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DNA computing
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===DNAzymes=== Catalytic DNA ([[deoxyribozyme]] or DNAzyme) catalyze a reaction when interacting with the appropriate input, such as a matching [[oligonucleotide]]. These DNAzymes are used to build logic gates analogous to digital logic in silicon; however, DNAzymes are limited to one-, two-, and three-input gates with no current implementation for evaluating statements in series. The DNAzyme logic gate changes its structure when it binds to a matching oligonucleotide and the fluorogenic substrate it is bonded to is cleaved free. While other materials can be used, most models use a fluorescence-based substrate because it is very easy to detect, even at the single molecule limit.<ref name="weiss"> {{Cite journal | last1 = Weiss | first1 = S. | s2cid = 9697423 | title = Fluorescence Spectroscopy of Single Biomolecules | doi = 10.1126/science.283.5408.1676 | journal = Science | volume = 283 | issue = 5408 | pages = 1676β1683 | year = 1999 | pmid = 10073925|bibcode = 1999Sci...283.1676W }}. Also available here: http://www.lps.ens.fr/~vincent/smb/PDF/weiss-1.pdf </ref> The amount of fluorescence can then be measured to tell whether or not a reaction took place. The DNAzyme that changes is then "used", and cannot initiate any more reactions. Because of this, these reactions take place in a device such as a continuous stirred-tank reactor, where old product is removed and new molecules added. Two commonly used DNAzymes are named E6 and 8-17. These are popular because they allow cleaving of a substrate in any arbitrary location.<ref> {{Cite journal |last1=Santoro |first1=S. W. |last2=Joyce |first2=G. F. |year=1997 |title=A general purpose RNA-cleaving DNA enzyme |journal=Proceedings of the National Academy of Sciences |volume=94 |issue=9 |pages=4262β4266 |bibcode=1997PNAS...94.4262S |doi=10.1073/pnas.94.9.4262 |pmc=20710 |pmid=9113977 |doi-access=free}}. Also available here: [http://www.pnas.org/content/94/9/4262.full.pdf] </ref> Stojanovic and MacDonald have used the E6 DNAzymes to build the [[MAYA I]]<ref> {{Cite journal |last1=Stojanovic |first1=M. N. |last2=Stefanovic |first2=D. |year=2003 |title=A deoxyribozyme-based molecular automaton |journal=Nature Biotechnology |volume=21 |issue=9 |pages=1069β1074 |doi=10.1038/nbt862 |pmid=12923549 |s2cid=184520}}. Also available here: [https://web.archive.org/web/20120401132040/http://www.cs.duke.edu/courses/cps296.6/current/papers/SS03.pdf] </ref> and [[MAYA II]]<ref> {{Cite journal |last1=MacDonald |first1=J. |last2=Li |first2=Y. |last3=Sutovic |first3=M. |last4=Lederman |first4=H. |last5=Pendri |first5=K. |last6=Lu |first6=W. |last7=Andrews |first7=B. L. |last8=Stefanovic |first8=D. |last9=Stojanovic |first9=M. N. |year=2006 |title=Medium Scale Integration of Molecular Logic Gates in an Automaton |journal=Nano Letters |volume=6 |issue=11 |pages=2598β2603 |bibcode=2006NanoL...6.2598M |doi=10.1021/nl0620684 |pmid=17090098}}. Also available here: [http://www.ece.gatech.edu/research/labs/bwn/nanos/papers/Medium_Scale_Integration_of_Molecular.pdf] </ref> machines, respectively; Stojanovic has also demonstrated logic gates using the 8-17 DNAzyme.<ref> {{Cite journal |last1=Stojanovic |first1=M. N. |last2=Mitchell |first2=T. E. |last3=Stefanovic |first3=D. |year=2002 |title=Deoxyribozyme-Based Logic Gates |url=https://figshare.com/articles/Deoxyribozyme-Based_Logic_Gates/3638808 |journal=Journal of the American Chemical Society |volume=124 |issue=14 |pages=3555β3561 |doi=10.1021/ja016756v |pmid=11929243|bibcode=2002JAChS.124.3555S }}. Also available at [http://www.dna.caltech.edu/courses/cs191/paperscs191/stojanovic_mitchell_stefanovic2002.pdf] </ref> While these DNAzymes have been demonstrated to be useful for constructing logic gates, they are limited by the need of a metal cofactor to function, such as Zn<sup>2+</sup> or Mn<sup>2+</sup>, and thus are not useful [[in vivo]].<ref name="weiss" /><ref> {{Cite journal | last1 = Cruz | first1 = R. P. G. | last2 = Withers | first2 = J. B. | last3 = Li | first3 = Y. | title = Dinucleotide Junction Cleavage Versatility of 8-17 Deoxyribozyme | doi = 10.1016/j.chembiol.2003.12.012 | journal = Chemistry & Biology | volume = 11 | issue = 1 | pages = 57β67 | year = 2004 | pmid = 15112995| doi-access = free | hdl = 11375/23673 | hdl-access = free }} </ref> A design called a ''stem loop'', consisting of a single strand of DNA which has a loop at an end, are a dynamic structure that opens and closes when a piece of DNA bonds to the loop part. This effect has been exploited to create several [[logic gate]]s. These logic gates have been used to create the computers MAYA I and [[MAYA II]] which can play [[tic-tac-toe]] to some extent.<!-- --><ref>Darko Stefanovic's Group, [https://digamma.cs.unm.edu/wiki/bin/view/McogPublicWeb/MolecularLogicGates Molecular Logic Gates] {{Webarchive|url=https://web.archive.org/web/20100618033006/https://digamma.cs.unm.edu/wiki/bin/view/McogPublicWeb/MolecularLogicGates |date=2010-06-18 }} and [https://digamma.cs.unm.edu/wiki/bin/view/McogPublicWeb/MolecularAutomataMAYAII MAYA II, a second-generation tic-tac-toe playing automaton] {{Webarchive|url=https://web.archive.org/web/20100618001044/https://digamma.cs.unm.edu/wiki/bin/view/McogPublicWeb/MolecularAutomataMAYAII |date=2010-06-18 }}.</ref>
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