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

通过该奖项，《生命过程》计划的化学计划是为迈克尔·J·塞里安（杜克大学），杰弗里·萨凡（Jeffery G.蛋白质在生物体中发挥许多作用，并催化生命所需的复杂化学反应集。这些功能最关键的是能量从一种形式转换为另一种形式，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，每年都会从大气中取出大量二氧化碳。在这项工作中，研究人员正在建立人造蛋白质，以模仿参与光合作用的植物中蛋白质的行为。该策略提供了测试自然光合蛋白如何工作的重要手段。然后，重要的见解可用于开发新型蛋白质，从而使能量转化过程在自然界中找不到。这项工作将通过对光合作用涉及的关键分子事件的加强了解，对生物学和能源等不同领域产生更广泛的影响。对下一代科学家的培训有进一步的广泛影响。独特的多机构结构为所有教育水平，研究生和本科生以及高中的学生提供了更多机会，以参与在三个不同州进行的激动人心的合作调查。在这项研究中，阐明了关键的蛋白质设计原理，这些蛋白质设计原理正在阐明光合作用的能量转换和存储。采用了综合的多学科方法来实现这一目标，而重点是经历光诱导的电荷转移反应的肽 - 配合物复合物的演变，其中蛋白质基质稳定电荷分离状态并指导有效的电子和孔分离。为此目的：（i）正在设计和合成轻度收获和氧化还原活性辅助因子； （ii）从头蛋白质也被设计为选择性地结合这些单元的链接组件； （iii）然后表达和表征这些从头蛋白； （iv）使用最先进的泵探针瞬态光学方法对经历光诱导的电子转移的从头光合蛋白进行询问； （v）实验数据是指导辅助因子和蛋白质设计和重新设计，最初着重于在供体和受体氧化还原位点附近适当的氨基酸侧链定位，以调节电荷分离和电荷重组动力学； （vi）通过自组装控制取向的重新设计的组件的光谱和动力学特性正在被视为其纳米结构电子环境的功能。 这项研究的信息正在为蛋白质结构和动态的各个方面提供新的见解，这些方面是高效的光子能量转化，推动了从头设计的限制，并指导具有独特光合作用功能的复杂肽 - 伴侣组件的设计。科学与工程计划