Abstract
Non-uniform sampling (NUS) has been established as a route to obtaining true sensitivity enhancements when recording indirect dimensions of decaying signals in the same total experimental time as traditional uniform incrementation of the indirect evolution period. Theory and experiments have shown that NUS can yield up to two-fold improvements in the intrinsic signal-to-noise ratio (SNR) of each dimension, while even conservative protocols can yield 20–40 % improvements in the intrinsic SNR of NMR data. Applications of biological NMR that can benefit from these improvements are emerging, and in this work we develop some practical aspects of applying NUS nD-NMR to studies that approach the traditional detection limit of nD-NMR spectroscopy. Conditions for obtaining high NUS sensitivity enhancements are considered here in the context of enabling 1H,15N-HSQC experiments on natural abundance protein samples and 1H,13C-HMBC experiments on a challenging natural product. Through systematic studies we arrive at more precise guidelines to contrast sensitivity enhancements with reduced line shape constraints, and report an alternative sampling density based on a quarter-wave sinusoidal distribution that returns the highest fidelity we have seen to date in line shapes obtained by maximum entropy processing of non-uniformly sampled data.
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Acknowledgments
The support of R15GM084443 from NIGMS, of NSF-RUI 1153052 and Bucknell University are gratefully acknowledged. We thank Geneive Henry of Susquehanna University for providing the plant natural product studied in Fig. 7: this sample was isolated from a butanol root extract of a sugar maple plant collected in Rhode Island, and purified by a combination of column chromatography and reversed-phase HPLC; a total sample mass of 9 mg was dissolved in approximately 0.5 mL d6-DMSO. We thank Brian Breczinski for instrument management and assistance. We are deeply grateful to Prof. J. Hoch and Prof. T. Polenova for supportive comments and advice in this work.
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Melissa R. Palmer and Broc R. Wenrich contributed equally to the described work.
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Palmer, M.R., Wenrich, B.R., Stahlfeld, P. et al. Performance tuning non-uniform sampling for sensitivity enhancement of signal-limited biological NMR. J Biomol NMR 58, 303–314 (2014). https://doi.org/10.1007/s10858-014-9823-5
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DOI: https://doi.org/10.1007/s10858-014-9823-5