Electron transport in energy production complexes of biology

亚利桑那州立大学的Dmitry Matyushov得到了化学部化学理论、模型和计算方法项目的支持，并得到了分子和细胞生物科学部分子生物物理学小组的共同资助，以发展一项关于生物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体为活细胞提供所有可用的能量。电荷转运中断会导致慢性疾病，并与氧化应激和衰老密切相关。Matyushov和他的研究小组试图了解化学能(从食物中获得)是如何转化为生物功能所需的能量的。在这个项目中，已经在单个蛋白质范围内确定的基本理论原理被扩展到更大的生物能源链范围内。主要目的是更好地了解影响活细胞能量效率的因素。一个仍未解决的挑战是，电子如何在不显著消耗能量转化为热量的情况下穿过薄膜。该项目将蛋白质-膜-水环境的结构和动力学与高效的电子传输联系起来。毕业生、学生和博士后助理对这项研究做出了贡献。作为这项计划的一部分，PI将为有才华的青年举办暑期计算机学校。该计划旨在开发一个预测模型，该模型考虑到身体状况的变化和相关蛋白质的突变对个别电子转移步骤的速度和整体跨膜电子传递的影响。所提出的机制涉及打破影响单个电子转移步骤的核涨落的平衡统计的条件。由于蛋白质-水-膜热浴的强烈弥散动力学在松弛时间方面扩散了许多数量级，因此系统的遍历性是可能的。没有一种单一的理论技术能够涵盖这一范围的时间尺度。这个问题是通过将膜结合复合体的大规模原子模拟与蛋白质电弹性波动的粗粒度模拟相结合来解决的，以涵盖目前原子模拟无法获得的长度和时间尺度。将模拟预测的蛋白质电子转移的力学性质与二维电子光谱的结果进行了比较。该项目致力于在纳米尺度和1-100纳秒的时间尺度上解决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)界面极化的德拜-昂萨格图是否是发展界面静电学预测模型的良好参考，以及c)是否可以建立一个适当的理论框架来有效地描述生物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.