Conformational analysis of the Ca(2+)-bound opioid peptides: implications for ligand-receptor interaction.

Based on our earlier proposal on the role of Ca2+ in ligand-receptor recognition and the demonstration of the similarity of the Ca(2+)-bound forms of Met-enkephalin and morphine (Zhorov, B.S. and Ananthanarayanan, V.S., FEBS Lett. 354, 131-134 (1994)) we have undertaken the conformational analysis of a series of the Ca(2+)-bound opioid peptides aiming to find their conformations matching Ca(2+)-bound morphine. A Monte Carlo-with-energy-minimization method was used to calculate 14 opioid peptides in the presence of Ca2+. Low-energy conformations of the Ca2+ complexes of peptides with high mu-affinity were found to resemble closely morphine-Ca2+ complex. In contrast, the Ca2+ complexes of peptides with low mu-affinity did not. The results are relevant for understanding the structure-activity relations of opioid receptor ligands.