Computer Led Design of Helical Arylamide Foldamer for Selective Water Transport

用于选择性水传输的螺旋芳酰胺折叠体的计算机设计

• 批准号: 1710466
• 负责人: Vojislava Pophristic
• 金额: $ 36万
• 依托单位: University of the Sciences in Philadelphia
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-06-15 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1710466&HistoricalAwards=false
• 关键词: Computer; Led; Design; Helical; Arylamide

To support continued economic growth and maintenance of human health, it is vital to have access to sufficient quantities of clean water. However, we are increasingly unable to meet this need, and water scarcity is now considered one of the most serious global challenges of this century. A key problem is the lack of low-cost and high-efficiency technologies for water purification. With support from the Macromolecular, Supramolecular and Nanochemistry Program of the NSF Chemistry Division, Drs. Vojislava Pophristic and Zhiwei Liu at the University of the Sciences are designing highly permeable and selective water channels that will significantly improve water filtration by allowing the passage of water, while blocking salts and other impurities. The channels are cylindrical hollow helices that are formed by assembly of specific chemical building blocks. The group first designs the channel on the computer by creating and optimizing the building block sequences. The promising candidates are then made in the laboratory and tested by experiments. This project is a training ground for students at a science-focused university, a community college and one of the nation's Historically Black Colleges and Universities (HBCU).The project builds upon the group's development of computational approaches for accurate structure and dynamics prediction of arylamide foldamers. The arylamide scaffolds form stable single or duplex helices of application-appropriate lengths and inner cavity dimensions. The modularity and tunability of arylamide foldamers make them excellent candidates for the design of water transport channels by mimicking structural characteristics of aquaporins. The group designs water channels by establishing sequence-structure-function relationship using rational and combinatorial sequence generation and molecular dynamics simulations, followed by optimization for selectivity. The project includes an international collaboration with Dr. Ivan Huc, who experimentally verifies computationally obtained structures and measures water/ion/proton conductivities. An important aspect to this project is that it helps us understand naturally occurring filtration processes, such as selective water transport by aquaporins, which play a critical role in human health.

为了支持持续的经济增长和维护人类健康，获得足够数量的清洁水至关重要。然而，我们越来越无法满足这一需求，水资源短缺现在被认为是本世纪最严重的全球挑战之一。一个关键问题是缺乏低成本、高效率的水净化技术。在 NSF 化学部高分子、超分子和纳米化学项目的支持下，博士。科学大学的 Vojislava Pophristic 和 Ziwei Liu 正在设计高渗透性和选择性的水通道，通过允许水通过，同时阻挡盐和其他杂质，从而显着改善水过滤。这些通道是由特定化学构件组装而成的圆柱形空心螺旋。该小组首先通过创建和优化构建块序列来在计算机上设计通道。然后在实验室中制造有前途的候选药物并通过实验进行测试。该项目是一所以科学为重点的大学、一所社区学院和美国历史上黑人学院和大学 (HBCU) 之一的学生的训练场。该项目建立在该小组开发的计算方法的基础上，用于芳基酰胺折叠体的精确结构和动力学预测。芳酰胺支架形成稳定的单螺旋或双螺旋，其长度和内腔尺寸适合应用。芳酰胺折叠体的模块化和可调节性使其成为通过模仿水通道蛋白的结构特征来设计水传输通道的优秀候选者。该小组通过使用理性和组合序列生成和分子动力学模拟建立序列-结构-功能关系来设计水通道，然后进行选择性优化。该项目包括与 Ivan Huc 博士的国际合作，Ivan Huc 博士通过实验验证计算获得的结构并测量水/离子/质子的电导率。该项目的一个重要方面是，它可以帮助我们了解自然发生的过滤过程，例如水通道蛋白的选择性水传输，这在人类健康中发挥着至关重要的作用。

项目成果

Hybrid Pyridine–Pyridone Foldamer Channels as M2‐Like Artificial Proton Channels

混合吡啶 - 吡啶酮折叠体通道为 M2 - 类似于人工质子通道

• DOI: 10.1002/anie.202200259
• 发表时间: 2022
• 期刊: Angewandte Chemie International Edition
• 作者: Shen, Jie;Ye, Ruijuan;Liu, Zhiwei;Zeng, Huaqiang
• 通讯作者: Zeng, Huaqiang