Molecular Dynamics Simulations of the Rotary Motor F0 under External Electric Fields across the Membrane

The membrane-bound component F0, which is a major component of the F0F1-ATP synthase, works as a rotary motor and plays a central role in driving the F1 component to transform chemiosmotic energy into ATP synthesis. We conducted molecular dynamics simulations of b2-free F0 in a 1-palmitoyl-2-oleoyl-phosphatidylcholine lipid bilayer for tens of nanoseconds with two different protonation states of the cAsp-61 residue at the interface of the a-c complex in the absence of electric fields and under electric fields of ±0.03 V/nm across the membrane. To our surprise, we observed that the upper half of the N-terminal helix of the c1 subunit rotated about its axis clockwise by 30°. An energetic analysis revealed that the electrostatic repulsion between this N-terminal helix and subunit c12 was a major contributor to the observed rotation. A correlation map analysis indicated that the correlated motions of residues in the interface of the a-c complex were significantly reduced by external electric fields. The deuterium order parameter (SCD) profile calculated by averaging all the lipids in the F0-bound bilayer was not very different from that of the pure bilayer system, in agreement with recent 2H solid-state NMR experiments. However, by delineating the lipid properties according to their vicinity to F0, we found that the SCD profiles of different lipid shells were prominently different. Lipids close to F0 formed a more ordered structure. Similarly, the lateral diffusion of lipids on the membrane surface also followed a shell-dependent behavior. The lipids in the proximity of F0 exhibited very significantly reduced diffusional motion. The numerical value of SCD was anticorrelated with that of the diffusion coefficient, i.e., the more ordered lipid structures led to slower lipid diffusion. Our findings will help elucidate the dynamics of F0 depending on the protonation state and electric field, and may also shed some light on the interactions between the motor F0 and its surrounding lipids under physiological conditions, which could help to rationalize its extraordinary energy conversion efficiency.