'WET' ELECTROSTATICS AND BIOMOLECULAR SELF-ASSEMBLY

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 人们对“湿”静电相互作用知之甚少，常常表现出违反直觉的行为。例如，水溶液中两个相同电荷的大分子有望相互排斥，这本质上是主流平均场理论的预测。然而，在多价离子存在的情况下，许多生物聚合物实际上相互吸引并凝聚成致密、有序的状态。例如，染色体中带电的组蛋白导致的DNA缩合，以及细菌和病毒衣壳中的多价鱼精蛋白包装DNA。在我们以前在SSRL的工作中，我们通过观察反离子组织，直接观察到棒状聚电解质之间吸引的分子机制。目前提议的方案的目的是发展我们对更复杂形式的静电组装的直觉。我们将考察一系列简单几何对象之间相互作用的范例，例如在不同价态的盐存在下，相同电荷的杆和片之间形成的复合体(阴离子DNA和阴离子膜)，或者相反电荷的杆和球体之间形成的复合体(F-肌动蛋白和单分散的阳离子球状蛋白(溶菌酶、乳铁蛋白))。特别是，我们将利用基因工程技术来制造基本上相同大小但具有不同净电荷和电荷分布的突变蛋白质，并研究这些变化如何影响它们的自组装行为。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 'Wet' electrostatic interactions are poorly understood and often exhibit counterintuitive behavior. For example, two like-charged macromolecules in aqueous solution are expected to repel one another, which is essentially the prediction of prevailing mean-field theories. In the presence of multivalent ions, however, many biopolymers actually attract one another and condense into compact, ordered states. Examples include DNA condensation by charged histones in chromosomes, and DNA packaging by multivalent protamines in bacteria and viral capsids. In our previous work at SSRL, we have directly observed a molecular mechanism for attractions between rod-like polyelectrolytes by observing counterion organization. The aim of the present proposed program is to develop our intuition for more complex forms of electrostatic assembly. We will examine a series of paradigmatic examples of interactions between simple geometric objects, such as complexes formed between like-charged rods and sheets (anionic DNA and anionic membranes), or complexes formed between oppositely charged rods and spheroids (F-actin and monodisperse cationic globular proteins (lysozyme, lactoferrin)) in the presence of salts of different valence. In particular, we will take advantage of genetic engineering techniques to make mutant proteins with essentially the same size but with different net charges and charge distributions, and examine how these changes impinge on their self-assembly behavior.