Conformational study of Met-enkephalin in its zwitterionic form

An extensive exploration of Met-enkephalin in its zwitterionic form has been carried out, in order to characterize the different low-energy conformational domains accessible to this pentapeptide. The study builds on previous studies carried out in our lab for the neutral molecule, which provided the initial geometries from which the conformational space of the charged molecule could be scanned. The initial conformations were subjected to a series of high- and lowtemperature molecular dynamics simulations. Snapshots along each trajectory were taken, minimized, and used as starting points in further MD trajectories until no lower-energy conformers could be characterized. The CHARMm force field was used throughout the study for this purpose. The same search strategy was used in these studies simulating two different environmental conditions, a distance-dependent dielectric ? = r and a high constant dielectric ? = 80. In the low dielectric environment, the formation of the salt bridge dominates the structure. In the high dielectric environment, the screening of the electrostatic interactions results in weaker intramolecular interactions. In both cases, the Gly²–Gly³ β-turn-type structures are preferred over the Gly³–Phe⁴ turns, in marked contrast to what is found for the neutral molecule. The lowest-energy structures from both environmental conditions were reoptimized in the presence of a cluster of explicit water molecules. Reoptimization of the structures considering explicit water structures did not result in significant conformational changes for the structures characterized with the ε = r or ε = 80 environments.