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.
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
Email: john.merle@nist.gov
Sigma Xi: not a member
Category: Chemistry