Macromolecular Structure in Refined Detail

本建议的总体目标是促进对精确原子模型中揭示的生物大分子功能特性的基本理解。这些模型对于产生和测试与不同系统中生物作用直接相关的假设具有重要意义。晶体的衍射研究可以提供蛋白质和其他大分子的详细和全面的结构信息，多维核磁共振波谱正在成为这类信息的另一种来源。重要的是，从这些实验中得到的原子模型要尽可能精确地定义。Hendrickson博士在这里寻求开发方法来优化实验确定的原子模型的准确性，将这些改进方法应用于特定的生化问题，并详细分析所得到的模型的结构和动态特性。特别是，(1)他将根据x射线衍射数据提炼一些重要的生物大分子，并分析所得模型的结构和动态特性，(2)他将确定表征可靠确定结构的属性，(3)他将尝试提高晶体学提炼程序的效率和便利性，(4)他将努力发展对晶体动态特性的适当处理方法，(5)他将把立体化学约束细化的方法扩展到二维核磁共振波谱中的问题，(6)他将继续维护和分发一个细化程序系统。

The overall objective of this proposal is to contribute to a basic understanding of the functional properties of biological macromolecules as revealed in accurate atomic models. Such models are significant for the generation and testing of hypotheses directly related to biological action in diverse systems. Diffraction studies on crystals can provide detailed and comprehensive structural information on proteins and other macromolecules, and multidimensional NMR spectroscopy is emerging as an alternative source of such information. It is important that the atomic models derived from these experiments be defined as accurately as possible. Dr. Hendrickson is seeking here to develop methods for optimizing the accuracy of experimentally determined atomic models, to apply these refinement methods to specific biochemical problems, and to analyze in detail the structural and dynamic properties of the resulting models. In particular, (1) he will refine a number of significant biological macromolecules against x-ray diffraction data, and analyze the structural and dynamic properties of the resulting models, (2) he will identify attributes that characterize reliably determined structures, (3) he will attempt to enhance the efficiency and convenience of crystallographic refinement procedures, (4) he will strive to develop appropriate treatments for dynamic properties in crystal, (5) he will extend the method of stereochemically restrained refinement to problems in 2D NMR spectroscopy, and (6) he will continue to maintain and distribute a system of refinement programs.