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有效地促进和利用功能所必需的室温或接近室温的非平凡量子现象。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。还有可能为新的量子科学和技术的发展提供信息和帮助，例如开发利用量子现象的从头系统。该项目提出了一个高度合作，协同的研究方法，需要在结构生物学，蛋白质生物化学，酶学，化学和物理学的多学科研究。导师制是该项目成功的关键，它根据“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。该项目还将开发一个创新的，跨机构的，以课程为基础的研究经验，将在本科课程实施。这项工作将针对生物学为重点的，主要是代表性不足的学生谁将从事研究，是与非平凡的量子效应在biology. Protein相关的，可能还有其他大分子，已经在某种程度上进化，以启动，维持，增强，和/或通信量子现象，包括隧道和自旋相干。对自然界如何实现这些相互作用以及它如何导致生物学结果的全面机械理解，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，以及功能测定和理论，以创建一个互补的和整体的数据驱动的理解蛋白质结构中的能量流与量子行为的热或光引发之间的关系。研究重点是两个不同的蛋白质系统，具有不同的折叠和互补的量子效应-脂氧合酶催化中的氢隧穿和与磁感受和生物钟相关的隐花色素中的自旋相干性。该研究的基本主题将是识别和绘制各向异性蛋白质网络，这些网络控制与生产性输出相关的振动运动和/或构象变化。从这项研究中出现的原则超越了氢隧穿和自旋相干的范围，通过扩展我们的知识基础的功能耦合热和光激活蛋白质网络。由此产生的见解可能被用来编码新的功能到（重新）设计的蛋白质中。该项目由分子和细胞生物科学部的分子生物物理学小组支持。该奖项反映了NSF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。