NMR spectroscopy is a powerful method for characterising protein structure and motion. Currently, however, NMR suffers from low throughput, with studies of even moderately sized proteins (15 kDa) requiring 3–4 weeks of data acquisition time. Considering that there is currently a huge effort to massively parallelise protein production, the long data acquisition and analysis times pose a huge bottleneck.
Here I will present recent developments in our efforts to speed up and automate protein NMR spectroscopy. I will focus on recent developments in the different strategies employed in sampling the time domain in multidimensional NMR spectroscopy, in particular in 3D and 4D experiments.1 I will present a novel Poisson based method that can be tailored to the signal envelope along multiple independent dimensions, and discuss how this relates to existing approaches and in general to other strategies for optimising data sampling in NMR.
I will show how non-uniform sampling improves the throughput of NMR spectroscopy by orders of magnitude and how this not only enables avenues for automation of routine spectroscopy but also enables studies of the most difficult facets of structural biology, including membrane proteins.