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

本项目的目标是完成MBO（N）D的开发 分子动力学模拟方法 特别用于核酸应用（例如，DNA，RNA），如 在抗癌药物研究中遇到的。MBO（N）D的独特方法 将分子亚结构化为柔性和/或刚性体允许MBO（N）D 需要很长的时间步长，在计算中产生100或更多的因子， 与全原子方法相比，速度更快。这提供了一条新的高效路线 到稳定的长时间持续的轨迹，从可靠的结构 可以计算稳定性、自由能和结合势。 第二阶段的主要目标是开发和评估可推广的 用于寡核苷酸、溶剂和盐的MBO（N）D亚结构化方案。 这是最终广泛的科学效用的关键， MBO（N）D的商业化 一系列的单、双、三重测试 将分析案例（包括溶剂和抗衡离子）， 制定适当的子结构方案，最大限度地提高MBO（N）D的 计算速度，同时保持准确的基本动态。 准确性评估将包括与全原子系综的比较 统计，包括RMS位置和角度波动，自由能， 等人 建议商业应用：成功完成该项目 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制。它将允许 可靠结构所需的长时间模拟 稳定性、自由能和结合势。这种能力是 抗癌和其它核酸药物研究者高度需求。

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.