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

这项工作的主要目标是研究和扩展方法，这些方法可以为高度复杂的生物聚合物（例如rna， dna，蛋白质等）系统的动态行为的有效自适应建模和模拟提供一个全面的框架，其中重要现象发生在多个空间和时间尺度上。为了减轻这些复杂问题的计算负担，通常需要改变局部或全局的系统分辨率。本研究利用高效、高度并行化的基于分而治之算法（DCA）的方法，以不同分辨率（从原子到连续体）同时对大型系统的不同域进行建模，并在这些分辨率之间自适应切换（以内部指标为指导），从而实现仿真速度和精度的近乎最佳组合。这项研究如果成功，将使这些系统的建模和详细的动态仿真大大超出目前可能的水平（在系统大小、保真度和仿真持续时间方面）。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以及演示性能。交付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、研究成果文档、工程学生教育和地区STEM教师的工程研究经验。如果成功，这项工作的影响将是这种复杂系统可以建模和分析的速度和程度的大大增加。这将使分析人员能够以比目前更节省成本、时间和资源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了解和理解，这可能有助于我们在未来学习修改和控制这些基本过程。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水平的动力学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。相关的教学辅助工具和基于网络的工具将被开发，相关的开源程序将被免费分发（这项工作也将成为POEMS、LAMMPS和SimTK计算工具的组成部分）。一些学生将通过本科生研究计划（URP）的参与来实现更直接的本科生参与，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.