Physical Chemistry of Macromolecules as Probed by High Resolution Solid State NMR

高分辨率固态核磁共振探测大分子的物理化学

• 批准号: 1413096
• 负责人: Kurt Zilm
• 金额: $ 51.25万
• 依托单位: Yale University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1413096&HistoricalAwards=false
• 关键词: Physical; Chemistry; Macromolecules; Probed; Resolution

The Chemical Measurement and Imaging Program in the Chemistry Division supports Professor Kurt Zilm of Yale University to develop new nuclear magnetic resonance methods for investigation of the chemistry, dynamics and structures of biomolecules. The research will use relaxation methods to identify how structure is related to the dispersion in internal protein and water motions, and to obtain distances in biologically relevant macromolecular complexes. To extend solid-state nuclear magnetic resonance to more complex and size limited samples, new instruments will be developed with 1 to 2 orders of magnitude higher specific sensitivity. These will combine paramagnetic condensed acquisition with very fast cryogenic magic angle sample spinning, as well as microliter sample size dynamic nuclear polarization hardware. When developed, these capabilities will be applied to characterize mutant visual pigments and functionally distinct isoforms of prion protein oligomers. Currently, these are samples where obtaining nuclear magnetic resonance data is impractical on sub-microliter samples. Magnetic resonance imaging (MRI) is a well-known diagnostic tool in medicine that uses nuclear spin information, often in water, to distinguish different types of tissue in the body. The study of nuclear spin properties of water in proteins is directly related to understanding and improving contrast in MRI technology. This research involves fundamental studies of the distribution of water in proteins, knowledge from which will help improve the sensitivity and the spatial resolution of MRI experiments. The research program also encourages under-represented minorities to enter science careers through involvement in the public education program "Science on Saturdays," a series of scientific lectures and hands-on demonstrations attended by up to 300 members of the public at a time.

化学部的化学测量和成像计划支持耶鲁大学的Kurt Zilm教授开发新的核磁共振方法，用于研究生物分子的化学，动力学和结构。该研究将使用松弛方法来确定结构如何与内部蛋白质和水运动的分散相关，并获得生物相关大分子复合物的距离。为了将固态核磁共振扩展到更复杂和尺寸有限的样品，将开发比灵敏度高1到2个数量级的新仪器。这些将结合联合收割机顺磁凝聚采集与非常快速的低温魔角样品旋转，以及微升样品大小的动态核极化硬件。 开发后，这些能力将被应用于表征突变的视色素和功能不同的朊病毒蛋白寡聚体亚型。 目前，这些样品中获得亚微升样品的核磁共振数据是不切实际的。磁共振成像（MRI）是一种众所周知的医学诊断工具，它使用核自旋信息（通常在水中）来区分体内不同类型的组织。蛋白质中水的核自旋性质的研究直接关系到理解和提高MRI技术中的对比度。 这项研究涉及蛋白质中水的分布的基础研究，从中获得的知识将有助于提高MRI实验的灵敏度和空间分辨率。该研究计划还鼓励代表性不足的少数民族通过参与公共教育计划“星期六科学”进入科学职业，这是一系列科学讲座和实践演示，每次最多有300名公众参加。