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

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，然后将其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，该软件将通过高级编程语言接口到抽象瓦片组装模拟器，为基于瓦片组件的自组装系统的设计创造一个无缝的途径，一直到完全指定的DNA链的最终输出，这些DNA链已通过高度精确和DNA特定的分子模拟进行验证。提出的工作的第二个主要组成部分是将理论技术和算法自组装系统的设计集成到基于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，有可能实现具有仔细指定特性的材料的原子精确制造，分子“机器人”的实现，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前景，重要的是要认识到它基本上是跨学科的，并结合了物理、化学、数学、计算机科学和生化工程等领域，并促进在这些领域有经验的研究人员的发展，并精通这一跨学科的工作。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，以及开发软件，使来自许多学科的科学家能够轻松使用，从而迅速精通该领域。这将有助于培养能够综合跨多个学科的知识和技术的极有价值的研究人员。该项目将创建一个自由发布的软件套件，能够自动设计基于dna的自组装系统。这项工作将包括扩展当前的模拟软件，使其具有大规模并行性，允许模拟在大型超级计算集群上运行，并创建能够对模拟结果进行自动化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仿真的验证的端到端解决方案，以及易于使用的基于web的前端和结果数据库存储。该项目的理论方面将包括将各种理论构建技术纳入分子设计，并验证这些设计。一些具体的理论技术将被开发和评估，包括几何障碍的结合，以强制正确的算法行为，和分层自组装。

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.