PROTEIN DYNAMICS AND NMR--SOLUTION STRUCTURE

蛋白质动力学和 NMR——解决方案结构

• 批准号: 3421729
• 负责人: OLEG JARDETZKY
• 金额: $ 18.2万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-09-01 至 1994-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3421729
• 关键词: chemical models; computer program /software; nuclear magnetic resonance spectroscopy; protein structure; solutions

With this grant we propose to continue our work in the domain of protein structure determination by NMR. We have recently reported the construction of a novel computer program, PROTEAN, which simultaneously determines molecular structure as well as the uncertainty in the position of each atom within the molecule. We have also reported another program, BLOCH, which calculates the expected build-up curve for NMR Nuclear Overhauser Enhancement (NOE) measurements. We propose to build two new computer programs which will allow us to investigate the dynamics of proteins in solution with a view to more accurately predicting structures that will match the observed spectra. The first program, BLOCH*, will allow the prediction of the build-up of NMR NOE measurements from an uncertain protein structure. The novel aspect of this program is that it will use explicit estimates of the uncertainty of atoms within the molecule to predict not only the spectra expected from a rigid molecule, but also the spectra of a molecule which has differential uncertainty in the position of each atom. This will allow us to predict more accurate spectra that take into account the effects of positional uncertainty within a molecule. The second program, PROTEAN*, will produce models of protein dynamic motion which explain the observed NMR spectra. These models will be derived from three sources: the known chemical structure of the molecule, the uncertainty in atomic positions as calculated by our structure determination program, and simple simulations of where and how molecular motion can take place in a large molecule.

有了这笔赠款，我们建议继续我们在蛋白质领域的工作 NMR确定结构。 我们最近报告了 构建新型计算机程序Protean，同时 确定分子结构以及位置的不确定性 分子内的每个原子的。 我们还报告了另一个程序， Bloch，它计算NMR核的预期堆积曲线 过度大关增强（NOE）测量。 我们建议构建两个新的计算机程序，这将使我们能够 研究溶液中蛋白质的动力学，以了解更多 准确预测将与观察到的光谱匹配的结构。 第一个程序Bloch*将允许预测建立 NMR NOE测量来自不确定的蛋白质结构。 小说 该程序的方面是它将使用明确的估计 分子内原子的不确定性不仅预测光谱 预期的是刚性分子，也可以从一个分子的光谱 每个原子的位置都有差异不确定性。 这会 允许我们预测更准确的光谱 分子内的位置不确定性的影响。 第二个程序， 蛋白*将产生蛋白质动态运动模型，以解释 观察到的NMR光谱。 这些模型将来自三个来源： 分子的已知化学结构，原子的不确定性 由我们的结构确定计划计算的职位，以及 简单的模拟分子运动在何处以及如何进行 大分子。