THEORETICAL-STUDY OF BLOCKED GLYCINE AND ALANINE PEPTIDE ANALOGS

We present a high-level ab initio study of the model blocked alanine and glycine dipeptide molecules, (S)-alpha-(formylamino)propanamide and alpha-(formylamino)ethanamide. Fully relaxed grids of the conventionally defined conformational space variables phi and psi have been evaluated for each molecule at the HF/3-21G level. In order to obtain the best results currently feasible, HF/6-31+G* fully optimized geometries and frequencies were obtained for all minima and transition structures observed on the HF/3-21G grid, and correlation corrections were explored with MP2/6-31+G**//HF/6-31+G* single-point energy calculations. The HF/3-21G structures are in reasonable agreement with the results of the larger basis, although the relative energies are sometimes poor. At the higher level of theory, we do not find minima in the regions of phi, psi-space corresponding to protein secondary structures, although these regions are relatively low in energy. We report the presence of a cusp in certain regions of the relaxed (phi,psi) map of both systems; the surfaces are double-valued in these regions, and the cusp occurs where the energies of the two surfaces cross. We also observe significant deviations from peptide planarity (up to 40-degrees) in several regions of the (phi,psi) map. The discontinuities and large peptide distortions indicate that the (phi,psi) degrees of freedom alone do not fully define the available conformational space of these dipeptide molecules. Finally we discuss the molecular origin of the differences between the alanine and glycine fully relaxed (phi,psi) surfaces, differences which are qualitatively consistent with those inferred from Ramachandran maps.