VIBRATIONS, STRUCTURE AND DYNAMICS OF BIOMACROMOLECULES

生物大分子的振动、结构和动力学

• 批准号: 6342776
• 负责人: HERBERT L STRAUSS
• 金额: $ 29.14万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 1980
• 资助国家: 美国
• 起止时间: 1980-04-01 至 2002-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6342776
• 关键词: Raman spectrometry; biophysics; calorimetry; chemical aggregate; chemical chain length; chemical models; chemical structure function; computer data analysis; computer program /software; computer simulation; computer system design /evaluation; conformation; infrared spectrometry; lipid bilayer membrane; lipid structure; mathematical model; membrane activity; membrane lipids; method development; molecular dynamics; phospholipids; structural biology; thermodynamics

DESCRIPTION: The principal goal of this research is to characterize the molecular organization of the bilayer and, in particular, to provide molecule-level information concerning the nature of the heterogeneity in the lateral distribution of lipids in membranes. This heterogeneity, only recently revealed, is manifest in membranes as a loose mosaic of lipid domains if varying size. Its study is important because of the role that lipid composition plays in modulating the biological activity of membrane-associated proteins. Little is known about the organization of these domains, especially of molecular-level size "microdomains". The primary techniques to be used in this investigation are infrared and Raman spectroscopy, complemented by calorimetry. The main focus will be on the development and use of our infrared isotope method for measuring lateral microaggregation in model membranes. This technique measures microdomains of the smallest possible size, 1 to 100 molecules, a range that is inaccessible to the other techniques currently being used. At present our method can be applied only to the gel phase, but will be adapted for the fluid phase by combining it with fast-freeze methods. The lateral organization of the lipids surrounding proteins in a membrane will be investigated since such organization may play an important role in processes such as visual transduction. Other studies will focus on determining the structure and properties of microdomains in mixed lipid bilayers, on identifying the factors that lead to domain formation and, where possible, on measuring the kinetics involved. The conformational statistics of the chains in computer-modeled bilayers - which are ever more realistic and now worthy of serious scrutiny - will be critically analyzed and compared with spectroscopic measurements. Much needed vibrational spectroscopic methods for measuring disorder in the unsaturated chains in bilayers will be developed along with new spectroscopic approaches for determining bilayer structure.

描述：这项研究的主要目标是描述 双分子层的分子组织，尤其是提供 分子水平的信息，关于异质性的性质 膜脂的横向分布。这种异质性，只有 最近发现，在膜上表现为脂类的松散马赛克 域，如果大小不同的话。它的研究很重要，因为它的作用是 脂类成分在调节细胞生物活性中的作用 膜相关蛋白。人们对其组织方式知之甚少 这些结构域，尤其是分子级大小的“微域”。这个 调查中使用的主要技术是红外线和拉曼光谱。 光谱学，辅之以量热法。主要焦点将放在 红外同位素侧向测量方法的研制与应用 模型膜中的微聚集。这项技术测量微域 最小的分子，1到100个分子，这个范围是 目前正在使用的其他技术无法访问。目前我们的 方法只能应用于凝胶相，但将适用于 通过将其与快速冷冻方法相结合来实现对液体相的检测。侧向 膜中蛋白质周围的脂类的组织将是 由于此类组织可能在流程中发挥重要作用，因此进行了调查 比如视觉转导。其他研究将集中在确定 混合脂类双层中微区的结构和性质 确定导致领域形成的因素，并在可能的情况下， 关于测量所涉及的动力学。分子的构象统计 计算机模拟的双层结构中的链条--它们比以往任何时候都更加真实 值得认真审查-将进行批判性分析并与 光谱测量。亟需的振动光谱方法 用于测量双分子层中不饱和链的无序度 与测定双分子层的新光谱方法一起发展 结构。