THEORETICAL ASPECTS OF DNA SUPERCOILING

描述：该项目结合了各种计算方法 （蒙特卡罗和分子动力学模拟，能量最小化， 数值积分）与弹性杆理论的发展，以检查 超螺旋DNA的结构和性质，拓扑 双螺旋的受约束形式受到高阶折叠， 补偿股捻。 序列依赖性特征的长， 线状聚合物被纳入弹性杆的理论中， 通过数值模拟进行处理。 循环闭合的约束是 以两种不同的方式处理，一种使用曲线拟合技术， 其他涉及欧拉参数。 前一种方法引入了简单的 数学公式-分段B样条曲线或有限傅立叶 系列表示-自动满足端到端 DNA的局限性。 欧拉参数是未知数 在超螺旋DNA的弹性棒处理中确定。 两 表示有助于链配置的快速优化。 这些模型 是有吸引力的，因为它们可以与已知的 理想系统的行为，以及扩展到真实的遗传序列 具有顺序相关的弯曲、扭曲和拉伸。 通过组合 分析研究与计算机模拟，奥尔森博士不仅获得 补充信息，但也有一系列内置的检查， 平衡评估她的发现的重要性。 计算 结果刺激新的理论发展，这反过来又可以用来 评估计算的有效性。 主链和局部化学环境的影响 将被视为隐式通过引入各种赝势之间 沿着链轮廓沿着分离的残基或通过结合明确的 外部力量。 当前的目标是描述链的配置， 在现实分子模型方面的性质。 拟议的研究可 阐明主要化学特征（碱基，序列， 糖-磷酸骨架）和配体结合（蛋白质，药物） 双螺旋的整体折叠。 第二个目标是揭示 超螺旋诱导的DNA跃迁的结构细节，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）序列依赖性局部的作用 结构和特定蛋白质构象对全局平衡的影响 超螺旋DNA的结构;（2）配体诱导解旋的影响 空间约束DNA的大尺度构型转变;（3） 多种蛋白质对整体形状的竞争作用， 超螺旋双链体的变形性;（4）局部和 超螺旋动力学中的全局结构;（5）离子的影响 分子形状和柔性的条件。

DESCRIPTION: This project combines a variety of computational approaches (Monte Carlo and molecular dynamics simulations, energy minimization, numerical integration) with developments in elastic rod theory 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. The constraints of loop closure are treated in two different ways, one using curve fitting techniques and the other involving Euler parameters. The former approach introduces simple mathematical formulations --piecewise B-spline curves or finite Fourier series representations --that automatically satisfy the end-to-end limitations on constrained DNA. The Euler parameters are unknowns determined in the elastic rod treatment of supercoiled DNA. Both representations aid rapid optimization of chain configuration. These models are attractive in the sense that they can be compared with the known behavior of ideal systems, as well as extended to real genetic sequences with sequence dependent bending, twisting, and stretching. By combining analytical studies with computer simulations, Dr. Olson not only obtains complementary information, but also has a series of built-in checks and balances for assessing the significance of her 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 will be treated implicitly by introducing various pseudo-potentials between residues separated along the chain contour or by incorporating explicit external forces. The 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. A second objective is to uncover structural details of supercoil-induced transitions of DNA, such as the helical unwinding implicated in biological processes. Among the scientific questions to be addressed are: (1) the role of sequence-dependent local structure and specific protein conformation on the global equilibrium structures of supercoiled DNA; (2) the effects of ligand-induced unwinding on large-scale configurational transition of spatially constrained DNAs; (3) the competing effects of multiple proteins on the overall 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 molecular shape and flexibility.