Rotational Mechanism of F(O) Motor in the F-Type ATP Synthase Driven by the Proton Motive Force

In F(O)F(1) ATP synthase, driven by the proton motive force across the membrane, the F(O) motor rotates the central rotor and induces conformational changes in the F(1) motor, resulting in ATP synthesis. Recently, many near-atomic resolution structural models have been obtained using cryo-electron microscopy. Despite high resolution, however, static information alone cannot elucidate how and where the protons pass through the F(O) and how proton passage is coupled to F(O) rotation. Here, we review theoretical and computational studies based on F(O) structure models. All-atom molecular dynamics (MD) simulations elucidated changes in the protonation/deprotonation of glutamate—the protein-carrier residue—during rotation and revealed the protonation states that form the “water wire” required for long-range proton hopping. Coarse-grained MD simulations unveiled a free energy surface based on the protonation state and rotational angle of the rotor. Hybrid Monte Carlo and MD simulations showed how proton transfer is coupled to rotation.