DNA CONDENSATION BY MULTIVALENT CATIONS

说明：（来自申请人的摘要）本项目的目标是 了解多价DNA缩合的物理机制， 阳离子，以便更好地了解控制冷凝的因素， 以及在核酸制备和基因工程中的应用 工程.这需要阐明的机制和速率常数， 凝聚过程中的基本步骤，分子间力 稳定凝聚态，共溶剂的作用，和具体的 行为，添加到一般原则，调节特定的行动， 缩合配体和DNA序列。它还提出了关于 在此条件下，其他聚电解质，也许不太高的电荷， 比DNA硬，也可以被诱导进行缩合成离散的 可能具有与健康相关的应用以及基本的 兴趣 具体目标：进行数值建模和解释的动力学 DNA凝聚的基本过程-初始成核和单分子 坍缩，环形粒子的中间时间增长，以及长期 二次聚集，得到一个完整的机理图。继续 发展了基于涨落的DNA间吸引力理论 考虑到配体的空间范围和 DNA表面的曲率。布卢姆菲尔德博士会用这个理论来理解 过量冷凝剂对能量学的影响，以及过渡 在密集DNA阵列中的两体力和多体力之间。继续DNA 渗透剂水溶液中的冷凝测量，并将它们联合收割机 混合溶剂体系的统计热力学处理，获得 深入了解DNA中优先溶剂化和介电效应的作用 凝研究DNA缩合通过广泛的阳离子 配体，以深入了解更高的电荷，电荷 分布，配体迁移率和空间特征的能量和 紧密堆积的DNA束结构。研究对DNA的影响 生物学上感兴趣的重复序列的浓缩， 和与遗传疾病相关的三联体重复序列。探讨 大分子和小分子DNA的共缩合，以及其他DNA分子的缩合。 生物聚合物，如RNA和多肽。

DESCRIPTION: (From the Applicant's Abstract) The objective of this project is to understand the physical mechanism of DNA condensation by multivalent cations, so as to understand better the factors controlling condensation in viruses and cells and in applications to nucleic acid preparation and genetic engineering. This requires elucidation of the mechanism and rate constants for the elementary steps in the condensation process, the intermolecular forces stabilizing the condensed state, the role of co-solvents, and the specific behavior, added to general principles, that modulates the action of particular condensing ligands and DNA sequences. It also raises questions about the conditions under which other polyelectrolytes, perhaps less highly charged and stiff than DNA, can also be induced to undergo condensation into discrete particles that may have health-related applications as well as fundamental interest. Specific aims: Perform numerical modeling and interpretation of the kinetics of elementary processes in DNA condensation-initial nucleation and monomolecular collapse, intermediate time growth of toroidal particles, and longer-term secondary aggregation, to get an integrated mechanistic picture. Continue development of a theory of attractive forces between DNAs based on fluctuations of the counterion atmosphere, taking into account ligand spatial extent and the curvature of the DNA surface. Dr. Bloomfield will use this theory to understand the effects of excess condensing agent on energetics, and the transition between two-body and many-body forces in dense DNA arrays. Continue DNA condensation measurements in aqueous solutions of osmolytes, and combine them with statistical thermodynamic treatment of mixed solvent systems, to gain insight into the role of preferential solvation and dielectric effects in DNA condensation. Investigate DNA condensation by a broad range of cationic ligands, to gain insight into the effects of higher charge, charge distribution, and ligand mobility and steric character on the energetics and structure of tightly-packed DNA bundles. Investigate the effects on DNA condensation of biologically interesting repetitive sequences such as A-ttracts and triplet repeats associated with genetic diseases. Investigate co-condensation of large and small DNA molecules, and condensation of other biopolymers, such as RNA and polypeptides.