Conformational stability and three-dimensional model of the delta-opioid pharmacophore for the extended antiparallel dimer structure of Met-enkephalin in water.

The conformational stability of the extended antiparallel dimer structure of Met-enkephalin in water was analyzed by examining the hydration structure of enkephalin using molecular dynamics simulations. The result shows that, despite of the hydrophicility of the terminal atoms in the pentapeptide, the main contributor for the stability of the dimer in water is the four intermolecular hydrogen bonds between the Gly(2) and Phe(4) groups. The three-dimensional model of the delta-opioid pharmacophore for this dimer structure was also established. Such a model was demonstrated to match the delta-opioid pharmacophore query derived from the non-peptides SIOM, TAN-67, and OMI perfectly. This result thus strongly supports the assumption that the dimer structure of Met-enkephalin is a possible delta-receptor binding conformation.