PROTEIN STRUCTURE VIA ANALYSIS OF 2D NMR SPECTRA

这项研究将提高确定高- 从二维NMR解析溶液中的蛋白质结构 实验 这一进展的一部分将通过实施 本实验室开发的完整松弛矩阵方法 二维核欧沃豪泽效应（2D NOE）的CORMA分析 光谱，能够确定大量的核间 远距离测量的精确度比以前高得多。 的 新的方法也应该使更长的距离， 确定-高达5埃或可能6埃。 最有效的手段 (as以及似是而非的错误和假设的影响）的推导 用完全松弛矩阵分析法研究蛋白质溶液结构 结合距离几何学的计算技术， 探讨分子力学及受约束的分子动力学。 通过2D NOE光谱获得的距离信息将通过 从基于标量耦合的2D NMR导出二面角约束 实验 分子运动和多重构象的影响 也将被审查。 这是由本公司开发的优秀计划 该项目将分发给其他研究实验室。 改进的 该方法将特别适用于蛋白质部分， 结构知识是非常需要的，即，在配体结合位点。 改进后的结构应导致更大的机械见解。

The proposed research will improve the capability for determining high- resolution protein structures in solution from two-dimensional NMR experiments. Part of this advance will come via implementation of methodology developed in this lab for the complete relaxation matrix analysis (CORMA) of two-dimensional nuclear Overhauser effect (2D NOE) spectra, enabling the determination of a large number of internuclear distances at considerably greater accuracy than previously possible. The new methodology should also enable somewhat longer distances to be determined-up to 5angstrom or possibly 6angstrom. The most effective means (as well as the influence of plausible errors and assumptions) of deriving protein solution structure by using the complete relaxation matrix analysis in conjunction with the computational techniques of distance geometry, molecular mechanics and restrained molecular dynamics will be explored. The distance information obtained via 2D NOE spectra will be augmented by dihedral angle constraints derived from scalar coupling-based 2D NMR experiments. The effects of molecular motions and multiple conformations will also be examined. Programs of merit which are developed by this project will be disseminated to other research labs. The improved methodology will be especially useful in protein moieties where improved structural knowledge is highly desirable, i.e., in ligand-binding sites. The improved structures should lead to greater mechanistic insights.