Identifying the protonation site and the scope of non-proline cis-peptide bond conformations: a first-principles...

The existence of non-proline cis-peptide bond conformations of protonated triglycine proposed by us has been verified through a recent IR-IR double resonance experiment. However, the scope of such unique structures in protonated oligopeptides and whether protonation at amide oxygen is more stable than that at traditional amino nitrogen remain unsolved. In this study, the most stable conformers of a series of protonated oligopeptides were fully searched. Our findings reveal that the special cis-peptide bond structure appears with high energies for diglycine and is energetically less favored for tetra- and pentapeptides, while it acts as the global minimum only for tripeptides. To explore the formation mechanism of the cis-peptide bond, electrostatic potential analysis, and intramolecular interactions were analyzed. Advanced theoretical calculations confirmed that amino nitrogen is still preferred as the protonated site in most cases except glycylalanylglycine(GAG). The energy difference between the two protonated isomers of GAG is only 0.03 kcal mol^-1, indicating that the tripeptide is most likely to be protonated on the amide oxygen first. We also conducted chemical (infrared (IR)) and electronic (X-ray photoelectron spectra (XPS) and near-edge X-ray absorption fine structure spectra (NEXAFS)) structure calculations of these peptides to identify their notable differences unambiguously. This study thus provides valuable information for exploring the scope of cis-peptide bond conformation and the competition between two different protonated ways.