Conformational Analysis of Peptide Models by Liquid-Crystal NMR

通过液晶 NMR 对肽模型进行构象分析

• 批准号: 0077517
• 负责人: James Weisshaar
• 金额: $ 23万
• 依托单位: University of Wisconsin-Madison
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-15 至 2002-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0077517&HistoricalAwards=false
• 关键词: Conformational; Analysis; Peptide; Models; Liquid

Professor James Weisshaar of the University of Wisconsin Madison is supported by the Experimental Physical Chemistry program to perform experimental and theoretical studies on peptides oriented in liquid crystals using Nuclear Magnetic Resonance. This proposal seeks to make detailed experimental NMR measurements on the structures adopted by small model peptides in solution to calibrate and sharpen the accuracy of molecular force fields. Di-, tri- and possibly tetra- peptides will be studied in liquid crystals, a means by which the problem of the rapid tumbling and averaging of molecules in solution can be overcome. In order to fully characterize the peptides in their conformational diversity, a large number of magnetic dipole couplings between nuclear spins will be measured. The signals will be fit to those predicted from ab initio theory for a superposition of possible stable structures, with iterations on the distribution of conformers and on the force fields. Successful fitting for small, flexible peptides would provide an important step towards cracking the multi-conformation problem in flexible regions of proteins. NMR and X-ray methods, the two major methods for solving protein structures, are limited in characterizing the flexible local conformations within proteins. Computational approaches can assist in obtaining these conformations, however, the calculations are only as good as the force fields used. This proposal seeks to provide experimental data aimed at improving the calculations. It is especially timely because of the increasing massive efforts to calculate protein structures and protein folding processes.

威斯康星州麦迪逊大学的James Weisshaar教授得到实验物理化学计划的支持，利用核磁共振对液晶中的肽进行实验和理论研究。 该提案旨在对溶液中小模型肽所采用的结构进行详细的实验NMR测量，以校准和提高分子力场的准确性。二肽、三肽和可能的四肽将在液晶中进行研究，通过这种方法，可以克服溶液中分子快速翻滚和平均化的问题。 为了充分表征肽的构象多样性，将测量核自旋之间的大量磁偶极耦合。 这些信号将与从头算理论预测的可能稳定结构的叠加相拟合，并对构象分布和力场进行迭代。 成功拟合小的柔性肽将为解决蛋白质柔性区域的多构象问题迈出重要一步。 核磁共振和X射线方法是求解蛋白质结构的两种主要方法，但在表征蛋白质内部灵活的局部构象方面受到限制。 计算方法可以帮助获得这些构象，然而，计算仅与所使用的力场一样好。 该提案旨在提供旨在改进计算的实验数据。 这是特别及时的，因为越来越多的大量努力，计算蛋白质结构和蛋白质折叠过程。