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

这个项目研究生物大分子如何能够有效地促进和利用在室温或接近室温时的非平凡量子现象，这些现象是功能所必需的。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。还有可能通知和帮助新的量子科学和技术的进步，例如开发利用量子现象的从头系统。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、酶学、化学和物理学方面进行多学科研究。导师是这个项目成功的关键，它有多层次的培训机会，建立在“团队科学”的原则上，向博士后学员以及研究生和本科生提供。该项目还将开发一种创新的、跨机构的、以课程为基础的研究经验，并将在本科课程中实施。这一努力将针对那些将从事与生物学中非平凡的量子效应相关的研究的生物学专业和主要代表不足的学生。蛋白质，可能还有其他大分子，已经以一种启动、维持、增强和/或传递量子现象的方式进化，包括隧道效应和自旋相干。对自然如何完成这些相互作用以及它如何导致生物结果的全面机械性理解，在于蛋白质的支架和活性部位量子行为之间的成功相互作用。该项目中的研究将利用实验方面的尖端进展，包括时间分辨和依赖温度的结构研究以及功能分析，以及建立对蛋白质结构中的能量流动与热或光启动量子行为之间的关系的补充和整体数据驱动的理解的理论。这项研究集中在两个不同的蛋白质系统上，它们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道效应，以及与磁接收和昼夜节律相关的隐色素中的自旋相干。这项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产出相关的振动运动和/或构象变化。这项研究中出现的原理超越了氢隧道和自旋相干的范围，扩展了我们关于功能耦合的热和光激活蛋白质网络的知识库。由此产生的洞察力可能被用来将新的功能编码到(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组支持。这一奖项反映了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。

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.