Figure 8.

Energetics of exchange of sequential subunit-a/subunit-c interactions in the rotary cycle. The interaction of the c-subunits with the key arginine on subunit-a was again mimicked with a GND⁺ ion (gray/blue sticks) added to the MPD/water buffer. (a) GND⁺ exchange between two unlocked glutamate side-chains (blue sticks) in adjacent Na⁺-binding sites, i.e. after Na⁺ release from the S_N site and prior to Na⁺ loading to the S_P site. The three panels on the left depict the end-point states in the exchange, and the transition state in between. The colored volumes are density maps extracted from the simulations, mapping the location of either GND⁺ (blue), the first hydration shell of GND⁺ (red), or the first hydration shell of the carboxylate groups (white). Representative snapshots are shown in Supplementary Fig. 11. The panel on the right shows the free-energy profile associated with the exchange, as a function of the distances between the GND⁺ ion and S_P and S_N (d_P and d_N). A two-dimensional free-energy surface is shown in Supplementary Fig. 11. (b) Exchange between the unlocked glutamine side-chain in the c₁ subunit (orange sticks) and the glutamate side-chain in the adjacent Na⁺ site, counter-clockwise. (c) Same as (b), clockwise. The c-ring is represented as in Fig. 2. Hydrogen atoms as well as protein side-chains and MPD/water molecules are omitted for clarity.