Journal of Biomolecular NMR

, Volume 32, Issue 1, pp 23–30 | Cite as

Sensitivity enhancement in NMR of macromolecules by application of optimal control theory

  • Dominique P. Frueh
  • Takuhiro Ito
  • Jr-Shin Li
  • Gerhard Wagner
  • Steffen J. Glaser
  • Navin Khaneja


NMR of macromolecules is limited by large transverse relaxation rates. In practice, this results in low efficiency of coherence transfer steps in multidimensional NMR experiments, leading to poor sensitivity and long acquisition times. The efficiency of coherence transfer can be maximized by design of relaxation optimized pulse sequences using tools from optimal control theory. In this paper, we demonstrate that this approach can be adopted for studies of large biological systems, such as the 800 kDa chaperone GroEL. For this system, the 1H–15N coherence transfer module presented here yields an average sensitivity enhancement of 20–25% for cross-correlated relaxation induced polarization transfer (CRIPT) experiments.

Key words:

cross-correlation GroEL optimal control macromolecular NMR relaxation 



Chemical Shift Anisotropy


Cross-Relaxation Induced Polarization Transfer


Single Quantum Coherence


Transverse Relaxation Optimized Polarization transfer Induced by Cross-correlation effects.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Supplementary material

supp.pdf (196 kb)
Supplementary material


  1. Abelson, J.N., Simon, M.I. 2001James, T.L.Doetsch, V.Schmitz, U. eds. Methods in Enzymology, Vol. 338. Nuclear Magnetic Resonance of Biological MacromoleculesAcademic PressSan DiegoGoogle Scholar
  2. Bax, A., Cornilescu, G. 2000J. Am. Chem. Soc.1221014310154CrossRefGoogle Scholar
  3. Bodenhausen, G., Ruben, D.J. 1980Chem. Phys. Lett.69185189CrossRefGoogle Scholar
  4. Boyd, J., Hommel, U., Krishnan, V.V. 1991Chem. Phys. Lett.187317324CrossRefGoogle Scholar
  5. Brüschweiler, R., Ernst, R.R. 1991J. Chem. Phys.9617581766CrossRefGoogle Scholar
  6. Brüschweiler, R., Liao, X., Wright, P.E. 1995Science268886889PubMedGoogle Scholar
  7. Brutscher, B., Skrynnikov, N.R., Bremi, T., Brüschweiler, R., Ernst, R.R. 1998J. Magn. Reson.130346351CrossRefPubMedGoogle Scholar
  8. Cavanagh, J., Fairbrother, W.J., Palmer, A.G., Skelton, N.J. 1996Protein NMR Spectroscopy Principles and PracticeAcademic PressSan DiegoGoogle Scholar
  9. Dalvit, C. 1992J. Magn. Reson.97645650Google Scholar
  10. Ferentz, A.E., Wagner, G. 2000Q. Rev. Biophys.332965CrossRefPubMedGoogle Scholar
  11. Fischer, M.W.F., Zeng, L., Pang, Y., Hu, W., Majumdar, A., Zuiderweg, E.R.P. 1997J. Am. Chem. Soc.1191262912642CrossRefGoogle Scholar
  12. Frueh, D. 2002Progr. NMR Spectrosc.41305324CrossRefGoogle Scholar
  13. Goldman, M. 1984J. Magn. Reson.60437452Google Scholar
  14. Grzesiek, S., Bax, A. 1993J. Am. Chem. Soc.1151259312594CrossRefGoogle Scholar
  15. Khaneja, N., Li, J.S., Kehlet, C., Luy, B., Glaser, S.J. 2004Proc. Natl. Acad. Sci. USA1011474214747CrossRefPubMedGoogle Scholar
  16. Khaneja, N., Luy, B., Glaser, S.J. 2003aProc. Natl. Acad. Sci. USA1001316213166CrossRefGoogle Scholar
  17. Khaneja, N., Reiss, T., Luy, B., Glaser, S.J. 2003bJ. Magn. Reson.162311319CrossRefGoogle Scholar
  18. Lienin, S.F., Bremi, T., Brutscher, B., Brüschweiler, R., Ernst, R.R. 1998J. Am. Chem. Soc.12098709879CrossRefGoogle Scholar
  19. Nishihara, K., Kanemori, M., Yanagi, H., Yura, T. 2000Appl. Environ. Microbiol.66884889CrossRefPubMedGoogle Scholar
  20. Pervushin, K., Riek, R., Wider, G., Wüthrich, K. 1997Proc. Natl. Acad. Sci. USA941236612371CrossRefPubMedGoogle Scholar
  21. Riek, R., Fiaux, J., Bertelsen, E.B., Horwich, A.L., Wüthrich, K. 2002J. Am. Chem. Soc.1241214412153CrossRefPubMedGoogle Scholar
  22. Riek, R., Wider, G., Pervushin, K., Wüthrich, K. 1999Proc. Natl. Acad. Sci. USA9649184923CrossRefPubMedGoogle Scholar
  23. Woessner, D.E. 1962J. Chem. Phys.37647CrossRefGoogle Scholar

Copyright information

© Springer 2005

Authors and Affiliations

  • Dominique P. Frueh
    • 1
  • Takuhiro Ito
    • 2
  • Jr-Shin Li
    • 3
  • Gerhard Wagner
    • 1
  • Steffen J. Glaser
    • 4
  • Navin Khaneja
    • 3
  1. 1.Department of Biological Chemistry and Molecular PharmacologyHarvard Medical SchoolBostonUSA
  2. 2.RIKEN Genomic Sciences CenterTsurumiJapan
  3. 3.Division of Engineering and Applied SciencesHarvard UniversityCambridgeUSA
  4. 4.Department of ChemistryTechnische Universität MünchenGarchingGermany

Personalised recommendations