SIMILARITY OF CA2-BOUND CONFORMATIONS OF MORPHINE AND MET-ENKEPHALIN - A COMPUTATIONAL STUDY()

The conformations of the free and Ca2+-bound forms of morphine and Met -enkephalin were compared based on an earlier proposal that extracellu lar Ca2+ may dictate the bioactive conformations of peptide hormones a nd drugs. A Monte Carlo with energy minimization method was used to ca lculate Met-enkephalin in the absence and presence of Ca2+. The Ca2+-b ound conformation of Met-enkephalin was found to have an overall shape that matched well with that of morphine. In contrast, the uncomplexed Met-enkephalin did not have such a match. The data suggest that a ter nary association of the mu-receptor, its ligands and Ca2+ may be an in itial process in the signal transduction mechanism of opioid peptides.