THEORETICAL ASPECTS OF DNA SUPERCOILING

描述：该项目结合了多种计算方法 (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来检验 拓扑结构的超螺旋DNA的构型和性质 受高阶折叠的双螺旋的约束形式和 补偿性绞股。长的序列依赖的特征， 线状聚合物被结合在弹性杆理论中，并 经过数值模拟处理。循环闭合的约束条件是 有两种不同的处理方式，一种使用曲线拟合技术，另一种使用 其他涉及欧拉参数。前一种方法引入了简单 数学公式--分段B-样条曲线或有限傅立叶 系列表示--自动满足端到端的 对受约束DNA的限制。欧拉参数是未知数 在超螺旋DNA的弹性棒处理中确定。两者都有 表示法有助于快速优化链结构。这些型号 在某种意义上是有吸引力的，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 与顺序相关的弯曲、扭曲和拉伸。通过组合 通过计算机模拟的分析研究，奥尔森博士不仅获得了 补充信息，但也有一系列内置的检查和 用于评估她的发现的意义的平衡。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。 聚电解质骨架与局部化学环境的影响 将被隐式处理，通过在 沿着链轮廓分离的残基或通过结合显式 外力。直接的目标是描述链的配置和 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-磷酸主链)和配基结合(蛋白质、药物) 双螺旋的整体折叠。第二个目标是发现 超线圈诱导的DNA转变的结构细节，如 螺旋解旋与生物过程有关。在科学界 需要解决的问题是：(1)序列依赖局部的作用 全球平衡中的结构和特定蛋白质构象 超螺旋DNA的结构；(2)配体诱导解离的效应 关于空间受限DNA的大规模构型转变；(3) 多个蛋白质对整体形状和形状的竞争效应 超螺旋双重体的变形性；(4)局部和局部的相互作用 超卷动力学中的整体结构；(5)离子效应 分子形状和柔韧性的条件。

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.