NMR Studies on Protein–Ligand Interactions

Protein–ligand interactions are fundamental to physiological processes and drug discovery. Based on the types of information on protein–ligand interactions provided by nuclear magnetic resonance (NMR) experiments, these NMR experiments can be categorized into three distinct classes: (i) molecular-level qualitative binding detection, (ii) residue-level mapping of binding interfaces, and (iii) atomic-level structure determination and conformational dynamics of protein–ligand complexes. This hierarchy enables a workflow that accelerates the progression from initial binding identification to structural and dynamic characterization. In this review, we discuss how these experiments characterize molecular recognition. Notably, the term “ligand” in this article refers exclusively to small molecules.