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

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 (QCMS(2)), 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 QCMS(2) and a number of conventional tools.