SHF: Large: Collaborative Research: Molecular computing for the real world

分子计算是一种在纳米尺度上评价计算功能的有前途的计算范式，在智能分子诊断和治疗中具有潜在的应用。分子计算系统包括生物分子，例如DNA链，其被设计为通过结合到某些输入分子来检测它们，并且随后经历用于基于所观察到的输入分子的模式来计算逻辑函数的化学反应的编程序列。例如，一个分子系统，需要它的两个输入同时存在，以产生一个输出信号将被称为计算一个逻辑“与”功能的两个输入。然而，尽管在该领域的最新进展，直接应用这些技术来解决现实世界中的问题的前景是有限的分子计算机和生物和化学系统之间缺乏强大的接口。该项目将通过针对两个特定的应用领域来解决这一限制：使用分子逻辑级联的广谱化学传感和细胞表面分析。通过计算机科学家、生物工程师、化学家和计算机工程师的跨学科研究组合，将推进分子计算机设计、建模和实现的最新技术水平，拟议活动的成功完成将是朝着常规部署分子计算机以解决化学和生物传感中的现实问题迈出的重要一步。在该项目中，将在实验室中设计、模拟和实现处理来自化学传感器和细胞表面分析反应的传感器输入的分子电路结构。这将需要在适体（对一个或多个目标非核酸分子表现出特定结合亲和力的DNA序列）的分离以及将其整合到分子计算系统中方面取得具体进展。在这种情况下，适体将作为一个接口，允许合理设计的基于DNA的分子计算系统使用小分子作为输入信号。此外，计算建模和模拟将用于预测和优化DNA适体和一系列结合靶之间的相互作用，并选择最佳适体组合以产生交叉反应的多传感器阵列，该阵列能够通过有效地将信号投射到多维适体响应空间中来区分靶配体。此外，先进的分子电路架构，能够适应，生物启发的行为，如动态学习和适应，将被设计，着眼于未来的实验实施这些功能的大规模分子计算机。这将包括对高度重复的、生物启发的信息处理网络的研究，以从潜在的非特异性适体传感器中提取有意义的反应。

Molecular computing is a promising computational paradigm in which computational functions are evaluated at the nanoscale, with potential applications in smart molecular diagnostics and therapeutics. A molecular computing system comprises biomolecules, such as DNA strands, which have been designed to detect certain input molecules by binding to them and subsequently to undergo programmed sequences of chemical reactions that serve to compute a logical function based on the observed pattern of input molecules. For example, a molecular system that requires both of its two inputs to be present simultaneously in order to generate an output signal would be referred to as computing a logical "AND" function on the two inputs. However, despite recent advances in the field, prospects for direct application of these techniques to solve real-world problems are limited by the lack of robust interfaces between molecular computers and biological and chemical systems. This project will address this limitation by targeting two specific application domains: wide-spectrum chemical sensing and cell surface analysis using molecular logic cascades. The state of the art in molecular computer design, modeling, and implementation will be advanced by an interdisciplinary combination of research by computer scientists, bioengineers, chemists, and computer engineers, and successful completion of the proposed activity will be a significant step towards routine deployment of molecular computers to address real-world problems in chemical and biological sensing.In this project, molecular circuit architectures that process sensor inputs from chemical sensors and cell-surface analysis reactions will be designed, modeled, and implemented in the laboratory. This will require specific advances in the isolation of aptamers (DNA sequences that exhibit particular binding affinity to one or more target non-nucleic acid molecules) and in their integration into molecular computing systems. In this context, the aptamer will serve as an interface that allows a rationally-designed DNA-based molecular computing system to use small molecules as input signals. Furthermore, computational modeling and simulation will be used to predict and optimize interactions between DNA aptamers and a range of binding targets, and to choose optimal aptamer combinations to produce cross-reactive multi-sensor arrays capable of discriminating between target ligands by effectively projecting the signal into a multi-dimensional aptamer response space. Furthermore, advanced molecular circuit architectures capable of adaptive, bio-inspired behavior, such as dynamic learning and adaptation, will be designed, with a view to future experimental implementations of these features in large-scale molecular computers. This will include research on highly recurrent, bio-inspired information processing networks to extract meaningful responses from potentially non-specific aptamer-based sensors.