Collaborative Research: De Novo Protein Constructs for Photosynthetic Energy Transduction

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 DeGrado教授正在研究设计定向、存储和释放能量的材料的新方法。生物学已经开发出许多执行这些功能的设计；然而，化学家们还没有创造出从头开始的能量收集、储存和释放系统，它拥有自然界中所见的那些系统的复杂性。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。通过设计基于蛋白质的材料来迁移和收集电荷和能量，将实现独特的光、电和化学功能。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以及能量储存和释放功能。这项研究将允许研究生和博士后研究员获得关于合成化学、蛋白质设计、蛋白质生物化学、现代计算方法以及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得到广泛应用，并能够构建具有生物灵感的新材料，实现自然界中未曾见过的新功能。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生涯重要的技能。生物能量转导依赖于具有远远超过迄今通过分子和大分子设计和合成实现的物理化学功能的蛋白质-辅因子组件。这项研究项目将通过利用结合非生物辅因子的从头蛋白来实现这种复杂的功能，并在此过程中阐明光合作用能量传递、储存和释放所需的基本设计原则。该项目利用一种集成的多学科方法来进化具有复杂电光功能的多肽-辅因子复合体，包括辅因子的设计和合成、提供以精确、有组织的空间排列结合这些辅因子的蛋白质的先进计算方法、蛋白质表达和表征、表征功能和反应动力学的最先进的泵浦-探测瞬变光学方法，以及高分辨率蛋白质结构确定。来自这项研究的信息有望阐明光合作用能量转导所需的基本原理，并设计具有新颖电光功能并通过创新途径进行能量转换的蛋白质。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.