关键词: DNA力学性质/
链替换反应/
分子计算/
自组装
English Abstract
DNA and DNA computation based on toehold-mediated strand-displacement reactions
Xiao Shi-Yan1,Liang Hao-Jun1,2
1.CAS Key Laboratory of Soft Matter Chemistry, Collaborative Innovation Center of Chemistry for Energy Materials, Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei 230026, China;
2.Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei 230026, China
Fund Project:Project supported bythe National Natural Science Foundation of China (Grant Nos. 91427304, 21434007, 21574122, 51573175, 21404098) and the National Basic Research Program of China (Grant No. 2012CB821500).Received Date:26 May 2016
Accepted Date:15 June 2016
Published Online:05 September 2016
Abstract:biocompatibility. Considering the critical role of DNA less than 150 base pairs (bp) in cellular processes such as regulated gene expression, quantifying the intrinsic bend ability of DNA on a sub-persistence length scale is essential to understanding its molecular functions and the DNA-protein interaction. From the classical point of view, double-stranded DNA is assumed to be stiff and can be treated by semi-flexible chain, but recent studies have yielded contradictory results. A lot of studies tried to prove that the worm-like chain model can be used to fully describe DNA chain. However, recent theoretical and experimental studies indicated that DNA exhibits high flexibility on a short length scale, which cannot be described by the worm-like chain model. Further studies are needed to address the extreme flexibility of DNA on a short length scale. On the basis of the predictability of the double helical structure and the Watson-Crick binding thermodynamics for DNA, a class of DNA reactions can be defined, called toehold-mediated strand-displacement reaction, in which one complementary single-stranded DNA sequence first binds to the dangling toehold domain of the substrate in a pre-hybridized double-stranded DNA, then triggers the strand-displacement reaction, and finally results in the dissociation of the third strand previously bound to the substrate with partial complementarity. In dynamic DNA nanotechnology, isothermal toehold-mediated DNA strand-displacement reaction has been used to design complex nanostructure and nanodevice for molecular computation. The kinetics of the strand-displacement can be modulated using the toehold length. In order to weaken the coupling between the kinetics of strand-displacement and the thermodynamics of the reaction, the concept of toehold exchange was introduced by Winfree et al. to improve the control of strand-displacement kinetics. More importantly, the biomolecular reaction (BM) rate constant of toehold exchange can be analytically derived using the three-step model. Through utilizing strand-displacement reactions and taking advantage of its programmable sequences and precise recognition properties, DNA can be used to build complex circuits which can proceed robustly at constant temperature, achieving specific functions. DNA strand-displacement reaction can be employed to fabricate logic gates, and large and complex circuits for DNA computing, to mimic the naturally occurring occurrence of biological systems. Based on that, DNA circuit can then be used to direct the assembly of nanodevice following the designed pathway, and modulate the chemical reaction networks on the surface of living cell or in cellular systems for biosensing, even program the cellular machinery in the future for genetic diagnostic or gene therapy. In the present paper, we reviewed the proceedings in the fields of DNA structure and conformational changes, and DNA flexibility, discussed the mechanism of DNA strand-displacement reaction at the molecular level, and introduced the recent studies in DNA computation as well as the dynamic DNA nanotechnology, such as self-assembly.
Keywords: DNA flexibility/
strand-displacement reaction/
DNA computation/
self-assembly
