Chapter 4: Multi-scale Molecular Simulations on Respiratory Complex I

Complex I (NADH:ubiquinone oxidoreductase) is a redox-driven proton pump that powers synthesis of adenosine triphosphate (ATP) and active transport in most organisms. This gigantic enzyme reduces quinone (Q) to quinol (QH₂) in its hydrophilic domain, and transduces the released free energy into pumping of protons across its membrane domain, up to ca. 200 Å away from its active Q-reduction site. Recently resolved molecular structures of complex I from several species have made it possible for the first time to address the energetics and dynamics of the complete complex I using multi-scale methods of computational biochemistry. Here it is described how molecular simulations can provide important mechanistic insights into the function of the remarkable pumping machinery in complex I and stimulate new experiments.