Conformational Analysis of the Ca²⁺-Bound Opioid Peptides: Implications for Ligand-Receptor Interaction

Abstract

Based on our earlier proposal on the role of Ca²⁺ in ligand-receptor recognition and the demonstration of the similarity of the Ca²⁺–bound forms of Met-enkephalin and morphine (Zhorov, B.S. and Ananthanarayanan, V.S., FEBSLett. 354, 131–134 (1994)) we have undertaken the conformational analysis of a series of the Ca²⁺-bound opioid peptides aiming to find their conformations matching Ca²⁺-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 (i-affinity were found to resemble closely morphine-Ca²⁺ complex. In contrast, the Ca²⁺ complexes of peptides with low |i-affinity did not. The results are relevant for understanding the structure-activity relations of opioid receptor ligands.