Molecular modeling study of the opioid receptor interactions with series of cyclic deltorphin analogues

In this study, ten tetra-and heptapeptide analogues of deltorphin containing the urea bridges between residues 2 and 4 have been docked into the delta- and mu-opioid receptors to explain their different biological activities. The important factors explaining particular ligand activity such as free energy of binding, conformation of the ligand, its location inside the binding pocket as well as the number and strength of the receptor-ligand interactions have been discussed. Several different binding modes for investigated ligands have been proposed. It appears that the binding site is not identical even for very similar ligands. Results of this study help to explain the differences in biological activity of the deltorphin analogues, their interaction with the opioid receptors at the molecular level and support designing a new generation of potent opioid drugs with improved selectivity. Copyright (C) 2011 European Peptide Society and John Wiley & Sons, Ltd.