Electrostatics of Soft Biomolecular Assemblies

这个理论项目结合到泊松玻尔兹曼理论离子自由度，并适用于四个不同的生物分子组装的扩展理论形式主义。每个组件突出了一个特定的自由度，从而阐明了细胞系统中静电相互作用的离子内相关性的至关重要性。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不能横向螯合单价脂质，目前还没有令人满意的解释。第二个项目模拟了以前被忽视的两性离子脂质的偶极距对静电膜大离子相互作用的影响。其目的是解释阳离子和阴离子膜及其与大离子如DNA的相互作用所观察到的差异。 第三个计画是研究棒状离子介导的大离子间的架桥作用。例如，这些离子以DNA凝聚剂如多胺或细胞骨架成分的形式出现。 第四个项目研究由DNA和可电离的阳离子聚合物形成的复合物。在这里，我们的目的是模拟质子海绵机制，通过该机制，DNA聚乙烯亚胺复合物被认为是逃脱endosome.In所有四种情况下，方法的方法是纳入变分形式主义的平均场静电离子自由度，其中包括可变极化，偶极和高阶矩，电离。离子内相关长度超过Debye长度将导致非定域PB方程，这一研究将提高我们理解和设计与生物相关的大离子组装体的能力，如膜-肽复合物和软阳离子大离子-DNA凝聚体。在国家会议和学术讨论会上传播结果将说明这项工作的跨学科性质。该项目整合到物理系的新重点软凝聚态，重点是计算方法和生物物理应用。教育方面涉及两名研究生的培训和引入一个新的研究生课程（从物理角度理解药物和药理学中的膜）由PI共享。非技术：在这个项目中，计算物理学的技术将被应用于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。 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理解。 这项研究是物理学系发生革命的一个例子，因为物理学研究的方法被应用于生物系统。 除了研究的重要性之外，同样重要的是培养新一代的学生在生物学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.