DYNAMIC AND STRUCTURAL ELUCIDATION OF GRAMICIDIN

这里提出的是一项关于继续进行一个项目的建议， 短杆菌肽A阳离子通道的设计，详细解释了 通过阐明通道的结构， 和原子分辨率的动力学。 组织结构方面的协议 这些努力来自于固态NMR测定 多肽内的共价键方向 一个共同的轴，磁场方向。 从债券 确定相邻组的扭转角方向 定义这些组的相对方向。 因为 共价结构是已知的扭转角的确定 （共52短杆菌肽）将导致原子分辨率 结构测定 这里描述的是这样一个完整的 结构测定 动态特性是 由两部分组成;首先是空间特征 运动，定义运动发生的轴，类型 无论是扩散的还是不连续的，如在跳跃中 构象子态的势能最小值之间， 最后是运动的范围或幅度。 仅当 运动的空间模型是完整的， 频率的确定可由NMR弛豫进行 数据 详细描述了每一个地方的动态， 短杆菌肽中的37个结构单元由52个扭转连接 在本提案中寻求角度。 通道的传输函数从计算中出现 研究依赖于主链的柔性。 的 这些局部运动的第一个实验证据是 在该赠款支持的头两年实现的目标 （Nicholson等人，1989）其中一组构象子状态 短杆菌肽骨架中的一个单一的肽键， 观察 该通道的结构还没有通过 衍射技术 在本报告的进度报告中， 研究计划是确定第一对 短杆菌肽骨架的扭转角 当结构 和动力学之间的独特关联已经被阐明 将实现该阳离子结构、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.