Molecular Simulations of Gram-Negative Bacterial Membranes Come of Age

Gram-negative bacteria are protected by a multicompartmental molecular architecture known as the cell envelope that contains two membranes and a thin cell wall. As the cell envelope controls influx and efflux of molecular species, in recent years both experimental and computational studies of such architectures have seen a resurgence due to the implications for antibiotic development. In this article we review recent progress in molecular simulations of bacterial membranes. We show that enormous progress has been made in terms of the lipidic and protein compositions of bacterial systems. The simulations have moved away from the traditional setup of one protein surrounded by a large patch of the same lipid type toward a more biologically representative viewpoint. Simulations with multiple cell envelope components are also emerging. We review some of the key method developments that have facilitated recent progress, discuss some current limitations, and offer a perspective on future directions.