Mapping of Electron Tunneling Pathways in Proteins

项目摘要 药物代谢，程序性细胞死亡，DNA生物合成和修复，呼吸， 光合作用和光合作用是对人类至关重要的熟悉的生物过程 依赖于蛋白质介导电子转移（ET）反应机制 它们的功能。因此，ET途径位于生命的核心，ET的功能障碍 是疾病的根本原因，特别是由氧化应激引发的疾病。 压力和线粒体机制的故障。由于ET是一种常见的过程， 对于所有形式的生命，病原体中ET途径的分子水平理解 生物体也可用于治疗优势。长期目标 这项研究的目的是了解，在分子，介观和宏观尺度上， 生物结构和动力学影响关键的ET反应。理论成果 二十多年来，这个实验室发现了蛋白质的结构和 动力学可以调节ET反应机制并且在纳米尺度上， 实验室已经建立了广泛使用的方法来预测相应的 ET率。在上一个资助期，我们把重点转向电荷传输系统， 在更长的尺度上发挥作用，其中出现了重大挑战问题 关于ET的机制和作用， 长度刻度。本文的研究主要集中在：（1）电荷跳跃 与基于氧化还原的信号传导相关的多纳米尺度上的运输， 电荷跳跃，缓解氧化应激;（2）微米上的电荷传输 规模，其中发现的异常动力学签名在多血红素细胞外 将检查细菌的附属物;（3）电缆上细菌的运输 厘米尺度，其中多细胞细菌组合体具有共享的外层 膜通过在还原和氧化之间物理桥接来提取能量 环境，利用一个共同的ET管道，使合作和 初步证明了多细胞的好处。这项研究的一个标志是 该计划一直是其理论和尖端实验之间的密切合作， 这一核心方法将继续与奥胡斯密切合作， 大学（丹麦）、安特卫普大学（比利时）、加州大学- Irvine（美国）和Caltech（美国）。

Project Summary Drug metabolism, programmed cell death, DNA biosynthesis and repair, respiration, and photosynthesis are familiar biological processes of critical importance to human health that rely on protein-mediated electron-transfer (ET) reaction mechanisms for their function. As such, ET pathways lie at the core of life, and the malfunction of ET pathways is an underlying cause of diseases, notably diseases triggered by oxidative stress and malfunction of the mitochondrial machinery. Since ET is a process common to all forms of life, a molecular-level understanding of ET pathways in pathogenic organisms may be exploited for therapeutic advantage as well. The long-term objective of this research is to understand, at the molecular, meso, and macro scales, how biological structure and dynamics influence crucial ET reactions. Theoretical findings from this laboratory over two decades have discovered how protein structure and dynamics can modulate ET reaction mechanisms and on the nanometer length scales, and the laboratory has established widely used methods to predict the corresponding ET rates. In the last grant period we turned our focus to charge-transport systems that function on much longer length scales, where grand challenge questions are emerging regarding ET mechanism and function on the multiple nanometer to the centimeter length scales. The research proposed here focuses on: (1) the charge hopping transport on the multiple nanometer scale associated with redox-based signaling and charge hopping that relieves oxidative stress; (2) charge transport on the micrometer scale, where the anomalous kinetic signatures discovered in multi-heme extracellular bacterial appendages will be examined; (3) transport in cable bacteria on the centimeter scale, where multi-cellular bacterial assemblies with a shared outer membrane extract energy by bridging physically between reducing and oxidizing environments, exploiting a common ET conduit that enables collaboration and a rudimentary demonstration of the benefits of multi-cellularity. A hallmark of this research program has been its close collaboration between theory and cutting-edge experiment, and this core approach will continue with intensive collaborations involving Aarhus University (Denmark), the University of Antwerp (Belgium), the University of California- Irvine (USA), and Caltech (USA).