Electron transport in energy production complexes of biology

亚利桑那州立大学的Dmitry Matyushov得到了化学系化学理论，模型和计算方法项目的资助，并得到了分子和细胞生物科学系分子生物物理学小组的共同资助，以开发生物学线粒体能量复合体中电荷传输的理论研究。位于线粒体膜上的蛋白质复合物为活细胞提供所有可用的能量。电荷传输的中断导致慢性疾病，并与氧化应激和衰老密切相关。 Matyushov和他的研究小组正试图了解化学能（从食物中获得）如何转化为生物功能所需的能量。 在这个项目中，已经在单个蛋白质的规模上确定的基本理论原则被扩展到生物能量链的更大规模。主要目标是更好地了解影响活细胞能量效率的因素。一个尚未解决的挑战是电子如何穿过膜传输而不显著地将能量耗散成热量。该项目将蛋白质-膜-水环境的结构和动力学与节能电子传输联系起来。 研究生和博士后同事为这项研究做出了贡献。 作为该项目的一部分，PI将为有才华的年轻人举办暑期计算机学校，该项目旨在开发一个预测模型，该模型将解释物理条件的变化和相关蛋白质的突变对单个电子转移步骤的速率和整体跨膜电子转移的影响。 所提出的机制涉及的条件，打破平衡的核波动影响个别电子转移步骤的统计。系统的遍历性的故障是可能的，由于强烈的分散动力学的蛋白质-水-膜热浴传播在许多数量级的弛豫时间。没有一种理论技术能够涵盖这一时间尺度范围。这个问题的解决相结合的膜结合的复合物的大规模原子模拟与粗粒建模的蛋白质电弹性波动，以涵盖目前无法访问的原子模拟的长度和时间尺度。通过模拟预测的蛋白质电子转移的机制特性进行了测试对二维电子光谱的结果。该项目旨在解决纳米尺度和1-100纳秒时间尺度上的界面统计和动力学的一些最基本的问题：a）吉布斯系综是否是描述反应活化势垒的适当工具，B）界面极化的Debye-Onsager图是否是开发界面静电预测模型的良好参考，以及c）是否可以建立有效描述生物学中的能量耗散和能量流动的适当理论框架。

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.