Native mass spectrometry (MS) has seen considerable development over the past decade and become a cornerstone for gas-phase structural biology. Especially when combined with ion mobility spectrometry it can probe the structures and dynamics of both native and activated mass-selected proteins and protein complexes, albeit at low spatial resolution, by effectively measuring the proteins' projected cross-sectional area – their collision cross section (CCS). Much remains unknown about how structures are affected by activation and other experimental conditions. Here, molecular dynamics simulations (MD) provide a superior level of detail compared to other methods and can shed light on the underlying processes. We will use gas-phase MD to study model proteins that are expected to give different response to activation, monitor what experimental readout they would give and compare with experiments. We sill use natural as well as designer proteins with specific structural features to investigate specific structural dynamics. Secondly, we will pursue an unexpected avenue from an observation in a previous simulation, where beta-galactosidase (Bgal) displayed large-scale dynamics around its native conformation at moderate activation. This violates the common assumption that proteins are kinetically trapped in the gas phase and could open up for a new view of the key processes that proteins undergo in native MS and related techniques. This project is possible because of our recent efforts in using the Fast Multipole Method and Gromacs for achieving good performance in gas-phase MD (Persson2024). It allows for time and length scales that would otherwise be highly challenging if not impossible. We have several systems ready to be simulated and can start virtually immediately once the project is granted.