Elucidating chemical features and biological functions of short hydrogen bonds

尽管量子效应在各种各样的生物过程中都很重要，但在描述生物体时，它们在很大程度上被忽视了。氢键被认为是帮助DNA、RNA和蛋白质折叠成其功能形状的相互作用。氢键使原子在很短的距离内聚集在一起，显示出突出的量子力学特性，并与从酶催化到抗生素耐药性的生物功能密切相关。凭借这一奖项，化学学部的生命过程化学项目资助了来自罗格斯大学的王璐博士，以计算方式阐明蛋白质中短氢键（SHBs）的量子性质和生物功能。该项目利用第一性原理计算和模拟（基于原子核和电子的概念）来揭示SHBs在蛋白质中的量子涨落和生物学作用，这些蛋白质指示细胞中的变化或催化化学反应。这些研究结果为设计具有增强功能的新型蛋白质和仿生材料提供了指导原则。该项目还使研究生和本科生，特别是女性和来自代表性不足的少数群体的学生，能够学习先进的计算方法，并发现量子效应在生物系统中的重要作用。本研究项目探讨化学特性和量子效应的相互作用如何决定SHBs的生物学功能。通过对蛋白质数据库的统计分析，揭示了促进shb形成的结构和化学因素。通过第一性原理模拟研究了电子和核量子效应对SHBs的质子行为、光谱位移和功能作用的影响，特别强调了细菌趋光性和酶催化的生物过程。本研究的信息有助于建立解释和预测生物shb功能的结构-性质关系。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。

Quantum effects are largely neglected in the description of living organisms, despite their importance in a wide variety of biological processes. Hydrogen bonds are best recognized as interactions that help fold DNA, RNA, and proteins into their functional shapes. Hydrogen bonds that bring atoms together to very short distances show prominent quantum mechanical properties and are closely associated with biological functions that range from enzymatic catalysis to antibiotic resistance. With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Lu Wang from Rutgers University to computationally elucidate the quantum nature and biological functions of short hydrogen bonds (SHBs) in proteins. This project utilizes first principles calculations and simulations (based on the concepts of atomic nuclei and electrons) to unravel the quantum fluctuations and biological roles of SHBs in proteins that signal changes in a cell or that catalyze chemical reactions. Results from these studies provide guiding principles to the design of novel proteins and bio-inspired materials with enhanced functions. This project also enables graduate and undergraduate students, particularly women and students from underrepresented minority groups, to learn advanced computational methods and to discover the essential roles of quantum effects in biological systems.This research project examines how the interplay of chemical features and quantum effects determines the biological functions of SHBs. The structural and chemical factors that facilitate the formation of SHBs are uncovered by statistically analyzing the Protein Data Bank. The impact of electronic and nuclear quantum effects on the proton behavior, spectroscopic shifts and functional roles of SHBs are studied by first principles simulations, with particular emphasis on the biological processes of bacterial phototaxis and enzyme catalysis. Information from this study helps establish a structure-property relation that explains and predicts the functions of biological SHBs.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.