Deciphering factors which determine the Ramachandran surface of peptides. The application of isodesmic surfaces, ΔEID(ϕ,ψ), to analyze the contribution of rotating moieties to the shape of potential energy surfaces

Abstract

A series of double rotors of the following types have been investigated via potential energy surfaces, E=E(ϕ,ψ), generated by ab initio Hartree–Fock molecular computations. Series of triply substituted methyne (H–C) moieties are called upon to mimic, the conformational behaviour of peptides. In substituents Z1 and Z2 the “first atoms” were of sp3 and sp2 hybridization having Z1=−CH3, –CH2F and –NHCHO, as well as Z2=−CH3, –CH2F, –CHO and –CONH2. The R group was chosen to be –H or –F and in one case –CH3 in order to reproduce the alanine model peptide. All potential energy surfaces, E=E(ϕ,ψ), were generated in the form of grids where points were separated by 15° intervals along both ϕ and ψ variables. This led to a total of 625 SCF points (25×25) for each surface, since both the initial (0°) and final (360°) values of both periodic variables (ϕ and ψ) were included in the grid. The interaction between substituents introduced were monitored by isodesmic reactions computed at each of the 625 grid points leading to isodesmic energy surfaces: ΔEID(ϕ,ψ). Comparing the influence of the different Z1 and Z2 substituents, undoubtedly, the introduction of two adjacent peptide bonds led to the greatest effect on the conformational energy surface.