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，如核糖体和血浆 膜。 主要的技术将采用中心的X射线衍射 从单晶或从溶液或部分有序系统;高 小蛋白质的氢交换研究;高分辨率 生物合成制备的同位素富集样品的NMR研究。 在 除了时间平均结构，这是最直接的 输出的衍射工作，该计划将特别针对 研究聚合物各部分（区域）的相对运动 链和亚基相对于彼此在较大的 集料. 运动可以部分地从不同的静态中推断出来 可以在各种环境条件下确定的结构 和结扎。 特别令人感兴趣的是运动期间：1）催化 聚合酶沿着其核酸模板和底物的循环; 2） 在配体调控的形成过程中蛋白质亚基的重排 特定的蛋白质/DNA复合物和复合物本身在 DNA重组; 3）核糖体的运动对信息的过程中， 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。 组合 理论和实验研究将包括新的方法 X射线晶体结构的测定和细化， 溶液NMR衍生结构。 理论方法将包括 各种系统的自由能微扰计算和 蛋白质-DNA和蛋白质-膜相互作用。

The Program is directed at structural studies of macromolecules, 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; high resolution hydrogen exchange studies on small proteins; and high resolution NMR studies of isotopically enriched samples prepared biosynthetically. 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. Combined theoretical and experimental investigations will include novel approaches to the determination and refinement of X-ray crystal structures and solution NMR-derived structures. The theoretical approaches will include free-energy perturbation calculations on various systems and modelling of protein-DNA and protein-membrane interactions.