Enkephalin: conformational analysis by means of empirical energy calculations.

Low-energy conformations of methionine-enkephalin were generated by means of an empirical method of computation. Many compact conformations, including those containing various standard bends, were of comparable energy. However, one conformation was found to have a potential energy about 5 kcal/mol (21 X 10(3) J/mol) below that of the large group of compact conformations. In this conformation, the 3-glycyl and 4-phenylalanyl residues form a bend of type II'. The conformation is stabilized by a hydrogen bond between the OH group of the 1-tyrosine side chain and the C==O group of 3-glycine or 4-phenylalanine. The phenylalanine and methionine side chains are relatively unrestricted. The conformation is consistent with published nuclear magnetic resonance parameters--coupling constants, temperature dependence of the chemical shift, and spin-lattice relaxation times. It is likely that the molecule undergoes a conformational change when it is bound to the receptor. Leucine-enkephalin appears to have the same conformation as its methionine homolog.