Conformational features of linear and cyclic enkephalins. A computational study

A theoretical conformational study using the CICADA program package (J. Mol. Struct. (Theochem), 337 (1995) 17) was performed for two linear enkephalins, Leu-enkephalin and Met-enkephalin, and two cyclic analogues, DLFE and DPDPE. The conformational flexibilities of whole molecules and selected torsions were calculated.

The low energy conformers obtained were compared with structures obtained by spectroscopic methods. The mutual space positions of key elements for receptor recognition were analyzed. Conformations were clustered using RMS deviation computed for selected atoms. The different conformational behavior of aromatic rings in cyclic analogues of enkephalins was observed. While aromatic rings of cyclic analogues exhibit different conformational behavior, the linear enkephalins show similar behavior in these key parts.

Hydrogen bonds predicted by spectroscopic measurements were confirmed by our calculations. Also very specific conformational features, like concerted conformational movement, were analyzed.