Skip to main content
Log in

Incorporation and use of modified nucleotides in aqueous DNA computing

  • Published:
Natural Computing Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12
Fig. 13

Similar content being viewed by others

References

  • Adleman L (1994) Molecular computation of solutions of combinatorial problems. Science 266:1021–1024

    Article  Google Scholar 

  • Gal S, Monteith N, Shkalim S, Huang H, Head T (2007) Methylation of DNA may be used as a computational tool: experimental evidence. In: Mahdavi K, Culshaw R, Boucher J (eds) Current developments in mathematical biology, vol 38. World Scientific, New Jersey, pp 1–14

    Chapter  Google Scholar 

  • Head T, Gal S (2001) Aqueous computing: writing into fluid memory. Bull Euro Assoc Theor Comput Sci 75:190–198

    MATH  MathSciNet  Google Scholar 

  • Head T, Chen X, Yamamura M, Gal S (2002a) Aqueous computing: a survey with an invitation to participate. J Comput Sci Technol 17:672–681

    Article  MATH  MathSciNet  Google Scholar 

  • Head T, Chen X, Nichols MJ, Yamamura M, Gal S (2002b) Aqueous solutions of algorithmic problems: emphasizing knights on a 3 × 3. In: Jonoska N, Seeman N (eds) DNA computing, 7th international workshop on DNA-based computers. Lecture Notes in Computer Science, vol 2340. Springer-Verlag, Berlin, pp 191–202

    Google Scholar 

  • Holmberg A, Blomstergren A, Nord O, Lukacs M, Lundeberg J, Uhlén M (2005) The biotin-streptavidin bond can be reversibly broken using water at elevated temperatures. Electrophoresis 26:501–510

    Article  Google Scholar 

  • Molecular Probes Handbook (2006) The handbook – a guide to fluorescent probes and labeling technologies, Section 8.2 Labeling oligonucleotides and nucleic acids. http://probes.invitrogen.com/handbook/sections/0802.html

  • Tasara T, Angerer B, Damond M, Winter H, Dörhöfer S, Hübscher U, Amacker M (2003) Incorporation of reporter molecule-labeled nucleotides by DNA polymerases. II. High-density labeling of natural DNA. Nucleic Acids Res 31:2636–2646

    Article  Google Scholar 

  • Zhu Z, Chao J, Yu H, Waggoner AS (1994) Directly labeled DNA probes using fluorescent nucleotides with different length linkers. Nucleic Acids Res 22:3418–3422

    Article  Google Scholar 

Download references

Acknowledgments

The authors would like to acknowledge support from the Air Force for this project, contract number AFOSR FA87500620002.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Angela M. Pagano.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pagano, A.M., Pishanider, S.D. & Gal, S. Incorporation and use of modified nucleotides in aqueous DNA computing. Nat Comput 7, 423–438 (2008). https://doi.org/10.1007/s11047-008-9072-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11047-008-9072-1

Keywords

Navigation