Chapter 10: Computational Means of Assessing Proton Pumping in Cytochrome c Oxidase (Complex IV)

Cytochrome c oxidase (CcO) is a paradigmatic proton pump that has fascinated the bioenergetic community for over four decades. As the terminal enzyme in the respiratory chain, CcO catalyzes the reduction of molecular oxygen to water and simultaneously moves protons across the mitochondrial or bacterial membrane to create a transmembrane proton gradient that is essential for ATP synthesis. In this chapter, we describe how computer modelling and simulations have been used to help explain the chemical and proton pumping mechanisms in CcO. Particular attention is given to the insights gleaned from explicit simulations of proton translocation, to the coupled role of hydration dynamics, and to the kinetic gates that enable proton pumping, even in the presence of a transmembrane electrochemical gradient.