MD For MS: Simulations of the Transfer of Membrane Protein-Detergent Complexes from Solution to Vacuum in Electrospray Ionisation Mass Spectrometry (ESI-MS)

Abstract

Recent developments in mass spectrometry have allowed membrane proteins in complex with detergent micelles to be studied in the gas phase - previously thought only possible for soluble proteins. This development paves the way for future studies of membrane protein stability, structure and oligomerisation. The gas phase environment is very different to that of a cell membrane, and questions have been raised over the conformation of proteins in the gas phase. Molecular dynamics (MD) simulations have been used extensively to explore the evolution of gas phase structures of soluble proteins, with some evidence that the native state may be stabilised in vacuum (although the timescale of this stability remains unclear). However, membrane protein-detergent complexes have been less well studied by simulations. We have used a combination of non-equilibrium and equilibrium MD simulations to elucidate some of the processes that occur during transition of a protein-detergent complex from aqueous solution to vacuum (thus mimicking electrospray ionisation). We compare two membrane protein architectures (an α-helical bundle vs a β-barrel) and different detergents with respect to protein-detergent complex dynamics and stability.