NMR-driven structure-based drug discovery by unveiling molecular interactions.

High-resolution 3D structural information is crucial for drug discovery and routinely used in structure-guided optimization to improve initial hits from screening campaigns to clinical drug candidates. X-ray crystallography is commonly the method of choice to guide medicinal chemistry in the design process, but it has its limitations and shortcomings. Here, we discuss the use of solution-state NMR spectroscopy in combination with selective side-chain labeling and advanced computational workflows to generate protein-ligand ensembles. This provides reliable and accurate structural information about protein-ligand complexes for medicinal chemists that is also suitable for high-throughput.