EAGER: Exploratory Software Development & Experiments of Dynamic DNA Nanosystems

非常需要（i）提供实验DNA纳米系统的快速开发的软件开发和（ii）新型DNA纳米系统的实验的协同组合，这将指导软件开发工作并提供反馈。 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，用于设计分子器件，这些器件基于一系列可编程的杂交反应，自组装为DNA纳米结构，并根据其环境改变状态。集成的方法将包括一个分子编程语言，允许高层次的规范状态的DNA纳米结构和它们的状态转换（涉及关键的杂交和链置换反应），而不完全指定潜在的链序列或纳米结构，并提供一个所见即所得（可视化）的输入方法。一个分子编译器将把分子程序编译成一个详细的组分DNA链和杂交反应的规范。热力学和动力学模拟器将计算组装的纳米结构的平衡密度和关键的动力学反应特性;通过将链分解成组分子序列域和状态空间的张量积分解的新用途来加速其计算。规范（序列域水平）和序列编译工具将与热力学和动力学模拟器集成，因此模拟可以在序列域水平而不是碱基对水平进行，从而导致相当大的加速。一个新的实验设计子系统将给出实验演示的建议设计，用于验证预期纳米结构的组装和关键反应步骤。EAGER计划的支持将允许为期两年的早期开发阶段，以测试和演示新的概念和设计。 教育目标包括研究生的跨学科培训，对本科生的认真监督指导，以及高中学生和教师的暑期实习。纳米科学，生物化学和化学将受到多学科的影响，这将得益于引入来自主流计算机科学的关键方法，例如编程语言和编译器以及编译器优化，特别是因为这些方法将高度专业化并针对DNA纳米结构和杂交反应的特定需求而量身定制。分子编程语言与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。为了最大限度地扩大这一软件的影响和使用，计划分阶段向外部分发原型软件系统，其中将纳入用户的反馈意见。

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.