A Practical Perspective on the Roles of Solution NMR Spectroscopy in Drug Discovery
Guangdong Provincial Engineering Laboratory of Biomass High Value Utilization, Guangdong Provincial Bioengineering Institute (Guangzhou Sugarcane Industry Research Institute), Guangzhou 510316, China
Experimental Drug Development Centre (EDDC), Agency for Science, Technology and Research (A*STAR), 10 Biopolis Road, Chromos, #05-01, Singapore 138670, Singapore
Authors to whom correspondence should be addressed.
Academic Editor: Derek J. McPhee
Molecules 2020, 25(13), 2974; https://doi.org/10.3390/molecules25132974
Received: 6 June 2020 / Revised: 21 June 2020 / Accepted: 26 June 2020 / Published: 28 June 2020
(This article belongs to the Special Issue NMR in the Drug Design)
Solution nuclear magnetic resonance (NMR) spectroscopy is a powerful tool to study structures and dynamics of biomolecules under physiological conditions. As there are numerous NMR-derived methods applicable to probe protein–ligand interactions, NMR has been widely utilized in drug discovery, especially in such steps as hit identification and lead optimization. NMR is frequently used to locate ligand-binding sites on a target protein and to determine ligand binding modes. NMR spectroscopy is also a unique tool in fragment-based drug design (FBDD), as it is able to investigate target-ligand interactions with diverse binding affinities. NMR spectroscopy is able to identify fragments that bind weakly to a target, making it valuable for identifying hits targeting undruggable sites. In this review, we summarize the roles of solution NMR spectroscopy in drug discovery. We describe some methods that are used in identifying fragments, understanding the mechanism of action for a ligand, and monitoring the conformational changes of a target induced by ligand binding. A number of studies have proven that 19F-NMR is very powerful in screening fragments and detecting protein conformational changes. In-cell NMR will also play important roles in drug discovery by elucidating protein-ligand interactions in living cells.