Combinatorial Displacement of DNA Strands: Application to Matrix Multiplication and Weighted Sums
Combinatorial Displacement of DNA Strands: Application to Matrix Multiplication and Weighted Sums
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DOI：
10.1002/anie.201206201
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发表时间：
2013-01-01
影响因子：
16.6
通讯作者：
Turberfield, Andrew J.
中科院分区：
文献类型：
--
作者：
Genot, Anthony J.;Bath, Jonathan;Turberfield, Andrew J.
通过DNA碱基序列设计编程相互作用是在分子计算中使用合成寡核苷酸的基础支点介导的链位移[2]通常用于协调计算的杂交反应。在这种机制中，一条DNA链从双链中被一条入侵链取代，这条入侵链首先杂交到一个悬垂的单链“支点”结构域。脚点杂交提供了热力学驱动力，加速了链的位移。该机制在分子计算、[2e， 3] DNA模板化学、[4]自主机制、[5]检测特定核酸序列、[6]以及DNA结构驱动等方面都有应用。在传统的链位移体系中，在合成过程中，支点和位移域是共价连接的。然而，特别是在需要控制许多相互竞争的相互作用的大型系统中，可能需要重新编程某些链的功能，而不必重新合成整个系统；[2a]链相互作用的动态重编程也可能增加计算能力。例如，应用于组合药物发现的dna模板化学可能需要控制大量成分库中的相互作用DNA逻辑电路可以对基因表达进行分类，通过搜索特定于病理的模式，[9]将依赖于矩阵乘法等操作，其中，对于n维系统，中间计算的数量随着n3而增长。在此，我们提出了一种“组合位移”机制，其中支点和位移域动态地组合连接以形成功能位移复合物。这种机制大大减少了必须合成的链的数量：2n条链可以被编程形成复合物侵入n2个底物。组合位移具有与矩阵乘法相似的结构，非常适合于线性运算的实现。我们演示Boo-
Programming interactions through DNA base sequence design underlies the use of synthetic oligonucleotides in molecular computing.[1] Toehold-mediated strand displacement [2] is often used to orchestrate hybridization reactions that compute. In this mechanism, a DNA strand is displaced from a duplex by an invading strand which hybridizes first to an overhanging single-stranded “toehold” domain. Toehold hybridization provides a thermodynamic driving force and accelerates strand displacement. The mechanism has applications in molecular computation,[2e, 3] DNA-templated chemistry,[4] autonomous machinery,[5] detection of specific nucleic acid sequences,[6] and in the actuation of DNA structures.[7]In conventional strand-displacement systems, the toehold and displacement domains are covalently linked during synthesis. However, particularly in large systems where it is necessary to control many competing interactions, it may be desirable to reprogram the function of some strands without having to re-synthesize the entire system;[2a] dynamic reprogramming of strand interactions may also add computational power. For example, DNA-templated chemistry applied to combinatorial drug discovery may require control of interactions within a large library of components.[8] DNA logic circuits that could classify gene expression, by searching for patterns specific to a pathology,[9] would rely on operations such as matrix multiplication in which, for an n-dimensional system, the number of intermediate computations grows as n3. Herein, we present a “combinatorial displacement” mechanism in which toehold and displacement domains are dynamically and combinatorially linked to form functional displacing complexes. This mechanism considerably reduces the number of strands that must be synthesized: 2n strands can be programmed to form complexes to invade n2 substrates. Combinatorial displacement has a similar structure to matrix multiplication and is well suited to the implementation of linear operations. We demonstrate Boo-