Structural comparison of ?-opioid receptor selective peptides confirmed four parameters of bioactivity
Structural determinants of binding to the ?-opioid receptor, an important target in analgesia, attract great scientific attention. Many natural and synthetic peptides and peptidomimetics were shown previously to bind to this receptor selectively but there is no consensus about the structure responsible for biological activity. No high resolution structure of this receptor is available and the binding site of ligands is not exactly known. However, ?-opioid ligands with similar affinity and selectivity should possess at least one common structural feature. Comparative structural analysis of such ligands, considering adequate representation of binding conditions, may reveal key features of bioactivity. In this study ten ?-opioid receptor ligands, DAMGO, Tyr-W-MIF-1, morphiceptin, endomorphin-1 and 2 and their analogues, possessing different affinity and selectivity, were examined using molecular dynamics. Conformational preference of these molecules was determined in H2O and DMSO along with structural properties previously proposed to be important for binding. Four of such structural requirements were confirmed to be important, providing a possible structural model of receptor binding. Simultaneous fulfillment of these requirements results most likely in high affinity binding to the ?-opioid receptor.
structure ?-opioid peptide molecular dynamics conformation endomorphin