Electron transport in energy production complexes of biology

Project: Research project

Description

Overview: This is a proposal for a theoretical study of charge transport in mitochondrial
energy complexes of biology. We want to understand how the structure and dynamics of the protein-membrane-water environment promotes energy efficient cross-membrane electron transport. A significant part of the proposed mechanism is in providing conditions for breaking the equilibrium statistics of nuclear fluctuations affecting individual electron transfer steps. The breakdown of systems 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 to cover this range of time-scales. We propose to bridge the gap by combining large-scale atomistic simulations of membrane-bound complexes with coarse-grain modeling of the protein electro-elastic fluctuations to cover the length- and time-scales currently not accessible by atomistic simulations. The coarse-grained models will be parametrized on relatively short (sub-microsecond) trajectories from atomistic simulations. The mechanistic properties of protein electron transfer predicted by simulations will be tested against two-dimensional electronic spectra operating in on the same time-scale. The anticipated result of this project is a predictive model that will be able to address the effect of changing physical conditions and mutations on the rates of individual electron-transfer steps and on the overall
cross-membrane electron transport.

Intellectual Merit: The proposed research will address some of most fundamental problems
of interfacial statistics and dynamics on the nanometer length-scale and the time-scale of 1-100 ns. We address the following questions: 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) what is the theoretical framework to describe the energy dissipation and energy flow in biologys energy chains? The project will develop theories that combine atomistic structure and dynamics with nanometer-scale electro-elastic deformations and with the general framework of entropy productions in non-ergodic ensembles required to understand the kinetics. The elastic motions of the protein will be combined with interfacial water polarization described in terms of the surface charge density. The model will capture coupled motions of the surface residues with the interfacial water polarization, which is the critical physical mechanism behind the intense electrostatic noise seen in simulations. The length- and time-scale covered by the model will allow to capture the mechanistic features of electron transport in large membrane-bound complexes of biology. Studies of individual reaction steps will be integrated into a general formalism of optimizing the redox energy flux in terms of the principle of maximum entropy production.

Broader Impacts: The problems addressed by this proposal will contribute to understanding
of how energy is transformed and carried in biological energy chains. This is a fundamental
and largely unresolved question in our quest to understand life. There are two molecular-scale principles that are fundamental for all life known to us: the storage of genetic information in DNA and the use of the proton-motive force to drive biochemical reactions. The second principle is our long-term target. We want to understand how energy of chemistry (food) is transformed into the energy stored for function. This project extends the principles of operation identified on the scale of individual proteins to a much larger scale of biologys energy complexes. The mechanistic principles and the analysis of the energy flow will help to understand the factors influencing the production of energy by biology and energetic efficiency of living cells. Project efforts will enhance education and dissemination at all levels. The PI will continue training graduate students and postdoctoral associates. We will provide the community with computational resources developed within the project by creating a public-access server for analyzing protein electrostatics and dynamics. The PI plans to organize summer computer schools for local talented youth and
continue to participate in science presentations to the general public to support the growth of STEM student enrollment.
StatusFinished
Effective start/end date4/1/153/31/18

Funding

  • National Science Foundation (NSF): $442,000.00

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biology
proteins
electrons
membranes
energy
electron transfer
electrostatics
simulation
students
water
proposals
education
polarization
statistics
entropy
elastic deformation
mutations
food
electronic spectra
summer