Structural dynamics of activated large electrosprayed protein complexes
Abstract
We have recently established how to use the fast multipole model (FMM) to greatly accellerate MD simulations of gas-phase protein by a considerable amount. This enables simulations at length- and timescales that have so far been intractable. We will now apply this approach to specific systems where we have access to complementary experimental data through collaborators, and where simulations can shed light on the processes the structures undergo at a level of detail that is beyond experimental view.
We will simulate the small heatshock protein sHSP16.5, which despite its name is a sizeable complex comprised of 24 subunits and weighs about 400 kDa. We know from our recent study that microsecond-long simulations can be done with FMM for proteins of this size, and we will carry out simulations at different level of collisional activation, represented by different temperatures, too see the impact on the protein structure. To enable a more direct comparison to experiments, we will calculate the collision cross sections, which can also be inferred from ion mobility experiments that we currently run at the University of Oxford.
We will also simulate beta-galactosidase, which was recently imaged at high resolution using cryo-EM, where the protein had been soft-landed on the EM grids after upstream separation with native mass spectrometry. This gives a unique view of the structures of proteins having spent time in near-vacuum conditions, complementing out simulations very well. To explore the structural dynamics of beta-galactosidase in the hope of understanding any perturbations to the structure, we will carry out simulations where we pay attention to the compaction of cavities and contraction of the protein surface specifically, which seems to happen to some degree in experiments, although the overall structure is largely unaffected.
