DYNAMIC AND STRUCTURAL ELUCIDATION OF GRAMICIDIN A

短杆菌肽 A 的动态和结构解析

• 批准号: 3134817
• 负责人: TIMOTHY A CROSS
• 金额: $ 12.46万
• 依托单位: FLORIDA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-01-01 至 1994-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3134817
• 关键词: branched chain aminoacid; chemical models; chemical structure; chemical structure function; high performance liquid chromatography; intermolecular interaction; lipid bilayer membrane; membrane channels; membrane lipids; membrane proteins; molecular dynamics; molecular polarity; nuclear magnetic resonance spectroscopy; protein structure; protein structure function; radiotracer; stable isotope; temperature

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.

这里提出的是关于继续实施一个项目的提案 短杆菌肽A阳离子通道旨在解释详细 通过阐明通道结构获得电导数据 和具有原子分辨率的动力学。 结构方面 固态核磁共振测定的努力结果 多肽内的共价键方向 共同轴，磁场方向。 来自债券 相邻组的方向，扭转角被确定 定义这些群体的相对方向。 因为 已知共价结构可确定扭转角 （总共 52 个短杆菌肽）将导致原子分辨率 结构测定。 这里描述的就是这样一个完整的 结构测定。 动态特性为 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 运动的程度，无论是扩散的还是不连续的（如啤酒花） 构象亚态的势能最小值之间，以及 最后是运动的范围或幅度。 只有当这个 运动的空间模型已完成，可以准确地 根据 NMR 弛豫确定频率 数据。 每个区域的本地动态的详细描述 短杆菌肽的 37 个结构单元通过 52 个扭转连接 该提案寻求角度。 通道的传输函数由计算得出 研究依赖于脊柱的灵活性。 这 这些局部运动的第一个实验证据是 在本次赠款的前两年获得的支持 (Nicholson et al., 1989) 其中一组构象亚状态 对于短杆菌肽主链中的单肽键已 观察到。 该通道的结构尚未实现 衍射技术。 在本次进度报告中提出 研究计划是确定第一对 短杆菌肽主链中的扭转角。 当结构 和动力学之间的独特相关性已被阐明 该阳离子的结构、动力学和功能将得到实现 渠道。