Abstract
In this paper we report on a module in the RTRACS (Reverse-transcription and TRanscription-based Autonomous Computing System) molecular computing system, constructed with DNA, RNA and enzymes. The module is a 2-input logic gate that receives input and produces output in the form of RNA molecules. Each of the two input molecules is chosen from a set of two, and the logic gate produces an output molecule for each of the four possible input combinations. Two output RNA molecules can be produced by this module, one for only one combination of inputs, whilst the remaining three combinations lead to the production of the other output. Since the RNA strands can be arbitrarily assigned logical values, this module is capable performing multiple logical operations, including AND, NAND, OR and NOR, given the appropriate mapping of RNA molecules to logical values. We performed numerical simulations of the logic gate reaction scheme, revealing the details of the kinetics of the production of output molecules and the theoretical input–output characteristics. We experimentally demonstrated the proper functioning of the logic gate and the real time production of output molecules. Furthermore, we demonstrate an implementation of the logic gate in diagnosing single nucleotide polymorphism patterns on samples of human genomic DNA. We believe this versatile logic gate has significant advantages as a basic module of RTRACS due to the wide variety of possible logical operations.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Explore related subjects
Discover the latest articles, news and stories from top researchers in related subjects.References
Hirano N, Haruki M, Morikawa M, Kanaya S (2000) Enhancement of the enzymatic activity of ribonuclease HI from Thermus thermophilus HB8 with a suppressor mutation method. Biochemistry 39(43):13285–13294
Kim S, Misra A (2007) SNP genotyping: technologies and biomedical applications. Ann Rev Biomed Eng 9(1):289–320
Kitajima T, Takinoue M, Shohda K, Suyama A (2008) Design of code words for DNA computers and nanostructures with consideration of hybridization kinetics. In: Garzon M, Yan H (eds) DNA computing. Lecture notes in computer science, vol 4848. Springer, Berlin, pp 119–129
Krug MS, Berger SL (1991) Reverse transcriptase from human immunodeficiency virus: a single template-primer binding site serves two physically separable catalytic functions. Biochemistry 30(44):10614–10623
Martin CT, Coleman JE (1987) Kinetic analysis of T7 RNA polymerase-promoter interactions with small synthetic promoters. Biochemistry 26(10):2690–2696
Nishida N, Tanabe T, Hashido K, Hirayasu K, Takasu M, Suyama A, Tokunaga K (2005) DigiTag assay for multiplex single nucleotide polymorphism typing with high success rate. Anal Biochem 346(2):281–288
Nitta N (2005) Retrovirus-based computer. Nat Comput 4:127–139
Sakai Y, Mawatari Y, Yamasaki K, Shohda K, Suyama A (2009) Construction of AND gate for RTRACS with the capacity of extension to NAND gate. In: Deaton R, Suyama A (eds) DNA computing and molecular programming. Lecture notes in computer science, vol 5877. Springer, Berlin, p 137–143
Takinoue M, Kiga D, Shohda K-i, Suyama A (2008) Experiments and simulation models of a basic computation element of an autonomous molecular computing system. Phys Rev E 78:041921
Yu H, Goodman MF (1992) Comparison of HIV-1 and avian myeloblastosis virus reverse transcriptase fidelity on RNA and DNA templates. J Biol Chem 267(15):10888–10896
Acknowledgments
The authors gratefully acknowledge Prof. Katsushi Tokunaga and Dr. Nao Nishida, Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, for their help with the preparation of encoding products from the human genomic DNA samples. This work was partly supported by Grant-in-Aid for Scientific Research on Innovative Areas 23119007 to AS from the Ministry of Education, Culture, Sports, Science, and Technology, Japan.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kan, A., Sakai, Y., Shohda, Ki. et al. A DNA based molecular logic gate capable of a variety of logical operations. Nat Comput 13, 573–581 (2014). https://doi.org/10.1007/s11047-013-9394-5
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11047-013-9394-5