Cogwheel phase cycling in common triple resonance NMR experiments for the liquid phase

We demonstrate that cogwheel phase cycling, which was previously only used in solid state NMR, can be applied to optimize the efficiency of commonly used pulse sequences in multiple resonance liquid-state biomolecular NMR. In favorable cases the required minimum number of scans can be reduced by more than 80% as compared to a corresponding sequence with nested phase cycles. Since cogwheel phase cycling procedures can be designed for a range of scan numbers, and can be combined with pulsed field gradients, the total experiment time can be adjusted closely to the required signal-to-noise ratio with minimal overhead. Examples are shown for 3D-TROSY-HNCO, 3D-TROSY-HNCACO, and 3D-HACACO experiments on diamagnetic and paramagnetic proteins.