Probing Hydration Patterns in Class-A GPCRs via Biased MD: The A2A Receptor.
J Chem Theory Comput
; 12(12): 6049-6061, 2016 Dec 13.
Article
em En
| MEDLINE
| ID: mdl-27951680
ABSTRACT
Herein, we present a new computational approach for analyzing hydration patterns in biomolecular systems. This protocol aims to efficiently identify regions where structural waters may be located and, in the case of protein-ligand binding, where displacing one or more water molecules could be advantageous in terms of affinity and/or residence time. We validated our approach on the adenosine A2A receptor, a target of significant pharmaceutical relevance. The results of the approach are enriched with an extensive analysis of hydration in A2A and other members of the A-family of GPCRs using available crystallographic evidence and reviewing existing literature. As per the protein-ligand complex case, we conducted a more detailed study of a series of triazine analogues inhibiting A2A. The proposed approach provides results in good agreement with existing data and offers interpretability and simple and fast applicability.
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Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Receptor A2A de Adenosina
Idioma:
En
Revista:
J Chem Theory Comput
Ano de publicação:
2016
Tipo de documento:
Article