Computational Prediction of Peptide Fragmentation Mechanisms in Tandem Mass Spectrometry



Tandem mass spectrometry (MS/MS) is a valuable tool for protein sequencing in the field of proteomics. Considerable efforts have been spent producing MS/MS spectra of peptide digests followed by bioinformatic identification of the original proteins. Modest efforts, however, have been spent toward understanding the fundamental chemistry affecting peptide fragmentation pathways. This gap in understanding provides a special opportunity for mechanistic chemists. We are using electronic structure methods to generate potential energy surfaces (PES) in order to understand fragmentation mechanisms and their thermodynamic and kinetic influences on observed peptide fragmentation products. We have examined mechanisms for neutral (H2O and C2H4O) loss in MS/MS experiments of tryptic peptides with two threonine residues at the N-terminus. These experiments show that the presence of a “mobile proton” is required but the mechanism is unknown. It is accepted that proton (charge) location is responsible for directing peptide fragmentation. We are also examining the proton probability density at basic peptide backbone sites resulting from multiple protonation. Computational models have been used to highlight molecular properties influencing the location of mobile protons.



Author Information

            Name:                          John K. Merle

            Mentor’s name:            Karl K. Irikura

            Division:                       Physical and Chemical Properties, 838

            Laboratory:                  CSTL

            Room/Building: 336B/221

            Mail Stop:                    8380

            Telephone #:                 301-975-4417

            Fax #:                           301-869-4020


            Sigma Xi:                      not a member

            Category:                     Chemistry