Paper Citing NAMD - Abstract
Soriano-Ursua, Marvin A.; Correa-Basurto, Jose; Trujillo-Ferrara, Jose G.; Kaumann, Alberto J.
Homology model and docking studies on porcine beta(2) adrenoceptor: description of two binding sites
JOURNAL OF MOLECULAR MODELING, 17:2525-2538, OCT 2011
The affinity of the classical beta(2) adrenoceptor-selective inverse agonist ICI118,551 is notoriously lower for porcine beta(2) adrenoceptors (p(2)beta AR) than for human beta(2) adrenoceptors (h beta(2)AR) but molecular mechanisms for this difference are still unclear. Homology 3-D models of p beta(2)AR can be useful in predicting similarities and differences, which might in turn increase the comparative understanding of ligand interactions with the h beta(2)AR. In this work, the p beta(2)AR amino acid sequence was used to carry out homology modeling. The selected p beta(2)AR 3-D structure was structurally and energetically optimized and used as a model for further theoretical study. The homology model of p beta(2)AR has a 3-D structure very similar to the crystal structures of recently studied h beta(2)AR. This was also corroborated by sequence identity, RMSD, Ramachandran map, TM-score and docking results. Upon performing molecular docking simulations with the AutoDock4.0.1 program on p beta(2)AR, it was found that a set of well-known beta(2)AR ligands reach two distinct binding sites on p beta(2)AR. Whereas one of these sites is similar to that reported on the h beta(2)AR crystal structure, the other can explain some important experimental observations. Additionally, the theoretical affinity estimated for ICI118,551 closely agrees with affinities estimated from experimental in vitro data. The experimental differences between the human/porcine beta(2)ARs in relation to ligand affinity can in part be elucidated by observations in this molecular modeling study.
