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下，并在化学系的化学结构，动力学和机制A计划的共同资助下，约翰·弗兰克博士和他在锡拉丘兹大学的研究小组正在开发仪器和相关软件，以常规表征分子-包围和渗透大分子的水的尺度特性。这种水在驱动生物反应和控制生物启发材料的所有过程中发挥着积极作用，但仍然相对缺乏特征。 新方法有望极大地促进表征这些独特水分子的艰巨任务，并已开始深入了解将小分子配体与其大分子靶点以及聚合物和蛋白质相互结合的力。该方法的推广将加速新药物和新材料的设计和开发，并在癌症治疗和能量收集等领域产生潜在影响。被招募从事这项研究的有才华的多样化学生将了解采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，从它们采用的形状到重要结合事件的能量学和动力学。由于任何类型的结合相互作用或任何构象波动，决定了蛋白质或合成聚合物的最终折叠结构，必须取代数百个水分子，这些水分子的性质决定了相关的动力学和热力学。目前对蛋白质-蛋白质结合以及合成聚合物和溶剂的相互作用了解甚少或难以预测的大部分可以归因于无法表征水合水分子，已知水合水分子具有与本体溶剂显著不同的性质。正在开发的液态ODNP（Overhauser动态核极化）技术提供了一个新的角度来揭示水合水的性质，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，并提供可以直接与完全原子分子动力学模拟相关的特定于位点的测量。这些技术正在开发和使用，以阐明纳米尺度的变化之间的联系，在水化动力学和热力学障碍，支配大分子相互作用，从而澄清水分子的贡献，在不同的时间尺度上移动。这个奖项反映了NSF的法定使命，并已被认为是值得通过评估使用基金会的智力价值和更广泛的影响审查标准的支持。

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.