基于DNA链置换构建逻辑计算模型
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摘要
近年来,随着电子元器件的微型化趋势,其传统制作工艺所面临的挑战也日益显著,寻找新型手段辅助甚至替代传统硅基计算机已逐渐成为科学家们的研究重点。所以,随着生物化学技术的不断发展,以DNA分子作为存储数据和运算媒介的新型计算模型引起了研究者的广泛关注。为此,提出了基于DNA链置换与荧光标记的分子逻辑计算模型。该方法利用重金属离子Hg~(2+)能够引发组成DNA分子中胸腺嘧啶(thymine,T)形成T-Hg~(2+)-T错配的形式,通过检测荧光信号强度的相对变化,构建了与非逻辑门(NAND)。之后,在前者的基础上利用DNA富含鸟嘌呤(guanine,G)的片段可以形成G-四链体结构的情况下,通过结合氯化血红素(Hemin)形成具有过氧化物酶的活性进而促进过氧化氢(H_2O_2)氧化四甲基联苯胺(TMB)得到蓝色的TMB~+,以此构建半加器。
In recent years,with the tendency of miniaturization of electronic components,the challenges faced by traditional manufacturing process have become more and more obvious. It is becoming more and more important for scientists to find new ways to supplement or even replace traditional silicon-based computers. Therefore,with the continuous development of biochemical technology,DNA molecules as a new computational model for storing data and computing media have drawn much attention from researchers. For this reason,we propose a molecular logic calculation model based on DNA strand displacement and fluorescent labeling. The method uses heavy metal ions Hg~(2+) to induce the formation of T-Hg~(2+)-T mismatch in thymine( T) of DNA molecules. By detecting the relative change of fluorescence signal intensity,a NAND gate is constructed. Then,using the guanine( G)-containing fragment of DNA on the basis of the former to form a G-quadruplex structure,a peroxidase-forming activity is formed by binding hemin. Half-adder is constructed by promoting hydrogen peroxide( H_2 O_2) tetramethyl benzidine( TMB) to give blue TMB~+.
In recent years,with the tendency of miniaturization of electronic components,the challenges faced by traditional manufacturing process have become more and more obvious. It is becoming more and more important for scientists to find new ways to supplement or even replace traditional silicon-based computers. Therefore,with the continuous development of biochemical technology,DNA molecules as a new computational model for storing data and computing media have drawn much attention from researchers. For this reason,we propose a molecular logic calculation model based on DNA strand displacement and fluorescent labeling. The method uses heavy metal ions Hg~(2+) to induce the formation of T-Hg~(2+)-T mismatch in thymine( T) of DNA molecules. By detecting the relative change of fluorescence signal intensity,a NAND gate is constructed. Then,using the guanine( G)-containing fragment of DNA on the basis of the former to form a G-quadruplex structure,a peroxidase-forming activity is formed by binding hemin. Half-adder is constructed by promoting hydrogen peroxide( H_2 O_2) tetramethyl benzidine( TMB) to give blue TMB~+.
引文
[1]张文逸,殷志祥.基于DNA链置换的分子逻辑门计算模型[J].安徽理工大学学报:自然科学版,2015,35(1):7-10.
[2] OGIHARA M,RAY A. Simulating Boolean circuits on a DNA computer[J]. Algorithmica,1999,25(2-3):239-250.
[3] FEYNMAN R P. There is plenty of room at the bottom[M]//Minaturization.[s. l.]:[s. n.],1961:282-296.
[4] ADLEMAN L M,LEONARD P,ADLEMAN M. Molecular computation of solutions to combinatorial problems[J]. Science,1994,266(5187):1021-1024.
[5]牛合利. DNA计算问题的研究进展[J].科技资讯,2008(17):2.
[6]王淑栋,许进,张成. DNA计算及其应用简介[J].数学建模及其应用,2014,3(3):18-25.
[7]杨静,张成. DNA自组装技术的研究进展及难点[J].计算机学报,2008,31(12):2138-2148.
[8]李肯立,罗兴,吴帆,等.基于自组装模型的最大团问题DNA计算算法[J].计算机研究与发展,2013,50(3):666-675.
[9]吴帆,李肯立.基于自组装的N皇后问题DNA计算算法[J].电子学报,2013,41(11):2174-2180.
[10]牛莹,张勋才,范瑞丽,等.三维DNA自组装在多维背包问题中的应用研究[J].科学技术与工程,2013,13(36):10787-10793.
[11]蓝雯飞,邢志宝,黄俊,等. DNA自组装计算模型求解二部图完美匹配问题[J].计算机研究与发展,2016,53(11):2583-2593.
[12]周旭,周炎涛,李肯立,等.基于Tile自组装模型的最大匹配问题算法研究[J].电子学报,2015,43(2):262-268.
[13]李孝东,周彩兰,黄林荃.基于DNA编码的安全高效的图像加密算法[J].计算机应用与软件,2018,35(1):318-324.
[14]韩英杰,朱维军,焦林枫,等.线性时序逻辑公式Xp模型检测的DNA计算方法[J].小型微型计算机系统,2017,38(3):553-558.
[15]马莹,殷志祥,方欢.可满足性问题生物芯片DNA算法[J].计算机应用研究,2017,34(8):2310-2311.
[16]崔光照,王茜,张俊亚,等.基于DNA链置换反应的圆环形逻辑门设计[J].轻工学报,2016,31(1):55-60.
[17]夏宏,张实君.基于分子计算的逻辑模型构建[J].科技通报,2016,32(5):11-15.
[18]高建帮.基于氯化血红素对G-四链体/盐酸小檗碱复合物的竞争作用构建DNA逻辑门[J].西南大学学报:自然科学版,2016,38(11):119-123.
[19]姚莉娜,田桂花,叶盟盟,等. DNA链置换技术的研究现状与展望[J].郑州轻工业学院学报:自然科学版,2014,29(1):15-21.
[20]万菲,董晨,杨静,等. DNA计算技术的发展与应用[J].中国科学院院刊,2014,29(1):94-105.
[21]王红钢.适当的茎环结构促进GFP报告基因表达的机制研究[C]//河北省免疫学会第六次免疫学大会资料汇编.石家庄:河北省免疫学会,2010:1.
[22] ZHANG D Y,WINFREE E. Control of DNA strand displacement kinetics using toehold exchange[J]. Journal of the American Chemical Society,2009,131(47):17303-17314.
[23] ZHANG D Y. Towards domain-based sequence design for DNA strand displacement reactions[C]//Proceedings of the16th international conference on DNA computing and molecular programming. Hong Kong,China:Springer,2011:162-175.
[24] SHI Xiaolong,WANG Zhiyu,DENG Chenyan,et al. A novel bio-sensor based on DNA strand displacement[J]. PLoS ONE,2014,9(10):1-16.
[25]李明慧.基于DNA链置换的核酸逻辑计算模型的研究[D].西安:陕西师范大学,2016.
[26]薛斌军.基于荧光标记发夹式DNA探针的汞离子定量检测技术的研究[D].太原:太原理工大学,2017.
[27]刘文斌.与非门(NAND)的DNA计算模型[J].生物数学学报,2008,23(2):357-363.
[28] PROKUP A,HEMPHILL J,DEITERS A. DNA computation:a photochemically controlled AND gate[J]. Journal of the American Chemical Society,2012,134(8):3810-3815.
[29]王忠霞,张立,梁汝萍,等.基于Hg2+和Ag+对DNA修饰金纳米粒子的作用构建DNA逻辑门[J].化学传感器,2012,32(1):36-37.
[30] HUPPERT J L. Structure,location and interactions of Gquadruplexes[J]. FEBS Journal,2010,277(17):3452-3458.
[31] TRAVASCIO P,LI Yingfu,SEN D. DNA-enhanced peroxidase activity of a DNA aptamer-hemin complex[J]. Chemistry&Biology,1998,5(9):505-517.
[32]郜湾.基于G-四链体构建DNA比色逻辑门的研究[D].南昌:南昌大学,2015.
[33] ZADEH J N,STEENBERG C D,BOIS J S,et al. NUPACK:analysis and design of nucleic acid systems[J]. Journal of Computational Chemistry,2011,32(1):170-173.
[2] OGIHARA M,RAY A. Simulating Boolean circuits on a DNA computer[J]. Algorithmica,1999,25(2-3):239-250.
[3] FEYNMAN R P. There is plenty of room at the bottom[M]//Minaturization.[s. l.]:[s. n.],1961:282-296.
[4] ADLEMAN L M,LEONARD P,ADLEMAN M. Molecular computation of solutions to combinatorial problems[J]. Science,1994,266(5187):1021-1024.
[5]牛合利. DNA计算问题的研究进展[J].科技资讯,2008(17):2.
[6]王淑栋,许进,张成. DNA计算及其应用简介[J].数学建模及其应用,2014,3(3):18-25.
[7]杨静,张成. DNA自组装技术的研究进展及难点[J].计算机学报,2008,31(12):2138-2148.
[8]李肯立,罗兴,吴帆,等.基于自组装模型的最大团问题DNA计算算法[J].计算机研究与发展,2013,50(3):666-675.
[9]吴帆,李肯立.基于自组装的N皇后问题DNA计算算法[J].电子学报,2013,41(11):2174-2180.
[10]牛莹,张勋才,范瑞丽,等.三维DNA自组装在多维背包问题中的应用研究[J].科学技术与工程,2013,13(36):10787-10793.
[11]蓝雯飞,邢志宝,黄俊,等. DNA自组装计算模型求解二部图完美匹配问题[J].计算机研究与发展,2016,53(11):2583-2593.
[12]周旭,周炎涛,李肯立,等.基于Tile自组装模型的最大匹配问题算法研究[J].电子学报,2015,43(2):262-268.
[13]李孝东,周彩兰,黄林荃.基于DNA编码的安全高效的图像加密算法[J].计算机应用与软件,2018,35(1):318-324.
[14]韩英杰,朱维军,焦林枫,等.线性时序逻辑公式Xp模型检测的DNA计算方法[J].小型微型计算机系统,2017,38(3):553-558.
[15]马莹,殷志祥,方欢.可满足性问题生物芯片DNA算法[J].计算机应用研究,2017,34(8):2310-2311.
[16]崔光照,王茜,张俊亚,等.基于DNA链置换反应的圆环形逻辑门设计[J].轻工学报,2016,31(1):55-60.
[17]夏宏,张实君.基于分子计算的逻辑模型构建[J].科技通报,2016,32(5):11-15.
[18]高建帮.基于氯化血红素对G-四链体/盐酸小檗碱复合物的竞争作用构建DNA逻辑门[J].西南大学学报:自然科学版,2016,38(11):119-123.
[19]姚莉娜,田桂花,叶盟盟,等. DNA链置换技术的研究现状与展望[J].郑州轻工业学院学报:自然科学版,2014,29(1):15-21.
[20]万菲,董晨,杨静,等. DNA计算技术的发展与应用[J].中国科学院院刊,2014,29(1):94-105.
[21]王红钢.适当的茎环结构促进GFP报告基因表达的机制研究[C]//河北省免疫学会第六次免疫学大会资料汇编.石家庄:河北省免疫学会,2010:1.
[22] ZHANG D Y,WINFREE E. Control of DNA strand displacement kinetics using toehold exchange[J]. Journal of the American Chemical Society,2009,131(47):17303-17314.
[23] ZHANG D Y. Towards domain-based sequence design for DNA strand displacement reactions[C]//Proceedings of the16th international conference on DNA computing and molecular programming. Hong Kong,China:Springer,2011:162-175.
[24] SHI Xiaolong,WANG Zhiyu,DENG Chenyan,et al. A novel bio-sensor based on DNA strand displacement[J]. PLoS ONE,2014,9(10):1-16.
[25]李明慧.基于DNA链置换的核酸逻辑计算模型的研究[D].西安:陕西师范大学,2016.
[26]薛斌军.基于荧光标记发夹式DNA探针的汞离子定量检测技术的研究[D].太原:太原理工大学,2017.
[27]刘文斌.与非门(NAND)的DNA计算模型[J].生物数学学报,2008,23(2):357-363.
[28] PROKUP A,HEMPHILL J,DEITERS A. DNA computation:a photochemically controlled AND gate[J]. Journal of the American Chemical Society,2012,134(8):3810-3815.
[29]王忠霞,张立,梁汝萍,等.基于Hg2+和Ag+对DNA修饰金纳米粒子的作用构建DNA逻辑门[J].化学传感器,2012,32(1):36-37.
[30] HUPPERT J L. Structure,location and interactions of Gquadruplexes[J]. FEBS Journal,2010,277(17):3452-3458.
[31] TRAVASCIO P,LI Yingfu,SEN D. DNA-enhanced peroxidase activity of a DNA aptamer-hemin complex[J]. Chemistry&Biology,1998,5(9):505-517.
[32]郜湾.基于G-四链体构建DNA比色逻辑门的研究[D].南昌:南昌大学,2015.
[33] ZADEH J N,STEENBERG C D,BOIS J S,et al. NUPACK:analysis and design of nucleic acid systems[J]. Journal of Computational Chemistry,2011,32(1):170-173.