A Comprehensive Approach Towards Adaptive Multiscale Modeling of Biopolymers Using Highly Parallelizable Methods

本论文的主要目的是研究和扩展能够为高度复杂的生物聚合物（例如RNA、DNA、蛋白质等）的动态行为的有效自适应建模和仿真提供全面框架的方法。在多个空间和时间尺度上发生重要现象的系统。为了减轻这些复杂问题的计算负担，通常需要局部或全局地改变系统分辨率。本研究利用高效的，高度并行化的分治算法（DCA）为基础的方法来模拟不同领域的大型系统同时在不同的分辨率（从原子到连续），以及自适应切换这些决议（由内部指标指导），以实现模拟速度和精度的接近最佳组合。这项研究如果成功，将允许这些系统的建模和详细的动态模拟的水平大大超出（在系统的大小，保真度和模拟持续时间），这是目前可能的。 框架组件和基本机制将被研究、设计、制造和测试，以验证底层方法和模型，并展示性能。这些成果将包括基本建模模型类型和模型类型转换工具的目录、源代码、演示和验证文件、研究结果文档、工程学生教育以及地区STEM教师的工程研究经验。如果成功，这项工作的影响将大大提高对此类复杂系统进行建模和分析的速度和程度。这将使分析师能够以比目前更有效的方式处理更复杂的系统（不仅仅是生物聚合物）。这将提供对关键生物分子过程的更深入的洞察和理解，这可能对我们未来学习修改和控制这些基本过程有很大贡献。这种理解和能力可以在许多积极方面对人类健康产生重大影响。这项工作的关键方面将在本科和研究生阶段的动态和计算课程中适当地介绍，展示这项研究如何与课程主题相关，并使学生熟悉先进的分析，多尺度，数值和自适应方法。将开发相关的教学辅助工具和基于网络的工具，相关的开源程序将免费分发（这项工作也将成为POEMS，LAMMPS和SimTK计算工具的组成部分）。一些学生更直接的本科生参与将通过本科生研究计划（URP）的参与来实现，目标是来自代表性不足的群体的学生。

The principal objective of this work is to research and extend methods which can provide a comprehensive framework for the efficient adaptive modeling and simulation of the dynamic behavior of highly complex bio-polymeric (e.g. RNAs, DNAs, proteins, etc.) systems where important phenomena take place at multiple spatial and temporal scales. In order to alleviate the computational burden of these complex problems it is often required to change the system resolution locally or globally. This research utilizes efficient, highly parallelizable Divide and Conquer Algorithm (DCA)-based methods to model different domains of large systems simultaneously in different resolutions (from atomistic to continuum), as well as, adaptively switching between these resolutions (as guided by internal metrics) so to realize a near optimal combination of simulation speed and accuracy. This research if successful will allow the modeling and detailed dynamic simulation of these systems to a level greatly beyond (in system size, fidelity, and simulation duration) that which is currently possible. Framework components and basic mechanisms will be researched, designed, fabricated, and tested to validate the underlying methods and models as well as demonstrate performance. Deliverables will include a catalog of fundamental modeling model types and model-type transitioning tools, source code, demonstration and validation files, documentation of research results, engineering student education, and engineering research experiences for area STEM teachers.If successful, the impact of this work will be a great increase in the rate and extent to which such complex systems may be modeled and analyzed. This will allow the analyst to treat far more complex systems (not just bio-polymers) in a more cost, time, and resource effective manner than is currently possible. This will provide greater insight into and understanding of key biomolecular processes, which may contribute greatly to our learning to modify and control such essential processes in the future. Such understanding and ability could significantly impact human health in many positive respects. Key aspects of this work will be presented as appropriate in undergraduate and graduate level courses in dynamics, and computation, demonstrating how this research relates to the course topics, and familiarizing the students with the advanced analysis, multiscale, numerical, and adaptive methods available. Related instructional aids and web-based tools will be developed, with the associated open source programs being freely distributed (this work will also become and integral part of the POEMS, LAMMPS, and SimTK computational tools). More direct undergraduate involvement by some students will be achieved through Undergraduate Research Program (URP) participation, targeting students from under-represented groups.