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DNA computing

DNA computing

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DNA computing is a form of computing
Computing
Computing is usually defined as the activity of using and improving computer hardware and software. It is the computer-specific part of information technology...

 which uses DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

, biochemistry
Biochemistry
Biochemistry, sometimes called biological chemistry, is the study of chemical processes in living organisms, including, but not limited to, living matter. Biochemistry governs all living organisms and living processes...

 and molecular biology
Molecular biology
Molecular biology is the branch of biology that deals with the molecular basis of biological activity. This field overlaps with other areas of biology and chemistry, particularly genetics and biochemistry...

, instead of the traditional silicon-based computer
Computer
A computer is a programmable machine designed to sequentially and automatically carry out a sequence of arithmetic or logical operations. The particular sequence of operations can be changed readily, allowing the computer to solve more than one kind of problem...

 technologies
Technology
Technology is the making, usage, and knowledge of tools, machines, techniques, crafts, systems or methods of organization in order to solve a problem or perform a specific function. It can also refer to the collection of such tools, machinery, and procedures. The word technology comes ;...

. DNA computing, or, more generally, biomolecular computing
Biocomputers
Biocomputers use systems of biologically derived molecules, such as DNA and proteins, to perform computational calculations involving storing, retrieving, and processing data....

, 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
Leonard Adleman
Leonard Max Adleman is an American theoretical computer scientist and professor of computer science and molecular biology at the University of Southern California. He is known for being a co-inventor of the RSA cryptosystem in 1977, and of DNA computing...

 of the University of Southern California
University of Southern California
The University of Southern California is a private, not-for-profit, nonsectarian, research university located in Los Angeles, California, United States. USC was founded in 1880, making it California's oldest private research university...

, in 1994. Adleman demonstrated a proof-of-concept use of DNA as a form of computation which solved the seven-point Hamiltonian path problem
Hamiltonian path problem
In the mathematical field of graph theory the Hamiltonian path problem and the Hamiltonian cycle problem are problems of determining whether a Hamiltonian path or a Hamiltonian cycle exists in a given graph . Both problems are NP-complete...

. Since the initial Adleman experiments, advances have been made and various Turing machine
Turing machine
A Turing machine is a theoretical device that manipulates symbols on a strip of tape according to a table of rules. Despite its simplicity, a Turing machine can be adapted to simulate the logic of any computer algorithm, and is particularly useful in explaining the functions of a CPU inside a...

s have been proven to be constructible.

While the initial interest was in using this novel approach to tackle NP-hard
NP-hard
NP-hard , in computational complexity theory, is a class of problems that are, informally, "at least as hard as the hardest problems in NP". A problem H is NP-hard if and only if there is an NP-complete problem L that is polynomial time Turing-reducible to H...

 problems, it was soon realized that they may not be best suited for this type of computation, and several proposal have been made to find a "killer application
Killer application
A killer application , in the jargon of marketing teams, has been used to refer to any computer program that is so necessary or desirable that it proves the core value of some larger technology, such as computer hardware, gaming console, software, or an operating system...

" for this approach. In 1997 computer scientist Mitsunori Ogihara working with biologist Animesh Ray suggested one to be the evaluation of Boolean circuit
Boolean circuit
A Boolean circuit is a mathematical model of computation used in studying computational complexity theory. Boolean circuits are the main object of study in circuit complexity and are a special kind of circuits; a formal language can be decided by a family of Boolean circuits, one circuit for each...

s and described an implementation.

In 2002, researchers from the Weizmann Institute of Science
Weizmann Institute of Science
The Weizmann Institute of Science , known as Machon Weizmann, is a university and research institute in Rehovot, Israel. It differs from other Israeli universities in that it offers only graduate and post-graduate studies in the sciences....

 in Rehovot, Israel, unveiled a programmable molecular computing machine composed of enzymes and DNA molecules instead of silicon microchips. On April 28, 2004, Ehud Shapiro
Ehud Shapiro
Ehud Shapiro is an Israeli computer scientist at the Weizmann Institute of Science. He received his Ph.D from Yale for his dissertation entitled "Algorithmic Program Debugging" which was an ACM distinguished dissertation for 1982. He has been an exponent of the Prolog computer language and logic...

, Yaakov Benenson, Binyamin Gil, Uri Ben-Dor, and Rivka Adar at the Weizmann Institute announced in the journal Nature
Nature (journal)
Nature, first published on 4 November 1869, is ranked the world's most cited interdisciplinary scientific journal by the Science Edition of the 2010 Journal Citation Reports...

 that they had constructed a DNA computer coupled with an input and output module which would theoretically be capable of diagnosing cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

ous activity within a cell, and releasing an anti-cancer drug upon diagnosis.

Capabilities


DNA computing is fundamentally similar to parallel computing
Parallel computing
Parallel computing is a form of computation in which many calculations are carried out simultaneously, operating on the principle that large problems can often be divided into smaller ones, which are then solved concurrently . There are several different forms of parallel computing: bit-level,...

 in that it takes advantage of the many different molecules of DNA to try many different possibilities at once.

DNA computing also offers much lower power consumption than traditional silicon computers. DNA uses adenosine triphosphate
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...

 (ATP) as fuel to allow ligation or as a means to heat the strand to cause disassociation. 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, 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.

For certain specialized problems, DNA computers are faster and smaller than any other computer built so far. Furthermore, particular mathematical computations have been demonstrated to work on a DNA computer. As an example, Aran Nayebi has provided a general implementation of Strassen's matrix multiplication algorithm
Strassen algorithm
In the mathematical discipline of linear algebra, the Strassen algorithm, named after Volker Strassen, is an algorithm used for matrix multiplication...

 on a DNA computer, although there are problems with scaling.

But DNA computing does not provide any new capabilities from the standpoint of computability theory
Computability theory (computer science)
Computability is the ability to solve a problem in an effective manner. It is a key topic of the field of computability theory within mathematical logic and the theory of computation within computer science...

, 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
EXPSPACE
In complexity theory, EXPSPACE is the set of all decision problems solvable by a deterministic Turing machine in O space, where p is a polynomial function of n...

 problems) on von Neumann machines
Von Neumann architecture
The term Von Neumann architecture, aka the Von Neumann model, derives from a computer architecture proposal by the mathematician and early computer scientist John von Neumann and others, dated June 30, 1945, entitled First Draft of a Report on the EDVAC...

, 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
DNA nanotechnology
DNA nanotechnology is a branch of nanotechnology which uses the molecular recognition properties of DNA and other nucleic acids to create designed, artificial structures out of DNA for technological purposes. In this field, DNA is used as a structural material rather than as a carrier of genetic...

. The latter uses the specificity of Watson-Crick basepairing
Base pair
In molecular biology and genetics, the linking between two nitrogenous bases on opposite complementary DNA or certain types of RNA strands that are connected via hydrogen bonds is called a base pair...

 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.

The Caltech researchers have created a circuit made from 130 unique DNA strands, which is able to calculate the square root of numbers up to 15.

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
Oligonucleotide
An oligonucleotide is a short nucleic acid polymer, typically with fifty or fewer bases. Although they can be formed by bond cleavage of longer segments, they are now more commonly synthesized, in a sequence-specific manner, from individual nucleoside phosphoramidites...

, enzymes, DNA tiling, and polymerase chain reaction
Polymerase chain reaction
The polymerase chain reaction is a scientific technique in molecular biology to amplify a single or a few copies of a piece of DNA across several orders of magnitude, generating thousands to millions of copies of a particular DNA sequence....

.

DNAzymes


Catalytic DNA (deoxyribozyme
Deoxyribozyme
Deoxyribozymes or DNA enzymes or catalytic DNA, or DNAzymes are DNA molecules with catalytic action. In contrast to the RNA ribozyme that has many catalytic capabilities, DNA is only associated with gene replication and nothing else...

 or DNAzyme) catalyze a reaction when interacting with the appropriate input, such as a matching oligonucleotide
Oligonucleotide
An oligonucleotide is a short nucleic acid polymer, typically with fifty or fewer bases. Although they can be formed by bond cleavage of longer segments, they are now more commonly synthesized, in a sequence-specific manner, from individual nucleoside phosphoramidites...

. 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. 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. Stojanovic and MacDonald have used the E6 DNAzymes to build the MAYA I and MAYA II machines, respectively; Stojanovic has also demonstrated logic gates using the 8-17 DNAzyme. 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
In vivo
In vivo is experimentation using a whole, living organism as opposed to a partial or dead organism, or an in vitro controlled environment. Animal testing and clinical trials are two forms of in vivo research...

.

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
Logic gate
A logic gate is an idealized or physical device implementing a Boolean function, that is, it performs a logical operation on one or more logic inputs and produces a single logic output. Depending on the context, the term may refer to an ideal logic gate, one that has for instance zero rise time and...

s. These logic gates have been used to create the computers MAYA I and MAYA II which can play tic-tac-toe
Tic-tac-toe
Tic-tac-toe, also called wick wack woe and noughts and crosses , is a pencil-and-paper game for two players, X and O, who take turns marking the spaces in a 3×3 grid. The X player usually goes first...

 to some extent.

Enzymes


Enzyme based DNA computers are usually of the form of a simple Turing machine
Turing machine
A Turing machine is a theoretical device that manipulates symbols on a strip of tape according to a table of rules. Despite its simplicity, a Turing machine can be adapted to simulate the logic of any computer algorithm, and is particularly useful in explaining the functions of a CPU inside a...

; there is analogous hardware, in the form of an enzyme, and software, in the form of DNA.

Benenson, Shapiro and colleagues have demonstrated a DNA computer using the FokI
FokI
The enzyme FokI, naturally found in Flavobacterium okeanokoites, is a bacterial type IIS restriction endonuclease consisting of an N-terminal DNA-binding domain and a non-specific DNA cleavage domain at the C-terminal...

 enzyme and expanded on their work by going on to show automata that diagnose and react to prostate cancer
Prostate cancer
Prostate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing; however, there are cases of aggressive prostate cancers. The cancer cells may metastasize from the prostate to other parts of the body, particularly...

: under expression of the genes PPAP2B
PPAP2B
Lipid phosphate phosphohydrolase 3 is an enzyme that in humans is encoded by the PPAP2B gene.-Further reading:...

 and GSTP1
GSTP1
Glutathione S-transferase P is an enzyme that in humans is encoded by the GSTP1 gene.-Interactions:GSTP1 has been shown to interact with Fanconi anemia, complementation group C and MAPK8.-Further reading:...

 and an over expression of PIM1
PIM1
Proto-oncogene serine/threonine-protein kinase Pim-1 is an enzyme that in humans is encoded by the PIM1 gene.Pim-1 is a proto-oncogene which encodes for the serine/threonine kinase of the same name. The pim-1 oncogene was first described in relation to murine T-cell lymphomas, as it was the locus...

 and HPN. Their 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
Mdm2 is an important negative regulator of the p53 tumor suppressor. It is the name of a gene as well as the protein encoded by that gene. Mdm2 protein functions both as an E3 ubiquitin ligase that recognizes the N-terminal trans-activation domain of the p53 tumor suppressor and an inhibitor of...

. MDM2 is a repressor of protein 53
P53
p53 , is a tumor suppressor protein that in humans is encoded by the TP53 gene. p53 is crucial in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer...

, which itself is a tumor suppressor. 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”. It should also be pointed out that the 'software' molecules can be reused in this case.

Toehold exchange


DNA computers have also been constructed using the concept of toehold exchange. In this system, an input DNA strand binds to a sticky end, or toehold, on another DNA molecule, which allows it to displace another strand segment from the molecule. This allows the creation of modular logic components such as AND, OR, and NOT gates and signal amplifiers, which can be linked into arbitrarily large computers. This class of DNA computers does not require enzymes or any chemical capability of the DNA.

Algorithmic self-assembly




DNA nanotechnology has been applied to the related field of DNA computing. DNA tiles can be designed to contain multiple sticky ends with sequences chosen so that they act as Wang tile
Wang tile
Wang tiles , first proposed by mathematician, logician, and philosopher Hao Wang in 1961, are a class of formal systems...

s. A DX array has been demonstrated whose assembly encodes an XOR operation; this allows the DNA array to implement a cellular automaton
Cellular automaton
A cellular automaton is a discrete model studied in computability theory, mathematics, physics, complexity science, theoretical biology and microstructure modeling. It consists of a regular grid of cells, each in one of a finite number of states, such as "On" and "Off"...

 which generates a fractal
Fractal
A fractal has been defined as "a rough or fragmented geometric shape that can be split into parts, each of which is a reduced-size copy of the whole," a property called self-similarity...

 called the Sierpinski gasket. This shows that computation can be incorporated into the assembly of DNA arrays, increasing its scope beyond simple periodic arrays.

See also

  • Biocomputers
    Biocomputers
    Biocomputers use systems of biologically derived molecules, such as DNA and proteins, to perform computational calculations involving storing, retrieving, and processing data....

  • Computational gene
  • Molecular electronics
    Molecular electronics
    Molecular electronics, sometimes called moletronics, involves the study and application of molecular building blocks for the fabrication of electronic components...

  • Peptide computing
    Peptide computing
    Peptide computing is a form of computing which uses peptides and molecular biology, instead of traditional silicon-based computer technologies. The basis of this computational model is the affinity of antibodies towards peptide sequences. Similar to DNA computing, the parallel interactions of...

  • Parallel computing
    Parallel computing
    Parallel computing is a form of computation in which many calculations are carried out simultaneously, operating on the principle that large problems can often be divided into smaller ones, which are then solved concurrently . There are several different forms of parallel computing: bit-level,...

  • Quantum computing
  • DNA code construction
    DNA code construction
    DNA code construction refers to the application of coding theory to the design of nucleic acid systems for the field of DNA–based computation.-Introduction:...

  • Wetware computer
    Wetware computer
    A wetware computer is an organic computer built from living neurons. , at the Georgia Institute of Technology, is the primary researcher driving the creation of these artificially constructed, but still organic brains...


Further reading



— The first general text to cover the whole field. — The book starts with an introduction to DNA-related matters, the basics of biochemistry and language and computation theory, and progresses to the advanced mathematical theory of DNA computing. — A new general text to cover the whole field.

External links