Ultra-low-temperature (6 K) static NMR-DNP for metalloproteins, proteins in cells, and materials

用于金属蛋白、细胞中蛋白质和材料的超低温 (6 K) 静态 NMR-DNP

• 批准号: 10546201
• 负责人: Francis DAVID Doty
• 金额: $ 29.96万
• 依托单位: DOTY SCIENTIFIC, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-01 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10546201
• 关键词: Alzheimer' s Disease; Amyloid Fibrils; Antibiotics; Area; Awareness; Bee Venoms; Binding; Biological; Biomedical Research; Budgets; Cells; Cellular Membrane; Country; DNA Repair Gene; Data; Development; Electrons; Equipment; Extremely High Frequency Radio Waves; Health; Human; Inflammasome; Laboratories; Lipids; Magic; Magnetism; Measures; Membrane Proteins; Metalloproteins; Methods; Molecular; Motion; Nisin; Nuclear; Nuclear Magnetic Resonance; Optics; Peptides; Pharmacologic Substance; Phase; Play; Price; Proline; Proteins; Relaxation; Reporting; Research; Research Personnel; Resolution; Role; Sampling; Signal Transduction; Small Business Innovation Research Grant; Solid; Source; Structure; System; Techniques; Temperature; amyloid structure; cold temperature; cost; design; enhancing factor; experimental study; improved; in silico; instrumentation; macromolecule; materials science; microwave electromagnetic radiation; novel; peptide structure; prototype; restraint; simulation; solid state; solid state nuclear magnetic resonance; structural biology; tool; waveguide

Ultra-low-temperature (6 K) static NMR-DNP for metalloproteins, proteins in cells, and materials Abstract The critical importance of solid-state NMR (ssNMR) was recently demonstrated by, after nearly two decades of intense efforts, yielding the first atomic-resolution structures of the A40 and A42 amyloid fibrils that play a crucial role in Alzheimer’s Disease (AD). Challenges posed by the inherently low sensitivity of NMR can be improved by reducing the sample and circuit temperature to below 100 K, or preferably below 35 K – also known as Ultra Low Temperature (ULT). Combining ULT NMR with another emerging technique, denoted as dynamic nuclear polarization (DNP), shows enormous promise for expanding the role of ssNMR by providing significant S/N enhancements in many cases. However, despite the huge gain in S/N that is possible from DNP, also performed at ~90 K, there are still only a handful of high-field MAS-DNP systems in the U.S. – pri- marily because they are so expensive ($3-10M). Further, no commercially available instrumentation is availa- ble for NMR experiments below 90 K, let alone ULT experiments combined with DNP. A huge step forward would include the development of a high-mode THz cavity for more efficient microwave delivery to the sample, thus enabling the use of a lower power and lower cost microwave source. An area of ssNMR that employs the use of non-spinning (static) samples would benefit immensely from the availability of such a commercially built ULT probe, with option for inclusion of DNP. Further, the static probe can serve as a prototype for a MAS ver- sion of such a probe. The developments proposed under this project aim to reduce entry level cost into DNP by more than an order of magnitude while reducing certain operational challenges.

超低温（6 K）静态NMR-DNP金属蛋白，细胞中的蛋白质和材料