Enkephalin: conformational analysis by means of empirical energy calculations.

Abstract

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. One conformation had a potential energy about 5 kcal/mol (21 .times. 103 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 H bond between the OH group of the 1-tyrosine side chain and the C .dbd. O group of 3-glycine or 4-phenylalanine. The phenylalanine and methionine side chains are relatively unrestricted. The conformation is consistent with published NMR 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.