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

Abstract

We report the results of experiments, simulations, and DFT calculations that focus on describing the reaction dynamics observed within the collision-induced dissociation of L-lysine-H + and its side-chain methylated analogues, N ε -Methyl-L-lysine-H + (Me 1 -lysine-H + ), N ε ,N ε -Dimethyl-L-lysine-H + (Me 2lysine-H + ), and N ε ,N ε ,N ε -Trimethyl-L-lysine-H + (Me 3 -lysine-H + ). The major pathways observed in the experimental measurements were m/z 130 and 84, with the former dominant at low collision energies and the latter at intermediate to high collision energies. The m/z 130 peak corresponds to loss of N(CH 3 ) n H 3−n while m/z 84 has the additional loss of H 2 CO 2 likely in the form of H 2 O+CO. Within the time frame of the direct dynamics simulations, m/z 130 and 101 were the most populous peaks, with the latter identified as an intermediate to m/z 84. The simulations allowed for the determination of several reaction pathways that result in these products. A graph theory analysis enabled the elucidation of the significant structures that compose each peak. Methylation results in the preferential loss of the side-chain amide group and a reduction of cyclic structures within the m/z 84 peak population in simulations.