Exploring the Effects of Methylation on the CID of Lysine: A Combined Experimental and Computational Approach

We report the results of both experiments, simulations, and DFT calculations that focus on describing the reaction dynamics observed within the collision-induced dissociation of L-lysine and its side-chain methylated analogues, $N_\epsilon$-Methyl-L-lysine (\methylLys{1}), $N_\epsilon$,$N_\epsilon$-Dimethyl-L-lysine (\methylLys{2}), and $N_\epsilon$,$N_\epsilon$,$N_\epsilon$-Trimethyl-L-lysine (\methylLys{3}). There is good qualitative agreement between simulations and experiments. The major pathways observed in the experimental measurements were {\it m/z} 130 and 84, with the former dominant at low collision energies and the latter at intermediate to high collision energies. The {\it m/z} peak corresponds to loss of H$_2$CO$_2$ while {\it m/z} 84 has the additional loss of N(CH$_3$)$_n$H$_{3-n}$. Within the time frame of the direct dynamics simulations, {\it m/z} 130 and 101 were the most populous peaks, with the latter identified as an intermediate to {\it m/z} 84. The simulations allowed for the determination of several reaction pathways that result in these products, and a graph theory analysis enabled the elucidation of the major structures that compose each peak. Methylation results in an increase in the preferential loss of the side-chain amide group and a reduced occurrence of cyclic structures within the population of the {\it m/z} 84 peak in simulations.