Details Matter in Structure-based Drug Design.
Chimia (Aarau)
; 77(7-8): 489-493, 2023 Aug 09.
Article
en En
| MEDLINE
| ID: mdl-38047790
ABSTRACT
Successful structure-based drug design (SBDD) requires the optimization of interactions with the target protein and the minimization of ligand strain. Both factors are often modulated by small changes in the chemical structure which can lead to profound changes in the preferred conformation and interaction preferences of the ligand. We draw from examples of a Roche project targeting phosphodiesterase 10 to highlight that details matter in SBDD. Data mining in crystal structure databases can help to identify these sometimes subtle effects, but it is also a great resource to learn about molecular recognition in general and can be used as part of molecular design tools. We illustrate the use of the Cambridge Structural Database for identifying preferred structural motifs for intramolecular hydrogen bonding and of the Protein Data Bank for deriving propensities for protein-ligand interactions.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Diseño de Fármacos
/
Minería de Datos
Idioma:
En
Revista:
Chimia (Aarau)
Año:
2023
Tipo del documento:
Article
País de afiliación:
Suiza