Journal of Biomolecular NMR

, Volume 37, Issue 3, pp 195–204 | Cite as

Mixed-time parallel evolution in multiple quantum NMR experiments: sensitivity and resolution enhancement in heteronuclear NMR

  • Jinfa Ying
  • Jordan H. Chill
  • John M. Louis
  • Ad Bax


A new strategy is demonstrated that simultaneously enhances sensitivity and resolution in three- or higher-dimensional heteronuclear multiple quantum NMR experiments. The approach, referred to as mixed-time parallel evolution (MT-PARE), utilizes evolution of chemical shifts of the spins participating in the multiple quantum coherence in parallel, thereby reducing signal losses relative to sequential evolution. The signal in a given PARE dimension, t 1, is of a non-decaying constant-time nature for a duration that depends on the length of t 2, and vice versa, prior to the onset of conventional exponential decay. Line shape simulations for the 1H–15N PARE indicate that this strategy significantly enhances both sensitivity and resolution in the indirect 1H dimension, and that the unusual signal decay profile results in acceptable line shapes. Incorporation of the MT-PARE approach into a 3D HMQC-NOESY experiment for measurement of HN–HN NOEs in KcsA in SDS micelles at 50°C was found to increase the experimental sensitivity by a factor of 1.7±0.3 with a concomitant resolution increase in the indirectly detected 1H dimension. The method is also demonstrated for a situation in which homonuclear 13C–13C decoupling is required while measuring weak H3′–2′OH NOEs in an RNA oligomer.


KcsA Mixed-time Multiple quantum NMR NOESY Parallel evolution Resolution enhancement RNA Sensitivity enhancement 



We thank Ed Nikonowicz (Rice U.) for the Helix-35 RNA sample. This work was supported by the Intramural Research Program of the NIDDK, NIH, and by the Intramural Antiviral Target Program of the Office of the Director, NIH.

Supplementary material

10858_2006_9120_MOESM1_ESM.pdf (202 kb)
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Copyright information

© Springer Science+Business Media B.V. 2007

Authors and Affiliations

  • Jinfa Ying
    • 1
  • Jordan H. Chill
    • 1
  • John M. Louis
    • 1
  • Ad Bax
    • 1
  1. 1.Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney DiseasesNational Institutes of HealthBethesdaUSA

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