Electron transport in energy production complexes of biology

亚利桑那州立大学的Dmitry Matyushov获得了化学学部化学理论、模型和计算方法项目的奖励，并获得了分子和细胞生物科学部分子生物物理集群的共同资助，对生物线粒体能量复合物中的电荷传输进行了理论研究。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（从食物中获得的）化学能是如何转化为储存在生物功能中的能量的。在这个项目中，已经在单个蛋白质的尺度上确定的基本理论原理被扩展到更大尺度的生物能量链。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在膜上传输而不大量耗散成热。该项目将蛋白质-膜-水环境的结构和动力学与节能电子传递联系起来。研究生和博士后对这项研究做出了贡献。作为该项目的一部分，PI将为有才华的青年组织暑期计算机学校。该项目旨在开发一个预测模型，该模型可以解释变化的物理条件和相关蛋白质的突变对单个电子转移步骤和整体跨膜电子传递速率的影响。所提出的机制涉及破坏影响单个电子转移步骤的核波动平衡统计的条件。由于蛋白质-水-膜热浴的强烈色散动力学在松弛时间方面扩散了许多数量级，系统遍遍性的破坏是可能的。没有任何一种理论技术能够涵盖这个时间尺度范围。通过结合膜结合复合物的大尺度原子模拟和蛋白质电弹性波动的粗粒度模型来覆盖目前原子模拟无法达到的长度和时间尺度，解决了这个问题。用二维电子能谱的结果对模拟预测的蛋白质电子转移的机理进行了验证。该项目寻求在纳米长度尺度和1-100纳秒的时间尺度上解决一些最基本的界面统计和动力学问题：a) Gibbs系综是否是描述反应激活势垒的适当工具；b) Debye-Onsager界面极化图是否为开发界面静电预测模型提供了良好的参考；c)是否可以建立一个适当的理论框架，有效地描述生物学中的能量耗散和能量流动。

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.