PROGRAM IN MACROMOLECULAR STRUCTURE, MOTION, CONTROL

该计划针对的是大分子的结构研究， 大分子组件和细胞器，如核糖体和 质膜。将采用的主要技术集中在X射线上 单晶、溶液或半有序的衍射 系统；关于高分辨率溶液核磁共振；关于一系列其他 生物物理技术，包括质谱学，它们本身 或与化学标签程序相结合。除 时间平均结构，这些结构是 对于衍射作品，本方案将特别针对研究对象 聚合物链的各个部分(结构域)和 在较大的聚集体中彼此相对的亚单位。动议 可以部分地从不同的静态结构推断，这些静态结构可以 在不同的环境和结扎条件下测定。的 特别感兴趣的是：1)催化循环中的运动 聚合酶及其核酸模板和底物；2) 蛋白质亚基在配体调控形成过程中的重排 DNA过程中特定的蛋白质/DNA复合体和复合体本身 重组；3)核糖体在信息传递过程中的运动 蛋白质合成的转位步骤；4)分泌 多肽链进入并通过膜双层。理论上的 这些方法将包括自由能微扰计算 系统，蛋白质-DNA和蛋白质-膜相互作用的模型， 模拟大分子-溶剂界面，并持续改进 X-射线和核磁共振数据的结构精炼程序。

The Program is directed at structural studies of macromolecules, a macromolecular assemblies, and cell organelles such as ribosomes and plasma membranes. The major techniques to be employed center on X-ray diffraction from single crystals or from solutions or partially ordered systems; on high resolution solution NMR; on a whole range of other biophysical techniques, including mass spectroscopy, either by themselves or in combination with chemical labeling procedures. In addition to the time-average structures, which are the most immediate output of the diffraction work, the Program will be especially aimed at studying the relative motion of various parts (domains) of the polymer chains and of the subunits with respect to each other in the larger aggregates. Motion can, in part, be inferred from different static structures that can be determined under varied conditions of environment and ligation. Of special interest is the motion during: 1) the catalytic cycles of polymerases along their nucleic acid templates and substrates; 2) the rearrangement of protein subunits during the ligand-regulated formation of specific protein/DNA complexes and of the complexes themselves during DNA recombination; 3) the movement of ribosomes on the message during the translocation step of protein synthesis; and 4) the secretion of polypeptide chains into and through the membrane bilayer. The theoretical approaches will include free-energy perturbation calculations on various systems, modeling of protein-DNA and protein-membrane interactions, modeling the macromolecule-solvent interface, and continuing improvement of the structure refinement procedures for both X-ray and NMR data.