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Electron-nuclear coupling, charge transport, and catalysis in biomolecules: the role of vibrational and conformational dynamics

生物分子中的电子-核耦合、电荷传输和催化：振动和构象动力学的作用

基本信息

批准号：
1764221
负责人：
Paul Champion
金额：
$ 48万
依托单位：
Northeastern University
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-01 至 2022-08-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1764221&HistoricalAwards=false
关键词：
Electron nuclear coupling charge transport

项目摘要

Chemical reactions involving molecules may involve the simple loss or gain of an electron or a proton (H+, a hydrogen atom missing its electron), or the breaking of bonds and the formation of new bonds that result in a new molecule. It is also true that molecules are always vibrating; their bonds act like springs that are constantly stretching, compressing or bending. The vibrational motion of molecules is an important factor in their reactivity and the outcome of chemical reactions. For large molecules like proteins, which can contain hundreds of atoms (carbon, nitrogen, oxygen) and bonds, the role of vibrations on reactivity is difficult to determine. And yet, it is important to understand the role of vibrations in protein chemical properties, as proteins are essential components of all living systems. In this project, funded by the Chemical Structure Dynamics and Mechanism (CSDM-A) program of the Chemistry Division, Professor Paul Champion of Northeastern University is using sophisticated laser techniques to study low-frequency (slow) vibrations and how they influence chemical reactions that facilitate the motion of charges (protons and electrons) in biological systems. These vibrational motions can also be associated with the flow of energy and the changes in structure that take place when large protein molecules like enzymes interact with each other or when smaller molecules bind to the protein and cause a signaling or catalytic response. This work is significant because it will generate fundamental new knowledge at the interface of chemistry and physics that will benefit a variety of biological applications. Within the broad class proteins called heme proteins (where the most well-known examples are hemoglobin and myoglobin)which contain iron atoms. An especially important protein, cytochrome c, which shuttles electrons in the cellular mitochondria (these are the structures of living cells that process energy). A new and very important reaction involving this protein has been recently discovered. Basically, a structural change at the heme iron atom takes place when cytochrome c interacts with the mitochondrial membrane and this reaction initiates apoptosis, a fundamental cellular process that leads to cell death. This is an important topic, which is providing a better understanding of tissue differentiation and development, as well as the evolution of cancer. This project has significance to society at large, because a better understanding of fundamental biochemical processes underpins the ability to make transformational improvements in human health. Students working on this project (both graduate and undergraduate) are being trained in cutting edge optical and biological techniques that benefit society through the enhancement of the human resource infrastructure that is crucial to the academic, medical, biotech, and optical communications industries.The reaction dynamics of several specific biomolecular and chemical systems involved in charge, group, and energy transport processes is being investigate. One investigation is focusing on proton transport in green fluorescent protein and is testing hypotheses related to both the excited and the ground state reactions. Proton "inventory" experiments will evaluate the participation of multiple protons in ground state tunneling. In the excited state, the temperature and excitation energy dependence of vibrational coherence, energy relaxation, dephasing, and population transfer is being examined. In another investigation, the photophysics that underlies a recent ultrafast x-ray study of ferrous cytochrome c is being investigated. Temperature dependent measurements of methionine (Met80) and NO ligand photolysis in cytochrome c is being carried out and the enthalpic barriers for the rebinding reactions are being determined. The strong vibrational coherence responses predicted for these photoreactions are also being compared. Low temperature kinetic methods are being used to probe the excited state photo-processes of photolyases, enzymes that use blue light to repair several types of ultraviolet-induced DNA damage. Finally, development of a new experimental methodology is focusing on the use of nanopores to probe dynamic allostery, conformational interconversions, and fluctuations of individual proteins. For example, the nanopore methodology is being used to investigate allosteric activation in proteins that regulate DNA transcription as well as protein complexes with effector functions that help to regulate enzyme activity. Proton and electron transport underlie highly evolved biological mechanisms of energy storage and enzymatic catalysis (including DNA photo repair).This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

涉及分子的化学反应可能涉及电子或质子（H+，失去电子的氢原子）的简单丢失或获得，或者键的断裂和导致新分子的新键的形成。分子总是在振动，它们的键就像弹簧一样不断地拉伸、压缩或弯曲，这也是事实。分子的振动运动是其反应性和化学反应结果的重要因素。对于像蛋白质这样的大分子，它可以包含数百个原子（碳，氮，氧）和键，振动对反应性的作用很难确定。然而，重要的是要了解振动在蛋白质化学性质中的作用，因为蛋白质是所有生命系统的重要组成部分。在这个由化学系化学结构动力学和机制（CSDM-A）计划资助的项目中，东北大学的Paul Champion教授正在使用复杂的激光技术来研究低频（慢）振动以及它们如何影响化学反应，促进生物系统中电荷（质子和电子）的运动。这些振动运动也可以与能量的流动和结构的变化有关，当大的蛋白质分子如酶相互作用时，或者当小分子与蛋白质结合并引起信号或催化反应时，就会发生这种变化。这项工作意义重大，因为它将在化学和物理学的界面上产生基础新知识，这将有利于各种生物学应用。在广泛的蛋白质类中，称为血红素蛋白质（其中最知名的例子是血红蛋白和肌红蛋白），含有铁原子。一种特别重要的蛋白质，细胞色素c，它在细胞线粒体（这些是处理能量的活细胞结构）中穿梭电子。最近发现了一种涉及这种蛋白质的新的非常重要的反应。基本上，当细胞色素c与线粒体膜相互作用时，血红素铁原子发生结构变化，并且该反应引发细胞凋亡，这是导致细胞死亡的基本细胞过程。这是一个重要的主题，它提供了对组织分化和发育以及癌症演变的更好理解。该项目对整个社会都具有重要意义，因为更好地了解基本的生物化学过程是改善人类健康的基础。本项目的学生（研究生和本科生）将接受尖端光学和生物技术的培训，通过加强对学术、医疗、生物技术和光通信行业至关重要的人力资源基础设施，使社会受益。正在研究涉及电荷、基团和能量传输过程的几种特定生物分子和化学系统的反应动力学。一项研究集中在绿色荧光蛋白中的质子传输，并测试与激发态和基态反应相关的假设。质子"库存"实验将评估多个质子参与基态隧穿的情况。在激发态，温度和激发能的振动相干性，能量弛豫，退相，和人口转移的依赖性正在检查。在另一项研究中，正在研究最近对亚铁细胞色素c进行超快x射线研究的基础物理学。甲硫氨酸（Met80）和NO配体在细胞色素c中的光解的温度依赖性测量正在进行和重结合反应的生物屏障正在确定。这些光反应预测的强振动相干响应也进行了比较。低温动力学方法正被用于探测光解酶的激发态光过程，光解酶使用蓝光修复几种类型的紫外线诱导的DNA损伤。最后，一种新的实验方法的开发集中在使用纳米孔来探测动态变构、构象相互转换和单个蛋白质的波动。例如，纳米孔方法正在用于研究调节DNA转录的蛋白质以及具有有助于调节酶活性的效应器功能的蛋白质复合物的变构激活。质子和电子传输是能量储存和酶催化（包括DNA光修复）的高度进化的生物机制的基础。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。