Exercises in molecular computing.
Exercises in molecular computing.
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DOI：
10.1021/ar5000538
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发表时间：
2014-06-17
影响因子：
18.3
通讯作者：
Rudchenko, Sergei
中科院分区：
文献类型：
--
作者：
Stojanovic, Milan N.;Stefanovic, Darko;Rudchenko, Sergei
在过去的半个世纪里，电子数字逻辑的成功改变了人类生活的方方面面。“计算机”这个词现在意味着一种无处不在的电子设备，而不是人类的职业。然而，显然，人类--分子的大集合--可以进行计算，而开发能够进行有用计算的更小、更简单的合成分子集合一直是一个令人兴奋的挑战。当我们说分子计算时，我们通常的意思是这样的分子对某些输入做出反应，例如，其他分子的存在或不存在，以一种精确定义但潜在复杂的方式。对于化学家来说，考虑计算分子的最简单方式是作为传感器，它可以将多个分析物的存在或不存在集成到单一报告性质的变化中。在这里，我们回顾了我们实验室开发的几种形式的分子计算。当我们开始我们的工作时，使用DNA进行计算的组合方法被用于搜索约束满足问题的解决方案。我们选择转而研究逻辑电路，从基于催化核酸的单元自下而上地构建，在单个电路元件的设计中专注于DNA二级结构，并保留DNA的组合机会来表示在大型电路中传播的多个信号。这样的电路设计直接对应于传感器的直觉，将分析物的检测转化为报告特性。虽然这种方法在当时并不常见，但后来被其他致力于生物分子计算的小组采用，这些小组使用不同的核酸化学。我们通过模块化地结合脱氧核酶(基于DNA的酶裂解或结合其他寡核苷酸)来创建逻辑门，以报告元件的角色，以茎环作为输入检测元件。例如，通常显示寡核苷酸底物识别区的脱氧核酶被修饰，使得茎环靠近底物识别区，使其对底物不可用，从而使脱氧核酶无效。但随后可以通过输入与环互补的寡核苷酸来诱导构象变化，以打开茎，允许底物结合，并允许其切割进行，这最终通过荧光报告。在这方面，回顾了几种这种形式的设计，以及它们在大型电路结构中的应用，这些电路在输入和输出之间表现出复杂的逻辑和时间关系。智能(在能够进行非平凡的信息处理的意义上)治疗(治疗+诊断)应用一直是开发计算(即决策)电路的最终动机，我们回顾了我们使用绑定到细胞表面的逻辑门元件来评估淋巴细胞上多个标记的近端存在的实验。
The successes of electronic digital logic have transformed every aspect of human life over the last half-century. The word “computer” now signifies a ubiquitous electronic device, rather than a human occupation. Yet evidently humans, large assemblies of molecules, can compute, and it has been a thrilling challenge to develop smaller, simpler, synthetic assemblies of molecules that can do useful computation. When we say that molecules compute, what we usually mean is that such molecules respond to certain inputs, for example, the presence or absence of other molecules, in a precisely defined but potentially complex fashion. The simplest way for a chemist to think about computing molecules is as sensors that can integrate the presence or absence of multiple analytes into a change in a single reporting property. Here we review several forms of molecular computing developed in our laboratories. When we began our work, combinatorial approaches to using DNA for computing were used to search for solutions to constraint satisfaction problems. We chose to work instead on logic circuits, building bottom-up from units based on catalytic nucleic acids, focusing on DNA secondary structures in the design of individual circuit elements, and reserving the combinatorial opportunities of DNA for the representation of multiple signals propagating in a large circuit. Such circuit design directly corresponds to the intuition about sensors transforming the detection of analytes into reporting properties. While this approach was unusual at the time, it has been adopted since by other groups working on biomolecular computing with different nucleic acid chemistries. We created logic gates by modularly combining deoxyribozymes (DNA-based enzymes cleaving or combining other oligonucleotides), in the role of reporting elements, with stem–loops as input detection elements. For instance, a deoxyribozyme that normally exhibits an oligonucleotide substrate recognition region is modified such that a stem–loop closes onto the substrate recognition region, making it unavailable for the substrate and thus rendering the deoxyribozyme inactive. But a conformational change can then be induced by an input oligonucleotide, complementary to the loop, to open the stem, allow the substrate to bind, and allow its cleavage to proceed, which is eventually reported via fluorescence. In this Account, several designs of this form are reviewed, along with their application in the construction of large circuits that exhibited complex logical and temporal relationships between the inputs and the outputs. Intelligent (in the sense of being capable of nontrivial information processing) theranostic (therapy + diagnostic) applications have always been the ultimate motivation for developing computing (i.e., decision-making) circuits, and we review our experiments with logic-gate elements bound to cell surfaces that evaluate the proximal presence of multiple markers on lymphocytes.
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影响因子：
38.3
作者：
通讯作者：
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影响因子：
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作者：
Tang, J;Breaker, RR
通讯作者：
Breaker, RR
影响因子：
15
作者：
Kolpashchikov, DM;Stojanovic, MN
通讯作者：
Stojanovic, MN
影响因子：
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作者：
BREAKER, RR;JOYCE, GF
通讯作者：
JOYCE, GF
影响因子：
3
作者：
Macdonald, Joanne;Stelanovic, Darko;Stojanovic, Milan N.
通讯作者：
Stojanovic, Milan N.