The goal of this project is to elucidate the proton pumping mechanism of cytochrome c oxidase (CcO) with the first dynamical simulation framework to incorporate all of the relevant phenomena, namely proton transport, electron transport, and the protonation of ionizable amino acids. These phenomena act in a coupled manner. Thus, the complete characterization of the proton pumping mechanism will require a unified methodology that treats them as such. This will be accomplished with the MS-EVB2 model, one of a few theories able to simulate proton dynamics, extended to incorporate electron transfer and residue ionization. CcO is not only a fundamental curiosity within bioenergetics, it is also medically important having been linked to diseases such as cancer, neurodegeneration, and aging. Understanding its proton pumping mechanism under normal and high energy physiological conditions will contribute to our knowledge of and fight against these diseases. Additionally, developing this framework will provide a tool for investigating any biological system where charge transfer or protonation-dependent activity is of importance. Thus, the use of this methodology is potentially quite broad. ? ? ?
|Swanson, Jessica M J; Simons, Jack (2009) Role of charge transfer in the structure and dynamics of the hydrated proton. J Phys Chem B 113:5149-61|
|Izvekov, Sergei; Swanson, Jessica M J; Voth, Gregory A (2008) Coarse-graining in interaction space: a systematic approach for replacing long-range electrostatics with short-range potentials. J Phys Chem B 112:4711-24|