TY - JOUR
T1 - Homology modeling and flex-ligand docking studies on the guinea pig β2 adrenoceptor
T2 - Structural and experimental similarities/differences with the human β2
AU - Soriano-Ursúa, Marvin A.
AU - Trujillo-Ferrara, José G.
AU - Correa-Basurto, José
N1 - Funding Information:
We are grateful for the scholarships and financial support that Consejo Nacional de Ciencia y Tecnología (62488), COFAA and SIP of Instituto Politécnico Nacional (20080026) provided the authors.
PY - 2009
Y1 - 2009
N2 - 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 β2 -adrenoceptor (Gβ2AR). In this work, the amino acid sequence of the Gβ2AR was searched to carry out homology modeling, using the Swiss-Model server, with the human β2 AR as the parent template. The Gβ2AR 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 β2AR ligands using the AutoDock 3.0.5 program. The results show that the homology model of Gβ2 AR has a 3-D structure very similar to the crystal structure of recently studied human β2AR. 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 β2AR. The R-enantiomer ligands showed correlation with in vitro data. We have obtained a Gβ2AR 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.
AB - 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 β2 -adrenoceptor (Gβ2AR). In this work, the amino acid sequence of the Gβ2AR was searched to carry out homology modeling, using the Swiss-Model server, with the human β2 AR as the parent template. The Gβ2AR 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 β2AR ligands using the AutoDock 3.0.5 program. The results show that the homology model of Gβ2 AR has a 3-D structure very similar to the crystal structure of recently studied human β2AR. 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 β2AR. The R-enantiomer ligands showed correlation with in vitro data. We have obtained a Gβ2AR 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.
KW - Docking
KW - Drug development
KW - Guinea pig
KW - Homology modeling
KW - β adrenergic receptor ligands
UR - http://www.scopus.com/inward/record.url?scp=68949168783&partnerID=8YFLogxK
U2 - 10.1007/s00894-009-0480-7
DO - 10.1007/s00894-009-0480-7
M3 - Artículo
C2 - 19263094
SN - 1610-2940
VL - 15
SP - 1203
EP - 1211
JO - Journal of Molecular Modeling
JF - Journal of Molecular Modeling
IS - 10
ER -