PROGRAM IN MACROMOLECULAR STRUCTURE, MOTION, CONTROL

该计划是针对大分子的结构研究， 大分子组装体和细胞器，如核糖体和 质膜 主要采用的技术集中在X射线上 从单晶或从溶液或部分有序衍射 系统;高分辨率溶液NMR;在整个范围内的其他 生物物理技术，包括质谱法， 或者与化学标记程序结合。 除了有 时间平均结构，这是最直接的输出 衍射工作，该计划将特别针对研究 聚合物链的各个部分（域）和聚合物链的各个部分（域）的相对运动 在更大的聚集体中亚单位之间的相对关系。 运动 可以部分地从不同的静态结构中推断出来， 在不同的环境和连接条件下测定。 的 特别感兴趣的是运动过程中：1）催化循环 聚合酶沿着它们的核酸模板和底物; 2）聚合酶的核酸模板和底物; 在配体调节的蛋白质亚基形成过程中的重排 特定的蛋白质/DNA复合物和复合物本身在DNA 重组; 3）核糖体在重组过程中的运动 蛋白质合成的易位步骤;和4）分泌 多肽链进入并穿过膜双层。理论 方法将包括自由能微扰计算各种 系统，蛋白质-DNA和蛋白质-膜相互作用的建模， 模拟大分子-溶剂界面，并继续改进 X射线和NMR数据的结构精修程序。

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.