A Resonator for Pulsed ODNP Spectroscopy to Study Surface Hydration Dynamics

用于研究表面水合动力学的脉冲 ODNP 光谱谐振器

• 批准号: 10325293
• 负责人: Thorsten Maly
• 金额: $ 49.18万
• 依托单位: BRIDGE 12 TECHNOLOGIES, INC.
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-12-28 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10325293
• 关键词: Alzheimer' s Disease; Area; Cell Nucleus; Cell physiology; Collaborations; Communities; Computer software; Data; Defect; Detection; Development; Dimensions; Disease; Electromagnetics; Electron Spin Resonance Spectroscopy; Electrons; Equipment; Evaluation; Fruit; Funding; Health; Heart; Heating; Home; Hydration status; Journals; Laboratories; Liquid substance; Maps; Mechanics; Membrane; Membrane Lipids; Membrane Proteins; Methods; NMR Spectroscopy; Non-Insulin-Dependent Diabetes Mellitus; Nuclear; Parkinson Disease; Performance; Phase; Physiologic pulse; Physiological Processes; Play; Process; Proliferating; Protein Dynamics; Proteins; Pythons; Research; Research Activity; Research Personnel; Resolution; Resources; Role; Sampling; Signal Transduction; Site; Small Business Innovation Research Grant; Solid; Spectrum Analysis; Spin Labels; Structure; Surface; Techniques; Technology; Time; United States National Institutes of Health; Universities; Water; X-Ray Crystallography; biophysical techniques; cost effective; design; electron diffraction; experimental study; improved; instrument; instrumentation; interest; irradiation; macromolecule; microwave electromagnetic radiation; novel; open source; protein structure; prototype; simulation; solid state nuclear magnetic resonance; structural biology; success; technology development; three dimensional structure

Project Summary / Abstract The proposed research focuses on the development of a turn-key resonator for liquid-state Overhauser Dynamic Nuclear Polarization (ODNP) spectroscopy to study the site-specific translational dynamics of water molecules located at the interface of bio-macromolecules such as membrane proteins. It will allow researchers to readily perform ODNP experiments in either a state-of-the-art commercially available X-band cw/pulsed electron paramagnetic resonance (EPR) spectrometer or using a benchtop ODNP spectrometer. In recent years, DNP has proven to be a robust method to increase signal intensities in NMR experiments in laboratories around the world and substantial progress has been made in adapting DNP for solid- and solution- state NMR spectroscopy. This progress has sparked a new interest in ODNP spectroscopy. Although the method is known since the 1960s it has just recently been applied successfully to study the site-specific translational dynamics of water located at the interface of large bio-macromolecules such as membrane proteins. ODNP can map out the local and site-specific hydration dynamics landscape of membrane proteins and lipid membranes and can provide critical information about the protein structure and dynamics. One of the major challenges in ODNP spectroscopy is microwave induced sample heating. During Phase I of this project, we successfully designed, fabricated and characterized a novel prototype ODNP resonator. This SBIR Phase II application will assure that the prototype can be turned into a customer product. As demonstrated by the prototype, the resonator will have a much higher microwave conversion factor compared to conventional rectangular or circular EPR cavities. In addition, the low Q resonance structure will allow pulsed ODNP experiments to further minimize microwave induced heating by reducing the average power required to saturate the EPR transitions. The successful development of this technology will provide researchers access to instrumentation allowing them to incorporate ODNP spectroscopy in their research routine without the hassle of troubleshooting home-built equipment. This will greatly proliferate the method and is of large interest to many projects funded by the U.S. National Institutes of Health.

项目概要/摘要 拟议的研究重点是开发用于液态 Overhauser 的交钥匙谐振器 动态核极化 (ODNP) 光谱研究水的特定位点平移动力学 位于生物大分子（例如膜蛋白）界面的分子。它将让研究人员 可以在最先进的商用 X 波段连续波/脉冲中轻松执行 ODNP 实验 电子顺磁共振 (EPR) 波谱仪或使用台式 ODNP 波谱仪。 近年来，DNP 已被证明是增强 NMR 实验中信号强度的可靠方法 在世界各地的实验室中，DNP 在固体和溶液中的应用已经取得了实质性进展 状态核磁共振波谱。这一进展引发了人们对 ODNP 光谱学的新兴趣。虽然方法 自 20 世纪 60 年代以来就广为人知，最近才成功应用于研究位点特异性翻译 位于膜蛋白等大生物大分子界面的水动力学。 ODNP 可以 绘制膜蛋白和脂质膜的局部和特定位点的水合动力学景观 并可以提供有关蛋白质结构和动力学的关键信息。 ODNP 光谱学的主要挑战之一是微波诱导样品加热。阶段期间 在这个项目中，我们成功设计、制造并表征了一种新型 ODNP 谐振器原型。这 SBIR 第二阶段应用将确保原型可以转化为客户产品。正如所证明的 通过原型，与传统谐振器相比，谐振器将具有更高的微波转换系数 矩形或圆形 EPR 腔。此外，低Q谐振结构将允许脉冲ODNP 通过降低饱和所需的平均功率来进一步最小化微波引起的加热的实验 EPR 转换。 这项技术的成功开发将为研究人员提供使用仪器的机会 使他们能够将 ODNP 光谱法纳入其研究常规中，而无需进行故障排除的麻烦 自制设备。这将极大地推广该方法，并且引起许多由 美国国立卫生研究院。