Importance of folded monomer and extended antiparallel dimer structures as enkephalin active conformation Molecular dynamics simulations of [Met⁵]enkephalin in water

Abstract

Simulations of the molecular dynamics of the [Met5]enkephalin monomer and dimer structures in water have been carried out. The dynamic trajectories have been analyzed in terms of the distances between intra‐ or intermolecular polar atoms. The time‐correlated conformational transitions of an extended monomer structure have been converged into a stationary state among the β‐bend folded forms. However, the dynamics simulation of an extended antiparallel dimer structure has shown no noticeable conformation change. These results imply that both the β‐bend monomer and the extended dimer structures exist together as the fundamental conformation of enkephalins.

Structural characterization of methionine and leucine enkephalins by hydrogen/deuterium exchange and electrospray ionization tandem mass spectrometry

“…In contrast, in the proposed structure of the 4→1 β ‐turn,6, 9–11 a β ‐turn is formed between the Gly‐2 and Gly‐3 residues and Tyr‐1 and Phe‐4 are brought close to each other by a hydrogen bond between the Phe‐4 amide proton and the Tyr‐1 carbonyl oxygen. The Gly‐3 amide proton is free in this structure, but, according to the HDX behavior observed in the present study, this hydrogen is protected from the deuterated solvents.…”

“…Their bioactive conformations are extremely important for recognition by their opioid receptors. In order to understand the structure‐function relationship and correlate their structures to those of the rigid morphine molecule, several studies have been undertaken both experimentally3–7 and theoretically 8–11. These studies have revealed a folded β ‐turn as the most stable enkephalin structure.…”

“…These studies have revealed a folded β ‐turn as the most stable enkephalin structure. However, a controversy exists whether the 5→2 β ‐turn3–5, 7, 8 or the 4→1 β ‐turn6, 9–11 is the favored structure. Several experimental studies3, 12, 13 have also suggested that the monomeric form of enkephalins coexists with a dimeric form.…”

Cross‐checking of nanoelectrospray ionization mass spectrometry and computer simulation for the evaluation of the interaction strength of non‐covalently bound enkephalins in solution

“…The basic strategy we employed in this study was as follows: the initial coordinates of the dimer complexes of the optical isomers of LE were chosen so that they had main‐chain and side‐chain conformations identical with those of the LE dimer complex except the chirality of corresponding amino acid(s). Similarly, the initial coordinates of the monomers of LE and its optical isomers were chosen so that they had main‐chain and side‐chain conformations similar to those of the corresponding dimer complexes 30–32. The local energy minima thus obtained for LE and its optical isomers may reflect the effect of the chirality difference, being relatively free from fortuity in the selection of the initial coordinates.…”