MACROMOLECULAR STRUCTURE DETERMINATION BASED ON PARAMAGNETIC NMR SHIFTS

我们正在研究解析良好的结构族 利用准接触位移实现DNA-药物-金属络合物 导出自结构计算中的金属缔合。我们 目前正在评估获得敏感度的方法 张量参数独立于结构并细化 张量在整体结构细化过程中。张量是一个 结构分析中的关键组件，被要求 从分子结构的角度来解释这种变化。我们有 成功地证明了张量可以独立获得或 在结构计算中通过改进而得到的。我们的比较 最终结构与几年前按标准获得的结构一致 核磁共振方法显示在程度上有很大的差异 药物结合引起的DNA扭曲。我们不遵守 碱基对扭曲和轴曲率，这是在 更早的结构。相反，DNA似乎通过以下方式适应药物 只不过是螺旋轴上的S形状的弯曲和加宽的 容纳药物的小凹槽。我们已经展示了和 匹配的结构，计算的均方根偏差，以及 生成了无数的图像，代表了 项目。我们使用了MidasPlus的功能来覆盖不同的 了解PDB文件和处理非常大的PDB文件 我们基于移位的结构的特点。

We are studying well-resolved structure families for a DNA-drug-metal complex by making use of the pseudocontact shifts derived from the metal association in the structure calculation. We are currently assessing methods for obtaining the susceptibility tensor parameters independently of a structure and refining that tensor during the overall structural refinement. The tensor is a crucial component in the structural analysis, being required to interpret the shifts in terms of molecular structure. We have successfully shown that the tensor can be obtained independently or derived by refinement in a structure calculation. A comparison of our final structure with that obtained several years earlier by standard NMR methods reveals a substantial difference in the degree of distortion of the DNA caused by drug binding. We do not observe the base pair distortion and axis curvature that was reported in the earlier structure. Instead, the DNA appears to accomodate the drug by little more than an S-shaped bend in the helix axis and a widening of the minor groove to accomodate the drug. We have displayed and matched structures, calculated root mean square deviations, and generated a myriad of images representing different facets of the project. We have used the ability of MidasPlus to overlay different pdb files and to handle very large pdb files to understand characteristics of our shift based structures.