Thermodynamics and Reaction Mechanisms for Decomposition of a Simple Protonated Tripeptide, HGGA: From HGGG to HGAG to HGGA.

We present a thorough characterization of fragmentations observed in threshold collision-induced dissociation (TCID) experiments of protonated glycylglycylalanine (HGGA) with Xe using a guided ion beam tandem mass spectrometer. Kinetic energy dependent cross sections for nine ionic products were obtained and analyzed to provide 0 K barriers for the five primary products, [b], [y + 2H], [b], [y + 2H], and [a]; and four secondary products, [a], [a], high-energy [y + 2H], and CHCHNH, after accounting for multiple ion-molecule collisions, the internal energy of reactant ions, unimolecular decay rates, competition between channels, and sequential dissociations. Relaxed potential energy surface scans performed at the B3LYP-GD3BJ/6-311+G(d,p) level of theory are used to identify transition states (TSs) and intermediates of the five primary and three secondary products (with the mechanism of the other secondary product previously established). Geometry optimizations and single point energy calculations of reactants, products, intermediates, and TSs were performed at several levels of theory. These theoretical energies are compared with experimental threshold energies and found to give reasonable agreement, with B3LYP-GD3BJ and M06-2X levels of theory performing slightly better than MP2 and better than B3LYP. The results obtained here are compared with previous results for decomposition of HGGG and HGAG to probe the effect of changing the amino acid sequence. Methylation in HGGA has a significant effect on the competition between the primary sequence products, [b] and [y + 2H], suppressing the [b] cross section by raising its threshold energy, while enhancing that of [y + 2H] by lowering its threshold energy.