Collaborative Research: De novo Protein Constructs for Photosynthetic Energy Transduction

合作研究：用于光合能量转导的从头蛋白质构建体

• 批准号: 1413295
• 负责人: William DeGrado
• 金额: $ 35.1万
• 依托单位: University of California-San Francisco
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-15 至 2017-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1413295&HistoricalAwards=false
• 关键词: Collaborative; Research; De; novo; Protein

With this award, the Chemistry of Life Processes Program is funding Michael J. Therien (Duke University), Jeffery G. Saven (University of Pennsylvania), and William F. DeGrado (University of California at San Francisco) for research to further the understanding of the precise way plants capture energy from sunlight. Proteins perform many functions in living organisms and catalyze the complex set of chemical reactions necessary for life. Among the most critical of these functions is the conversion of energy from one form to another, such as during photosynthesis, when plants convert sunlight to chemical energy. As a result of this process, tons of carbon dioxide are removed from the atmosphere every year. In this work, the investigators are building artificial proteins that mimic the behavior of proteins in plants involved in photosynthesis. This strategy provides an important means to test how natural photosynthetic proteins work. Important insights can then be used to develop novel proteins that enable energy conversion processes not found in nature. The work will have a broader impact on diverse fields such as biology and energy storage, through the heightened understanding of key molecular events involved in photosynthesis. There is further broad impact on the training of the next generation of scientists. The unique multi-institution structure provides additional opportunities for students of all educational levels, graduate and undergraduate as well as high school, to participate in an exciting collaborative investigation being carried out in three different states.In this research, key protein design principles that provide for photosynthetic energy transduction and storage are being elucidated. An integrated, multi-disciplinary approach is employed toward this goal, and focus is on the evolution of peptide-cofactor complexes that undergo photoinduced charge-transfer reactions, where the protein matrix stabilizes the charge-separated state and guides the efficient separation of electrons and holes. Toward this end: (i) light-harvesting and redox-active cofactors are being designed and synthesized; (ii) de novo proteins are also being designed to selectively bind linked assemblies of these units; (iii) these de novo proteins are then expressed and characterized; (iv) de novo photosynthetic proteins that undergo photo-induced electron transfer are being interrogated using state-of-the-art pump-probe transient optical methods; (v) experimental data is guiding cofactor and protein design and redesign, initially focusing on the positioning of appropriate amino acid side chains near donor and acceptor redox sites to modulate charge separation and charge recombination dynamics; and (vi) the spectroscopic and dynamical properties of re-designed assemblies that control orientation via self-assembly are being characterized as functions of their nanostructured electronic environments. Information from this study is providing new insights into aspects of protein structure and dynamics that are integral for highly efficient photonic energy conversion, pushing the limits of functional de novo design, and guiding the design of complex peptide-cofactor assemblies that have unique photosynthetic functionality.This project is co-funded by the Molecular Biophysics Cluster in the Division of Molecular and Cellular Biosciences and the Computational and Data-Enabled Science and Engineering program

有了这个奖项，生命过程的化学计划正在资助迈克尔J Therien（杜克大学），杰弗里G。Saven（宾夕法尼亚大学）和William F. DeGrado（加州大学旧金山分校弗朗西斯科）的研究，以进一步了解植物从阳光中捕获能量的精确方式。蛋白质在生物体中执行许多功能，并催化生命所必需的复杂化学反应。这些功能中最关键的是将能量从一种形式转化为另一种形式，例如在光合作用期间，植物将阳光转化为化学能。由于这一过程，每年从大气中清除数吨二氧化碳。在这项工作中，研究人员正在构建人工蛋白质，以模仿植物中参与光合作用的蛋白质的行为。这种策略为测试天然光合蛋白如何工作提供了重要手段。然后，重要的见解可以用于开发新的蛋白质，使能量转换过程在自然界中没有发现。这项工作将通过提高对光合作用中关键分子事件的理解，对生物学和能量储存等不同领域产生更广泛的影响。对下一代科学家的培训也有更广泛的影响。独特的多机构结构为所有教育水平的学生提供了额外的机会，研究生和本科生以及高中，参加一个令人兴奋的合作调查正在三个不同的州进行。一个综合的，多学科的方法是朝着这个目标，重点是肽辅因子复合物的演变，经历光诱导的电荷转移反应，其中蛋白质基质稳定的电荷分离状态，并引导有效的电子和空穴分离。为此目的：（i）正在设计和合成集光和氧化还原活性辅因子;（ii）还正在设计从头蛋白质以选择性地结合这些单元的连接组件;（iii）然后表达和表征这些从头蛋白质;（iv）正在使用最先进的泵浦-探测瞬态光学方法来询问经历光诱导电子转移的从头光合作用蛋白质; ㈤实验数据正在指导辅因子和蛋白质的设计和重新设计，最初侧重于在供体和受体氧化还原位点附近定位适当的氨基酸侧链，以调节电荷分离和电荷重组动力学;以及（vi）通过自组装控制取向的重新设计的组装的光谱和动力学性质。组装的特征在于其纳米结构电子环境的功能。 这项研究的信息为蛋白质结构和动力学方面提供了新的见解，这些方面是高效光子能量转换不可或缺的，推动了功能性从头设计的极限，该项目由分子和细胞生物科学部的分子生物物理学小组和计算和数据中心共同资助。启用科学和工程计划