Determinants of Neutral Antagonism and Inverse Agonism in the ß2-Adrenergic Receptor.
J Chem Inf Model
; 64(6): 2045-2057, 2024 Mar 25.
Article
em En
| MEDLINE
| ID: mdl-38447156
ABSTRACT
Free-energy profiles for the activation/deactivation of the ß2-adrenergic receptor (ADRB2) with neutral antagonist and inverse agonist ligands have been determined with well-tempered multiple-walker (MW) metadynamics simulations. The inverse agonists carazolol and ICI118551 clearly favor single inactive conformational minima in both the binary and ternary ligand-receptor-G-protein complexes, in accord with the inverse-agonist activity of the ligands. The behavior of neutral antagonists is more complex, as they seem also to affect the recruitment of the G-protein. The results are analyzed in terms of the conformational states of the well-known microswitches that have been proposed as indicators of receptor activity.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores Adrenérgicos beta 2
/
Agonismo Inverso de Drogas
Idioma:
En
Revista:
J Chem Inf Model
Assunto da revista:
INFORMATICA MEDICA
/
QUIMICA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Alemanha