Benchtop Q-Band Pulsed EPR Spectrometer for Intermolecular Distance Measurements

用于分子间距离测量的台式 Q 波段脉冲 EPR 光谱仪

• 批准号: 10668508
• 负责人: Thorsten Maly
• 金额: $ 64.27万
• 依托单位: BRIDGE 12 TECHNOLOGIES, INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-10 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10668508
• 关键词: Alzheimer' s Disease; Cell physiology; Complex; Computers; Confusion; Crying; Cryoelectron Microscopy; Dedications; Defect; Development; Disease; Electron Spin Resonance Spectroscopy; Electrons; Evaluation; Extravasation; Feedback; Frequencies; Funding; Generations; Goals; Hand; Health; Heart; Length; Liquid substance; Magnetic Resonance Spectroscopy; Measurement; Measures; Membrane Proteins; Methods; Morphologic artifacts; NMR Spectroscopy; Non-Insulin-Dependent Diabetes Mellitus; Parkinson Disease; Performance; Phase; Physiologic pulse; Physiological Processes; Play; Proliferating; Protein Dynamics; Proteins; Research; Research Personnel; Resolution; Resources; Role; Sampling; Scientist; Shapes; Signal Transduction; Site; Small Business Innovation Research Grant; Spectrum Analysis; Spin Labels; Standardization; Structure; System; Techniques; Temperature; Testing; Time; Training; United States National Institutes of Health; X-Ray Crystallography; biomacromolecule; cost effective; cryostat; design; expectation; experimental study; fabrication; improved; instrument; instrumentation; interest; operation; phase 1 designs; prevent; protein structure; prototype; structural biology; success; three dimensional structure; tool; vector

Project Summary / Abstract Complex bio-macromolecules such as membrane proteins play crucial roles in many cellular and physiological processes and specific defects are associated with many known. Determining their three- dimensional structures is one of the main objectives in structural biology and the NIH devotes considerable resources towards this goal. In recent years, pulse EPR spectroscopy, in particular Double Electron-Electron Resonance (DEER) has contributed valuable structural constraints to solve structures of bio-macromolecules. However, currently these methods are only available to experts in the field because operating the complex instrument requires lots of training making it difficult for a non-EPR expert to access this highly valuable information. State-of-the-art spectrometer configurations may be the most versatile option; however, many features of current commercially available systems are unnecessary or simply confusing. Options such as continuous wave (cw) EPR are unnecessary when the main objective is to measure distances. In addition, it is also often overwhelming to applications scientist that are not experts in pulsed EPR spectroscopy. Much of the experiment setup and processing can be standardized but current commercial instruments don’t come with these streamlined features. With DEER becoming more popular it is time to propose a solution that is geared specifically towards distance measurements rather than offering a universal research instruments. Removing unnecessary options and focusing only on DEER spectroscopy will allow us to design a compact, turn-key instrument. In this SBIR application we propose to develop a compact, turn-key Q-band pulsed EPR spectrometer for pulsed dipolar spectroscopy. The system will feature a liquid cryogen-free magnet and cryostat, a low-Q but high-sensitivity resonator and a compact, EPR bridge with state-of-the-art pulse shaping capabilities. The system will be fully computer controlled and easy to operate with minimal training. The successful development of this compact, Q-band pulsed EPR spectrometer will provide researchers access to turn-key instrumentation allowing them to easily incorporate experiments such as DEER in their research. This will greatly proliferate the method and is of large interest to many projects funded by the U.S. National Institutes of Health.

项目摘要 /摘要 复杂的生物大分子（例如膜蛋白）在许多细胞中起着至关重要的作用 生理过程和特定缺陷与许多已知的相关。确定他们的三 尺寸结构是结构生物学的主要目标之一，NIH致力于相当大的目标 资源实现这一目标。近年来，脉冲EPR光谱，特别是双电子电子 共振（鹿）为解决生物大分子的结构提供了宝贵的结构限制。 但是，目前这些方法仅适用于该领域的专家，因为操作该综合体 仪器需要大量的培训，使得非EPR专家很难访问这一非常有价值的 信息。 最先进的光谱仪配置可能是最通用的选项。但是，许多功能 当前可商购的系统是不必要的，或者简直令人困惑。诸如连续的选项 当主要目标是测量距离时，波（CW）EPR是不必要的。另外，它也经常 对脉冲EPR光谱的专家的应用科学家压倒性的科学家。大部分实验 设置和处理可以标准化，但是当前的商业仪器不会随附 简化的功能。随着鹿变得越来越流行，是时候提出一种适合的解决方案 专门针对距离测量，而不是提供通用的研究工具。去除 不必要的选择，并且仅专注于鹿光谱法将使我们能够设计一个紧凑的钥匙 乐器。 在此SBIR应用中，我们建议开发紧凑的旋转Q波段脉冲EPR光谱仪 用于脉冲偶极光谱。该系统将配备无液体冷冻磁铁和低温恒温器，低Q但是 高敏性谐振器和紧凑的EPR桥，具有最先进的脉冲塑形功能。系统 通过最少的培训，将受到完全计算机控制且易于操作的。 这种紧凑的Q波段脉冲EPR光谱仪的成功开发将为研究人员提供 使用旋转仪器，使他们可以轻松地将实验（例如鹿）纳入 研究。这将极大地扩散该方法，并且对美国资助的许多项目引起了人们的关注。 国立卫生研究院。