ABSTRACT
Computer Simulations ......................................................88 4.6 Calculation of Redox-Coupled Protonation States of Key
Residues of CcO: The Search for the Pump Element ...................................88 4.6.1 Density Functional Calculations: ∆∆Eel, ∆Gstrain Terms .................93 4.6.2 Continuum Electrostatic Calculations: ∆∆GBorn, ∆∆Gq Terms ........94 4.6.3 Microscopic Modeling of Polarizable Protein Medium: Fixing
Empirical Parameters for Continuum Calculations .........................94 4.6.4 Contribution of the Electronic Polarization
to Solvation Energy: MDEC Method ...............................................95 4.7 Kinetic Gating Mechanism for Chemical and Pumped
Protons in CcO ..............................................................................................96 4.8 Conclusions ...................................................................................................99 Acknowledgments .................................................................................................. 100 References ............................................................................................................. 100
The correlated transport of electrons and protons in cytochrome c oxidase (CcO), the terminal enzyme in the respiratory electron transport chain of aerobic organisms, is discussed. This enzyme catalyzes the reduction of atmospheric oxygen to water, and converts the free energy of oxygen reduction into the membrane proton gradient by pumping protons across the membrane. The proton gradient subsequently drives the synthesis of ATP. This enzyme is a quantum mechanical energy-converting machine, for the electron transport in it is solely due to quantum tunneling. Computer simulations and theoretical modeling point to a possible molecular mechanism of this redox-driven proton pump. Recent progress in this area is discussed.
