COMP 252 |
| We recently built and compared to the corresponding crystal structure molecular models of the β2-adrenergic receptor (β2-AR) in complex with the inverse agonist Carazolol. The homology models were built using rhodopsin as template and docking was performed through an induced fit procedure that allows flexibility to the ligands and the receptor binding pocket. Here, to probe if homology modeling of G protein-coupled receptors (GPCRs) can generate structures applicable to computer-aided drug discovery, we subjected the crystal structure and our homology models of the β2-AR to a simulated virtual screening. In particular, 67 β2-AR ligands were dispersed within over 50,000 diverse molecules selected from the ZINC lead-like database, and the capacity of prioritizing the active over the inactive compounds through molecular docking was assessed by plotting ROC curves. Our results demonstrate that GPCR homology models are indeed applicable to virtual screenings, in some cases almost as effectively as the experimental structure. |
|
Poster Session
6:00 PM-8:00 PM, Tuesday, August 18, 2009 Walter E. Washington Convention Center -- Ballroom A, Poster
Division of Computers in Chemistry |