Resolution-enhanced 4D 15N/13C NOESY protein NMR Spectroscopy by application of the covariance transform

The combination of shared-evolution 4D N-15/C-13-edited NOESY spectroscopy with covariance NMR is introduced, which yields, as sub-spectrum, an asymmetric 4D N-15/C-13-edited NOESY spectrum at a resolution enhanced 5-fold over the one of a non-shared N-15/C-13-edited NOESY measured with the same sweep widths and number of increments. The achieved resolution enhancement allows for a substantial increase in the number of assigned NOEs over that of the 4D Fourier transform spectrum and should useful for efficient, high-resolution NMR-based studies of protein structure.