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: 1709506
• 负责人: William DeGrado
• 金额: $ 50万
• 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: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2021-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1709506&HistoricalAwards=false
• 关键词: Collaborative; Research; De; novo; Protein

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.

该项目由化学系生命过程化学项目、分子和细胞生物科学系分子生物物理学小组和物理系生命系统物理学共同资助。DeGrado（加州大学旧金山弗朗西斯科）和Jeffery G. Saven（宾夕法尼亚大学）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。 在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的设计功能的蛋白质，和（ii）表征这些蛋白质的结构和能量储存和释放功能。 这项研究培养研究生和博士后研究员在合成化学，蛋白质设计，蛋白质生物化学和现代计算方法。学生和研究员还接受技术培训，以监测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。它们能够构建新的生物启发系统，实现自然界中看不到的新功能。 该项目的推广活动向大学生和大学预科生介绍重要的新技术。这些活动还教授对未来科学和工程职业很重要的技能。生物能量转导依赖于蛋白质-辅因子组装，其物理化学复杂性远远超过迄今为止通过分子，超分子和大分子设计和合成实现的复杂性。 本研究项目旨在通过利用从头蛋白质的“从头设计”策略来实现这种复杂性。这些从头蛋白结合非生物辅因子和阐明光合能量收集，储存和释放所需的基本设计原则。 该项目利用一个综合的，多学科的方法来发展具有复杂的电光功能的肽-辅因子复合物。这种功能包括辅因子设计和合成、先进的计算方法、蛋白质表达和表征以及最先进的泵浦-探测瞬态光学方法。计算方法允许蛋白质的设计，结合辅因子在一个精确组织的空间排列。国家的最先进的，泵浦探测，瞬态光学方法表征功能和反应动力学。 本研究的信息阐明了光合能量转导所需的基本原理，并提供了一般策略，询问重要的蛋白质结构-功能关系。

项目成果

De Novo Design, Solution Characterization, and Crystallographic Structure of an Abiological Mn-Porphyrin-Binding Protein Capable of Stabilizing a Mn(V) Species.

从头设计，溶液表征和晶体学结构的晶状体结合蛋白，能够稳定Mn（V）物种。

• DOI: 10.1021/jacs.0c10136
• 发表时间: 2021-01-13
• 期刊: Journal of the American Chemical Society
• 影响因子: 15
• 作者: Mann SI;Nayak A;Gassner GT;Therien MJ;DeGrado WF
• 通讯作者: DeGrado WF

Packing of apolar side chains enables accurate design of highly stable membrane proteins

• DOI: 10.1126/science.aav7541
• 发表时间: 2019-03-29
• 期刊: SCIENCE
• 影响因子: 56.9
• 作者: Mravic, Marco;Thomaston, Jessica L.;DeGrado, William F.
• 通讯作者: DeGrado, William F.

X-ray Crystal Structure of the Influenza A M2 Proton Channel S31N Mutant in Two Conformational States: An Open and Shut Case

两种构象状态下甲型流感 M2 质子通道 S31N 突变体的 X 射线晶体结构：打开和关闭的情况

• DOI: 10.1021/jacs.9b02196
• 发表时间: 2019
• 期刊: Journal of the American Chemical Society
• 影响因子: 15
• 作者: Thomaston, Jessica L.;Wu, Yibing;Polizzi, Nicholas;Liu, Lijun;Wang, Jun;DeGrado, William F.
• 通讯作者: DeGrado, William F.