THEORETICAL ASPECTS OF DNA SUPERCOILING

DNA 超螺旋的理论方面

• 批准号: 2177587
• 负责人: Wilma K Olson
• 金额: $ 16.71万
• 依托单位: RUTGERS, THE STATE UNIV OF N.J.
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-08-01 至 1997-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2177587
• 关键词: DNA; DNA binding protein; analytical method; circular DNA; computer data analysis; computer simulation; conformation; elasticity; electric field; intermolecular interaction; ionic strengths; mathematical model; molecular dynamics; nucleic acid sequence; nucleic acid structure; nucleoproteins; structural biology; thermodynamics

The major objective of this research is to understand and visualize the structure and properties of supercoiled DNA. The trajectories of the long spatially constrained molecules are generated with curve fitting techniques commonly used in computer aided design and engineering. These approaches automatically satisfy the ring closure constraints of cyclic DNA and/or the end-to-end limitations on spatially fixed open DNA, and involve a relatively limited number of independent variables. Because of the use of mathematical representations, the number of variables that can be placed on the curves is unlimited and it is possible to treat very long chain molecules. Furthermore, because the number of independent variables is limited, it is possible to simulate the large conformational changes found in supercoiled DNAs. The immediate goal of the research is to describe chain configuration and properties in terms of realistic molecular models. The energy of the DNA will be described in terms of simple elastic terms that mimic the sequence-dependent bending and twisting of the chain observed at the local level. The proposed studies may clarify the role of local structure (primary base sequence and polyelectrolyte sugar-phosphate backbone) and ligand binding (proteins and drugs) on the overall folding of the chain. A second goal is to uncover structural details of supercoil-induced transitions of DNA, such as those involving right- and left-handed duplexes. The research combines a variety of computational approaches (Monte Carlo and molecular dynamics simulations, potential energy minimizations, finite element analysis, systematic molecular modeling) with new developments in elasticity theory. Among the scientific issues to be addressed are: (1) the competing effects of two or more bound proteins on the spatial configurations and range of flexibility of the double helix; (2) the possible role of highly bent fragments on the overall structure of kinetoplast DNA minicircles; (3) the extent to which local sequence fixes the branching in long, naturally occurring supercoils; (4) the effects of twist density and fragment length on large-scale supercoiling transitions; (5) the degree of non-uniformity of local twist in protein-bound DNAs; (6) the role of chain fluctuations on the X-ray scattering of supercoiled DNA; (7) the relative time scales of different supercoiling motions; (8) the effect of salt concentration and/or external electric field on molecular shape and flexibility.

这项研究的主要目标是理解和可视化 超螺旋DNA的结构和性质。长河的轨迹 用曲线拟合法生成空间受限的分子 计算机辅助设计和工程中常用的技术。这些 自动满足循环的环闭合约束的方法 DNA和/或空间固定的开放DNA的端到端限制，以及 涉及的自变量数量相对有限。因为. 使用数学表示法，变量的数量可以 被放置在曲线上是无限的，而且有可能治疗很长时间 链状分子。此外，由于自变量的数量 是有限的，所以有可能模拟大的构象变化 在超螺旋DNA中发现。这项研究的直接目标是 根据实际情况描述链的结构和属性 分子模型。DNA的能量将用以下方面来描述 简单的弹性项，模拟顺序相关的弯曲和 在地方一级观察到链条的扭曲。建议进行的研究 可以阐明局部结构(初级碱基序列和 聚电解质、糖-磷酸主链)和配体结合(蛋白质和 毒品)在链条的整体折叠上。第二个目标是发现 超线圈诱导的DNA转变的结构细节，如那些 涉及右手和左手的双重人。这项研究结合了各种 计算方法(蒙特卡洛和分子动力学 模拟，势能最小化，有限元分析， 系统分子模拟)和弹性理论的新发展。 需要解决的科学问题包括：(1)相互竞争的影响 两个或更多结合蛋白的空间构型和范围 双螺旋的柔韧性；(2)高度弯曲的可能作用 动质粒DNA小环整体结构上的片段；(3) 局部序列在多大程度上自然地固定了长分支 超线圈的产生；(4)绞合密度和碎片长度的影响 关于大规模超卷转变；(5)不均匀程度 蛋白质结合的DNA的局部扭曲；(6)链波动的作用 超螺旋DNA的X射线散射；(7)相对时间尺度 不同的超卷运动；(8)盐浓度的影响 和/或外加电场对分子形状和柔性的影响。