QCMS2 as a new method for providing insight into peptide fragmentation: The influence of the side-chain and inter-side-chain interactions

J Mass Spectrom. 2020 Jul;55(7):e4446. doi: 10.1002/jms.4446. Epub 2019 Nov 19.

Abstract

The identification of peptides and proteins from tandem mass spectra is a difficult task and multiple tools have been developed to aid this identification. We present a new method called quantum chemical mass spectrometry for materials science (QCMS2 ), which is based on quantum chemical calculations of bond orders, reaction, and transition-state energies at the DFT/B3LYP/6-311+G* level of theory. The method was used to describe the fragmentation pathways of five X-His-Ser tripeptides with X = Asn, Asp, Glu, Ser, and Trp, thereby focusing on the influence of the side chain and inter-side-chain interactions on the fragmentation. The main features in the mass spectra of the five tripeptides were correctly reproduced, and a number of fragments were assigned to fragmentations involving the side chain and the influence of inter-side-chain interactions. Product ion spectra were recorded to evaluate the capabilities and limitations of QCMS2 and a number of conventional tools.

Keywords: Density Functional Theory; MS/MS; Quantum Chemical Mass Spectrometry (QCMS2); fragmentation pathways; tripeptides.

MeSH terms

  • Hydrogen Bonding
  • Models, Molecular
  • Molecular Structure
  • Peptide Fragments / chemistry*
  • Peptides / chemistry*
  • Spectrometry, Mass, Electrospray Ionization / methods*
  • Tandem Mass Spectrometry / methods*

Substances

  • Peptide Fragments
  • Peptides