Application of the distance geometry algorithm to cyclic oligopeptide conformation searches

The distance geometry algorithm as embodied in the program DGEOM was examined as a method for searching cyclic peptide conformations. Conformations were randomly generated using covalent distance and chirality constraints, but torsion angle rather than distance sampling was used for 1, 4 relationships. Structures so generated were energy minimized by a fixed number of iterations using the molecular mechanics program AMBER 3.0; electrostatic terms were excluded in the minimization. The effectiveness of this procedure in sampling conformational space for cyclic peptides was measured by the ability to recover, from a set of 500 structures, conformations similar to those experimentally observed for six cyclic peptides containing from 8 to 20 rotatable backbone bonds. Structures similar to experimental structures were recovered in a 16‐bond case, but not for a 20‐bond example. The method was also applied, with constraints on the peptide bond angles ω, to an additional example containing 21 ring bonds.

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