EAGER: Exploratory Software Development & Experiments of Dynamic DNA Nanosystems

EAGER：探索性软件开发

• 批准号: 1141847
• 负责人: John Reif
• 金额: $ 20万
• 依托单位: Duke University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2013-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1141847&HistoricalAwards=false
• 关键词: EAGER; Exploratory; Software; Development; &amp

There is important need for a synergistic combination of (i) software development that provides rapid development of the experimental DNA nanosystems and (ii) experiments of novel DNA nanosystems, which will guide and provide feedback to the software development efforts. The project will develop software that will provide an integrated design/specification/simulation/optimization environment for designing molecular devices that self-assemble as DNA nanostructures and change state in reaction to their environment, based on a programmable series of hybridization reactions. The integrated methodology will include a molecular programming language that allows high-level specification of states of DNA nanostructures and their state-transitions (involving key hybridization and strand displacement reactions), without fully specifying underlying strand sequences or nanostructures, and provide a WYSIWYG (visual) method for input. A molecular compiler will compile the molecular program into a detailed specification of component DNA stands and hybridization reactions. A thermodynamic and kinetic simulator will calculate equilibrium densities of assembled nanostructures and key kinetic reaction properties; speeding its computations by novel use of decompositions of the strands into component subsequence domains and tensor product decompositions of the state space. Specification (sequence domain-level) and sequence compilation tools will be integrated with thermodynamic and kinetic simulators, so simulations can be done at sequence-domain level, rather than base-pair level, resulting in considerable speedups. A novel experiment design subsystem will give suggested design of experimental demonstrations for verifying assembly of the intended nanostructures, and key reaction steps. Support by the EAGER program will allow a two-year early development phase to test and demonstrate novel concepts and designs. Educational Objectives include cross-disciplinary training of graduate students, carefully supervised mentoring for undergraduates, and summer internships for high school students and teachers. There is substantial multidisciplinary impact to nanoscience, biochemistry and chemistry, which will profit from the introduction of key methodologies derived from mainstream computer science, such as programming languages and compilers, and compiler optimization, particularly since these will be highly specialized and tailored for the specific needs of DNA nanostructures and hybridization reactions. The integration of a molecular programming language, with a molecular compiler, and simulator, with feedback to provide optimization will provide unique enhanced design capabilities for these science disciplines. To maximize impact and use of this software, there is a planned staged external distribution of prototype software system that will incorporate feedback from users.

对于(i)软件开发提供实验性DNA纳米系统的快速开发和（ii）新型DNA纳米系统的实验，这将指导和提供反馈给软件开发工作的协同组合，这是一个重要的需求。该项目将开发软件，提供一个集成的设计/规范/模拟/优化环境，用于设计分子设备，这些设备可以自组装为DNA纳米结构，并根据环境改变状态，基于一系列可编程的杂交反应。集成的方法将包括一种分子编程语言，该语言允许对DNA纳米结构及其状态转换（涉及关键杂交和链位移反应）的状态进行高级规格说明，而无需完全指定潜在的链序列或纳米结构，并提供所见即所得（可视化）输入方法。分子编译器将把分子程序编译成详细的组分DNA序列和杂交反应说明。热力学和动力学模拟器将计算组装纳米结构的平衡密度和关键的动力学反应性质；通过将链分解为分量子序列域和状态空间的张量积分解来加快其计算速度。规范（序列域级）和序列编译工具将与热力学和动力学模拟器集成，因此可以在序列域级别而不是碱基对级别进行模拟，从而获得相当大的速度。一个新的实验设计子系统将给出实验演示的建议设计，以验证预期纳米结构的组装，以及关键的反应步骤。在EAGER项目的支持下，将有两年的早期开发阶段来测试和演示新颖的概念和设计。教育目标包括研究生的跨学科培训，本科生的精心监督指导，以及高中学生和教师的暑期实习。对纳米科学、生物化学和化学有重大的多学科影响，这将受益于引入主流计算机科学的关键方法，如编程语言和编译器，以及编译器优化，特别是因为这些将高度专业化，并为DNA纳米结构和杂交反应的特定需求量身定制。分子编程语言、分子编译器和模拟器的集成，以及提供优化的反馈，将为这些科学学科提供独特的增强设计能力。为了最大限度地影响和使用该软件，将合并用户反馈的原型软件系统计划分阶段进行外部分发。