Collaborative Research: De novo Protein Constructs for Photosynthetic Energy Transduction

有了这个奖项，生命过程化学项目将资助Michael J. Therien（杜克大学）、Jeffery G. Saven（宾夕法尼亚大学）和William F.退化（加州大学旧金山分校）进行研究，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一系列复杂的化学反应。在这些功能中，最关键的是能量从一种形式转化为另一种形式，比如光合作用，当植物将阳光转化为化学能时。由于这一过程，每年从大气中去除大量的二氧化碳。在这项工作中，研究人员正在构建人工蛋白质，模仿植物中参与光合作用的蛋白质的行为。这一策略为测试天然光合作用蛋白的工作原理提供了重要手段。重要的见解可以用来开发新的蛋白质，使自然界中没有的能量转换过程成为可能。这项工作将对生物学和能源储存等不同领域产生更广泛的影响，通过提高对光合作用中涉及的关键分子事件的理解。这对培养下一代科学家有进一步广泛的影响。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，参与在三个不同州进行的令人兴奋的合作调查。在这项研究中，提供光合能量转导和储存的关键蛋白质设计原理正在被阐明。为了实现这一目标，采用了一种综合的、多学科的方法，重点是进行光诱导电荷转移反应的肽辅因子复合物的进化，其中蛋白质基质稳定电荷分离状态并指导电子和空穴的有效分离。为此目的：(i)正在设计和合成光收集和氧化还原活性辅助因子；（ii）新生蛋白也被设计成选择性地结合这些单元的连接组装；（iii）然后对这些新生蛋白进行表达和表征；（iv）利用最先进的泵浦探针瞬态光学方法研究光诱导电子转移的新生光合蛋白；(v)实验数据是辅助因子和蛋白质设计和重新设计的指导，最初的重点是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；(6)重新设计的通过自组装控制取向的组件的光谱和动力学特性被表征为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一部分，推动了功能从头设计的极限，并指导了具有独特光合功能的复杂肽辅因子组件的设计。该项目由分子和细胞生物科学部的分子生物物理集群以及计算和数据支持科学与工程项目共同资助

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