We will study proton-coupled electron transfer (PCET) reactions and proton translocation (PTR) with the goal of understanding energy conversion in the Photosystem II Oxygen Evolving Complex and cytochrome c oxidase (CcO). These two metalloenzymes form an important part of the biochemical oxygen cycle, and it is well appreciated that both rely on PCET and PTR for their energy transduction function. Both photosynthesis and oxidative phosphorylation couple the movement of electrons and protons across a membrane to the generation of an electrochemical proton gradient. These gradients are used to generate ATP and provide the energy """"""""currency"""""""" for biosynthesis. If the process is defective, with a membrane that cannot maintain an electrochemical proton gradient, ATP is no longer synthesized. Many diseases associated with aging are related to deficiencies in the operation of CcO. As mitochondrial mutations accumulate, damage to the electron transfer mechanism occurs, and oxygen radicals, that are implicated in the aging process, accumulate. Theories that couple the transfer of electrons and protons together are not well developed, and will be a goal of this research. We will obtain formal expressions for the rates of PCET reactions and, with suitable numerical schemes, evaluate the parameters that enter these rate expressions, to make quantitative predictions of rates and mechanisms for PCET. These PCET events are intimately connected with the transport of protons through membrane-bound proteins; consequently, theories of PTR are the other goal of this research. We will develop theoretical methods that permit the description of proton transport through hydrogen-bonded water and residue pathways. Contemporaneously, we will explore PTR by simulation methodologies that we are developing, which combine quantum mechanics and molecular dynamics to quantitatively describe proton translocation.
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