RUI: Study of Small Molecule Activation by Molybdenum Enzymes using Computational Methods

RUI：利用计算方法研究钼酶的小分子活化

• 批准号: 1807643
• 负责人: Dalia Biswas
• 金额: $ 18.84万
• 依托单位: Whitman College
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1807643&HistoricalAwards=false
• 关键词: RUI; Study; Small; Molecule; Activation

Dalia Rokhsana of Whitman College is supported by an award from the Chemistry of Life Processes Program in the Division of Chemistry to investigate the reactivity of molybdenum-based enzymes, bacterial proteins that catalyze water-splitting reactions to produce hydrogen gas. Hydrogen is an important "green" energy source for fuel cells, propulsion systems, and combustion engines. Rokhsana and her group are using state-of-the-art computational chemistry and molecular modeling techniques to understand how the protein active site controls structure, function, specificity, and reactivity. This research has potential applications to the biomimetic design and optimization of large-scale hydrogen gas production. The project is supporting undergraduate student engagement at this primarily undergraduate institution. These students co-author scientific papers, and make presentations at national meetings and regional conferences. External collaborations with leading computational scientists enhance the integration of scientific discovery with student education, in keeping with the teacher-scholar model promoted at Whitman College. Problems based on the research are integrated with coursework in computational chemistry and biochemistry. One chemical functions of biological systems is the activation of inert small molecules under ambient conditions. Understanding the molecular mechanism of these processes is a challenging areas at the interface of biology and chemistry. In this project, Rokhsana and her group are focusing on a diverse family of molybdenum enzymes that catalyze oxo-transfer to interconvert various substrates (carbon monoxide, sulfite, arsenite, etc.) into products, while splitting water into protons and electrons. This research focuses on a poorly-understood bimetallic [Mo-S-Cu] active site of a Mo-enzyme, CO dehydrogenase. The first aim is to investigate the composition of the active site as a function of redox-, spin-, and protonation-states. The second aim is to characterize geometric and electronic structures of intermediates and transition states during the non-reversible, catalytic transformation of carbon monoxide into carbon dioxide. A computational approach is necessary due to the lack of direct and unambiguous information about intermediates from experiments. Rokhsana and her group are utilizing realistic quantum mechanical (QM) and extended quantum mechanical/molecular mechanical (QM/MM) models to systematically and comprehensively investigate the effect of protein environment on the geometric and electronic structure of the active site, and understand how the inner coordination sphere and outer protein environment control and tune metalloenzyme function. This work may providing insights into the overall catalytic mechanism of CO oxidation, with application to molecular engineering of biomimetic systems for the water splitting reaction. The project is immersing undergraduate students in comprehensive and complementary bioinorganic and computational chemistry research involving state-of-the-art modeling and simulation techniques. The new course is helping meet the considerable demand for research opportunities requested by students at Whitman College, and facilitating new collaborations and engagement with the broader chemistry community.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.

惠特曼学院的达莉亚·罗克萨娜 (Dalia Rokhsana) 获得了化学系生命过程化学项目的资助，以研究钼基酶和细菌蛋白的反应性，这些酶催化水分解反应产生氢气。 氢是燃料电池、推进系统和内燃机的重要“绿色”能源。 Rokhsana 和她的团队正在使用最先进的计算化学和分子建模技术来了解蛋白质活性位点如何控制结构、功能、特异性和反应性。该研究在大规模氢气生产的仿生设计和优化方面具有潜在的应用。该项目支持本科生在这所主要本科院校的参与。 这些学生共同撰写科学论文，并在国家会议和区域会议上发表演讲。 与领先的计算科学家的外部合作增强了科学发现与学生教育的整合，这与惠特曼学院提倡的师生模式保持一致。基于研究的问题与计算化学和生物化学的课程相结合。 生物系统的一种化学功能是在环境条件下激活惰性小分子。了解这些过程的分子机制是生物学和化学交叉领域的一个具有挑战性的领域。 在这个项目中，Rokhsana 和她的团队专注于多种钼酶家族的研究，这些酶催化氧化转移，将各种底物（一氧化碳、亚硫酸盐、亚砷酸盐等）相互转化为产物，同时将水分解为质子和电子。本研究重点关注 Mo 酶 CO 脱氢酶的一个鲜为人知的双金属 [Mo-S-Cu] 活性位点。第一个目标是研究活性位点的组成作为氧化还原态、自旋态和质子化态的函数。第二个目标是表征一氧化碳不可逆催化转化为二氧化碳过程中中间体和过渡态的几何和电子结构。 由于实验中缺乏有关中间体的直接且明确的信息，因此需要采用计算方法。 Rokhsana 和她的团队利用现实量子力学（QM）和扩展量子力学/分子力学（QM/MM）模型系统、全面地研究蛋白质环境对活性位点几何和电子结构的影响，并了解蛋白质环境如何影响活性位点的几何结构和电子结构。内部配位层和外部蛋白质环境控制和调节金属酶功能。这项工作可以深入了解一氧化碳氧化的整体催化机制，并将其应用于水分解反应的仿生系统的分子工程。 该项目让本科生沉浸在涉及最先进的建模和模拟技术的全面且互补的生物无机和计算化学研究中。 新课程有助于满足惠特曼学院学生对研究机会的巨大需求，并促进与更广泛的化学界的新合作和接触。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力评估进行评估，被认为值得支持。优点和更广泛的影响审查标准。