Homology modeling and flex-ligand docking studies on the guinea pig beta(2) adrenoceptor: structural and experimental similarities/ differences with the human beta(2).
The trachea of a guinea pig is widely used in drug development assays focused on the treatment of pulmonary diseases. Some of these drugs relax the airways by binding to the guinea pig beta(2)-adrenoceptor (Gbeta(2)AR). In this work, the amino acid sequence of the Gbeta(2)AR was searched to carry out homology modeling, using the Swiss-Model server, with the human beta(2)AR as the parent template. The Gbeta(2)AR 3-D structure was structurally and energetically optimized in vacuo using NAMD 2.6 program. The refined 3-D model obtained was used for further study. Molecular docking simulations were performed by testing a set of well-known beta(2)AR ligands using the AutoDock 3.0.5 program. The results show that the homology model of Gbeta(2)AR has a 3-D structure very similar to the crystal structure of recently studied human beta(2)AR. This was also corroborated by identity (94.23%), Ramachandran map, and docking results. The theoretical simulation showed that the ligands bind at sites that are similar to those reported for the human beta(2)AR. The R-enantiomer ligands showed correlation with in vitro data. We have obtained a Gbeta(2)AR 3-D model which can be used to carry out computational screening as a complementary tool during the drug design and experimental tests under guinea pig models.
Soriano-Ursúa
Marvin A
MA
Departamento de Fisiología y Farmacología, Plan de San Luis y Díaz Mirón, México. soum13mx@gmail.com
Trujillo-Ferrara
José G
JG
Correa-Basurto
José
J
D000818:Animals; D015195:Drug Design; D006168:Guinea Pigs; D006801:Humans; D008024:Ligands; D008171:Lung Diseases / Q000188:drug therapy; D008958:Models, Molecular; D011485:Protein Binding; D018343:Receptors, Adrenergic, beta-2 / Q000737:chemistry*
D008024:Ligands; D018343:Receptors, Adrenergic, beta-2