Characterizing Membrane Association and Periplasmic Transfer of Bacterial Lipoproteins through Molecular Dynamics Simulations

Escherichia coli lipoprotein precursors at the inner membrane undergo three maturation stages before transport by the Lol system to the outer membrane. Here, we develop a pipeline to simulate themembrane association of bacterial lipoproteins in their four maturation states. This has enabled us to model and simulate 81 of the predicted 114 E. coli lipoproteins and reveal their interactions with the host lipid membrane. As part of this set we characterize themembrane contacts of LolB, the lipoprotein involved in periplasmic translocation. We also consider the means and bioenergetics for lipoprotein localization. Our calculations uncover a preference for LolB over LolA and therefore indicate how a lipoprotein may be favorably transferred from the inner to outer membrane. Finally, we reveal that LolC has a role in membrane destabilization, thereby promoting lipoprotein transfer to LolA.