Multi-variate Minimization Techniques and Molecular Dynamics Simulations for Predicting 3-D Structures of DNA and RNA on Supercomputers

本文提出的研究目标是开发 计算三维结构的数学工具 大生物分子。 特别是，建模和大型- 规模最小化技术将被设计来预测 单链和双链RNA和DNA分子的构象。 计算工具包括半经验势能 最小化和分子动力学，在Cray X-MP上执行 并借助交互式计算机图形在埃文斯和 Sutherland PS-330 计划在以下四个方面开展工作 程序开发的领域：（1）全局优化 策略;测试确定Tunnel方法的Levy和 Gomez和随机模拟退火的一个变体：（2） 更快地操纵能量中的成对相互作用 功能;调查最近提出的新方法， Greengard和Rokhlin提出的一个算法，该算法的时间复杂度为O（N2） N粒子系统排序的计算复杂性 O（N）：（3）分子动力学的实现：动力学 模拟将能够检查动态 最小化得到的结构轨迹; 和：（4）溶剂和金属离子的掺入到 分子模型;这将提供一个更现实的潜力 场表示影响RNA的分子力， 自然环境中的DNA 开发的计算工具 将产生的能力，调查一些问题的解决， 三维分子结构。 这些问题包括 DNA构象对核酸碱基的依赖性 序列、结构和复杂的折叠模式 单链RNA。最小化和动态结果将 用于制作16毫米电影和录像带， 结构的动态范围，并允许我们 具有已知生物学功能的构象特征。 该建议项目开发数学工具，使用 最先进的优化算法，用于检查 溶剂与金属离子相互作用的动力学模拟 生物学上重要的分子RNA和DNA。 计算科学与工程项目主任 建议提供69 370美元的支助，为期一年。

The goal for the research proposed here is to develop mathematical tools for computing three-dimensional structures of large biological molecules. In particular, modeling and large- scale minimization techniques will be devised to predict the conformations of single and doublestranded RNA and DNA molecules. The computational tools involve semi-empirical potential energy minimization and molecular dynamics, executed on the Cray X-MP and aided by interactive computer graphics on the Evans and Sutherland PS-330. The plan is to work on the following four areas of program development: (1) Global optimization strategies; test the determination Tunneling method of Levy and Gomez and a variant of the stochastic Simulated Annealing: (2) Faster manipulation of the pairwise interactions in the energy function; investigate the new method recently proposed by Greengard and Rokhlin which could reduce the order O(N2) computational complexity for an N - particle system to order O(N): (3) Implementation of molecular dynamics: dynamics simulations will enable an examination of the dynamic trajectories of the structures obtained from minimization; and: (4) Incorporation of solvent and metalions into the molecular model; this will provide a more realistic potential field to represent the molecular forces influencing the RNA and DNA in its natural milieu. The developed computational tools will yield the ability to investigate some intriquing problems of three-dimensional molecular structures. These problems include the dependence of DNA conformation on the nucleic acid base sequence and the structure and the complex folding patterns of single-stranded RNA. The minimizations and dynamics results will be used to make 16 mm films and videotapes that will reveal the dynamic range of structures and permit us to relate conformational features with known biological functions. This proposal projects to develop mathematical tools, using state-of-the-art optimization algorithms, for examination of dynamics simulation of solvent and metal-ion interaction in the biologically important molecular RNA and DNA. The Program Director for Computational Science and Engineering recommends support in the sum of $69,370 for a period of one year.