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，并在纳米级上对这些输入执行自主信息处理任务。最近的工作已经探索了分子计算设备的使用，其中计算组件被拴在DNA折纸瓦片上，组件的布局影响它们的计算功能。这种器件具有许多优点，包括更快的计算时间和重用器件以扩大电路的能力。该项目将开发计算模型，算法和软件工具，以自动设计，实施和分析这类新的分子计算设备。该合同将使这些系统的设计更加可靠，从而更好地保证它们在实验室中构建时能够按预期运行。制作的软件将向更广泛的研究界发布。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科学参与计划参加。在建模和模拟分子电路时，分子相互作用的几何形状是至关重要的。该项目将通过对代表结构特定部分物理位置的变量的几何约束集来使用分子结构的新表示。找到这些约束的解决方案对应于证明指定的结构可以采用相应的物理构象。这将被用作过滤器，以消除任何束缚反应，例如，如果反应物相距太远而不能实际相互作用，则所产生的产物结构实际上不能形成。这些模型将通过湿实验室实验验证其预测进行测试和参数化，并将开发模块化电路的新设计作为概念验证。所开发的算法将作为可用的软件工具来实现和分发，从而实现栓系分子系统的计算机辅助设计。因此，该项目将采用理论计算机科学的成熟技术来应对拴系分子计算的独特挑战。该奖项反映了NSF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.