Collaborative Research: De novo Protein Constructs for Photosynthetic Energy Transduction

这个项目由化学系的生命过程化学计划、分子和细胞生物科学系的分子生物物理组和物理系的生命系统物理学共同资助。有了这个奖项，三名研究人员，杜克大学的Michael J.Therien博士、加州大学旧金山分校的William F.DeGrado博士和宾夕法尼亚大学的Jeffery G.Saven博士正在研究设计收集、储存和释放能量的蛋白质的新方法。科学家们还不能模仿生物学来创造基于蛋白质的能量收集、储存和释放系统。蛋白质设计的最新进展使化学家能够构建能够捕获和引导电荷和能量流动的大分子。这项工作中使用的实验程序(I)提供了新的工具来构建具有新设计功能的蛋白质，以及(Ii)表征了这些蛋白质的结构和能量储存和释放功能。这项研究在合成化学、蛋白质设计、蛋白质生物化学和现代计算方法方面培训研究生和博士后研究员。学生和研究员还接受了技术培训，以监控移动电荷和能量的快速过程，特别是与太阳能转换有关的过程。所开发的蛋白质设计方法具有广泛的适用性。它们能够构建受生物启发的新系统，执行自然界中未曾见过的新功能。该项目的外展活动向大学生和大学预科学生介绍重要的新技术。这些活动还传授了对未来科学和工程职业非常重要的技能。生物能量转导依赖于具有物理化学复杂性的蛋白质-辅因子组件，远远超过迄今通过分子、超分子和大分子设计和合成实现的。这项研究项目是通过利用从头开始蛋白质的“从头开始设计”策略来实现这种复杂性的。这些从头蛋白结合非生物辅因子，阐明了光合作用能量获取、储存和释放所需的基本设计原则。该项目利用一种综合的、多学科的方法来进化具有复杂电光功能的多肽-辅因子复合体。这些功能包括辅因子设计和合成、先进的计算方法、蛋白质的表达和表征以及最先进的泵浦探测瞬变光学方法。这种计算方法允许设计出在精确组织的空间排列中结合辅助因子的蛋白质。最先进的泵浦探测瞬变光学方法表征功能和反应动力学。这项研究的信息阐明了光合作用能量转导所需的基本原理，并提供了询问重要蛋白质结构-功能关系的一般策略。

This project is jointly funded by the Chemistry of Life Processes Program in the Division of Chemistry, the Molecular Biophysics Cluster in the Division of Molecular and Cellular Biosciences, and the Physics of Living Systems in the Division of Physics.With this award, the three investigators, Dr. Michael J. Therien (Duke University), Dr. William F. DeGrado (University of California at San Francisco), and Dr. Jeffery G. Saven (University of Pennsylvania) are investigating new approaches to design proteins that collect, store, and release energy. Scientists are not yet able to mimic biology in creating protein-based energy harvesting, storage, and release systems. Recent advances in protein design enable chemists to construct large molecules that can capture and direct the flow of charge and energy. The experimental procedures used in this effort (i) provide new tools to build proteins having novel designed functions, and (ii) characterize the structures and energy storage and release functions of these proteins. This research trains graduate students and postdoctoral fellows in synthetic chemistry, protein design, protein biochemistry, and modern computational methods. The students and fellows are also trained in techniques to monitor fast processes that move charge and energy, especially related to solar energy conversion. The protein design methods developed are broadly applicable. They enable construction of new biologically-inspired systems that carry out novel functions not seen in nature. Outreach activities of this project introduce college and pre-college students to important new technologies. These activities also teach skills important for future careers in science and engineering.Biological energy transduction relies on protein-cofactor assemblies that possess physico-chemical complexity that far exceeds that realized to date through molecular, supramolecular, and macromolecular design and synthesis. This research project is undertaken to realize such complexity through "design from scratch" strategies that exploit de novo proteins. These de novo proteins bind abiological cofactors and elucidate fundamental design principles required for photosynthetic energy harvesting, storage, and release. This project takes advantage of an integrated, multi-disciplinary approach to evolve peptide-cofactor complexes that possess sophisticated electro-optic functionality. Such functionality encompasses cofactor design and synthesis, advanced computational methods, protein expression and characterization and state-of-the-art pump-probe transient optical methods. The computational methods allow the design of proteins that bind co-factors in a precisely organized spatial arrangement. State-of-the-art, pump-probe, transient optical methods characterize function and reaction dynamics. Information from this study elucidates fundamental principles required for photosynthetic energy transduction, and provide general strategies to interrogate important protein structure-function relationships.