Molecular Dynamics‐Based Conformational Simulation Method for Analysis of Arrival Time Distributions in Ion Mobility Mass Spectrometry

Abstract Ion mobility‐mass spectrometry (IM‐MS) has recently contributed to the structural analysis of molecules, including supramolecules and proteins, by determining the ion arrival time distributions correlated with the collision cross sections (CCSs), as well as the mass‐to‐charge ratios. However, its application range is still limited owing to the lack of general CCSs simulation methods based on possible molecular conformations. Here, a molecular dynamics‐based conformational search method for simulating CCS distributions using projection approximation is reported. As a case study, the gas‐phase conformations of the sodium adducts of conformationally flexible polyketones with 3,3‐dimethylpentane‐2,4‐dione as the monomer are analyzed. The sodium adduct of the hexamer ( m/z 781.4 for [ 1 + Na] + ) showed a monomodal arrival time distribution, but that of the octamer sodium adduct ( m/z 1033.5 for [ 2 + Na] + ) is multimodal. The conformational analysis indicated an unimodal CCS distribution of simulated [ 1 + Na] + conformations in which the sodium cation is mainly bound at the chain terminal. Conversely, four clusters of conformations are obtained for [ 2 + Na] + based on the Na + ‐coordination sites, which qualitatively reproduced the observed CCS distribution. This approach will extend the utility of IM‐MS for the conformational analysis of flexible molecules in the gas phase.