Mapping of Electron Tunneling Pathways in Proteins

项目摘要 药物代谢，细胞程序性死亡，DNA生物合成和修复，呼吸， 和光合作用是常见的对人类至关重要的生物过程 依赖于蛋白质介导的电子转移(ET)反应机制的健康 它们的功能。因此，ET通路处于生命的核心，而ET的故障 途径是疾病的根本原因，尤其是由氧化引发的疾病 线粒体机械的应激和故障。因为ET是一个常见过程 对于所有形式的生命，从分子水平上了解ET在致病中的途径 生物体也可能被利用来获得治疗优势。长期目标 这项研究的目的是在分子、中观和宏观尺度上理解如何 生物结构和动力学影响着关键的ET反应。理论发现 二十多年来从这个实验室发现了蛋白质的结构和 动力学可以调节ET反应机理，并在纳米尺度上， 实验室已经建立了广泛使用的方法来预测相应的 ET率。在上一次拨款期间，我们将重点转向充电运输系统， 在更长的范围内发挥作用，其中正在出现重大挑战问题 关于ET在多纳米到厘米上的机理和作用 长度刻度。本文的研究内容主要集中在：(1)电荷跳跃 在多纳米尺度上与基于氧化还原的信号和 电荷跳跃，缓解氧化应激；(2)千分尺上的电荷传输 规模，在多个血红素胞外发现的异常动力学特征 将检查细菌附属物；(3)在电缆上传输细菌 厘米尺度，其中多细胞细菌聚集在一个共享的外层 膜在还原和氧化之间架起物理桥梁来提取能量 环境，利用一个通用的ET管道实现协作和 初步演示了多细胞的好处。这项研究的一个标志 该计划一直是其理论和前沿实验之间的密切合作， 这一核心方法将继续与奥胡斯进行密集的合作 丹麦大学、比利时安特卫普大学、加利福尼亚大学- 欧文(美国)和加州理工(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).