Fast-HMQC using Ernst angle pulses: An efficient tool for screening of ligand binding to target proteins

The application of Ernst angle pulses in multidimensional NMR spectroscopy is theoretically and experimentally investigated. Theory shows that only for a few pulse sequences employed at high repetition rate, a remarkable gain in sensitivity is possible using Ernst angle pulses. As an example, a new variant of the heteronuclear multiple quantum coherence (HMQC) experiment, the fast-(¹H,¹⁵N)-HMQC, is described. This sequence allows, with a 1 mM protein sample in H₂O, the acquisition of a highly resolved two-dimensional (¹H,¹⁵N) correlated spectrum within 37 s. The high efficiency of the fast-HMQC to detect ligand binding to a target protein is demonstrated.