Identifying small-molecules binding sites in RNA conformational ensembles with SHAMAN.
Nat Commun
; 15(1): 5725, 2024 Jul 08.
Article
em En
| MEDLINE
| ID: mdl-38977675
ABSTRACT
The rational targeting of RNA with small molecules is hampered by our still limited understanding of RNA structural and dynamic properties. Most in silico tools for binding site identification rely on static structures and therefore cannot face the challenges posed by the dynamic nature of RNA molecules. Here, we present SHAMAN, a computational technique to identify potential small-molecule binding sites in RNA structural ensembles. SHAMAN enables exploring the conformational landscape of RNA with atomistic molecular dynamics simulations and at the same time identifying RNA pockets in an efficient way with the aid of probes and enhanced-sampling techniques. In our benchmark composed of large, structured riboswitches as well as small, flexible viral RNAs, SHAMAN successfully identifies all the experimentally resolved pockets and ranks them among the most favorite probe hotspots. Overall, SHAMAN sets a solid foundation for future drug design efforts targeting RNA with small molecules, effectively addressing the long-standing challenges in the field.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
RNA
/
RNA Viral
/
Simulação de Dinâmica Molecular
/
Conformação de Ácido Nucleico
Idioma:
En
Revista:
Nat Commun
Assunto da revista:
BIOLOGIA
/
CIENCIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
França
País de publicação:
Reino Unido