Supercoiled DNA energetics and dynamics by computer simulation.
Supercoiled DNA energetics and dynamics by computer simulation.
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通过计算机模拟的超螺旋 DNA 能量学和动力学。
DOI：
10.1016/0022-2836(92)90263-j
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发表时间：
1992
影响因子：
5.6
通讯作者：
Olson,WK
中科院分区：
文献类型：
--
作者：
Schlick,T;Olson,WK
提出了一种通过确定性技术研究超螺旋 DNA 构型的新公式。到目前为止，将确定性方法应用于超螺旋 DNA 研究所涉及的计算困难通常将计算机模拟限制为随机方法。虽然随机方法（例如模拟退火和 Metropolis-Monte Carlo 采样）可以成功生成大量构型并估计拓扑异构体整体的热力学性质，但确定性方法可以准确表征最小值并系统地跟踪其动力学。为了使这一点可行，我们通过 B 样条带状模型根据 控制顶点数量较少。我们将由弯曲和扭转积分组成的弹性变形能关联起来，并通过 6-12 Lennard Jones 势来表示链内接触。后者被参数化以在观察到的 DNA 螺旋直径（包括水合壳）处产生能量最小值。还包括确保固定轮廓长度的惩罚项。能量函数的一阶和二阶偏导数已通过使用各种数学简化导出。一阶导数对于牛顿型最小化以及分子动力学至关重要，部分二阶导数信息可以通过预处理显着加速最小化收敛。在这里，我们应用一种新的大规模截断牛顿算法进行最小化，并应用朗之万/隐式欧拉方案进行分子动力学。我们的截断牛顿方法利用势能函数的可分离性来划分不同复杂度的项。它依赖于预条件共轭梯度方法，该方法对于大规模问题非常有效，可以近似求解每一步的搜索方向。我们的动力学算法在大时间步长上是数值稳定的。它还引入了一种频率辨别机制，以便该方法基本上冻结频率大于所选截止频率的振动模式。利用这些工具，我们可以快速识别小 DNA 环的相应圆形和缠绕能量最小值，以实现一系列施加的连接数差异。这些结构与现有的电子显微镜数据一致。圆和 8 字形之间的稳定性能量交换也很详细，与分析结果非常一致。 100 飞秒时间步长的分子动力学轨迹揭示了不稳定圆形状态快速折叠成超螺旋形式。还观察到缠绕结构的显着弯曲和扭转运动。这些信息可能有助于理解折叠途径的过渡态以及调节超螺旋的酶的作用。更一般地说，通过这种确定性方法获得的新定量数据可能有助于解释超螺旋对关键生物过程的影响。
A new formulation is presented for investigating supercoiled DNA configurations by deterministic techniques. Thus far, the computational difficulties involved in applying deterministic methods to supercoiled DNA studies have generally limited computer simulations to stochastic approaches. While stochastic methods, such as simulated annealing and Metropolis-Monte Carlo sampling, are successful at generating a large number of configurations and estimating thermodynamic properties of topoisomer ensembles, deterministic methods offer an accurate characterization of the minima and a systematic following of their dynamics.To make this feasible, we model circular duplex DNA compactly by aB-spline ribbon-like model in terms of a small number of control vertices. We associate an elastic deformation energy composed of bending and twisting integrals and represent intrachain contact by a 6–12 Lennard Jones potential. The latter is parameterized to yield an energy minimum at the observed DNA-helix diameter inclusive of a hydration shell. A penalty term to ensure fixed contour length is also included. First and second partial derivatives of the energy function have been derived by using various mathematical simplifications. First derivatives are essential for Newton-type minimization as well as molecular dynamics, and partial second-derivative information can significantly accelerate minimization convergence through preconditioning. Here we apply a new large-scale truncated-Newton algorithm for minimization and a Langevin/implicit-Euler scheme for molecular dynamics. Our truncated-Newton method exploits the separability of potential energy functions into terms of differing complexity. It relies on a preconditioned conjugate gradient method that is efficient for large-scale problems to solveapproximatelyfor the search direction at every step. Our dynamics algorithm is numerically stable over large time steps. It also introduces a frequency-discriminating mechanism so that vibrational modes with frequencies greater than a chosen cutoff frequency are essentially frozen by the method.With these tools, we rapidly identify corresponding circular and interwound energy minima for small DNA rings for a series of imposed linking-number differences. These structures are consistent with available electron microscopy data. The energetic exchange of stability between the circle and the figure-8, in very good agreement with analytical results, is also detailed. Molecular dynamics trajectories at 100 femtosecond time steps then reveal the rapid folding of the unstable circular state into supercoiled forms. Significant bending and twisting motions of the interwound structures are also observed. Such information may be useful for understanding transition states along the folding pathway and the role of enzymes that regulate supercoiling. More generally, new quantitative data obtained by such deterministic approaches may help in interpreting the effects of supercoiling on key biological processes.
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影响因子：
4.4
作者：
BARKLEY, MD;ZIMM, BH
通讯作者：
ZIMM, BH
DOI：
10.1137/0911064
发表时间：
1990-11
期刊：
SIAM J. Sci. Comput.
影响因子：
--
作者：
Bobby Schnabel;E. Eskow
通讯作者：
Bobby Schnabel;E. Eskow
评估和微分 cos ψ 表达式的方法
影响因子：
3
作者：
T. Schlick
通讯作者：
T. Schlick
使用朗之万/隐式欧拉方案通过分子动力学研究跃迁率
影响因子：
4.4
作者：
A. Nyberg;T. Schlick
通讯作者：
T. Schlick
计算机和国际象棋
DOI：
10.1007/bf03022853
发表时间：
1980
期刊：
The Mathematical Intelligencer
影响因子：
--
作者：
R. Filman
通讯作者：
R. Filman