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（Whitman College）的达利亚·鲁克萨纳（Dalia Rokhsana）得到了化学过程中化学过程的奖励，以研究基于钼的酶，细菌蛋白的反应性，该蛋白会催化水分促进水反应产生氢气。 氢是燃料电池，推进系统和燃烧发动机的重要“绿色”能源。 Rokhsana和她的小组正在使用最先进的计算化学和分子建模技术来了解蛋白活性位点如何控制结构，功能，特异性和反应性。这项研究在大规模氢气产生的仿生设计和优化中具有潜在的应用。该项目正在支持这个主要是本科机构的学生参与。 这些学生合着科学论文，并在国家会议和区域会议上进行演讲。 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，并与惠特曼学院（Whitman College）促进的教师模型保持一致。基于研究的问题与计算化学和生物化学方面的课程融合。 生物系统的一种化学功能是在环境条件下惰性小分子的激活。了解这些过程的分子机制是生物学和化学界面上的一个具有挑战性的领域。 在这个项目中，Rokhsana和她的小组专注于多样化的钼酶家族，这些酶将氧气转移催化以将各种底物（一氧化碳，亚硫酸盐，砷等）互连为产品，同时将水散布到质子和电子中。这项研究的重点是mo-酶CO脱氢酶的较差的双金属[Mo-S-Cu]活性位点。第一个目的是研究活性位点作为氧化还原，自旋和质子化园的函数的组成。第二个目的是表征中间体和过渡状态的几何和电子结构在不可逆的，一氧化碳向二氧化碳中的催化转化。 由于缺乏有关实验中间体的直接和明确的信息，因此需要一种计算方法。 Rokhsana和她的小组正在利用逼真的量子机械（QM）和扩展的量子机械/分子机械（QM/MM）模型来系统地，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，并了解内部协调球体和外部蛋白质环境和外部蛋白质环境控制和Tune Metalloeenzyme Metalloeenzeme eentalloeenzeme encome formical函数。这项工作可以提供有关CO氧化的整体催化机制的见解，并将其用于仿生系统的分子工程进行水分分解反应。 该项目正在将本科生沉浸在涉及最先进的建模和仿真技术的综合和互补的生物学和计算化学研究中。 新课程有助于满足惠特曼学院学生要求的研究机会的大量需求，并促进了新的合作和与更广泛的化学社区的合作。该奖项反映了NSF的法定任务，并被认为是通过基金会的知识分子优点和更广泛的影响审查标准通过评估来通过评估来支持的。