Theoretical Aspects of DNA Supercoiling

DNA 超螺旋的理论方面

• 批准号: 6472960
• 负责人: Wilma K Olson
• 金额: $ 22.52万
• 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 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6472960
• 关键词: DNA; DNA binding protein; chemical structure function; circular DNA; computer data analysis; computer simulation; conformation; elasticity; gene induction /repression; genetic regulation; genetic regulatory element; intermolecular interaction; ionic bond; ionic strengths; mathematics; model design /development; molecular dynamics; molecular shape; nucleic acid sequence; nucleic acid structure; physical model; structural biology; thermodynamics

DESCRIPTION (provided by applicant): The research combines computer simulation (energy optimization and normal mode analysis at the level of neighboring base pairs) with new developments in the theory of elastic rods to examine the configurations and properties of supercoiled DNA, a topologically constrained form of the double helix subject to higher-order folding and compensatory strand twisting. Sequence-dependent features of the long, threadlike polymer are incorporated in the theory of elastic rods and treated by numerical simulations. By combining analytical studies with computer simulations, we obtain complementary information and have a series of built-in checks and balances for assessing the significance of our findings. The computational results stimulate new theoretical developments, which in turn can be used to assess the validity of the calculations. The effects of the polyelectrolyte backbone and local chemical environment are treated implicitly with knowledge-based potentials extracted from high resolution structures of double helical DNA and, in representative cases, with explicit treatment of electrostatic forces. Our immediate goal is to describe chain configuration and properties in terms of realistic molecular models. The proposed studies may clarify the role of primary chemical features (base sequence, sugar-phosphate backbone) and ligand binding (proteins, drugs) on the overall folding of the double helix. We aim to develop an accurate and comprehensive model of the configurational properties of the DNA loops tethered to the Lac repressor-operator assembly with the possibility of learning new details about the role of DNA structure in the regulation of transcription. A second goal is to uncover structural details of supercoil-induced transitions of DNA, such as the helical unwinding implicated in biological processes. Among the scientific issues to be addressed are: (1) the role of sequence-dependent local structure and specific protein conformation on the global features of supercoiled chains; (2) the role of sequence and ligand binding on large-scale configurational transitions of spatially constrained DNA; (3) the competing effects of multiple proteins on the shape and deformability of the supercoiled duplex; (4) the interplay of local and global structure in supercoiling dynamics; (5) the effect of ionic conditions on loop configuration.

描述(申请人提供)：该研究结合了计算机模拟 (相邻基地层面的能量优化和简正波分析 对)，与弹性杆理论的新发展，以检查 拓扑受限的超螺旋DNA的构型和性质 受高阶折叠和补偿的双螺旋形式 股线缠绕。长的线状聚合物的序列相关特性 被结合到弹性杆理论中，并用数值方法处理 模拟。通过将分析研究与计算机模拟相结合，我们 获取补充信息，并有一系列内置检查和 用于评估我们发现的重要性的余额。计算性的 结果刺激了新的理论发展，这反过来可以用来 评估计算的有效性。聚电解质的作用 主干和局部化学环境被隐含地处理 从双分子的高分辨结构中提取基于知识的势 螺旋DNA，在有代表性的病例中，明确治疗 静电力。我们的直接目标是描述链结构和 在真实的分子模型方面的性质。拟议的研究可能 阐明主要化学特征(碱基序列、糖-磷酸)的作用 主干)和配基结合(蛋白质，药物)上的整体折叠 双螺旋。我们的目标是开发一个准确和全面的模型 与紫胶连接的DNA环的构型特性 抑制器-运算器程序集，可以了解有关 DNA结构在转录调控中的作用。第二个目标是 为了揭示超级线圈诱导的DNA转变的结构细节，例如 与生物过程有关的螺旋解旋。在科学界 需要解决的问题是：(1)序列依赖的局部结构的作用 和超螺旋链全局特征上的特定蛋白质构象； (2)序列和配体结合在大规模构型中的作用 空间受限DNA的跃迁；(3)多个 蛋白质对超螺旋双链的形状和变形能力的影响；(4) 局部和全局结构在超卷动力学中的相互作用；(5) 离子条件对环构型的影响。