Determination of cyclopeptide conformations in solution using NMR data and conformational energy calculations

The three-dimensional structure of the cyclic analogs of bradykinin and substance P C-terminal hexapeptide was studied using conformational energy calculations. Initial conformations for energy minimization were selected with the aid of the measured intensities of local nuclear Overhauser effects (NOEs) and other 1H-NMR data. Expected values of the 1H-NMR parameters for low-energy conformations of the cyclopeptides were calculated and compared with those observed experimentally using semiquantitative gradation of NOE intensities. Several low-energy structures of the cyclic bradykinin analog, possessing similar backbone conformations stabilized by two beta-turns, are in agreement with experimental data. None of the low-energy conformations of the substance P cyclic hexapeptide were in satisfactory agreement with the experimental set of NOEs. The agreement was achieved only by averaging of the calculated 1H-NMR parameters over several combinations of the low-energy conformations.