SGER: Discrete Event Simulation of Self-Assembly Kinetics

EIA-0320595 Russell Schwartz卡内基梅隆大学项目摘要：自组装动力学的离散事件模拟本项目的目标是开发一种用于模拟广义自组装系统的新型计算工具。自组装系统由许多小的组件或子单元组成，它们在适当的条件下自发地将自己排列成更大的结构。 在许多医学上重要的自组装系统中，有病毒蛋白质外壳或衣壳，它们在病毒的遗传物质周围形成保护性外壳;淀粉样蛋白，与阿尔茨海默氏病、亨廷顿氏病和朊病毒病有关的蛋白质纤维聚集体;以及不规则的蛋白质聚集体。 对于所有这些系统，组装过程只是部分理解。 此外，自组装作为在纳米尺度上构建人造器件和材料的一种手段，最近引起了人们的兴趣。 由于许多自组装过程的小尺寸、速度和复杂性，它们已被证明很难进行实验分析。 因此，模拟方法已成为深入了解自组装过程的重要途径。 该项目旨在建立在该领域的先前工作的基础上，通过创建自组装过程的模型，该模型具有足够的通用性，可以捕获各种各样的自组装系统，但速度足够快，可以在合理的时间内处理逼真的模拟尺寸。 基本的方法将涉及到结合技术开发在以前的建模工作，这个问题的计算方法，以前没有被用于自组装模拟。 该模拟器将使用自组装动力学模型，主要基于先验局部规则动力学。模型，它提供了一个通用的表示高层次的自组装行为在低层次的亚基相互作用。 它将有效地实现使用一种称为离散事件优先级队列的计算数据结构。这将允许模拟器在离散状态（例如子单元彼此绑定）的变化之间步进，而不需要在所有时间步长上进行显式积分。 其结果将是更快的模拟一个高度通用的自组装模型比以前的方法是可能的。 该模拟器将在Java中实现，以便于开发，可扩展性和可移植性。 实施将通过不同的阶段进行，专门用于开发一个对象模型（其中规定了计算机代码片段如何相互作用），编码和测试原型模拟器，并最终确定一个优化和记录良好的发布质量版本。 最终的结果将是一个独立的模拟工具和一组可用于扩展和在其他程序中使用的计算类。 这项工作将需要创新，主要是在自组装过程的数学模型和算法，其有效的模拟离散事件队列方法。 在整合生物物理学、算法、软件工程和用户界面设计等领域的现有知识方面需要进一步创新，以产生一种通用的、易于使用的图形模拟工具。 预计该项目将产生若干效益。 它的影响将主要是在自组装领域，通过提供一个通用的工具，可用于整个领域的研究人员在不同规模和时间尺度上建模已知系统，开发新系统的计算原型，并在两者中进行干预实验。 它还将提供新的方法和经验，生物物理模拟的一般领域，通过一个新的模拟方法的发展，其实施在一个计算模拟器，并优化算法，这个问题。 该项目的跨学科性质将加强其影响，为计算界提供关于生物物理系统问题的新变化，并为生物物理界提供可用于解决其他问题的新计算技术。 这项工作也将通过为学生提供跨学科的研究经验，包括两名本科生，并通过提供一个模拟器，可用作研究和教学工具，具有教育价值。

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.