Docking ligands to vasopressin and oxytocin receptors via genetic algorithm

The aim of the study was to computer-dock selected ligands to neurophyseal receptors in order to identify amino acid residues responsible for ligand-receptor interactions. To this aim, reliable oxytocin receptor (OTR) and arginine-vasopressin receptor (V1aR/V2R) models were built. The OTR-selective agonist Thr4,Gly7]OT, the OTR-selective cyclohexapeptide antagonist L-366,948 and OT itself were docked via genetic algorithm to OTR, V1aR, and V2R and relaxed using a constrained simulated annealing protocol. For the analysis of receptor/ligand interactions a subset of initial conformations was chosen using energetic and steric criteria. All three ligands seem to prefer similar modes of binding to the receptors, manifested by repetitive residues of the receptors which directly interact with the ligands. Taking into account that many aspects of mechanisms of G protein-coupled receptor (GPCR) action are still unsolved, the results obtained with the docking simulations may propose future experimental research, especially in site-directed mutagenesis analysis and searching for key amino acid residues responsible for drug activities.