Computer Led Design of Helical Arylamide Foldamer for Selective Water Transport

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和高效率的水净化技术。在美国国家科学基金会化学部大分子、超分子和纳米化学项目的支持下，俄罗斯科学大学的Vojislava Pophristic和刘志伟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，从而显著提高水的过滤能力。通道是圆柱形的空心螺旋，由特定的化学构件组装而成。该小组首先通过创建和优化构建块序列在计算机上设计通道。然后在实验室中制作有希望的候选材料并通过实验进行测试。该项目是一所以科学为重点的大学、一所社区学院和一所美国历史悠久的黑人学院和大学（HBCU）的学生的训练场。该项目建立在该小组对芳酰胺文件夹精确结构和动力学预测的计算方法的发展之上。芳基酰胺支架形成稳定的单螺旋或双螺旋，具有适合应用的长度和内腔尺寸。芳酰胺文件夹的模块化和可调性使其成为模仿水通道蛋白结构特征设计水运通道的优秀候选材料。该团队通过合理组合序列生成和分子动力学模拟，建立序列-结构-功能关系，设计水渠，并进行选择性优化。该项目包括与Ivan Huc博士的国际合作，他通过实验验证计算获得的结构并测量水/离子/质子电导率。这个项目的一个重要方面是，它帮助我们了解自然发生的过滤过程，如水通道蛋白的选择性水运输，这对人类健康起着至关重要的作用。

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.