The Free Energy Landscape of Dimerization of a Membrane Protein, NanC
(A–C) Snapshots taken from umbrella sampling windows for the orientational configuration at inter-protein separations of 3.3 nm, 3.6 nm, and 4.1 nm, respectively. These snapshots correspond to the local minima in Figure 2B, which are labelled , and . The membrane is viewed from the periplasmic face, with the water and ions removed. The proteins are represented by traces through the particles of each residue, with one protein coloured blue and the other red. The lipid molecules are represented by spheres and are coloured by the lipid molecule, so that individual lipids can be identified. We see in the snapshot of state (A) that there is only one lipid between the two proteins, which is coloured purple. In the snapshot of state (B) there is room for two lipid molecules, coloured green and blue, to fit between the two proteins. In the snapshot of state (C) there is room for three lipids to fit between the two proteins, coloured in yellow, pink and orange. (D) Species density plot for the third coarse-grained particle in one of the tails for the lipids in the upper leaflet. The density is measured relative to the position of a freely diffusing NanC protein. The blue line is a projection of the particles onto the plane of the membrane. The arrow is the same arrow used throughout the text to show the protein's orientation and is drawn from the centre of mass through the of the isoleucine at residue 209. The dashed lines mark the angular region over which the mean lipid density (E) is measured and corresponds to the direction of the other protein in the orientational configuration . The mean is taken over both leaflets and all coarse-grained lipid particles. (F–H) The distribution is overlaid with a reversed version and aligned such that either one (F), two (G), or three (H) peaks occur in the region between the two proteins. The dashed line sections correspond to regions that are occupied by the proteins. The thick lines represent the overlaid lipid distributions around both proteins that correspond to the prediction of the lipid packed region between the two proteins. The vertical dotted lines indicate the edge of the reversed density plot. These edges correspond to the predicted position of the second protein and are located at 3.24 nm (F), 3.63 nm (G), and 4.02 nm (H).