Understanding Ligand Binding Selectivity in a Prototypical GPCR Family.
J Chem Inf Model
; 59(6): 2830-2836, 2019 06 24.
Article
em En
| MEDLINE
| ID: mdl-31125224
ABSTRACT
Adenosine receptors are involved in many pathological conditions and are thus promising drug targets. However, developing drugs that target this GPCR subfamily is a challenging task. A number of drug candidates fail due to lack of selectivity which results in unwanted side effects. The extensive structural similarity of adenosine receptors complicates the design of selective ligands. The problem of selective targeting is a general concern in GPCRs, and in this respect adenosine receptors are a prototypical example. Here we use enhanced sampling simulations to decipher the determinants of selectivity of ligands in A2a and A1 adenosine receptors. Our model shows how small differences in the binding pocket and in the water network around the ligand can be leveraged to achieve selectivity.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Receptores Acoplados a Proteínas G
/
Simulação de Dinâmica Molecular
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article