EAGER: Exploratory Software Development & Experiments of Dynamic DNA Nanosystems

重要的是需要(I)软件开发提供实验DNA纳米系统的快速开发和(Ii)新DNA纳米系统的实验的协同结合，这将指导软件开发工作并为其提供反馈。该项目将开发软件，为设计分子装置提供一个集成的设计/规范/模拟/优化环境，这些分子装置以DNA纳米结构的形式自组装，并根据环境的反应改变状态，基于一系列可编程的杂交反应。综合方法学将包括一种分子编程语言，允许高水平地指定DNA纳米结构及其状态转换(涉及关键杂交和链置换反应)的状态，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(WYSIWYG)(可视化)输入方法。分子编译器将把分子程序编译成DNA组分和杂交反应的详细规范。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性质；通过新颖地使用链到组分子序列域的分解和状态空间的张量积分解来加快计算速度。规范(序列结构域级别)和序列编译工具将与热力学和动力学模拟器集成，因此可以在序列结构域级别而不是碱基对级别进行模拟，从而带来相当大的加速。一个新颖的实验设计子系统将为验证预期纳米结构的组装和关键反应步骤提供建议的实验演示设计。在EIGER计划的支持下，将有两年的早期开发阶段来测试和演示新的概念和设计。教育目标包括对研究生进行跨学科培训，对本科生进行认真监督的指导，以及为高中生和教师提供暑期实习。这将对纳米科学、生物化学和化学产生重大的多学科影响，这将得益于采用源自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，特别是因为这些方法将高度专业化，并为DNA纳米结构和杂交反应的具体需要量身定做。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。为了最大限度地发挥该软件的影响和使用，有计划的分阶段对外分发原型软件系统，该系统将纳入用户的反馈。

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.