CHARACTERIZATION OF LOW-ENERGY CONFORMATIONAL DOMAINS FOR MET-ENKEPHALIN

An extensive exploration of the conformational hypersurface of Met-enkephalin has been carried out, in order to characterize different low-energy conformational domains accessible to this pentapeptide. The search strategy used consisted of two steps. First, systematic nested rotations were performed using the ECEPP potential. Ninety-two low-energy structures were found and minimized using the CHARMm potential. High and low-temperature molecular dynamics trajectories were then computed for the lowest energy structures in an iterative fashion until no lower energy conformers could be found. The same search strategy was used in these studies simulating three different environments, a distance-dependent dielectric-epsilon = r, and two constant dielectrics-epsilon = 10 and epsilon = 80. The lowest energy structure found in a distance-dependent dielectric is a Gly-Gly beta-II'-type turn. All other structures found for epsilon = r within 10 kcal/mol of this lowest energy structure are also bends. In the more polar environments, the density of conformational states is significantly larger compared to the apolar media. Moreover, fewer hydrogen bonds are formed in the more polar environments, which increases the flexibility of the peptide and results in less structured conformers. Comparisons are made with previous calculations and experimental results.