(A) The topologies of the EmrE monomers first inserted into the cytoplasmic membrane (blue band) at the end of translation (left) do not necessarily reflect the final topologies, which are subsequently achieved through thermodynamics-driven annealing. The interhelical loops in red represent the loops that flip most slowly, and thereby have a major influence on the kinetics of folding. EmrE can take on two different, antiparallel topologies; each row in the figure shows how one of these topologies may develop. (B) Van Lehn et al. used a coarse-grained model to simulate the insertion and folding of the EmrE dual-topology membrane protein (Zhang and Miller, 2012). Coarse-grained beads are assigned approximate hydrophobicity values (indicated by the shadings of the beads). The ribosome (brown) and translocon (green) are also represented as coarse-grained beads. The translocon is negatively charged on the cytoplasmic end and positively charged at the periplasmic end to represent the known charge distribution of the Sec 61 translocon (Goder et al., 2004). The simulation proceeds by adding a bead at the C-terminus of the nascent chain every 125 milliseconds; the panel on the right shows the chain on the left at a later point in time. Figure adapted from Figures 1 and 4 of Van Lehn et al. (2015).