NMR fragment screening: Advantages and applications.

Abstract

Nuclear magnetic resonance (NMR)-fragment-screening is a useful tool for lead identification and optimization in cases where shallow binding pockets have to be targeted, where highly selective lead structures are to be designed, and where novel, best-fit scaffolds for combinatorial library design are required. Robust and complementary protein- and ligand-detected NMR-screening methods are available for target proteins of various molecular weights and from different expression systems. The advantages of the NMR assay over other analytical techniques are high sensitivity toward loose fragment binders, comparatively high throughput and the ability to offer unique structural binding site information.