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.

该项目研究了生物学大分子如何在功能所需的室温下或附近有效地促进和利用非平凡的量子现象。该项目将为生物学如何将量子行为纳入大分子功能提供新的理解。还有可能为新量子科学和技术的发展提供信息，例如利用量子现象的从头系统的发展。该项目提出了一种高度协作的协同研究方法，需要在结构生物学，蛋白质生物化学，酶学，化学和物理学方面进行多学科研究。通过多层培训机会，基于“团队科学”的原则，在博士后学员以及研究生和本科生的原则上，指导是该项目成功的关键。该项目还将开发一种创新的，跨机构的基于课程的研究经验，将在本科课程中实施。这项工作将针对以生物学为重点的和主要代表性的学生，他们将从事与生物学中的非客气量子效应有关的研究。蛋白质以及其他可能的大分子，以一种启动，维持，增强，增强和/或传达量子现象（包括隧道和触发器）（包括隧道和自旋旋转固定）的方式发展。对自然如何实现这些相互作用及其如何导致生物学结果的充分理解在于蛋白质的支架与活性位点量子行为之间的成功相互作用。该项目中的研究将借鉴实验的最前沿进步，包括时间分辨和依赖温度的结构研究以及功能测定法，以及理论，以对蛋白质结构中能量流以及量子行为的热或光的启动的能量流之间的关系产生完整而整体的数据驱动的理解。该研究的重点是两个不同的蛋白质系统，具有独特的折叠和互补量子效应 - 脂氧合酶催化中的氢隧穿以及与磁受体和昼夜节律时钟相关的加密chromes中的自旋相干性。该研究的基本主题将是控制振动动作和/或构象变化与生产率输出相关的各向异性蛋白网络的识别和映射。这项研究中出现的原理超出了氢隧穿和自旋连贯性的范围，通过扩展我们的功能耦合热和光激活蛋白网络的知识库。可能的见解可能会被利用，以将新功能编码为（RE）设计的蛋白质。该项目得到了分子和细胞生物科学划分的分子生物物理学群集的支持。该奖项反映了NSF的法定任务，并使用基金会的智力优点和更广泛的影响审查标准，通过评估来诚实地支持。