CONFORMATIONAL-ANALYSIS OF THE CA2-BOUND OPIOID-PEPTIDES - IMPLICATIONS FOR LIGAND-RECEPTOR INTERACTION()

Based on our earlier proposal on the role of Ca2+ in ligand-receptor r ecognition and the demonstration of the similarity of the Ca2+-bound f orms of Met-enkephalin and morphine (Zhorov, B.S. and Ananthanarayanan , V.S., FEES Lett. 354, 131-134 (1994)) we have undertaken the conform ational analysis of a series of the Ca2+-bound opioid peptides aiming to find their conformations matching Ca2+-bound morphine. A Monte Carl o-with-energy-minimization method was used to calculate 14 opioid pept ides in the presence of Ca2+. Low-energy conformations of the Ca2+ com plexes of peptides with high mu-affinity were found to resemble closel y morphine-Ca2+ complex. In contrast, the Ca2+ complexes of peptides w ith low mu-affinity did not. The results are relevant for understandin g the structure-activity relations of opioid receptor ligands.