'WET' ELECTROSTATICS AND BIOMOLECULAR SELF-ASSEMBLY

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。“湿”静电相互作用的理解很少，经常表现出违反直觉的行为。例如，水溶液中两个带同种电荷的大分子被认为是相互排斥的，这基本上是流行的平均场理论的预测。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紧凑有序的状态。例子包括染色体中带电组蛋白的DNA凝聚，细菌和病毒衣壳中多价蛋白的DNA包装。在我们之前在SSRL的工作中，我们通过观察反离子组织直接观察了棒状聚电解质之间吸引的分子机制。目前提出的程序的目的是发展我们对更复杂形式的静电组装的直觉。我们将研究简单几何物体之间相互作用的一系列典型例子，例如在带同种电荷的棒和片（阴离子DNA和阴离子膜）之间形成的复合物，或在不同价盐存在下在带相反电荷的棒和球体（f -肌动蛋白和单分散阳离子球状蛋白（溶菌酶，乳铁蛋白））之间形成的复合物。特别是，我们将利用基因工程技术制造具有基本相同大小但具有不同净电荷和电荷分布的突变蛋白，并研究这些变化如何影响其自组装行为。

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.