Abstract
For the past decade chemical exchange saturation transfer (CEST) experiments have been successfully applied to study exchange processes in biomolecules involving sparsely populated, transiently formed conformers. Initial implementations focused on extensive sampling of the CEST frequency domain, requiring significant measurement times. Here we show that the lengthy sampling schemes often used are not optimal and that reduced frequency sampling schedules can be developed without a priori knowledge of the exchange parameters, that only depend on the chosen B1 field, and, to a lesser extent, on the intrinsic transverse relaxation rates of ground state spins. The reduced sampling approach described here can be used synergistically with other methods for reducing measurement times such as those that excite multiple frequencies in the CEST dimension simultaneously, or make use of non-uniform sampling of indirectly detected time domains, to further decrease measurement times. The proposed approach is validated by analysis of simulated and experimental datasets.
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The datasets generated during and/or analyzed during the current study are available from the corresponding authors on reasonable request. Additional information can be found as electronic supplementary materials.
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Acknowledgements
The authors are grateful to Professor Pramodh Vallurupalli (TIFR Hdyerbad) for a gift of the A39G FF sample, and to Dr. Guillaume Bouvignies (ENS, Paris) for helpful discussions regarding Chemex. N.B.C acknowledges post-doctoral support from the Canadian Institutes of Health Research (CIHR). DFH is supported by the Biotechnology and Biological Sciences Research Council UK (BBSRC) (ref: BB/T011831/1). LEK acknowledges support from the CIHR (FND-503573) and the Natural Sciences and Engineering Council of Canada (2015-04347).
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Bolik-Coulon, N., Hansen, D.F. & Kay, L.E. Optimizing frequency sampling in CEST experiments. J Biomol NMR 76, 167–183 (2022). https://doi.org/10.1007/s10858-022-00403-2
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DOI: https://doi.org/10.1007/s10858-022-00403-2