Preprints
https://doi.org/10.5194/mr-2021-46
https://doi.org/10.5194/mr-2021-46

  20 May 2021

20 May 2021

Review status: this preprint is currently under review for the journal MR.

Rapid measurement of heteronuclear transverse relaxation rates using non-uniformly sampled R accordion experiments

Sven Wernersson1, Göran Carlström2, Andreas Jakobsson3, and Mikael Akke1 Sven Wernersson et al.
  • 1Biophysical Chemistry, Center for Molecular Protein Science, Department of Chemistry, Lund University, Box 124, SE-22100 Lund, Sweden
  • 2Centre for Analysis and Synthesis, Department of Chemistry, Lund University, Box 124, SE-22100 Lund, Sweden
  • 3Department of Mathematical Statistics, Lund University, Box 118, SE-22100 Lund, Sweden

Abstract. Multidimensional, heteronuclear NMR relaxation methods are used extensively to characterize the dynamics of biological macromolecules. Acquisition of relaxation datasets on proteins typically require significant measurement time, often several days. Accordion spectroscopy offers a powerful means to shorten relaxation rate measurements by encoding the 'relaxation dimension' into the indirect evolution period in multidimensional experiments. Time savings can also be achieved by nonuniform sampling (NUS) of multidimensional NMR data, which is used increasingly to improve spectral resolution or increase sensitivity per unit time. However, NUS is not commonly implemented in relaxation experiments, because most reconstruction algorithms are inherently nonlinear, leading to problems when estimating signal intensities, relaxation rate constants and their error bounds. We have previously shown how to avoid these shortcomings by combining accordion spectroscopy with NUS, followed by data reconstruction using sparse exponential mode analysis, thereby achieving a dramatic decrease in the total length of longitudinal relaxation experiments. Here, we present the corresponding transverse relaxation experiment, taking into account the special considerations required for its successfully implementation in the framework of the accordion-NUS approach. We attain the highest possible precision in the relaxation rate constants by optimizing the NUS scheme with respect to the Cramér-Rao lower bound of the variance of the estimated parameter, given the total number of sampling points and the spectrum-specific signal characteristics. The resulting accordion-NUS R relaxation experiment achieves comparable precision in the parameter estimates, compared to conventional CPMG R2 or spin-lock R experiments, while saving an order of magnitude in experiment time.

Sven Wernersson et al.

Status: final response (author comments only)

Comment types: AC – author | RC – referee | CC – community | EC – editor | CEC – chief editor | : Report abuse
  • RC1: 'Referee comment (Frueh)', Dominique Frueh, 28 May 2021
  • RC2: 'Comment on mr-2021-46', Anonymous Referee #2, 30 May 2021
  • RC3: 'Comment on mr-2021-46', Anonymous Referee #3, 08 Jun 2021
  • EC1: 'Comment on mr-2021-46', Paul Schanda, 18 Jun 2021

Sven Wernersson et al.

Sven Wernersson et al.

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Short summary
Multidimensional NMR relaxation experiments provide a powerful means of studying protein dynamics, but typically require long acquisition times. Here, we combine two approaches that individually shorten the length of the experiment: accordion spectroscopy and non-uniform sampling (NUS). We extract relaxation rate constants by applying maximum likelihood estimation of sparse exponential modes modeled on the accordion-NUS interferograms, resulting in time savings by a factor of roughly 10.