On the biophysics and kinetics of toehold-mediated DNA strand displacement.
On the biophysics and kinetics of toehold-mediated DNA strand displacement.
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DOI：
10.1093/nar/gkt801
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发表时间：
2013-12
影响因子：
14.9
通讯作者：
Winfree E
中科院分区：
文献类型：
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作者：
Srinivas N;Ouldridge TE;Sulc P;Schaeffer JM;Yurke B;Louis AA;Doye JP;Winfree E
动态DNA纳米技术通常使用脚趾介导的链置换来控制反应动力学。虽然链置换动力学对脚趾长度的依赖已经被实验表征和现象学建模，但详细的生物物理理解仍然难以捉摸。在这里，我们使用一维能量景观上随机行走的直观模型，单碱基对步骤的二级结构动力学模型和结合了三维几何和空间效应的粗粒度分子模型，在多个细节水平上研究了链的位移。此外，我们还对三向分支迁移的热力学进行了实验研究。有两个因素可以解释链移动动力学对脚趾长度的依赖：(I)分支迁移的单个步骤发生的物理过程明显慢于单个碱基对的磨损；(Ii)启动分支迁移会招致热力学惩罚，这是最先进的DNA最近邻模型所没有捕捉到的，因为它在连接处产生了额外的悬垂。我们的发现与之前测量或推断的杂交、磨损和分支迁移速率一致，并为链置换动力学提供了生物物理解释。我们的工作为链位移级联的精确建模铺平了道路，这将有助于模拟和构建更复杂的分子系统。
Dynamic DNA nanotechnology often uses toehold-mediated strand displacement for controlling reaction kinetics. Although the dependence of strand displacement kinetics on toehold length has been experimentally characterized and phenomenologically modeled, detailed biophysical understanding has remained elusive. Here, we study strand displacement at multiple levels of detail, using an intuitive model of a random walk on a 1D energy landscape, a secondary structure kinetics model with single base-pair steps and a coarse-grained molecular model that incorporates 3D geometric and steric effects. Further, we experimentally investigate the thermodynamics of three-way branch migration. Two factors explain the dependence of strand displacement kinetics on toehold length: (i) the physical process by which a single step of branch migration occurs is significantly slower than the fraying of a single base pair and (ii) initiating branch migration incurs a thermodynamic penalty, not captured by state-of-the-art nearest neighbor models of DNA, due to the additional overhang it engenders at the junction. Our findings are consistent with previously measured or inferred rates for hybridization, fraying and branch migration, and they provide a biophysical explanation of strand displacement kinetics. Our work paves the way for accurate modeling of strand displacement cascades, which would facilitate the simulation and construction of more complex molecular systems.
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影响因子：
14.9
作者：
Gao Y;Wolf LK;Georgiadis RM
通讯作者：
Georgiadis RM
DOI：
10.1073/pnas.0407024101
发表时间：
2004-10-26
影响因子：
11.1
作者：
Dirks, RM;Pierce, NA
通讯作者：
Pierce, NA
影响因子：
64.8
作者：
KALLENBACH, NR;MA, RI;SEEMAN, NC
通讯作者：
SEEMAN, NC
影响因子：
15
作者：
Chen, Xi
通讯作者：
Chen, Xi
影响因子：
46.9
作者：
通讯作者：
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