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通过严格的分子动力学模拟进行开发和评估，然后整合到物理分子设计和实现中。将要开发的软件将由一套完全集成的开源软件组成，它将为基于称为瓷砖的组件的自组装系统的设计创造一条无缝的途径，通过到抽象瓷砖组装模拟器的高级编程语言接口，一直到完全指定的DNA链的最终输出，这些DNA链已经通过高精度和DNA特定的分子模拟得到验证。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，以开发组件的分子设计，这些组件产生的系统比当前的系统对错误和变化的环境条件更健壮，使它们更具可扩展性和广泛性。开发健壮和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，潜在地使具有仔细指定属性的材料的原子精密制造成为可能，分子“机器人”的实施，以及能够在体内诊断和治疗疾病的靶向药物输送机制。为了实现这一领域的巨大希望，重要的是认识到它从根本上是跨学科的，包括物理、化学、数学、计算机科学和生化工程等领域，并培养在这些领域有经验并熟练从事这一跨学科工作的研究人员的发展。该项目侧重于跨学科合作和学生教育，包括开发一门跨学科课程(“DNA纳米技术导论”)，为高中生和有经验的研究人员举办跨学科研讨会，举办跨部门研讨会，以及开发可供许多学科的科学家轻松使用的软件，以迅速精通这一领域。这将有助于培训非常有价值的研究人员，他们能够综合跨越许多学科的知识和技术。该项目将创建一个免费发布的软件套件，能够自动设计基于DNA的自组装系统。这项工作将涉及将当前的模拟软件扩展为可大规模并行化，允许模拟跨大型超级计算集群运行，以及创建能够对模拟结果进行自动、定量分析的新软件模块。将创建其他模块，使该套件能够提供从理论设计到基于模拟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，并对这些设计进行验证。一些具体的理论技术将被开发和评估，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。