title: Computer simulations of cyclic enkephalin analogues.
abstract: Molecular dynamics simulations and energy minimization studies of cyclic enkephalin analogues incorporating retro-inverso modifications have been carried out. The dynamic trajectories are analyzed in terms of the relative mobility of the 14-membered rings, conformational transitions among equilibrium states, and hydrogen-bonding patterns. The cyclization of the molecules reduces the motion of the ring structures substantially. Time-correlated conformational transitions resulting in the reorientation of peptide units are observed. Hydrogen bonds form principally C7 structures. Because of the incorporation of retro-inverso residues, C6 and C8 structures are also formed. Starting conformations for energy minimizations were obtained from the molecular dynamics simulations and from a systematic search of the conformational space available to the molecules. Several minimum energy backbone and side-chain conformations were found for each analogue. The effect of retro-inverso residues on hydrogen-bonding patterns and backbone conformations is discussed.
mesh_terms: D000595:Amino Acid Sequence; D003198:Computer Simulation; D004745:Enkephalins; D006860:Hydrogen Bonding; D008958:Models, Molecular; D010456:Peptides, Cyclic; D011487:Protein Conformation; D013329:Structure-Activity Relationship
chemical_list: D004745:Enkephalins; D010456:Peptides, Cyclic