Electrostatics of Soft Biomolecular Assemblies

这一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。每个组件都突出了一个特定的自由度，从而说明了离子内相互作用对于细胞系统中静电相互作用的关键重要性。第一个项目涉及带电脂质在生物膜中的横向分布。它解决了实验观察到的小肽不能横向隔离单价脂类的问题，目前还没有令人满意的解释。第二个项目模拟了以前被忽略的两性离子脂的偶极矩对静电膜-大离子相互作用的影响。目的是解释观察到的阳离子和阴离子膜的差异，以及它们与DNA等大离子的相互作用。第三个项目研究棒状离子介导的大离子之间的桥联相互作用。例如，这些离子以DNA冷凝剂的形式出现，如多胺或细胞骨架成分。第四个项目研究DNA和可电离阳离子聚合物形成的络合物。在这里，目的是模拟质子海绵机制，通过它DNA聚乙烯亚胺复合体被认为逃脱内体。在所有四种情况下，方法论方法都是在平均场静电离子自由度的变分形式中结合，其中包括可变极化、偶极和高阶矩以及电离。超过德拜长度的离子内关联长度将产生非局域PB方程，这将提高我们理解和设计几种生物相关大离子组件的能力，如膜-肽复合物和软阳离子-DNA凝聚体。在国家会议和学术讨论会上传播成果将说明这项工作的跨学科性质。该项目纳入了物理系对软凝聚物质的新关注，重点放在计算方法和生物物理应用上。教育方面包括培训两名研究生和引入一门新的研究生课程(从物理角度理解药剂学和药理学)。非技术性：在这个项目中，计算物理技术将被应用于模拟一系列与生物膜有关的问题。生物膜是构成所有生命物质的所有细胞的重要组成部分。根据该奖项进行的研究将进一步加深我们对这些重要系统的了解。这项研究是物理系发生革命的一个例子，因为物理研究的方法被应用到生物系统中。除了研究的重要性之外，同样重要的是训练新一代学生在生物兴趣问题上使用这些技术。

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.