Current NMR Techniques for Structure-Based Drug Discovery

Abstract

A variety of nuclear magnetic resonance (NMR) applications have been developed for structure-based drug discovery (SBDD). NMR provides many advantages over other methods, such as the ability to directly observe chemical compounds and target biomolecules, and to be used for ligand-based and protein-based approaches. NMR can also provide important information about the interactions in a protein-ligand complex, such as structure, dynamics, and affinity, even when the interaction is too weak to be detected by ELISA or fluorescence resonance energy transfer (FRET)-based high-throughput screening (HTS) or to be crystalized. In this study, we reviewed current NMR techniques. We focused on recent progress in NMR measurement and sample preparation techniques that have expanded the potential of NMR-based SBDD, such as fluorine NMR (19F-NMR) screening, structure modeling of weak complexes, and site-specific isotope labeling of challenging targets.

Keywords

• nuclear magnetic resonance (NMR)
• NMR-based fragment screening
• NMR-based lead optimization
• ligand-based NMR
• protein-based NMR
• fluorine-19 (19F) NMR
• site-specific isotope labeling
• protein-protein interaction (PPI) breaker/stabilizer