NMR approaches in structure-based lead discovery: recent developments and new frontiers for targeting multi-protein complexes.
Prog Biophys Mol Biol
; 116(2-3): 101-12, 2014.
Article
em En
| MEDLINE
| ID: mdl-25175337
ABSTRACT
Nuclear magnetic resonance (NMR) spectroscopy is a pivotal method for structure-based and fragment-based lead discovery because it is one of the most robust techniques to provide information on protein structure, dynamics and interaction at an atomic level in solution. Nowadays, in most ligand screening cascades, NMR-based methods are applied to identify and structurally validate small molecule binding. These can be high-throughput and are often used synergistically with other biophysical assays. Here, we describe current state-of-the-art in the portfolio of available NMR-based experiments that are used to aid early-stage lead discovery. We then focus on multi-protein complexes as targets and how NMR spectroscopy allows studying of interactions within the high molecular weight assemblies that make up a vast fraction of the yet untargeted proteome. Finally, we give our perspective on how currently available methods could build an improved strategy for drug discovery against such challenging targets.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Espectroscopia de Ressonância Magnética
/
Proteínas
/
Descoberta de Drogas
Idioma:
En
Revista:
Prog Biophys Mol Biol
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Reino Unido