Conformational features of linear and cyclic enkephalins. A computational study

A theoretical conformational study using the CICADA program package (J. Mel . Struct. (Theochem), 337 (1995) 17) was performed for two linear enkephali ns, Leu-enkephalin and Met-enkephalin, and two cyclic analogues, DLFE and D PDPE. The conformational flexibilities of whole molecules and selected tors ions were calculated. The low energy conformers obtained were compared with structures obtained b y spectroscopic methods. The mutual space positions of key elements for rec eptor recognition were analyzed. Conformations were clustered using RMS dev iation computed for selected atoms. The different conformational behavior o f aromatic rings in cyclic analogues of enkephalins was observed. While aro matic 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 ou r calculations. Also very specific conformational features, like concerted conformational movement, were analyzed. (C) 2001 Elsevier Science B.V. All rights reserved.