Bond-optimized ring closure for proline: comparison of conformations and semiempirical energies with small molecule X-ray structures.

A method is described for generating proline ring structures by successive addition of atoms, wherein ring closure is achieved by optimizing the fit to known ring bond-angles and one closing bond-length ("bond-optimized ring closure"). Two ring torsion angles are fixed independently within broad, allowed ranges, and the remaining torsion angles are determined uniquely in most cases. The independent torsion angles are chosen as phi and chi 2, and ring closure is achieved without prohibitive strain through most of the ranges -130 degrees less than phi less than -20 degrees and -60 degrees less than chi 2 less than 60 degrees. Comparisons of predicted ring structures to 191 X-ray diffraction structures from the literature, starting with the known values of phi and chi 2, yielded root-mean-square deviations of 4.8 degrees in chi 1, 4.7 degrees in chi 3, 8.3 degrees in chi 4, and 0.3-2% in the ring bond angles and the N-C delta distance. Semiempirical energies were calculated for the optimized structures using three sets of energy parameters from the literature. The energy surfaces show broad minima coinciding with the torsion angle regions in which the highest concentrations of observed structures are found. Two of the sets of energy parameters produce double minima corresponding to the "up" and "down" puckered conformations.