DNA computing

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DNA computing is a form of computing which uses DNA, biochemistry and molecular biology, instead of the traditional silicon-based computer technologies. DNA computing, or, more generally, molecular computing, is a fast developing interdisciplinary area. Research and development in this area concerns theory, experiments and applications of DNA computing.

History

This field was initially developed by Leonard Adleman of the University of Southern California, in 1994.^[1] Adleman demonstrated a proof-of-concept use of DNA as a form of computation which solved the seven-point Hamiltonian path problem. Since the initial Adleman experiments, advances have been made and various Turing machines have been proven to be constructible.^{[2] [3]}

In 2002, researchers from the Weizmann Institute of Science in Rehovot, Israel, unveiled a programmable molecular computing machine composed of enzymes and DNA molecules instead of silicon microchips.^[4] On April 28, 2004, Ehud Shapiro, Yaakov Benenson, Binyamin Gil, Uri Ben-Dor, and Rivka Adar at the Weizmann Institute announced in the journal Nature that they had constructed a DNA computer.^[5] This was coupled with an input and output module and is capable of diagnosing cancerous activity within a cell, and then releasing an anti-cancer drug upon diagnosis.

Capabilities

DNA computing is fundamentally similar to parallel computing in that it takes advantage of the many different molecules of DNA to try many different possibilities at once. ^[6]

DNA computing also offers much lower power consumption than traditional silicon computers. DNA uses adenosine triphosphate (ATP) as fuel to allow ligation or as a means to heat the strand to cause disassociation. ^[7] Both strand hybridization and the hydrolysis of the DNA backbone can occur spontaneously, powered by the potential energy stored in DNA. Consumption of two ATP molecules releases 1.5 x 10⁻¹⁹ J. Even with a large number of transitions per second using two ATP molecules, power output is still low. For instance, Kahan reports 109 transitions per second with an energy consumption of 10⁻¹⁰ W,^[8] and similarly Shapiro reports a system producing 7.5 x 10¹¹ outputs in 4000 sec resulting in an energy consumption rate of ~ 10⁻¹⁰ W.^[9]

For certain specialized problems, DNA computers are faster and smaller than any other computer built so far. But DNA computing does not provide any new capabilities from the standpoint of computability theory, the study of which problems are computationally solvable using different models of computation. For example, if the space required for the solution of a problem grows exponentially with the size of the problem (EXPSPACE problems) on von Neumann machines, it still grows exponentially with the size of the problem on DNA machines. For very large EXPSPACE problems, the amount of DNA required is too large to be practical. (Quantum computing, on the other hand, does provide some interesting new capabilities).

DNA computing overlaps with, but is distinct from, DNA nanotechnology. The latter uses the specificity of Watson-Crick basepairing and other DNA properties to make novel structures out of DNA. These structures can be used for DNA computing, but they do not have to be. Additionally, DNA computing can be done without using the types of molecules made possible by DNA nanotechnology.

Methods

There are multiple methods for building a computing device based on DNA, each with its own advantages and disadvantages. Most of these build the basic logic gates (AND, OR, NOT) associated with digital logic from a DNA basis. Some of the different bases include DNAzymes, deoxyoligonucleotides, enzymes, DNA tiling, and polymerase chain reaction.

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 1-, 2-, and 3-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.^[10] 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.^[11] Stojanovic and MacDonald have used the E6 DNAzymes to build the MAYA I^[12] and MAYA II^[13] machines, respectively; Stojanovic has also demonstrated logic gates using the 8-17 DNAzyme.^[14] While these DNAzymes have been demonstrated to be useful for constructing logic gates, they are limited by the need for a metal cofactor to function, such as Zn²⁺ or Mn²⁺, and thus are not useful in vivo.^[10][15]

Enzymes

Enzyme based DNA computers are usually of the form of a simple Turing machine; there is analogous hardware, in the form of an enzyme, and software, in the form of DNA. ^[16]

Shapiro has demonstrated a DNA computer using the FokI enzyme^[17] and expanded on his work by going on to show automata that diagnose and react to prostate cancer: under expression of the genes PPAP2B and GSTP1 and an over expression of PIM1 and HPN.^[5] His automata evaluated the expression of each gene, one gene at a time, and on positive diagnosis then released a single strand DNA molecule (ssDNA) that is an antisense for MDM2. MDM2 is a repressor of protein 53, which itself is a tumor suppressor.^[18] On negative diagnosis it was decided to release a suppressor of the positive diagnosis drug instead of doing nothing. A limitation of this implementation is that two separate automata are required, one to administer each drug. The entire process of evaluation until drug release took around an hour to complete. This method also requires transition molecules as well as the FokI enzyme to be present. The requirement for the FokI enzyme limits application in vivo, at least for use in “cells of higher organisms”.^[19] It should also be pointed out that the 'software' molecules can be reused in this case.

Examples

• MAYA II

• Computational Genes

See also

• Peptide computing
• Parallel computing
• Quantum computing

References

Additional Literatures

External links

• How Stuff Works explanation
• Physics Web
• Ars Technica
• NY Times DNA Computer for detecting Cancer
• Bringing DNA computers to life, in Scientific American
• Japanese Researchers store information in bacteria DNA
• International Meeting on DNA Computing and Molecular Programming