DNA自组装与信息存储

脱氧核糖核酸(Deoxyribonucleic acid,DNA)作为未来数据的存储介质具有巨大的潜力.近年来,DNA自组装技术发展迅速,其中DNA折纸(origami)和DNA瓦片(tile)设计及组装技术已经实现了纳米结构的原子级精度.DNA自组装纳米结构因其具有空间可寻址性、可编程性等优点,为基于DNA自组装的信...     

基于氮化硅薄膜纳米孔制备及DNA分子检测

通过对影响聚焦离子束溅射氮化硅纳米孔的溅射时间和离子束束流2个主要参数的研究,优化了聚焦离子束溅射纳米孔加工工艺.提出了利用聚焦离子束对氮化硅薄膜进行减薄后再溅射纳米孔的加工工艺.采用该加工工艺不仅可以减小纳米孔的直径和厚度,还可以减小纳米孔的锥度.最后利用氮化硅纳米孔研究了不同孔径的纳米孔对48 kbλ-DNA过孔姿态的影响,结果表明,孔径较大时,DNA分子过孔存在多种过孔姿态,孔径越小,DNA分子越容易被拉直过孔.同时针对DNA过孔时引起的阻塞电流,提出了简易的计算模型.     

DNA折纸术——全编程的信息工具

DNA作为信息分子在构建2D及3D几何形状的纳米级结构上有多种优点.二维和三维结构的组装可以通过DNA链的组合、DNA块的拼接实现.而随着DNA折纸术的出现,更是实现任意平面结构设计的可能.DNA二维平面的设计已被证实是图灵等价的.本文主要介绍基于DNA折纸的计算模型及DNA折纸术在信息领域方面的应用.     

纳米孔DNA测序:我们在哪了?(英文)

纳米孔DNA测序技术是一类重要的DNA测序技术,可以实现长链DNA序的快速读取.一个DNA分子可以以毫秒每碱基,甚至更快的速度通过纳米孔,从而有可能实现在1 h以内完成人类全基因组测序.与下一代DNA测序技术(next generation DNA sequencing,NGS)相比较,纳米孔DNA测序技术可以实现单分子测序,无需使用酶进行样品扩增.纳米孔DNA测序技术是后NGS时代极具潜力的DNA测序技术.本文将介绍纳米孔DNA测序技术的研究现状,并讨论在这个快速发展的领域当中面临的挑战和机遇.     

基于“DNA折纸术”设计图着色问题的解决方案

色数是图论中的一个重要的参数,其属于著名NP(Non-deterministic Polynomial)-完全问题范畴.巨量的着色方案使验证变得相当困难,以至于在传统计算机上无法实现.目前已经有多种算法用于研究图定点着色问题,比如遗传算法,粒子群算法,神经网络算法和模拟退火算法等.随着DNA自组装技术与DNA计算机研究的展开,一些NP-完全问题以及NP-难问题的计算模型被相继提出.除了传统的DNA分子结构被用作计算材料外,其他的DNA分子结构也被用于分子生物计算,比如质粒DNA分子、分子信标结构以及DNA Tile等.采用DNA纳米折纸结构编码信息,借助于纳米结构之间的粘性末端进行自组装,给出了一种非确定性的图着色模型.通过创建数以亿计的参与计算的DNA纳米折纸结构,该算法可以并行的测试每种可能的着色方案.     

一种新型DNA纳米结构的构建与结晶

DNA三角形纳米结构的拐角是由DNA同源重组中的Holliday基序构成的.为进一步研究DNA三角形纳米结构,对其拐角截断并引入黏性末端到其基序上,使其能够自组装成为一种新型DNA纳米结构.对该DNA纳米结构进行凝胶电泳分析,发现其迁移速率要比DNA三角形迁移速率小.在这种没有扭曲张力的情况下,该基序只是自组装形成一个二聚体结构,而不是三聚体结构(DNA三角形).对该新型DNA纳米结构进行结晶,并合成得到了硒代核酸,同时也得到了较高质量的硒代单晶,以帮助相位测定.希望对其晶体结构进行测定研究,以便发现该新型DNA纳米二聚体结构和该Holliday基序组装的三维结构,从而更深入地认识DNA纳米材料的组装规律.     

DNA与CdS-NH2纳米粒子的相互作用研究

采用荧光光谱、紫外光谱(UV-vis)、圆二色谱(CD)、透射电镜(TEM)、原子力显微镜(AFM)、琼脂糖凝胶电泳等技术研究Cd S-NH2-EcoRI复合物与DNA的相互作用.研究发现:Cd S-NH2纳米粒子与p BR322DNA结合后会延迟EcoRI的酶切反应.DNA的曲率和纳米粒子的粒径都是影响结合作用的因素,曲率较大的环状DNA比线性DNA能更好地与纳米粒子结合,小粒径的Cd S-NH2纳米粒子则更易结合到DNA上.并研究了DNA与Cd S-NH2纳米粒子之间的作用机理.     

拓扑DNA在壳聚糖纳米粒子中的固定化负载

为了体外固定化不稳定单链拓扑DNA,采用阴阳离子共聚法制备壳聚糖/拓扑DNA复合纳米粒子,并进行傅立叶变换红外光谱、粒径/zeta电位和透射电子显微镜等分析表征。结果显示,纳米粒子中DNA上磷酸基团振动峰显著减弱,高温制备样品中双链DNA含量少于低温样品,表明DNA的不稳定单链结构获得了体外固定化;同时,伴随DNA单链比例升高,复合纳米粒子的平均水合粒径由573.9 nm降到205 nm,zeta电位由19.53 mV降到9.75 mV,复合纳米粒子结构由核壳结构转变为实心胶束结构。几种差异结构壳聚糖/DNA纳米粒子的成功制备,可为后续生物活性或载药研究提供良好的技术支持。     

基于DNA纳米结构的药物递送系统用于癌症治疗的研究进展

DNA作为生物界中用于传递遗传信息的物质,具有良好的生物相容性.因此,以DNA为模板自组装的DNA纳米结构在无转染剂时能顺利通过细胞膜,且高效无毒.与其他纳米材料相比,DNA纳米结构还具有高度的可编程性和精确的可寻址性,体内稳定性和易于修饰等优点.近年来,随着DNA纳米结构的发展,其特异性的靶向识别能力以及高载药量的优...     

DNA Tile计算简述

自1953年Watson和Crick首次提出DNA双螺旋结构以来,DNA作为遗传物质、信息载体和纳米材料被广泛研究,并成为多个领域的研究对象,如基因工程、DNA酶、生物信息学、信息存储、DNA纳米技术等.DNA作为一种天然的纳米材料,具备自组装的能力(A-T、C-G),使其在纳米结构领域成为备受瞩目的材料之一.以DNA构建的纳米结构形态不一,其构建的方法则主要分为两种:DNA Tile和DNA折纸.文章主要阐述DNA Tile的发展历程及其在纳米结构构建领域的应用,并着重介绍DNA Tile在计算领域的广泛应用.     

Logical computation using algorithmic self-assembly of DNA triple-crossover molecules

Recent work has demonstrated the self-assembly of designed periodic two-dimensional arrays composed of DNA tiles, in which the intermolecular contacts are directed by 'sticky' ends. In a mathematical context, aperiodic mosaics may be formed by the self-assembly of 'Wang' tiles, a process that emulates the operation of a Turing machine. Macroscopic self-assembly has been used to perform computations; there is also a logical equivalence between DNA sticky ends and Wang tile edges. This suggests that the self-assembly of DNA-based tiles could be used to perform DNA-based computation. Algorithmic aperiodic self-assembly requires greater fidelity than periodic self-assembly, because correct tiles must compete with partially correct tiles. Here we report a one-dimensional algorithmic self-assembly of DNA triple-crossover molecules that can be used to execute four steps of a logical (cumulative XOR) operation on a string of binary bits.     

Complex shapes self-assembled from single-stranded DNA tiles

Programmed self-assembly of strands of nucleic acid has proved highly effective for creating a wide range of structures with desired shapes. A particularly successful implementation is DNA origami, in which a long scaffold strand is folded by hundreds of short auxiliary strands into a complex shape. Modular strategies are in principle simpler and more versatile and have been used to assemble DNA or RNA tiles into periodic and algorithmic two-dimensional lattices, extended ribbons and tubes, three-dimensional crystals, polyhedra and simple finite two-dimensional shapes. But creating finite yet complex shapes from a large number of uniquely addressable tiles remains challenging. Here we solve this problem with the simplest tile form, a 'single-stranded tile' (SST) that consists of a 42-base strand of DNA composed entirely of concatenated sticky ends and that binds to four local neighbours during self-assembly. Although ribbons and tubes with controlled circumferences have been created using the SST approach, we extend it to assemble complex two-dimensional shapes and tubes from hundreds (in some cases more than one thousand) distinct tiles. Our main design feature is a self-assembled rectangle that serves as a molecular canvas, with each of its constituent SST strands--folded into a 3 nm-by-7 nm tile and attached to four neighbouring tiles--acting as a pixel. A desired shape, drawn on the canvas, is then produced by one-pot annealing of all those strands that correspond to pixels covered by the target shape; the remaining strands are excluded. We implement the strategy with a master strand collection that corresponds to a 310-pixel canvas, and then use appropriate strand subsets to construct 107 distinct and complex two-dimensional shapes, thereby establishing SST assembly as a simple, modular and robust framework for constructing nanostructures with prescribed shapes from short synthetic DNA strands.     

Hierarchical self-assembly of DNA into symmetric supramolecular polyhedra

DNA is renowned for its double helix structure and the base pairing that enables the recognition and highly selective binding of complementary DNA strands. These features, and the ability to create DNA strands with any desired sequence of bases, have led to the use of DNA rationally to design various nanostructures and even execute molecular computations. Of the wide range of self-assembled DNA nanostructures reported, most are one- or two-dimensional. Examples of three-dimensional DNA structures include cubes, truncated octahedra, octohedra and tetrahedra, which are all comprised of many different DNA strands with unique sequences. When aiming for large structures, the need to synthesize large numbers (hundreds) of unique DNA strands poses a challenging design problem. Here, we demonstrate a simple solution to this problem: the design of basic DNA building units in such a way that many copies of identical units assemble into larger three-dimensional structures. We test this hierarchical self-assembly concept with DNA molecules that form three-point-star motifs, or tiles. By controlling the flexibility and concentration of the tiles, the one-pot assembly yields tetrahedra, dodecahedra or buckyballs that are tens of nanometres in size and comprised of four, twenty or sixty individual tiles, respectively. We expect that our assembly strategy can be adapted to allow the fabrication of a range of relatively complex three-dimensional structures.     

A DNA-fuelled molecular machine made of DNA

Molecular recognition between complementary strands of DNA allows construction on a nanometre length scale. For example, DNA tags may be used to organize the assembly of colloidal particles, and DNA templates can direct the growth of semiconductor nanocrystals and metal wires. As a structural material in its own right, DNA can be used to make ordered static arrays of tiles, linked rings and polyhedra. The construction of active devices is also possible--for example, a nanomechanical switch, whose conformation is changed by inducing a transition in the chirality of the DNA double helix. Melting of chemically modified DNA has been induced by optical absorption, and conformational changes caused by the binding of oligonucleotides or other small groups have been shown to change the enzymatic activity of ribozymes. Here we report the construction of a DNA machine in which the DNA is used not only as a structural material, but also as 'fuel'. The machine, made from three strands of DNA, has the form of a pair of tweezers. It may be closed and opened by addition of auxiliary strands of 'fuel' DNA; each cycle produces a duplex DNA waste product.     

一种基于DNA自组装模型求解最大团问题的算法

基于tiles理论模型和已有DNA自组装模型,结合最大团问题给出基于DNA自组装模型的算法设计,得到具体设计初始分子、规则分子和检测分子所需的DAE块种类.在此基础上采用荧光标记和凝胶电泳生物操作提出了一种求解最大团问题算法.该算法设计tiles的种类为Θ(n2+|E|),其生物操作复杂性为Θ(1).此算法降低了实验的复杂度,而且保证了实验的易操作性和结果的准确性。     

Self-assembly of two-dimensional DNA crystals

Self-assembly of synthetic oligonucleotides into two-dimensional lattices presents a 慴ottom-up?approach to the fabrication of devices on nanometer scale. We report the design and observation of two-dimensional crystalline forms of DNAs that are composed of twenty-one plane oligonucleo-tides and one phosphate-modified oligonucleotide. These synthetic sequences are designed to self-assemble into four double-crossover (DX) DNA tiles. The 憇ticky ends?of these tiles that associate according to WatsonCrick抯 base pairing are programmed to build up specific periodic patterns upto tens of microns. The patterned crystals are visualized by the transmission electron microscopy.     

Arithmetic computation using self-assembly of DNA tiles: subtraction and division

Recently,experiments have demonstrated that simple binary arithmetic and logical operations can be computed by the process of selfassembly of DNA tiles.In this paper,we show how the tile assembly process can be used for subtraction and division.In order to achieve this aim,four systems,including the comparator system,the duplicator system,the subtraction system,and the division system,are proposed to compute the difference and quotient of two input numbers using the tile assembly model.This work indicates that these systems can be carried out in polynomial time with optimal O(1)distinct tile types in parallel and at very low cost.Furthermore,we provide a scheme to factor the product of two prime numbers,and it is a breakthrough in basic biological operations using a molecular computer by self-assembly.     

A robust DNA mechanical device controlled by hybridization topology.

Controlled mechanical movement in molecular-scale devices has been realized in a variety of systems-catenanes and rotaxanes, chiroptical molecular switches, molecular ratchets and DNA-by exploiting conformational changes triggered by changes in redox potential or temperature, reversible binding of small molecules or ions, or irradiation. The incorporation of such devices into arrays could in principle lead to complex structural states suitable for nanorobotic applications, provided that individual devices can be addressed separately. But because the triggers commonly used tend to act equally on all the devices that are present, they will need to be localized very tightly. This could be readily achieved with devices that are controlled individually by separate and device-specific reagents. A trigger mechanism that allows such specific control is the reversible binding of DNA strands, thereby 'fuelling' conformational changes in a DNA machine. Here we improve upon the initial prototype system that uses this mechanism but generates by-products, by demonstrating a robust sequence-dependent rotary DNA device operating in a four-step cycle. We show that DNA strands control and fuel our device cycle by inducing the interconversion between two robust topological motifs, paranemic crossover (PX) DNA and its topoisomer JX2 DNA, in which one strand end is rotated relative to the other by 180 degrees. We expect that a wide range of analogous yet distinct rotary devices can be created by changing the control strands and the device sequences to which they bind.     

三维DNA自组装在多维背包问题中的应用研究

利用DNA自组装执行计算的思想已从实验上被证明了其可行性．已有多种理论模型被提出用以解决各种NP问题．基于DNA Tile自组装模型理论在二维下的扩展,本文设计了可以实现这一算法的三维DNA Tile组装系统,提出了一种用于解决多维背包问题的三维DNA自组装模型．该模型可以非确定性的输出可行性解决方案．分析表明系统可以在线性组装步骤内完成计算,所需的Tile种类数与问题维数无关．为探索三维DNA自组装的计算能力进行了一次有意义的尝试．     

Basis for recognition of cisplatin-modified DNA by high-mobility-group proteins.

The anticancer activity of cis-diamminedichloroplatinum(II) (cisplatin) arises from its ability to damage DNA, with the major adducts formed being intrastrand d(GpG) and d(ApG) crosslinks. These crosslinks bend and unwind the duplex, and the altered structure attracts high-mobility-group domain (HMG) and other proteins. This binding of HMG-domain proteins to cisplatin-modified DNA has been postulated to mediate the antitumour properties of the drug. Many HMG-domain proteins recognize altered DNA structures such as four-way junctions and cisplatin-modified DNA, but until now the molecular basis for this recognition was unknown. Here we describe mutagenesis, hydroxyl-radical footprinting and X-ray studies that elucidate the structure of a 1:1 cisplatin-modified DNA/HMG-domain complex. Domain A of the structure-specific HMG-domain protein HMG1 binds to the widened minor groove of a 16-base-pair DNA duplex containing a site-specific cis-[Pt(NH3)2[d(GpG)-N7(1),-N7(2)]] adduct. The DNA is strongly kinked at a hydrophobic notch created at the platinum-DNA crosslink and protein binding extends exclusively to the 3' side of the platinated strand. A phenylalanine residue at position 37 intercalates into a hydrophobic notch created at the platinum crosslinked d(GpG) site and binding of the domain is dramatically reduced in a mutant in which alanine is substituted for phenylalanine at this position.