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

本项目研究生物大分子如何能够在室温或室温附近有效地促进和利用功能所必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。还有可能为新的量子科学和技术的进步提供信息和帮助，例如开发利用量子现象的从头系统。该项目提出了一种高度协作，协同的研究方法，涉及结构生物学，蛋白质生物化学，酶学，化学和物理学的多学科研究。师徒制是项目成功的关键，以“团队科学”为原则，为博士后学员、研究生和本科生提供多层次的培训机会。该计划亦会发展一种创新的、跨学院的、以课程为基础的研究经验，以推行于本科课程。这项工作将针对以生物学为重点，主要是代表性不足的学生，他们将从事与生物学中重要量子效应相关的研究。蛋白质，可能还有其他大分子，已经进化成一种启动、维持、增强和/或交流量子现象的方式，包括隧道和自旋相干性。对大自然如何完成这些相互作用以及它如何导致生物学结果的完整机制理解，存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中。该项目的研究将利用实验方面的前沿进展，包括时间分辨和温度依赖的结构研究以及功能分析，以及理论，以创建一个互补的整体数据驱动的理解，了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。该研究主要关注两种不同的蛋白质系统，它们具有不同的褶皱和互补的量子效应——脂氧合酶催化中的氢隧道效应和与磁接受和生物钟相关的隐色素中的自旋相干性。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，这些蛋白质网络控制着与生产产出相关的振动运动和/或构象变化。从这项研究中产生的原理超越了氢隧穿和自旋相干的范围，扩展了我们对功能耦合热和光激活蛋白质网络的知识库。由此产生的见解可能被用于将新功能编码到（重新）设计的蛋白质中。本项目由分子与细胞生物科学部分子生物物理组支持。该奖项反映了美国国家科学基金会的法定使命，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。

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.