Non‐Uniform and Absolute Minimal Sampling for High‐Throughput Multidimensional NMR Applications

Abstract

Many biomolecular NMR applications can benefit from the faster acquisition of multidimensional NMR data with high resolution and their automated analysis and interpretation. In recent years, a number of non-uniform sampling (NUS) approaches have been introduced for the reconstruction of multidimensional NMR spectra, such as compressed sensing, thereby bypassing traditional Fourier-transform processing. Such approaches are applicable to both biomacromolecules and small molecules and their complex mixtures and can be combined with homonuclear decoupling (pure shift) and covariance processing. For homonuclear 2D TOCSY experiments, absolute minimal sampling (AMS) permits the drastic shortening of measurement times necessary for high-throughput applications for identification and quantification of components in complex biological mixtures in the field of metabolomics. Such TOCSY spectra can be comprehensively represented by graphic theoretical maximal cliques for the identification of entire spin systems and their subsequent query against NMR databases. Integration of these methods in webservers permits the rapid and reliable identification of mixture components. Recent progress is reviewed in this Minireview.

Rapid nuclear magnetic resonance data acquisition with improved resolution and sensitivity for high‐throughput metabolomic analysis

“…[97] Recently, Brüschweiler et al addressed this issue by introducing the absolute minimal sampling (AMS) method, which is a generalization of the SPEED method. [97][98][99] AMS method involves the evolution of a few points in the indirect dimension and later using nonlinear methods to search for the frequencies encoded. This concept initially demonstrated for three-dimensional HNCO and HN (CA)CO spectra for proteins [97] was later demonstrated for the TOCSY spectrum with applications in metabolomics.…”

“…This concept initially demonstrated for three-dimensional HNCO and HN (CA)CO spectra for proteins [97] was later demonstrated for the TOCSY spectrum with applications in metabolomics. [98,99] The pure shift method has also been employed to improve the resolution of crowded metabolomic spectra; this also results in an increase in sensitivity because of the collapse of the scalar multiplet structure. [100,101] Two or more fast NMR methods can be combined to get better results in a short duration.…”

Quo Vadis Biomolecular NMR Spectroscopy?

“…Faced with the dilemma of exponential signal multiplication with target size and correspondingly adverse relaxation properties, the biomolecular NMR community devised several ingenious ways to deal with such samples. These include (transverse) relaxation-optimized spectroscopy (TROSY) [26,27], amino acid-specific, site-selective, and segmental isotope labeling [28], higher-dimensionality NMR experiments [29], and non-uniform sampling schemes [30]. Despite these developments, structure determination efforts of large, folded proteins by solution-state NMR spectroscopy remained challenging and cumbersome.…”

Expedited Nuclear Magnetic Resonance Assignment of Small- to Medium-Sized Molecules with Improved HSQC−CLIP−COSY Experiments

“…For instance, NOAH-type (NMR by Ordered Acquisition using 1 H-detection) experiments, − which allow a sequential recording of up to four 2D spectra with only one relaxation delay employed in the combined pulse sequence, offer significant time saving compared to the conventional data recording. Also, considerable progress has been made in the development of nonuniform sampling (NUS) methods − for the reconstruction of multidimensional NMR spectra with high digital resolution using only a fraction of increments along the indirect dimension(s), cutting down the measurement time substantially. Furthermore, the resolution of 1 H- 1 H COSY, NOESY, or TOCSY experiments can be improved so that unambiguous spectral interpretation is greatly facilitated within a single spectrum.…”