The 3D structure of the binding pocket of the human oxytocin receptor for benzoxazine antagonists, determined by molecular docking, scoring functions and 3D-QSAR methods
Molecular docking and 3D-QSAR studies were performed to determine the binding mode for a series of benzoxazine oxytocin antagonists taken from the literature. Structural hypotheses were generated by docking the most active molecule to the rigid receptor by means of AutoDock 3.05. The cluster analysis yielded seven possible binding conformations. These structures were refined by using constrained simulated annealing, and the further ligands were aligned in the refined receptor by molecular docking. A good correlation was found between the estimated Delta G(bind) and the pK(i) values for complex F. The Connolly-surface analysis, CoMFA and CoMSIA models (q(CoMFA)(2) = 0.653; q(CoMSA)(2) = 0.630 and r(2) (pred, CoMFA) = 0.852; r(2) (pred, CoMSIA) = 0.815) confirmed the scoring function results. The structural features of the receptor - ligand complex and the CoMFA and CoMSIA fields are in closely connected. These results suggest that receptor - ligand complex F is the most likely binding hypothesis for the studied benzoxazine analogs.
binding pocket oxytocin receptor benzoxazine scoring function 3d-qsar binding mode autodock