PROTEIN STRUCTURE VIA ANALYSIS OF 2D NMR SPECTRA

这项拟议的研究将提高确定高污染水平的能力。 从二维核磁共振中分辨溶液中的蛋白质结构 实验。这一进步的一部分将通过实施 本实验室开发的用于完全松弛矩阵的方法 二维核Overhauser效应(2D NOE)的CORMA分析 光谱，使大量核间化合物的测定成为可能 距离的精确度比以前高得多。这个 新的方法还应该能够使更长的距离 确定--最高可达5埃，也可能达到6埃。最有效的手段 (以及似是而非的错误和假设的影响) 用完全松弛矩阵分析蛋白质溶液结构 结合距离几何的计算技术， 将探索分子力学和约束分子动力学。 通过2D NOE谱获得的距离信息将被增强 基于标量耦合的二维核磁共振得到的二面角约束 实验。分子运动和多重构象的影响 还将接受检查。由该机构开发的功绩计划 该项目将传播到其他研究实验室。改进后的 方法学将在改进的蛋白质部分中特别有用 结构知识是非常可取的，即在配体结合部位。 改进的结构应该会带来更大的机械性洞察力。

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.