NMR studies of ligand binding

NMR spectroscopy is an established tool in drug discovery, but its strength is commonly regarded to be largely confined to the early stages of hit discovery and fragment based drug design, where NMR offers unique capabilities of characterizing the binding modes of ligand molecules that bind sufficiently weakly to be in rapid exchange between bound and free state. Here we, first, provide a meta-review of recent reviews on NMR studies of ligand binding and, second, review recent progress towards NMR characterization of the ligand binding mode in stable protein-ligand complexes, with particular emphasis on the global positioning system (GPS) approach enabled by paramagnetic lanthanide tags.