Electrostatics of Soft Biomolecular Assemblies

软生物分子组装体的静电

• 批准号: 0605883
• 负责人: Sylvio May
• 金额: $ 24万
• 依托单位: North Dakota State University Fargo
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-15 至 2011-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0605883&HistoricalAwards=false
• 关键词: Electrostatics; Soft; Biomolecular; Assemblies

This theoretical project incorporates into Poisson-Boltzmann theory ionic degrees of freedom and applies the extended theoretical formalism to four different biomolecular assemblies. Each assembly highlights a particular degree of freedom and thus exemplifies the crucial importance of intraionic correlations for electrostatic interactions in cellular systems.The first project concerns the lateral distribution of charged lipids in a biomembrane. It addresses the experimentally observed inability of small peptides to laterally sequester monovalent lipids which has currently no satisfactory explanation. The second project models the previously neglected influence of the dipolar moments of zwitterionic lipids on electrostatic membrane-macroion interactions. Theobjective is to explain differences that are observed for cationic and anionic membranes and their interactions with macroions such as DNA. The third project investigates the bridging interaction between macroions mediated by rod-like ions. These ions appear, for example, as DNA condensing agents such as polyamines or cytoskeletal components. The fourth project studies complexes formed from DNA and ionizable cationic polymers. Here, the aim is to model the proton sponge mechanism through which a DNA polyethylenimine complex is believed to escape the endosome.In all four cases, the methodological approach is to incorporate into the variational formalism of mean-field electrostatics ionic degrees of freedom, among them variable polarization, dipolar and higher-order moments, and ionization. Intra-ionic correlation lengths that exceed the Debye length will give rise to a non-local PB equation.The research will improve our ability to understand and design several bio-relevant macro-ionic assemblies, such as membrane-peptide complexes and soft cationic macroion-DNA condensates. Dissemination of the results in national meetings and colloquia will account for the inter-disciplinary character of the work. The project integrates into the Physics Department's new focus on soft condensed matter with emphasis on computational methods and biophysical applications. The educational aspect involves training of two graduate students and the introduction of a new graduate course (Understanding Membranes in Pharmaceutics andPharmacology from a Physical Perspective) shared by the PI.Non-Technical :In this project the techniques of computational physics will be applied to simulate a series of problems related to biomembranes. Biomembranes comprise a significant part of all cells that make up all living matter. The research conducted under this award will further our understanding of these important systems. The research is an example of a revolution occurring in physics departments as the methods of physics research are applied to biological systems. In addition to the importance of the research, of equal importance is the training of a new generation of students in using these techniques on problems of biological interest.

该理论项目将离子自由度纳入泊松-玻尔兹曼理论，并将扩展的理论形式应用于四种不同的生物分子组装体。每个组件都突出了特定的自由度，因此例证了离子内相关性对于细胞系统中静电相互作用的至关重要性。第一个项目涉及生物膜中带电脂质的横向分布。它解决了实验观察到的小肽无法横向隔离单价脂质的问题，目前尚无令人满意的解释。第二个项目模拟了先前被忽视的两性离子脂质偶极矩对静电膜-大分子相互作用的影响。目的是解释在阳离子膜和阴离子膜中观察到的差异以及它们与 DNA 等大离子的相互作用。 第三个项目研究由棒状离子介导的大离子之间的桥联相互作用。这些离子例如以 DNA 缩合剂的形式出现，例如多胺或细胞骨架成分。 第四个项目研究由 DNA 和可电离阳离子聚合物形成的复合物。这里，我们的目的是模拟质子海绵机制，据信 DNA 聚乙烯亚胺复合物可以通过该机制逃逸内体。在所有四种情况下，方法论都是将平均场静电离子自由度的变分形式纳入其中，其中它们具有可变的极化、偶极矩和高阶矩以及电离。超过德拜长度的离子内相关长度将产生非局部PB方程。该研究将提高我们理解和设计几种生物相关大离子组装体的能力，例如膜肽复合物和软阳离子大离子-DNA凝聚物。在全国会议和座谈会上传播成果将体现该工作的跨学科特征。该项目融入了物理系对软凝聚态物质的新关注，重点是计算方法和生物物理应用。教育方面包括培训两名研究生以及引入由 PI 共享的新研究生课程（从物理角度理解药剂学和药理学中的膜）。非技术：在该项目中，将应用计算物理技术来模拟一系列与生物膜相关的问题。 生物膜是构成所有生命物质的所有细胞的重要组成部分。 该奖项下进行的研究将进一步加深我们对这些重要系统的理解。 这项研究是物理系发生革命的一个例子，因为物理研究方法应用于生物系统。 除了研究的重要性之外，同样重要的是培训新一代学生使用这些技术来解决生物学感兴趣的问题。