SGER: Discrete Event Simulation of Self-Assembly Kinetics

SGER：自组装动力学的离散事件模拟

• 批准号: 0320595
• 负责人: Russell Schwartz
• 金额: $ 9.96万
• 依托单位: Carnegie-Mellon University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-01 至 2004-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0320595&HistoricalAwards=false
• 关键词: SGER; Discrete; Event; Simulation; Self

EIA-0320595Russell SchwartzCarnegie Mellon UniversityProject Summary: Discrete Event Simulation of Self-Assembly Kinetics The goal of this project is to develop a novel computational tool for simulating generalized self-assembly systems. Self-assembly systems consist of many small components, or subunits, that spontaneously arrange themselves into larger structures under appropriate conditions. Among the many medically important self-assembly systems are viral protein shells, or capsids, which form protective coats around the genetic material of viruses; amyloids, fibrous agglomerations of proteins that are implicated in Alzheimer.s disease, Huntington.s disease, and the prion diseases; and irregular protein aggregates. For all of these systems, the process of assembly is only partially understood. In addition, self-assembly has attracted recent interest as a means of constructing man-made devices and materials on the nanometer scale. Due to the small size, speed, and complexity of many self-assembly processes, they have proven difficulty to analyze experimentally. Simulation approaches have therefore emerged as a crucial avenue for gaining insight into the self-assembly process. This project seeks to build on the prior work in the area by creating a model of the self-assembly process sufficiently versatile to capture a wide variety of self-assembly systems, yet fast enough to handle realistic simulation sizes in a reasonable time. The basic methodology will involve combining techniques developed in prior modeling work on this problem with a computational method that has not previously been used for self-assembly simulation. The simulator will use a model of self-assembly dynamics based largely on the prior .local rules dynamics. model, which provided a versatile representation of high-level self-assembly behavior in terms of low-level subunit interactions. It will be efficiently implemented using a computational data structure called a .discrete event priority queue,. which will allow the simulator to step between changes in discrete state (such as subunits binding to one another) without the need for explicit integration over all time steps. The result will be faster simulation of a highly general self-assembly model than was possible with prior methods. The simulator will be implemented in Java to facilitate ease of development, extensibility, and portability. Implementation will be conducted through distinct phases devoted to developing an object model (which specifies how pieces of computer code interact with one another), coding and testing a prototype simulator, and finalizing an optimized and well documented release-quality version. The end result will be both a stand-alone simulation tool and a set of computational classes available for extension and use in other programs. This work will require innovation primarily in mathematical models of self-assembly processes and in algorithms for their efficient simulation by a discrete event queue methodology. Further innovation will be needed in the integration of existing knowledge from such areas as biophysics, algorithms, software engineering, and user interface design to produce a versatile, easy-to-use graphical simulation tool. The project can be expected to yield several benefits. Its impact will be primarily on the field of self-assembly, by providing a general tool that can be used by researchers throughout the field for modeling known systems across size and time scales, developing computational prototypes of novel systems, and experimenting with interventions in both. It will also provide new methods and experience to the general field of biophysical simulation through the development of a novel simulation methodology, its implementation in a computational simulator, and optimization of algorithms for this problem. The cross-disciplinary nature of the project will enhance its impact by providing for the computational community new variations on problems to be found in biophysical systems and providing for the biophysics community new computational techniques that can be brought to bear on other problems. The work will also have educational value by providing interdisciplinary research experience to students, including two undergraduates, and by providing a simulator that can be used as both a research and a teaching tool.

EIA-0320595RUSSELL SCHWARTZCARNEGIE MELLON UNIVESSIONPROXPONT摘要：自组装动力学的离散事件模拟该项目的目标是开发一种新型的计算工具，用于模拟广义自组装系统。自组装系统由许多小型组件或亚基组成，它们在适当的条件下自发地将自己安排成较大的结构。 在许多具有医学重要的自组装系统中，有病毒蛋白壳或衣壳，它们围绕病毒的遗传物质形成保护性毛皮。与阿尔茨海默氏病，亨廷顿氏病和prion疾病有关的蛋白质的淀粉样蛋白和蛋白质的纤维结构；和不规则的蛋白质聚集体。 对于所有这些系统，组装过程仅被部分理解。 此外，自组装引起了最近的兴趣，作为在纳米尺度上构建人造设备和材料的一种手段。 由于许多自组装过程的尺寸，速度和复杂性较小，因此证明很难进行实验分析。 因此，仿真方法已成为洞悉自组装过程的关键途径。 该项目旨在通过创建足够多功能的自组装过程的模型来捕获各种各样的自组装系统，但足够快，可以在合理的时间内处理现实的模拟大小，从而在该领域的先前工作中构建基于先前的工作。 基本方法将涉及将有关此问题的先前建模工作中开发的技术与以前尚未用于自组装模拟的计算方法相结合。 模拟器将主要基于先前的.Local规则动力学使用自组装动力学的模型。模型，提供了高级自组装行为的多功能表示，就低级亚基相互作用而言。 它将使用称为.discrete事件优先级队列的计算数据结构有效地实现。这将允许模拟器在离散状态的变化（例如彼此绑定的亚基）之间的变化，而无需在所有时间步骤上进行明确集成。 结果将是对高度通用的自组装模型的模拟，而不是先前的方法。 模拟器将在Java中实施，以促进易于开发，可扩展性和便携性。 实现将通过致力于开发对象模型（指定计算机代码如何相互作用），编码和测试原型模拟器的不同阶段进行实现，并最终确定了优化且文化良好的发行质量版本。 最终结果将既是独立的仿真工具，又是一组可用于扩展和在其他程序中使用的计算类。 这项工作将主要需要在自组装过程的数学模型和算法中进行创新，以通过离散事件队列方法进行有效的仿真算法。 从生物物理学，算法，软件工程和用户界面设计等领域的现有知识集成中，将需要进一步的创新，以生成多功能，易于使用的图形模拟工具。 可以预期该项目将带来一些好处。 它的影响主要是通过提供一种通用工具来对自组装领域的影响，该工具可以被整个领域的研究人员使用，用于对跨大小和时间尺度的已知系统建模，开发新型系统的计算原型，并在两者的干预措施中进行实验。 它还将通过开发新型的模拟方法，计算模拟器中的实现以及针对此问题的算法优化，为生物物理模拟的一般领域提供新的方法和经验。 该项目的跨学科性质将通过为在生物物理系统中发现的问题提供新的变化来增强其影响，并为生物物理学社区提供新的计算技术，这些技术可以带来其他问题。 这项工作还将通过为包括两个本科生在内的学生提供跨学科的研究经验，并提供可以用作研究和教学工具的模拟器来具有教育价值。