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: 2108660
• 负责人: William DeGrado
• 金额: $ 37.5万
• 依托单位: University of California-San Francisco
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-11-01 至 2024-10-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2108660&HistoricalAwards=false
• 关键词: Collaborative; Research; De; Novo; Protein

With the support of the Chemistry of Life Processes (CLP) Program in the Division of Chemistry, Professors Michael Therien and David Beratan of Duke University and William DeGrado of University of California-San Francisco are studying new approaches to design materials that direct, store, and release energy. Biology has developed numerous designs that carry out these functions; chemists, however, have yet to create energy harvesting, storage, and release systems from scratch that possess the sophistication of those seen in nature. Recent advances in protein design enable chemists to construct large molecules that capture and manage the flow of positive charges, negative charges, and energy. By designing protein-based materials that migrate and collect charges and energy, unique optical, electrical, and chemical functions will be realized. The experimental procedures used in this effort will (i) provide new tools to build proteins having innovative designed functions, and (ii) characterize the structures and energy storage and release functions of these proteins. This pursuit will allow graduate students and postdoctoral fellows to acquire specialized training in synthetic chemistry, protein design, protein biochemistry, modern computational methods, and techniques to monitor fast processes that move charge and energy. The protein design methods developed will be broadly applicable, and enable construction of new biologically inspired materials that carry out novel functions not seen in nature. Outreach activities of this project will introduce college and pre-college students to important new technologies, and teach skills important for future careers in science and engineering.Biological energy transduction relies on protein-cofactor assemblies that possess physico-chemical functionality that far exceeds that realized to date through molecular and macromolecular design and synthesis. This research project will be undertaken to realize such complex functionality through “design from scratch” strategies that exploit de novo proteins that bind abiological cofactors, and in the process, elucidate fundamental design principles required for photosynthetic energy transduction, storage, and release. This project takes advantage of an integrated, multi-disciplinary approach to evolve peptide-cofactor complexes that possess sophisticated electro-optic functionality, encompassing cofactor design and synthesis, advanced computational methods that provide proteins that bind these cofactors in precise, organized spatial arrangements, protein expression and characterization, state-of-the-art pump-probe transient optical methods that characterize function and reaction dynamics, and high resolution protein structure determination. Information from this study is expected to elucidate fundamental principles required for photosynthetic energy transduction, and designed proteins that possess novel electro-optical function and transduce energy via innovative pathways.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.

在化学系生命过程化学（CLP）项目的支持下，杜克大学的Michael Therien和David Beratan教授以及加州大学旧金山分校的William降格罗教授正在研究设计能引导、储存和释放能量的材料的新方法。生物学已经发展出许多实现这些功能的设计；然而，化学家们还没有从零开始创造出能量收集、储存和释放系统，这些系统具有自然界中看到的复杂程度。蛋白质设计的最新进展使化学家能够构建大分子来捕获和管理正电荷、负电荷和能量的流动。通过设计迁移和收集电荷和能量的蛋白质基材料，将实现独特的光学、电学和化学功能。在这项工作中使用的实验程序将(i)提供新的工具来构建具有创新设计功能的蛋白质，以及（ii）表征这些蛋白质的结构和能量储存和释放功能。这种追求将使研究生和博士后获得合成化学、蛋白质设计、蛋白质生物化学、现代计算方法和监测快速移动电荷和能量过程的技术方面的专门培训。开发的蛋白质设计方法将广泛适用，并使构建新的生物启发材料能够实现自然界中未见的新功能。该项目的推广活动将向大学生和大学预科学生介绍重要的新技术，并教授对未来科学和工程职业重要的技能。生物能量转导依赖于具有物理化学功能的蛋白质辅助因子组合，其功能远远超过迄今为止通过分子和大分子设计和合成实现的功能。该研究项目将通过“从头开始设计”的策略来实现这种复杂的功能，该策略利用结合非生物辅助因子的新生蛋白，并在此过程中阐明光合能量转导、储存和释放所需的基本设计原则。该项目利用综合的多学科方法来发展具有复杂电光功能的肽辅因子复合物，包括辅因子的设计和合成，先进的计算方法，提供精确、有组织的空间排列结合这些辅因子的蛋白质，蛋白质表达和表征，最先进的泵探针瞬态光学方法，表征功能和反应动力学，以及高分辨率蛋白质结构测定。这项研究的信息有望阐明光合能量转导所需的基本原理，并设计出具有新型电光功能并通过创新途径转导能量的蛋白质。该奖项反映了美国国家科学基金会的法定使命，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。