Conformational analysis of the highly potent bradykinin antagonist Hoe-140 by means of two different computational methods.

Abstract The AMBER 4.0 force field was used to perform the characterization of the conformational profile of the highly potent bradykinin antagonist Hoe-140 (D-Arg0-Arg1-Pro2-Hyp3-Gly4- Thi5-Ser6-D-Tic7-Oic8-Arg9). The structural features of the peptide were assessed using two different computational methods, both capable to provide a good sampling of the low-energy conformations of the molecule. Specifically, the conformational space of the peptide was explored: i) computing molecular dynamics trajectories in cycles of high (900 K) and low (300 K) temperature and ii) using simulated annealing (SA) in an iterative fashion. Analysis of the structures characterized indicates that most of the low-energy conformations of the peptide exhibit a βII′-turn motif at its C-terminus, in agreement with previous experimental and theoretical studies. On the other hand, about a 50% of the low-energy conformations characterized also exhibit different β-turn type motifs at the N-terminus, whereas the rest of the conformat...