Fig. 1: Outline of NMR-SBDD.
From: NMR-driven structure-based drug discovery by unveiling molecular interactions

Starting from 13C-labeled amino acids or precursors (left) the protein of interest can be selectively labeled for NMR spectroscopy. X-ray structure (PDB ID 4QL1) and 1H-13C HSQC spectrum of selective leucine and isoleucine labeled WDR5 (34 kDa) highlights the benefits of this methodology; significantly simplified NMR spectra also amenable for larger protein targets usually outside the range of conventional NMR methods (middle). Substantial chemical shift changes of protein signals induced by aromatic ligand ring-systems can be directly incorporated into 3D structural calculations of protein-ligand complexes. Shown is the example of a ligand interacting with selectively leucine labeled BRD4-BD1 (PDB ID 6XV3)(right)22.