Identification of the smallest peptide with a zwitterion as the global minimum: a first-principles study on arginine-containing peptides
Zwitterions are believed to play an important role in determining the structures,properties and functions of peptides and proteins. However, the smallest peptide that with the zwitterionic structure as the global minimum in the gas phase is still not yet identified. In this study, the effective step-by-step strategy has been used to characterize the stable conformers of arginine-containing peptides arginylalanine (ArgAla) and arginylserine (ArgSer). Energy calculations at the DSD-PBEP86-D3BJ/aug-cc-pVTZ level and further extrapolation to the complete basis set (CBS) limit have confirmed, for the first time, that ArgSer appears to be the promising candidate to be the smallest peptide with the unique zwitterion. First-principles simulations have been performed for near-edge X-ray absorption fine-structure (NEXAFS) spectra and X-ray photoelectron spectra (XPS) at C, N and O K-edges, as well as for infrared (IR) spectra of these arginine-containing peptides. Notable spectral differences were found which enable the unambiguous identification of different neutral forms in the future experiments. Our study thus provides valuable insights into structure stability with the increase of the molecular size and illustrates the competitions between the canonical and zwittterionic isomers.