Biophysical studies of weakly aligned biomolecules

在过去的十年里，核磁共振波谱法在大分子结构测定中使用残余偶极偶联发生了革命性的变化。在液晶中，大分子部分排列，偶极耦合发生非零平均。这些“残余”偶极耦合提供了角度和距离信息，并可用于确定原子结构。在上一个资助期内，我们开发了使用聚合物稳定液晶测量残余偶极耦合的新方法。通过以魔角旋转这些介质，偶极耦合和化学位移各向异性被去除，但可以选择性地用类似REDOR的再耦合脉冲序列重新引入。我们建议继续我们的研究弱排列的生物分子的NMR光谱，作为一个新的方向，在小角X射线散射（SAXS）的应用。 NMR和SAXS都是可视化生物分子三维结构的重要工具。 通过使用液晶和其他定向系统，我们可以扩展这些技术的范围和实用性。 实际的好处是更好地了解涉及蛋白质和其他生物分子的基本生命过程，以及改进健康研究中药物开发和设计的工具。

The last ten years have seen a revolution in the use of residual dipolar couplings in macromolecular structure determination by NMR spectroscopy. In liquid crystals, macromolecules partially align and non-zero averaging of the dipolar couplings occurs. These 'residual' dipolar couplings provide both angular and distance information and can be used to determine atomic structures. Under the previous funding period, we developed new methods for measuring residual dipolar couplings using polymer-stabilized liquid crystals. By spinning these media at the magic angle, dipolar couplings and chemical shift anisotropies are removed but can be selectively re-introduced with REDOR-like recoupling pulse sequences. We propose to continue our research on weakly aligned biomolecules for NMR spectroscopy and, as a new direction, for applications in small-angle X-ray scattering (SAXS).  Both NMR and SAXS are important tools for visualizing the three dimensional structures of biomolecules.  By using liquid crystals and other orienting systems, we can extend the range and usefulness of these techniques.  The tangible benefits are a better understanding of basic life processes involving proteins and other biomolecules and improved tools for drug development and design in health research.