Determinants of Neutral Antagonism and Inverse Agonism in the ß2-Adrenergic Receptor.
J Chem Inf Model
; 64(6): 2045-2057, 2024 03 25.
Article
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| 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
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Receptores Adrenérgicos beta 2
/
Agonismo Inverso de Drogas
Idioma:
En
Revista:
J Chem Inf Model
Asunto de la revista:
INFORMATICA MEDICA
/
QUIMICA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Alemania