MOLECULAR-DYNAMICS SIMULATIONS OF LEU-ENKEPHALIN IN WATER AND DMSO

The structure of Leu-enkephalin (L-Enk) and Met-enkephalin (M-Enk) hav e frequently been studied, in particular by nuclear magnetic resonance spectroscopy. After more than 20 years of research, it was concluded that enkephalins have no preferred structure in aqueous solution, but that they may have in other solvents. We have performed molecular dyna mics simulations of zwitterionic L-Enk in water, and zwitterionic as w ell as neutral L-Enk dimethyl sulfoxide (DMSO). In water the peptide i s very flexible, although there seems to be a preference for compact c onformations. In DMSO, the peptide forms a clear salt bridge in the zw itterionic form, but has no preferred conformation in the neutral form . This difference in conformation may provide an explanation for measu rements in DMSO in which multiple conformations were found to exist. I n this paper we introduce a new formulation for a dihedral angle autoc orrelation function, and apply it to study side-chain dynamics in L-En k. We find that the side-chain dynamics of the large Tyr and Phe resid ues cannot be adequately sampled in 2.0-ns simulations, while this doe s seem to be possible for the smaller Leu side chain.