Figure 4. Substrate binding, translocation and unbinding coupled to protein conformational changes.

PMF in the (QPC₁,) space is shown for the regions in which P_i is present in the lumen. (a–e) Snapshots of the binding site conformation at a select number of images representing the early stages of binding/unbinding in the peri- (a) and cytoplasmic (e) sides, the fully-bound OF_b (b) and IF_b (d), and the TS_b transition state c. (f) D_min (minimum hydrogen donor-acceptor distance) between the P_i and side chains shown in a–e, grouped into three classes based on the functional state in which they interact with the substrate: OF state (top panel), IF state (bottom panel) and both states (middle panel). The residues shown in a–e are those strongly interacting with P_i (defined by D_min<3 Å) at least at one image. D_min of each image is an unweighted average over all sampled conformations of the image. The error bars represent the s.d. (see Analysis techniques in Methods section).