MBO(N)D LONG TIME STEP DYNAMICS FOR NUCLEIC ACIDS

核酸的 MBO(N)D 长时间步长动力学

• 批准号: 2429780
• 负责人: HON M CHUN
• 金额: $ 45.42万
• 依托单位: MOLDYN, INC.
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-09-15 至 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2429780
• 关键词: computer program /software; method development; molecular dynamics; nucleic acids; oligonucleotides; salts; solvents

The goal of this project is to complete the development of the MBO(N)D (Multi-Body Order (N) Dynamics) molecular dynamics (MD) simulation method specifically for nucleic acid applications (e.g., DNA, RNA), such as encountered in anticancer drug research. MBO(N)D's unique approach of substructuring molecules into flexible and/or rigid bodies allows MBO(N)D to take long time steps, yielding factors of 100 or more in computational speed compared to all-atom methods. This offers a new and efficient route to stable long time duration trajectories from which reliable structural stabilities, free energies and binding potentials can be calculated. The primary Phase II objective is to develop and evaluate generalizable MBO(N)D substructuring schemes for oligonucleotides, solvent and salt. This is key to ultimate widespread scientific utility and commercialization of MBO(N)D. A series of single, duplex and triplex test cases (including solvent and counterions) will be analyzed in an effort to develop suitable substructuring schemes that maximize MBO(N)D's computational speed, while maintaining accurate essential dynamics. Accuracy evaluations will consist of comparison with all-atom ensemble statistics, including RMS position and angle fluctuations, free energy, and others. PROPOSED COMMERCIAL APPLICATION: Successful completion of this project will result in a highly efficient software code, MBO(N)D/NAD (Nucleic Acid Dynamics), specifically tailored for oligonucleotides. It will allow the long time duration simulations required for reliable structural stabilities, free energies, and binding potentials. Such a capability is in high demand by anticancer and other nucleic acid drug researchers.

本项目的目标是完成MBO(N)D的开发 多体有序(N)动力学分子动力学(MD)模拟方法 特别用于核酸应用(例如，DNA、RNA)，例如 在抗癌药物研究中遇到。MBO(N)D的独特方法 将分子亚结构化为柔性和/或刚体允许MBO(N)D 采取长时间步长，在计算中产生100或更多的系数 与全原子方法相比，速度更快。这提供了一条新的高效路线 到稳定的长持续时间轨迹，可靠的结构 可以计算其稳定性、自由能和结合势。 第二阶段的主要目标是开发和评估概括性 寡核苷酸、溶剂和盐的MBO(N)D亚结构方案。 这是最终广泛应用科学的关键，而且 MBO(N)D商业化一系列单、双、三联试验 将对案例(包括溶剂和反离子)进行分析，以努力 开发合适的子结构方案，使MBO(N)D最大化 计算速度，同时保持准确的基本动力学。 准确度评估将包括与全原子系综的比较 统计，包括均方根位置和角度波动，自由能， 还有其他人。 拟议的商业应用：成功完成本项目 将产生高效的软件代码MBO(N)D/NAD(核酸 动力学)，专门为寡核苷酸量身定做。它将允许 可靠的结构需要长时间的模拟 稳定性、自由能和结合势。这样的能力是 在抗癌和其他核酸药物研究人员中需求量很大。