Collaborative Research: Mapping and comparing the link of the protein scaffold to quantum events in thermally activated enzymes and flavin-based photoreceptors

合作研究：绘制和比较蛋白质支架与热激活酶和黄素光感受器中量子事件的联系

• 批准号: 2231082
• 负责人: Michael Thompson
• 金额: $ 38.45万
• 依托单位: University of California - Merced
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2027-03-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2231082&HistoricalAwards=false
• 关键词: Collaborative; Research; Mapping; comparing; link

This project studies how biological macromolecules are able to efficiently promote and utilize non-trivial quantum phenomena at or near room temperatures that are necessary for function. This project will provide a new understanding for how biology integrates quantum behavior into macromolecular function. There is also the potential to inform and aid the advancement of new quantum science and technologies, such as the development of de novo systems that harness quantum phenomena. This project puts forth a highly collaborative, synergistic research approach entailing a multi-disciplinary study in structural biology, protein biochemistry, enzymology, chemistry, and physics. Mentorship is key to the success of this project with multi-layered training opportunities, built on the principles of “team science”, available to postdoctoral trainees as well as graduate and undergraduate students. The project will also develop an innovative, cross-institutional, course-based research experience to be implemented in the undergraduate curriculum. This effort will be aimed at biology-focused and primarily underrepresented students who will be engaged in research that is related to non-trivial quantum effects in biology.Proteins, and possibly other macromolecules, have evolved in a manner to initiate, sustain, enhance, and/or communicate quantum phenomena, including tunneling and spin coherence. A full mechanistic understanding into how nature accomplishes these interactions, and how it leads to a biological outcome, resides in the successful interplay between the scaffold of the protein and active site quantum behavior. Investigations within this project will draw on cutting edge advances in experimentation, including time-resolved and temperature-dependent structural studies coupled with functional assays, and theory to create a complementary and holistic data-driven understanding of the relationship between energy flow in a protein structure and either thermal or light initiation of quantum behavior. The research focuses on two disparate protein systems with distinct folds and complementary quantum effects – hydrogen tunneling in lipoxygenase catalysis and spin coherence in cryptochromes associated with magnetoreception and circadian clocks. The underlying theme of the research will be the identification and mapping of anisotropic protein networks that control vibrational motions and/or conformational changes linked to a productive output. The principles that emerge from this research go beyond the scope of hydrogen tunneling and spin coherence, by expanding our knowledge base of function-coupled thermal and light activated protein networks. The resulting insights could potentially be leveraged to encode new functionalities into (re)designed proteins. This project is supported by the Molecular Biophysics Cluster in the Division of Molecular and Cellular Biosciences.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.

该项目研究生物大分子如何能够在室温或接近室温下有效地促进和利用功能所需的非平凡量子现象。该项目将为生物学如何将量子行为整合到大分子功能中提供新的理解。该项目提出了一种高度协作、协同的研究方法，需要在结构生物学、蛋白质生物化学方面进行多学科研究。 ,酶学、化学和物理学是该项目成功的关键，该项目还将根据“团队科学”的原则为博士后学员以及研究生和本科生提供多层次的培训机会。将在本科课程中实施创新的、跨机构的、基于课程的研究经验，这项工作将针对以生物学为重点且代表性不足的学生，他们将从事与重要量子效应相关的研究。生物学。蛋白质，可能还有其他大分子，已经以启动、维持、增强和/或传达量子现象的方式进化，包括隧道效应和自旋相干性，对自然如何实现这些相互作用以及它如何导致量子现象的完整机械理解。生物学成果在于蛋白质支架和活性位点量子行为之间的成功相互作用。该项目的研究将利用实验的前沿进展，包括时间分辨和温度依赖性结构研究以及分析功能。理论该研究的重点是具有不同折叠和互补量子效应（脂氧合酶中的氢隧道效应）的两个不同的蛋白质系统，以建立对蛋白质结构中的能量流与量子行为的热或光引发之间关系的互补和整体数据驱动的理解。该研究的基本主题是识别和绘制控制与生产输出相关的振动运动和/或构象变化的各向异性蛋白质网络。通过扩展我们的功能耦合热和光激活蛋白质网络的知识库，这项研究得出的原理超出了氢隧道和自旋相干的范围，由此产生的见解可能会被用来将新功能编码到（重新）设计中。该项目得到了分子和细胞生物科学部分子生物物理学集群的支持。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响进行评估，被认为值得支持。审查标准。