvist, B. U. R. Anal. Chem. 1996, 68, 4060–4063.CrossRefGoogle Scholar
  51. 51.
    Ghaemmaghami, S.; Fitzgerald, M. C.; Oas, T. G. Proc. Natl. Acad. Sci. U.S.A. 2000, 97, 8296–8301.CrossRefGoogle Scholar
  52. 52.
    Gygi, S. P.; Rist, B.; Gerber, S. A.; Turecek, F.; Gelb, M. H.; Aebersold, R. Nature Biotech. 1999, 17, 994–999.CrossRefGoogle Scholar
  53. 53.
    Geng, M.; Junyan, J.; Regnier, F. E. J. Chromatogr. A. 2000, 870, 295–313.CrossRefGoogle Scholar

Copyright information

© American Society for Mass Spectrometry 2001

Authors and Affiliations

  1. 1.Division of Ion Physics, Ångström LaboratoryUppsala UniversityUppsalaSweden
  2. 2.BiacoreUppsalaSweden

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