DNA CONDENSATION BY MULTIVALENT CATIONS

描述：(摘自申请者的摘要)本项目的目标是 了解DNA多价缩合的物理机制 阳离子，以便更好地了解控制凝结的因素 病毒和细胞及其在核酸制备和遗传研究中的应用 工程学。这需要阐明其机理和速率常数。 缩合过程中的基本步骤，分子间力 稳定凝聚态，共溶剂的作用，以及特定的 行为，添加到一般原则中的行为，它调节特定的行为 浓缩配体和DNA序列。这也引发了人们对 在这种情况下，其他聚电解质，可能不那么高电荷和 比DNA僵硬，也可以诱导经历缩合成离散 可能具有与健康相关的应用以及基本应用的粒子 利息。 具体目标：进行动力学的数值模拟和解释 DNA缩合的基本过程--初始成核和单分子 崩塌，环状粒子的中间时间增长，以及更长期的 二次聚合，以获得完整的机理图景。继续 基于涨落的DNA间引力理论的发展 考虑到配体的空间范围和 DNA表面的曲率。布卢姆菲尔德博士将利用这一理论来理解 过量冷凝剂对能级的影响及其相变 在密集DNA阵列中的二体力和多体力之间。继续DNA 渗透分子水溶液中的冷凝测量及其组合 用混合溶剂体系的统计热力学处理，以获得 洞察优先溶剂化和介电效应在DNA中的作用 冷凝。研究大范围阳离子的DNA缩合反应 配体，为了深入了解更高电荷的影响，电荷 能量和空间性质的分布、配位体迁移率和空间性质 紧密堆积的DNA束的结构。调查对DNA的影响 生物学上有意义的重复序列的缩合，如A-ttracts 以及与遗传病相关的三联体重复序列。调查 大小DNA分子的共缩合以及其他分子的缩合 生物聚合物，如核糖核酸和多肽。

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.