Molecular Dynamics Simulations of the Mutated Proton-Transferring -Subunit of FF-ATP Synthase.

The membrane F factor of ATP synthase is highly sensitive to mutations in the proton half-channel leading to the functional blocking of the entire protein. To identify functionally important amino acids for the proton transport, we performed molecular dynamic simulations on the selected mutants of the membrane part of the bacterial FF-ATP synthase embedded in a native lipid bilayer: there were nine different mutations of -subunit residues (E219, H245, N214, Q252) in the inlet half-channel. The structure proved to be stable to these mutations, although some of them (H245Y and Q252L) resulted in minor conformational changes.

Membrane Lipid Composition Influences the Hydration of Proton Half-Channels in FF-ATP Synthase.

The membrane lipid composition plays an important role in the regulation of membrane protein activity. To probe its influence on proton half-channels' structure in FF-ATP synthase, we performed molecular dynamics simulations with the bacterial protein complex (PDB ID: 6VWK) embedded in three types of membranes: a model POPC, a lipid bilayer containing 25% (in vivo), and 75% (bacterial stress) of cardiolipin (CL). The structure proved to be stable regardless of the lipid composition.