Gram-negative bacteria such as E. coli are typically regarded as "simple" model organisms, yet their cell envelopes are surprisingly complex. Recent experimental and theoretical studies have revealed that contrary to the traditional view of the cell membrane as a passive bystander in membrane protein function, it plays a key role in protein folding, assembly, and function. Furthermore it is becoming apparent that the interplay between membrane and protein is intricate and complex. We are using molecular modelling and simulation to study this membrane-protein interplay. To do so, we have constructed models of realistic membranes and atomistic and coarse-grain levels of detail. Our aim has been to incorporate as much of the natural heterogeneity of these membranes as possible. We have been able to explore the conformational dynamics and substrate permeation pathways of individual proteins, as well as aggregation and diffusion of multiple proteins. Thus, our simulations have thus enabled us to explore the differences between bacterial inner and outer membranes and crucially, to provide a link between the in vivo and traditional in vitro realms. I will present some of our successes, areas of on-going work and some thoughts for future directions.
 Piggot et al, J. Phys. Chem. B 115, page 13381-13388,(2011)
 Piggot et al, BBA, 1828, page 284-293, (2012)
 Holdbrook et al, BBA 1828, page 715-723, (2012)
 Eren et al et al, J Biol.Chem, 288, page 12042-12053, (2013)