Postdoc: Brownian Dynamics of DNA Slithering

PI将在高性能计算机上开发和应用新的计算建模技术，以增强我们在全球水平上(即数千个碱基对)对DNA的理解。具体地说，PI将描述超螺旋DNA在微秒到毫秒的时间范围内滑动的动力学特征。滑动在重组机制中被认为是重要的，它是一种爬行动物的运动，在这种运动中，单个碱基对以传送带的方式相互滑动。PI将扩展先前开发的超螺旋DNA的朗之万动力学模型，以纳入流体动力学相互作用。DNA分子将由B-Spline模型表示，该模型将平滑地转换为珠子模型。奇异值分解将用于将定义DNA曲线(控制点)的自变量空间中的向量变换为实际曲线(DNA)点空间中的向量。由于毫秒级模拟是计算密集型的，因此将采用12处理器的Power Challenge型计算机和高效的并行策略。为了测量与滑动相关的特征时间，PI将使用三维图形工具来分析颗粒间距离和曲率随时间的演变，从而确定位点并列时间与DNA大小的比例。该项目的计算模型将补充实验，并提供对超螺旋DNA在复制、重组和转录中的关键作用的洞察。这里开发的算法是通用的，可以应用于广泛的其他重要的生物分子问题。

The PI's will develop and apply novel computational modeling techniques on high-performance computers to enhance our understanding of DNA on a global level, i.e., thousands of base pairs. Specifically, the PI's will describe the dynamical features of slithering in supercoiled DNA over microsecond to millisecond time frames. Slithering, which is thought to be important in recombination mechanisms, is a reptilian motion in which individual base pairs slide against each other in a "conveyor-belt" fashion. The PI's will extend a previously developed Langevin dynamics model of supercoiled DNA to incorporate hydrodynamic interactions. The DNA molecule will be represented by a B-spline model that smoothly transforms into a bead model. The singular value decomposition will be used to transform a vector in the space of the independent variables defining the DNA curve ("control" points) to a vector in the space of the actual curve (DNA) points. Because the millisecond simulations are computationally intensive, a 12-processor Power Challenge computer and efficient parallel strategies will be employed. To measure characteristic times related to slithering, the PI's will use three-dimensional graphics tools to analyze interparticle distance and curvature time-evolution, and thus determine the scaling of site juxtaposition times with DNA size. The computational modeling of this project will complement experiments and provide insight into the vital role of supercoiled DNA in replication, recombination, and transcription. The algorithms developed here are general and can be applied to a wide range of other important biomolecular problems.