SHF: Small: Models and Design Tools for Tethered Molecular Circuits

分子计算设备检测输入信号，包括指示疾病状态的分子，并在纳米尺度上对这些输入执行自主信息处理任务。最近的工作探索了分子计算设备的使用，其中计算组件被拴在DNA折纸瓷砖上，组件的布局影响它们的计算功能。这样的设备有许多优点，包括更快的计算时间和重用设备以扩大电路的能力。该项目将开发计算模型、算法和软件工具，以自动设计、实现和分析这种新型分子计算设备。该合同将使这些系统的设计更加可靠，提供增强的保证，当在实验室建造时，它们将按预期运行。制作的软件将发布给更广泛的研究社区。该项目将支持本科生和研究生的培训和教育，代表性不足的群体的成员将通过跟踪的科学参与计划参与其中。当建模和模拟涉及系留元件的分子电路时，分子相互作用的几何结构是至关重要的。该项目将使用一种新颖的分子结构表示，通过对变量的几何约束集来表示结构特定部分的物理位置。找到这些约束的解对应于证明指定结构可以采用相应的物理构象。这将被用作过滤器，以消除任何无法形成最终产物结构的束缚反应，例如，如果反应物相隔太远而无法实际相互作用。这些模型将通过湿实验室实验验证其预测来进行测试和参数化，并且将开发模块化电路的新设计作为概念验证。开发的算法将作为可用的软件工具实施和分发，使计算机辅助设计系留分子系统成为可能。因此，该项目将采用理论计算机科学的现有技术来处理系绳分子计算的独特挑战。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Molecular computing devices detect input signals, including molecules indicative of disease states, and carry out autonomous information processing tasks on these inputs at the nanoscale. Recent work has explored the use of molecular computing devices in which the computing components are tethered to a DNA origami tile, with the layout of the components influencing their computational functionality. Such devices have a number of advantages, including faster computation times and the ability to reuse devices to scale up a circuit. This project will develop computational models, algorithms, and software tools to automate the design, implementation, and analysis of this new class of molecular computing devices. The award will enable more reliable design of these systems, providing enhanced guarantees that they will function as intended when constructed in the laboratory. The software produced will be released to the broader research community. The project will support training and education of undergraduate and graduate students, and members of underrepresented groups will take part via tracked science involvement programs. When modeling and simulating molecular circuits involving tethered components, the geometry of molecular interactions is of vital importance. This project will use a novel representation of molecular structures via sets of geometric constraints on variables that represent the physical positions of specific parts of the structure. Finding a solution to these constraints corresponds to proving that the specified structure can adopt the corresponding physical conformation. This will be used as a filter to eliminate any tethered reactions for which the resulting product structure could not actually form, for example, if the reactants are too far apart to actually interact. These models will be tested and parameterized by experimentally validating their predictions with wet lab experiments, and novel designs for modular circuits will be developed as a proof of concept. The developed algorithms will be implemented and distributed as usable software tools that enable computer-aided design of tethered molecular systems. Thus, the project will adapt established techniques from theoretical computer science to handle the unique challenges of tethered molecular computing.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.