DYNAMIC AND STRUCTURAL ELUCIDATION OF GRAMICIDIN A

这里提出了一项继续项目的提案，该项目 Granicidin A阳离子通道旨在详细解释 通过阐明通道的结构获得电导数据 和原子分辨率的动力学。的结构方面 工作的结果是固体核磁共振的测定 多肽内的共价键相对于 一个共同的轴，磁场的方向。从债券中 确定了相邻群的取向和扭角 定义这些组的相对方向。因为 共价结构是已知的扭转角的决定因素 (总共52个格拉西丁)将导致原子解析 结构确定。这里描述的就是这样一个完整的 结构确定。动态表征是 由两部分组成；第一部分是对 Motion，定义发生运动的轴、类型 无论它是扩散的还是不连续的，如在跳跃中 在构象亚态的势能极小值之间，以及 最后是运动的范围或幅度。只有当这个 运动的空间模型是否完整才能准确 根据核磁共振弛豫来确定频率 数据。详细描述了以下各项的本地动态 语法中的37个结构单元由52个扭转连接起来 这项建议寻求的是角度。 航道的输运函数从计算上看 学习要依靠脊梁的灵活性。这个 这些局部运动的第一个实验证据是 在这笔赠款的支持下的头两年取得的成绩 (Nicholson等人，1989)其中一组构象亚态 对于革兰菌素主干中的单肽连接， 观察到的。这个渠道的结构还没有通过 衍射技术。在该项目的进度报告中介绍 研究方案是确定第一对 脊椎骨的扭转角。当结构 和动力学已经阐明了两者之间的独特关联 该阳离子将实现结构、动力学和功能 频道。

Presented here is a proposal for the continuation of a project on the gramicidin A cation channel designed to explain the detailed conductance data by the elucidation of the channel's structure and dynamics with atomic resolution. The structural aspects of the effort result from the solid state NMR determination of covalent bond orientations within the polypeptide with respect to a common axis, the magnetic field direction. From the bond orientations of adjacent groups the torsion angles are determined defining the relative orientation of these groups. Because the covalent structure is known a determination of the torsion angles (a total of 52 gramicidin) will result in an atomic resolution structure determination. Described here is such a complete structure determination. The dynamic characterization is composed of two parts; first a spatial characterization of the motion, defining the axis about which the motion occurs, the type of motion whether it is diffusional or discontinuous as in hops between potential energy minima of conformational substates, and finally the range or amplitude of the motion. Only when this spatial model for the motion is complete can an accurate determination of the frequency be made from the NMR relaxation data. A detailed description of the local dynamics for each of the 37 structural units in gramicidin connected by the 52 torsion angles is sought in this proposal. The transport function of the channel appears from computational studies to be dependent on the flexibility of the backbone. The first experimental evidence for these local motions has been achieved in the first two years of support under this grant (Nicholson et al., 1989) where a set of conformational substates for a single peptide linkage in the gramicidin backbone has been observed. The structure of this channel has not been achieved by diffraction techniques. Presented in the Progress Report of this research program is the determination of the first pair of torsion angles in the gramicidin backbone. When the structure and dynamics have been elucidated unique correlations between structure, dynamics and function will be achieve for this cation channel.