CAREER: Bridging the gap between theoretical and experimental self-assembly through computational modeling

职业：通过计算建模弥合理论和实验自组装之间的差距

• 批准号: 1553166
• 负责人: Matthew Patitz
• 金额: $ 50万
• 依托单位: University of Arkansas
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1553166&HistoricalAwards=false
• 关键词: CAREER; Bridging; gap; between; theoretical

The goal of this project is to develop software which enables techniques from theoretical modeling of self-assembling systems based on DNA nanotechnology to be developed and evaluated using rigorous molecular dynamics simulations, and then incorporated into physical molecular designs and implementations. The software to be developed will consist of a fully integrated suite of open source software which will create a seamless pathway for the design of self-assembling systems based on components called tiles, via a high-level programming language interface to an abstract tile assembly simulator, all the way through the final output of the fully specified DNA strands which have been verified via highly accurate and DNA specific molecular simulations. The second main component of the proposed work is the integration of theoretical techniques and designs for algorithmic self-assembling systems into DNA-based motifs, and the performance of extensive simulation-based experiments to develop molecular designs for components which yield systems that are more robust to error and varying environmental conditions than current systems, allowing them to be more scalable and widely utilized.Developing robust and scalable molecular self-assembling systems has the promise to greatly impact many aspects of science and technology, potentially enabling atomically precise manufacturing of materials with carefully specified properties, implementation of molecular "robots", and targeted drug delivery mechanisms which are able to diagnose and treat diseases in vivo. To realize the great promise of this field, it is important to recognize that it is fundamentally interdisciplinary and incorporates fields such as physics, chemistry, mathematics, computer science, and biochemical engineering, among others, and to foster the development of researchers experienced in these areas and also skilled at this interdisciplinary work. This project focuses on interdisciplinary collaboration and student education, includes the development of an interdisciplinary course ("Introduction to DNA Nanotechnology''), the hosting of interdisciplinary workshops for high school students and also for experienced researchers, conducting interdepartmental seminars, and the development of software which can be easily used by scientists from many disciplines to quickly become proficient in this area. This will help train extremely valuable researchers capable of synthesizing knowledge and techniques spanning many disciplines.This project will create a freely released software suite capable of automating the design of DNA-based self-assembling systems. The work will involve extending current simulation software to be massively parallelizable, allowing simulations to be run across large supercomputing clusters, and the creation of new software modules able to perform automated, quantitative analyses of simulation results. Additional modules will be created to enable the suite to provide an end-to-end solution from theoretical design to simulation-based validation, along with an easily used web-based front end and database storage of results. The theoretical aspects of the project will involve incorporation of various theoretical construction techniques into molecular designs, and validation of those designs. Some specific theoretical techniques which will be exploited and evaluated include the incorporation of geometric hindrance to enforce correct algorithmic behavior, and hierarchical self-assembly.

该项目的目标是开发软件，使基于 DNA 纳米技术的自组装系统的理论建模技术能够使用严格的分子动力学模拟进行开发和评估，然后纳入物理分子设计和实现中。 待开发的软件将由一套完全集成的开源软件组成，该软件将为基于称为图块的组件的自组装系统的设计创建一条无缝途径，通过高级编程语言接口连接到抽象图块组装模拟器，一直到完全指定的 DNA 链的最终输出，这些 DNA 链已通过高精度和 DNA 特定分子模拟进行验证。 拟议工作的第二个主要组成部分是将算法自组装系统的理论技术和设计整合到基于 DNA 的基序中，并进行广泛的基于模拟的实验来开发组件的分子设计，从而产生更稳健的系统与当前系统相比，它们能够适应错误和变化的环境条件，从而使其更具可扩展性和更广泛的应用。开发强大且可扩展的分子自组装系统有望极大地影响科学和技术的许多方面，有可能实现原子级精确制造材料仔细指定的属性，分子“机器人”的实现，以及能够诊断和治疗体内疾病的靶向药物递送机制。为了实现这一领域的巨大前景，重要的是要认识到它从根本上来说是跨学科的，融合了物理、化学、数学、计算机科学和生物化学工程等领域，并培养在这些领域经验丰富的研究人员的发展。领域，并且也擅长这项跨学科工作。该项目侧重于跨学科合作和学生教育，包括开发跨学科课程（“DNA 纳米技术导论”）、为高中生和经验丰富的研究人员举办跨学科研讨会、举办跨部门研讨会以及开发该软件可以被许多学科的科学家轻松使用，从而快速精通该领域，这将有助于培养能够综合跨学科知识和技术的极其有价值的研究人员。该项目将创建一个能够免费发布的软件套件。自动化基于 DNA 的自组装系统的设计将涉及扩展当前的模拟软件以实现大规模并行化，从而允许模拟在大型超级计算集群上运行，以及创建能够执行自动化定量分析的新软件模块。将创建其他模块，以使该套件能够提供从理论设计到基于仿真的验证的端到端解决方案，以及易于使用的基于网络的前端和结果数据库存储。该项目的理论方面将涉及将各种理论构建技术纳入分子设计中，并对这些设计进行验证。 将利用和评估的一些具体理论技术包括结合几何障碍来强制执行正确的算法行为，以及分层自组装。