CAREER: Spin Dynamics Measurements of Site-to-Site Variations in Hydration Water at Soft Nanoscale Interfaces

该奖项的部分资金来自《2021年美国救援计划法案》(公法117-2)。在化学测量和成像计划的支持和化学结构、动力学和机制的共同资助下，锡拉丘兹大学的约翰·弗兰克博士和他的团队正在开发仪器和相关软件，以常规地表征包围和渗透大分子的水的分子尺度性质。这种水在推动生物反应和控制生物灵感材料的所有过程中发挥着积极的作用，但仍然相对较差。预计新的方法将极大地方便表征这些独特的水分子的困难任务，并已开始更深入地了解将小分子配体与其大分子靶标以及聚合物和蛋白质相互结合的作用力。该方法的传播将加快新药和材料的设计和开发，并在癌症治疗和能源收集等领域产生潜在影响。被招募参与这项研究的有才华的不同类型的学生将学习利用现代技术和编程来构建新型化学表征工具的可能性。这项工作将提供独特的开放源码数据处理库供公众使用。水合水控制着大分子的广泛性质，从它们所采用的形状到重要结合事件的能量学和动力学。因为任何类型的结合作用或任何决定蛋白质或合成聚合物最终折叠结构的构象波动都必须取代数百个水分子，所以这些水分子的性质至关重要地决定了相关的动力学和热力学。目前关于蛋白质-蛋白质结合以及合成聚合物和溶剂之间的相互作用的许多方面仍然知之甚少或难以预测，这可以归因于无法表征水化水分子，众所周知，水化水分子具有与主体溶剂截然不同的性质。正在开发的液态ODNP(Overhauser动态核极化)技术通过跟踪水的核中心相对于化学放置的目标部分(称为自旋探针)的运动，并提供可直接与完全原子分子动力学模拟相关的特定位置的测量，为揭示水合水的性质提供了一个新的攻击角度。这些技术正在开发和使用，以阐明水化动力学的纳米级变化与控制大分子相互作用的热力学障碍之间的联系，从而澄清水分子在不同时间尺度上运动的贡献。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

This award is funded in part under the American Rescue Plan Act of 2021 (Public Law 117-2).With support from the Chemical Measurement and Imaging program and co-funding from the Chemical Structure, Dynamics, and Mechanisms A program in the Division of Chemistry, Dr. John Franck and his group at Syracuse University are developing instrumentation and associated software to routinely characterize the molecular-scale properties of the water that surrounds and permeates large molecules. This water plays an active role in all the processes that drive biological reactions and control bioinspired materials but remains relatively poorly characterized. The new methodology is expected to greatly facilitate the difficult task of characterizing these unique water molecules and has begun to unlock a deeper understanding of the forces that bind small molecule ligands to their macromolecular targets and polymers and proteins to each other. Dissemination of the methodology will speed the design and development of new drugs and materials, with potential impacts in areas such as cancer treatment and energy harvesting. Talented diverse students recruited to engage in this research will learn about the possibilities of employing modern technology and programming to build new types of chemical characterization tools. The work will provide unique open-source data-processing libraries for public use. Hydration water controls far-ranging properties of macromolecules, from the shapes they adopt to the energetics and kinetics of important binding events. Because any type of binding interaction or any conformational fluctuation that determines the final folded structure of a protein or synthetic polymer must necessarily displace hundreds of water molecules, the properties of those water molecules crucially determine the relevant kinetics and thermodynamics. Much that currently remains poorly understood or difficult to predict about protein-protein binding and the interactions of synthetic polymers and solvents can be attributed to an inability to characterize the hydration water molecules, which are known to have dramatically different properties from the bulk solvent. The liquid-state ODNP (Overhauser Dynamic Nuclear Polarization) techniques being developed offer a new angle of attack for revealing the properties of hydration water by tracking the motion of the nuclear centers of water relative to a chemically placed target moiety (known as the spin probe) and offering a site-specific measurement that can be directly related to fully atomistic molecular dynamics simulations. These techniques are being developed and used to elucidate the connection between nanometer-scale variations in hydration dynamics and the thermodynamic barriers that govern macromolecular interactions, thereby clarifying the contributions of water molecules moving on different timescales.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.