Multi-Nuclear, Multi-Dimensional Experiments for Biomolecular NMR

生物分子 NMR 的多核、多维实验

• 批准号: 9218573
• 负责人: Erik Zuiderweg
• 金额: $ 30万
• 依托单位: Regents of the University of Michigan - Ann Arbor
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-01-01 至 1995-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9218573&HistoricalAwards=false
• 关键词: Multi; Nuclear; Dimensional; Experiments; Biomolecular

This investigation is concerned with the further development of Nuclear Magnetic Resonance Spectroscopy (NMR) as a method to determine the three-dimensional structures of larger biomolecules in solution. It is only very recently that labeling with stable isotopes and the use of three- and four- dimensional heteronuclear NMR has allowed the structure determination of proteins larger than 10 kDa in solution. Here the solution structure determination of a larger alpha helical proteins. These challenges form the backbone of the proposal and will be approached with improvements in efficiency by using heteronuclear cross polarization, with improvements in resolution by using multiple quantum filters and a larger number of dimensions and with improvements in analysis of key multi-dimensional NMR experiments. %%% Recent developments in the methods of Nuclear Magnetic Resonance Spectroscopy have made possible the determination of the three- dimensional structures of smaller proteins in solution. Three dimensional solution structures are relevant to the understanding of their biological functioning, can convey dynamic information and may be obtained by NMR in cases where other methods fail because of lack of crystals. This proposal describes investigations into the development of more advanced NMR methods to help analyze the solution NMR spectra of larger proteins, nucleic acids and complexes thereof. The studies will be carried out with a medium- sized protein as a model system. The new methods will make NMR structure determination possible for larger proteins and nucleic acids and thus contribute to the better understanding of structure and function in this larger class of biomolecules.

这项研究涉及核磁共振波谱 (NMR) 作为确定溶液中较大生物分子三维结构的方法的进一步发展。 直到最近，稳定同位素标记以及三维和四维异核 NMR 的使用才允许对溶液中大于 10 kDa 的蛋白质进行结构测定。 这里测定较大α螺旋蛋白的溶液结构。 这些挑战构成了该提案的支柱，并将通过使用异核交叉极化来提高效率、通过使用多个量子滤波器和更多维度来提高分辨率以及改进关键多维核磁共振实验的分析来解决这些挑战。 %%% 核磁共振波谱方法的最新发展使得测定溶液中较小蛋白质的三维结构成为可能。 三维溶液结构与其生物功能的理解相关，可以传达动态信息，并且在其他方​​法因缺乏晶体而失败的情况下可以通过核磁共振获得。 该提案描述了对更先进 NMR 方法开发的研究，以帮助分析较大蛋白质、核酸及其复合物的溶液 NMR 谱。 这些研究将以中等大小的蛋白质作为模型系统进行。 新方法将使核磁共振结构测定更大的蛋白质和核酸成为可能，从而有助于更好地理解这一更大类生物分子的结构和功能。