MAPPING OF ELECTRON TUNNELING PATHWAYS IN PROTEINS

电子隧穿反应在光合作用、氧化作用中是至关重要的 磷酸化、药物代谢、生物合成和催化。成功之路 或衰竭或新陈代谢途径取决于这些 反应，而反应又由介质的结构控制 在电子供体和受体之间。蛋白质、核糖核酸 酸和蛋白质-蛋白质复合体控制这些反应的速度将是 我们调查的主题(竞标续期R01- GM48043)。蛋白质对初级、次级、三级和 四级结构、蛋白质/蛋白质对接相互作用和蛋白质 电子传输速率的动态将使用新的 光合作用反应中的定量可靠方法 中心/细胞色素c/2复合体、细胞色素c过氧化物酶/细胞色素c 复合体，细胞色素b/562和细胞色素c。此外，新的还原但 蛋白质电子转移结果的精确表示方法 计算将产生简单直观的解释工具，如 路径分析，但在数量上可靠。 电子转移过程在生物合成和生物合成中的普遍性质 能量传递使它们成为研究的自然目标。这些 研究涉及电子的量子力学隧穿，以及 隧道过程对结构表现出极高的敏感性 被跨越的障碍。因此，如果从数量上理解， 这些电子隧穿反应可以用来诊断 大分子结构(蛋白质中的二级结构，DNA损伤， 等)并且可以在医疗环境中被操纵以控制毒品 代谢(通过细胞色素P/450)或DNA生物合成(通过核苷酸 还原酶)。这项研究项目将以合作方式进行 匹兹堡大学化学系和 加州大学圣地亚哥分校物理系。这项建议 旨在允许继续合作研究，这些研究导致 蛋白质电子转移反应的路径模型，相关的多个 路径方法及其数值实现。

Electron tunneling reactions are critical in photosynthesis, oxidative phosphorylation, drug metabolism, biosynthesis, and catalysis. The success or failure or metabolic pathways depends upon the rates of these reactions, which in turn, are controlled by the structure of the medium between electron donor and acceptor. The means by which proteins, nucleic acids, and protein-protein complexes control these reaction rates will be the subject of our investigations (competitive renewal of Grant R01- GM48043). The influence of protein primary, secondary, tertiary, and quaternary structure, protein/protein docking interactions, and protein dynamics on electron transport rates will be probed using new quantitatively reliable methods in the photosynthetic reaction center/cytochrome c/2 complex, cytochrome c peroxidase/cytochrome c complex, cytochrome b/562 and cytochrome c. In addition, new reduced but exact methods of representing the results of protein electron transfer calculations will produce interpretative tools as simple and intuitive as Pathways analysis, but quantitatively reliable. The ubiquitous nature of electron transfer processes in biosynthesis and energy transduction makes them a natural target for investigation. These investigations involve quantum mechanical tunneling of an electron, and tunneling processes display an exquisite sensitivity to the structure of the barrier being traversed. Therefore, if quantitatively understood, these electron tunneling reactions could be used as diagnostics of macromolecule structure (secondary structure in proteins, DNA lesions, etc.) and could be manipulated in a medical setting to control drug metabolism (by cytochrome P/450) or DNA biosynthesis (by ribonucleotide reductase). This research project will be carried out collaboratively between the University of Pittsburgh Department of Chemistry and the University of California, San Diego Department of Physics. This proposal is intended to allow the continuation of collaborative studies that led to the Pathway model of protein electron transfer reactions, related multi- pathway methods, and their numerical implementations.