Computer simulation of the conformational properties of retro–inverso peptides. II. Ab initio study, spatial electron distribution, and population analysis of N‐formylglycine methylamide, N‐formyl N′‐acetyldiaminomethane, and N‐methylmalonamide

Ab initio minimal and split‐valence basis set calculations have been performed on compounds that are involved in retro–inverso modifications, i.e., gem ‐diaminoalkyl and malonyl structures. These calculations are compared with empirical force field calculations and the minor differences discussed. All calculations agree that the preferred helical conformation of the isolated gem ‐diaminoalkyl and malonyl derivatives of residues found in the retro‐inverso modified peptides is 5–8 kcal/mol lower than the C conformation preferred by the isolated peptide residues. Population analysis and contour plots of the charge distribution are used to help explain the differences between the model compounds.