Molecular Dynamics Simulations of the Rotary Motor F 0 under External Electric Fields across the Membrane

Abstract

The membrane-bound component F 0, which is a major component of the F 0F 1-ATP synthase, works as a rotary motor and plays a central role in driving the F 1 component to transform chemiosmotic energy into ATP synthesis. We conducted molecular dynamics simulations of b 2 -free F 0 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 c 1 subunit rotated about its axis clockwise by 30°. An energetic analysis revealed that the electrostatic repulsion between this N-terminal helix and subunit c 12 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 ( S CD) profile calculated by averaging all the lipids in the F 0-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 F 0, we found that the S CD profiles of different lipid shells were prominently different. Lipids close to F 0 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 F 0 exhibited very significantly reduced diffusional motion. The numerical value of S CD 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 F 0 depending on the protonation state and electric field, and may also shed some light on the interactions between the motor F 0 and its surrounding lipids under physiological conditions, which could help to rationalize its extraordinary energy conversion efficiency.