A Practical Perspective on the Roles of Solution NMR Spectroscopy in Drug Discovery.
Molecules
; 25(13)2020 Jun 28.
Article
em En
| MEDLINE
| ID: mdl-32605297
ABSTRACT
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.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas
/
Bibliotecas de Moléculas Pequenas
Idioma:
En
Revista:
Molecules
Assunto da revista:
BIOLOGIA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
China