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Knowledge-based nonuniform sampling in multidimensional NMR

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The full resolution afforded by high-field magnets is rarely realized in the indirect dimensions of multidimensional NMR experiments because of the time cost of uniformly sampling to long evolution times. Emerging methods utilizing nonuniform sampling (NUS) enable high resolution along indirect dimensions by sampling long evolution times without sampling at every multiple of the Nyquist sampling interval. While the earliest NUS approaches matched the decay of sampling density to the decay of the signal envelope, recent approaches based on coupled evolution times attempt to optimize sampling by choosing projection angles that increase the likelihood of resolving closely-spaced resonances. These approaches employ knowledge about chemical shifts to predict optimal projection angles, whereas prior applications of tailored sampling employed only knowledge of the decay rate. In this work we adapt the matched filter approach as a general strategy for knowledge-based nonuniform sampling that can exploit prior knowledge about chemical shifts and is not restricted to sampling projections. Based on several measures of performance, we find that exponentially weighted random sampling (envelope matched sampling) performs better than shift-based sampling (beat matched sampling). While shift-based sampling can yield small advantages in sensitivity, the gains are generally outweighed by diminished robustness. Our observation that more robust sampling schemes are only slightly less sensitive than schemes highly optimized using prior knowledge about chemical shifts has broad implications for any multidimensional NMR study employing NUS. The results derived from simulated data are demonstrated with a sample application to PfPMT, the phosphoethanolamine methyltransferase of the human malaria parasite Plasmodium falciparum.

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We thank Drs. Alan Stern and Mehdi Mobli for useful discussions. We thank Dr. Choukri Ben Mamoun for providing the PfPMT construct used to prepare the sample. Financial support from the US National Institutes of Health (GM047467 and RR020125) is gratefully acknowledged.

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Correspondence to Jeffrey C. Hoch.

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Schuyler, A.D., Maciejewski, M.W., Arthanari, H. et al. Knowledge-based nonuniform sampling in multidimensional NMR. J Biomol NMR 50, 247–262 (2011).

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