Electron transport in energy production complexes of biology

Arizona State University, Scottsdale AZ

Investigators

Abstract

Dmitry Matyushov of Arizona State University is supported by an award from the Chemical Theory, Models and Computational Methods program in the Chemistry Division, with co-funding from the Molecular Biophysics Cluster in the Molecular and Cellular Biosciences Division, to develop a theoretical study of charge transport in mitochondrial energy complexes of biology. Protein complexes located in mitochondrial membranes provide all energy available to living cells. Disruptions of charge transport result in chronic diseases and are closely related to oxidative stress and aging. Matyushov and his research group are attempting to understand how chemical energy (obtained from food) is transformed into the energy stored for biological function. In this project, basic theoretical principles that have been identified on the scale of individual proteins are extended to the much larger scale of biology's energy chains. The main goal is better understand the factors influencing the energetic efficiency of living cells. A still unresolved challenge is how electrons are transported across the membrane without significant dissipation of energy into heat. The project links the structure and dynamics of the protein-membrane-water environment to energy-efficient electron transport. Graduates students and postdoctoral associates contribute to this research. As part of this project, the PI will organize summer computer schools for talented youth. The project aims at developing a predictive model that accounts for the effect of changing physical conditions and mutations in relevant proteins upon the rates of individual electron transfer steps and on overall cross-membrane electron transport. The proposed mechanism involves the conditions for breaking the equilibrium statistics of nuclear fluctuations affecting individual electron transfer steps. The breakdown of the system's ergodicity is possible due to strongly dispersive dynamics of the protein-water-membrane thermal bath spreading over many orders of magnitude in terms of relaxation times. No single theoretical technique is capable of covering this range of timescales. The problem is resolved by combining large-scale atomistic simulations of membrane-bound complexes with coarse-grain modeling of protein electro-elastic fluctuations to cover length- and timescales that are currently inaccessible by atomistic simulations. The mechanistic properties of protein electron transfer predicted by simulation are tested against the results of two-dimensional electronic spectroscopy. The project seeks to solves some of the most fundamental problems of interfacial statistics and dynamics on the nanometer length-scale andon the timescale of 1-100 nanoseconds: a) whether the Gibbs ensemble is an adequate tool for describing the reaction activation barriers, b) whether the Debye-Onsager picture of interfacial polarization is a good reference for developing predictive models of interfacial electrostatics, and c) whether an appropriate theoretical framework can be established that effectively describes energy dissipation and energy flow in biology.