Sticky-free and overhang-free DNA languages

An essential step of any DNA computation is encoding the input data on single or double DNA strands. Due to the biochemical properties of DNA, complementary single strands can bind to one another forming double-stranded DNA. Consequently, data-encoding DNA strands can sometimes interact in undesirable ways when used in computations. It is crucial thus to analyze properties that guard against such phenomena and study sets of sequences that ensure that no unwanted bindings occur during any computation. This paper formalizes and investigates properties of DNA languages that guarantee their robusteness during computations. After defining and investigating several types of DNA languages possessing good encoding properties, such as sticky-free and overhang-free languages, we give algorithms for deciding whether regular DNA languages are invariant under bio-operations. We also give a method for constructing DNA languages that, in addition to being invariant and sticky-free, possess error-detecting properties. Finally, we present the results of running tests that check whether several known gene languages (the set of genes of a given organism) as well as the input DNA languages used in Adlemans DNA computing experiment, have the defined properties.Received: 6 February 2003, Published online: 2 September 2003Research partially supported by Grants R2824A01 and R220259 of the Natural Sciences and Engineering Research Council of Canada.     

基于抗原中介三链DNA结构的0-1整数规划

利用同源的存在抗原蛋白质的脱氧核苷酸定位于双链DNA中很容易形成三螺旋结构的DNA链,可以利用这种独特的结构来研究一些可能的或可行的的计算模型。尝试了用三螺旋结构的DNA链来解决简单的0-1整数规划问题。而对于整数规划和可满足问题都可以转化为0-1整数规划来解决,从而都可以利用三链DNA计算模型得以解决。     

计算科学的新领域：DNA计算（Ⅲ）

DNA计算是应用分子生物技术进行计算的新方法.从理论上研究DNA计算方法，有利于推动理论计算科学的发展.本系列文章应用形式语言及自动机理论技术，系统地探讨了DNA分子的可计算性及其计算能力.本文主要介绍DNA剪接计算模型的文法结构和剪接计算方法，探讨了不同DNA剪接计算模型的计算能力，证明了所有图灵机可计算的函数理论上都可以通过DNA剪接计算模型来计算.     

DNA计算方法

DNA计算是应用分子生物技术进行计算的新方法。本文主要介绍了DNA计算的基本思想及在解决NP完全问题中的应用。     

Protein output for DNA computing

In recent years, several strategies for DNA based molecular computing have been investigated. An important area of research is the detection and analysis of output molecules. We demonstrate how DNA computing can be extended with in vivo translation of the output. In the resulting proteins, the information per kilogram is about 15-fold higher than in the original DNA output. The proteins are therefore of correspondingly smaller mass, which facilitates their subsequent detection using highly sensitive mass spectrometry methods. We have tested this approach on an instance of the Minimal Dominating Set problem. The DNA used in the computation was constructed as an open reading frame in a plasmid, under the control of a strong inducible promoter. Sequential application of restriction endonucleases yielded a library of potential solutions to the problem instance. The mixture of plasmids was then used for expression of a protein representation. Using MALDI-TOF mass spectrometry, a protein corresponding to the correct solution could be detected. The results indicate the feasibility of the extension of DNA computing to include protein technology. Our strategy opens up new possibilities for both scaling of DNA computations and implementations that employ output of functional molecules or phenotypes.     

DNA计算机中二叉树存储结构的研究*

在参考已有研究的基础上提出DNA计算机中二叉树存储结构的研究思路,并结合生物操作和DNA分子的特性,阐述了三种设计方法的基本思想,即利用双链DNA分子可实现二叉树的顺序存储结构和基本操作,利用单、双链DNA混合编码方法构造的DNA双链对应于二叉树的中序遍历序列,利用3臂DNA分子可以实现二叉树的链式存储结构。仿真实例表明这三种设计方法具有可行性。     

A computer scientist's guide to molecular biology

 In this paper, we explain the basic structure and properties of both single- and double-stranded DNA in vivo (in living organisms). We also review the first in vitro (test tube) experiment that solved a mathematical problem, The Directed Hamiltonian Path Problem, by manipulating DNA strands. Lastly, we give a list of bio-operations that have so far been used in DNA computation.     

计算科学的新领域：DNA计算（Ⅱ）

DNA计算是应用分子生物技术进行计算的新方法。从理论上研究DNA计算方法，有利于推动理论计算科学的发展。本系列文章应用形式语言及自动机理论技术，系统地探讨了DNA分子的可计算性及其计算能力。本文主要介绍DNA分子粘接计算模型的文法结构和计算方法，探讨了不同粘接计算模型的计算能力，并证明了DNA有穷自动机与正规文法的等价性。     

Multiplying with DNA

A functional machine is not only an assembly of parts, but also an assembly of processes. The processing of each part must obey laws that respect to the property of this part. For example, building any kind of computer entails selecting appropriate components and assembling their properties to function in computation. Here, we describe computation using a DNA strand as the basic unit and we have used this unit to achieve the function of multiplication. We exploit the phenomenon of DNA hybridization, in which each strand can represent two individual units that can pair to form a single unit. We represent the numbers we multiply in binary, with different lengths representing each digit present in the number. In principle, all combinations of the numbers will be present in solution. Following hybridization, there is present a collection of duplex molecules that are tailed by single-stranded ends. These intermediates are converted to fully duplex molecules by filling in the ends with DNA polymerase. The lengths that are present represent the digits that are present, and they may be separated by denaturing PAGE. The results give a series of bands for each power of two. The number of bands in the size domain for a particular power of two is converted to binary and the sum of all present bands is then added together. Experimentally, the result of this process always yields the correct answer.     

图论中的DNA计算

DNA计算是一种模拟生物分子DNA结构并借助分子生物技术进行计算的新方法,其高度并行性和巨大的信息存储量为解决NP-完全问题提供全新的途径.介绍DNA计算的基本原理,详细介绍哈密顿图的DNA算法以及图着色问题的表面DNA计算,最后介绍DNA计算在图论中的进展以及DNA计算存在的问题.     

DNA计算中的数据与计算模型

对DNA计算的通用性及单链、双链、粘性末端、发夹、质粒、k-臂DNA分子等各种数据作了简单介绍,并对基于DNA分子结构特性和基于DNA计算机研制过程两个方面的DNA计算模型进行了分析对比。针对各种不同的DNA数据及特性,提出了混合DNA计算模型的研究思路,并从不同角度论述了混合DNA计算模型的可行性。     

信息安全中的DNA编码技术

DNA计算是一种模拟生物分子的结构并借助于分子生物技术进行计算的新模式。它引入了崭新的数据结构和计算方法,为解决NP完全问题提供了全新的途径。用DNA分子作为信息载体,以实现数据隐藏、认证、加密等安全技术。本文借鉴生物DNA的表达方式,定义了用户DNA、文件DNA的串结构,从而提高系统中信息安全控制的可靠性。     

计算科学的新领域：DNA计算（Ⅰ）

DNA计算是应用分子生物技术进行计算的新方法。从理论上研究DNA计算方法，有利于推动理论计算科学的发展。本系列文章应用形式语言及自动机理论技术，系统地探讨了DNA分子的可计算性及其计算能力。本文主要介绍常用DNA分子操作方法，并根据DNA分子的结构及特点，给出了DNA分子的形式化描述。     

DNA计算机中二叉树存储结构分析

DNA计算机是未来计算机发展的重要方向,其优势十分明显,本文以顺序二叉树为思路的双链DNA分子法为例,介绍的是DNA计算机存储结构的基本理论和具体操作方式。     

DNA计算机中二叉树的链式存储结构*

利用DNA分子和连接酶的生物特性,提出DNA计算机中二叉树的链式存储结构的设计方法,并给出二叉树链式存储结构的形式描述。在连接酶的作用下,各节点之间产生杂交和连接反应形成DNA双链,其中用到的生物技术在实验室中都能实现。为了验证方法的可行性,给出一棵二叉树的链式存储结构实例,实例表明该设计方法构造的DNA双链对应于二叉树的中序遍历序列。     

Incorporation and use of modified nucleotides in aqueous DNA computing

The concept of aqueous computing involves the use of large numbers of initially identical molecules to serve as memory registers in a fluid environment. Here, we test a new approach to aqueous computing where modified nucleotides are used to “write” on double-stranded DNA molecules to establish the logical values of true or false for a set of clauses. We introduce an implementation scenario where binding proteins specific to each modification can be used to selectively isolate DNA fragments with these modified nucleotides. In addition, we present initial results showing successful incorporation and detection of modifications. We have successfully labeled DNA fragments with four modifications, specifically Alexa Fluor-488, BODIPY-FL, biotin, and digoxigenin using polymerase chain reaction. The first two produce fluorescent molecules that can be distinguished by their color. We have confirmed that binding proteins or antibodies to these four modifications are specific and do not detect the other modifications. We have also successfully separated the DNAs labeled with Alexa Fluor and biotin using binding proteins. We present attempts at rebinding these modified molecules to a second binding protein; the equivalent of applying more than one clause to a set of values. We have found some challenges with this approach that likely can be resolved with further work. As there are millions of molecules with corresponding binding proteins, this approach has the potential to yield unlimited computing power as compared with other aqueous computing methods.     

Symmetric-key cryptosystem with DNA technology

DNA cryptography is a new field which has emerged with progress in the research of DNA computing. In our study, a symmetric-key cryptosystem was designed by applying a modern DNA biotechnology, microarray, into cryptographic technologies. This is referred to as DNA symmetric-key cryptosystem (DNASC). In DNASC, both encryption and decryption keys are formed by DNA probes, while its ciphertext is embedded in a specially designed DNA chip (microarray). The security of this system is mainly rooted in difficult biology processes and problems, rather than conventional computing technology, thus it is unaffected by changes from the attack of the coming quantum computer. The encryption process is a fabrication of a specially designed DNA chip and the decryption process is the DNA hybridization. In DNASC, billions of DNA probes are hybridized and identified at the same time, thus the decryption process is conducted in a massive, parallel way. The great potential in vast parallelism computation and the extraordinary information density of DNA are displayed in DNASC to some degree.     

基于特定模数集的并行DNA算术运算

在DNA算术运算的模型中普遍应用二进制,受制于进位的影响,难以实现并行运算。但在剩余数制中,算术运算（加、减、乘）在剩余位之间不存在进位,故可降低运算过程的复杂度,可以充分利用DNA计算巨大并行性的优势,简化实际编码的难度。基于Adleman-Lipton模型,分析了剩余数制的基本原理,基于特定的模数集,改进了整数的DNA链表示,并将其应用于DNA算术运算,给出了特定剩余数制下进行并行DNA算术运算的具体算法。     

DNA计算中的信息安全技术

DNA计算是一种模拟生物分子的结构并借助于分子生物技术进行计算的新模式。它引入了崭新的数据结构和计算方法,为解决NP完全问题提供了全新的途径。由于DNA计算具有信息处理的高并行性、低能耗及高存储密度等优点,对传统的基于计算安全的密码体系提出了挑战。DNA密码便是近年来伴随着DNA计算的研究而出现的密码学新领域。用DNA分子作为信息载体,以实现数据隐藏、认证、加密等安全技术。在简要回顾DNA计算原理的基础上,详细分析了基于DNA的一次一密方案以及Boneh用DNA计算机破解DES的方法;最后探讨在DNA计算中的信息安全技术。     

Automating the DNA computer: solving n-Variable 3-SAT problems

In the decade since the first molecular computation was performed, it has been shown that DNA molecules can perform sophisticated, massively parallel computations avoiding the Von Neumann bottleneck. However, progress in the field has been slow. The largest problem solved to date is an instance of the 20-variable 3-CNF SAT problem. Performing the computation took more than two man-weeks to complete because every aspect of the computation was performed by hand. Molecular computations are extremely labor intensive and error prone–automation is necessary for further progress. The next step, (the second generation DNA computer—that of taking the laborious, laboratory bench protocols performed by hand, and automating them), has been achieved with the construction of an automated DNA computer dubbed EDNAC. It employs the same paradigm that was used to solve the labor-intensive instance of the 20-variable 3-CNF SAT problem. Using a combinatorial DNA library and complementary probes, EDNAC solves instances of the n-variable 3-CNF SAT problem. A 10 variable instance of the 3-CNF SAT problem was essayed. The computation took 28 h to perform. EDNAC correctly computed nine of the 10 variables, with a tenth variable remaining ambiguous. This result is comparable to current results in the molecular computation community. This research tested the critical properties, such as complexity, robustness, reliability, and repeatability necessary for the successful automation of a molecular computer.