Insights into the molecular mechanism of complex I from atomistic molecular dynamics simulations.

Complex I (NADH:quinone oxidoreductase) is the first elec-
tron acceptor in the respiratory chains of mitochondria and
many bacteria. It catalyzes the reduction of quinone (Q),
which is coupled to the proton pumping across the mem-
brane. The redox reactions in the hydrophilic domain, and
proton pumping in the membrane domain of the enzyme are
spatially as well as temporally separated, and how the two
are coupled remains unclear. In order to shed light on the
early reactions of the catalytic cycle of complex I, we have
performed atomistic classical molecular dynamics (MD) sim-
ulations on the entire structure of complex I from
Thermus
thermophilus
[1], immersed in a lipid-solvent environment
comprising ca. 1 million atoms. MD simulations (
∼
100 ns)
in different redox and protonation states of Q show that the
long-range redox coupled proton pumping in complex I is
activated by a combination of electrostatic interactions and
conformational transitions [2].