Carbonyl charge solvation patterns may relate to fragmentation classes in collision-activated dissociation

Here, we investigate the hypothesis that the origin of Class I fragmentation in tryptic peptide dications corresponding to the cleavage of the first two amino acids from the N-terminus is due to a dominant charge solvation pattern. Molecular dynamics simulations (MDS) of model A(n)R dications confirmed the existence of a persistent solvation of the protonated N-terminus on the second backbone carbonyl. Additionally, MDS predicted a new distinct fragmentation class corresponding to the loss of two amino acids from the C-terminus. This prediction was confirmed experimentally at very low excitation levels. The pattern produced by electron transfer dissociation of the same dications gave markedly decreased cleavage frequencies at the second peptide bond, which, within the non-local fragmentation mechanism, supports the preferential charge solvation on the second carbonyl. Taken together, these results confirm the role of a charge solvation pattern in the origin of fragmentation classes.