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DNA Computing 1
COLLEGE OF APPLIED SCIENCE
PEERUMADE
( Affiliated by Mahatma Gandhi University Kottayam )
SEMINAR REPORT
On
DNA COMPUTING
Submitted in partial fulfillment with the
requirement for the award of the degree
of Bachelor of Science in Electronics of
Mahatma Gandhi University, Kottayam.
Submitted By
NAME : JOM JOY KURIAN
REG NO : 8310
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DNA Computing 2
COLLEGE OF APPLIED SCIENCEPEERUMADE
( Affiliated by Mahatma Gandhi University )
CERTIFICATE
This is to certify that seminar report entitled as “ DNA COMPUTING ’’
being submitted by JOM JOY KURIAN ( 6 TH SEMESTER ) BSC
electronics with hard ware , CAS Peerumade, during the year 2011
in partial fulfillment of the requirements for the completion of BSC
degree of Mahatma Gandhi University is a bona fide record of the
work done by him under by guidance & supervision.
PRINCIPAL H O D SEMINAR GUIDE
Date :
Place :
ACKNOWLEDGEMENT
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DNA Computing 3
Many people have contributed to the success of this. Although a single sentence
hardly suffices, I would like to thank almighty God for blessing us with His grace. I
extend my sincere and heart felt thanks to
Mr. .Jothys sir Head of the electronics for providing us the right ambience for
carrying out this work. …
………………
I am profoundly indebted to my seminar Guide Elezabath mis for innumerable
acts of timely advice encouragement and I sincerely express my gratitude to her.
I express my immense pleasure and thankfulness to all the teachers and staff of
the Department of electronics , for their cooperation and support.
Last but not the least , I thank all others, and especially my classmates who in
one way or another helped me in the successful completion of this.
JOM JOY KURIAN
ABSTRACT
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DNA Computing 4
Molecular biologists are beginning to unravel the information-processing tools such as
enzymes that evolution has spent billions of years refining. These tools are now been
taken in large numbers of DNA molecules and using them as biological computer
processors.
Dr. Leonard Adleman, a well-known scientist, found a way to exploit the speed and
efficiency of the biological reactions to solve the “Hamiltonian path problem”, also
known as the “traveling salesman problem”.
Based on Dr. Adleman’s experiment, we will explain DNA computing, its algorithms,
how to manage DNA based computing and the advantages and disadvantages of DNA
computing.
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DNA Computing 5
CONTENT
CAS Peerrmade BSc. Electronics.
Introduction 6
History 7
DNA fundamentals 8
Principles of DNA Computing 11
Synthesizing 12
Algorithm 19
Hamiltanion path problem 20
DNA Computing technology 23
How DNA Computer will work? 24
Silicon v/s DNA Microprocessor 25
Present and future DNA Computers 26
Advantages 27
Disadvantages 28
Conclusion 29
Reference 30
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DNA Computing 6
INTRODUCTION
DNA (Deoxyribose Nucleic Acid) computing, also known as
molecular computing is a new approach to massively parallel
computation based on groundbreaking work by Adleman. DNA
computing was proposed as a means of solving a class of intractable
computational problems in which the computing time can grow
exponentially with problem size (the 'NP-complete' or non-
deterministic polynomial time complete problems).A DNA computer
is basically a collection of specially selected DNA strands whosecombinations will result in the solution to some problem, depending
on the problem at hand. Technology is currently available both to
select the initial strands and to filter the final solution. DNA
computing is a new computational paradigm that employs
(bio)molecular manipulation to solve computational problems, at the
same time exploring natural processes as computational models. In
1994, Leonard Adleman at the Laboratory of Molecular Science,
Department of Computer Science, University of Southern California
surprised the scientific community by using the tools of molecular
biology to solve a different computational problem. The main idea was the encoding of data in
DNA strands and the use of tools from molecular biology to execute computational operations.
Besides the novelty of this approach, molecular computing has the potential to outperform
electronic computers. For example, DNA computations may use a billion times less energy
than an electronic computer while storing data in a trillion times less space. Moreover,
computing with DNA is highly parallel: In principle there could be billions upon trillions of
DNA molecules undergoing chemical reactions, tha is, performing computations,
simultaneously.
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DNA Computing 7
History & Motivation
"Computers in the future may weigh no more than 1.5 tons." So said Popular Mechanics in1949. Most of us today, in the age of smart cards and wearable PCs would find that statement
laughable. We have made huge advances in miniaturization since the days of room-sized
computers, yet the underlying computational framework has remained the same. Today's
supercomputers still employ the kind of sequential logic used by the mechanical dinosaurs of the
1930s. Some researchers are now looking beyond these boundaries and are investigating entirely
new media and computational models. These include quantum, optical and DNA-based
computers. It is the last of these developments that this paper concentrates on.
The current Silicon technology has following limitations:
Circuit integration dimensions
Clock frequency
Power consumption
Heat dissipation.
The problem's complexity that can be afforded by modern processors grows up, but great
challenges require computational capabilities that neither most powerful and distributed systems
could reach.
The idea that living cells and molecular complexes can be viewed as potential machiniccomponents dates back to the late 1950s, when Richard Feynman delivered his famous paper
describing "sub-microscopic" computers. More recently, several people have advocated the
realization of massively parallel computation using the techniques and chemistry of molecular
biology. DNA computing was grounded in reality at the end of 1994, when Leonard Adleman,
announced that he had solved a small instance of a computationally intractable problem using a
small vial of DNA. By representing information as sequences of bases in DNA molecules,
Adleman showed how to use existing DNA-manipulation techniques to implement a simple,
massively parallel random search. He solved the traveling salesman problem also known as the
“Hamiltonian path" problem.
There are two reasons for using molecular biology to solve computational problems.
(i) The information density of DNA is much greater than that of silicon : 1 bit can be stored inapproximately one cubic nanometer. Others storage media, such as videotapes, can store 1 bit in
1,000,000,000,000 cubic nanometer.
(ii) Operations on DNA are massively parallel: a test tube of DNA can contain trillions of
strands. Each operation on a test tube of DNA is carried out on all strands in the tube in parallel.
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DNA Computing 8
DNA Fundamentals
DNA (deoxyribonucleic acid) is a double stranded sequence of four nucleotides; the four
nucleotides that compose a strand of DNA are as follows:
1) adenine (A),
2) guanine (G),
3) cytosine(C),
4) thymine (T);
they are often called bases. DNA supports two key functions for life:
coding for the production of proteins,
self-replication.
Each deoxyribonucleotide consists of three components:
a sugar — deoxyribose
five carbon atoms: 1´ to 5´
hydroxyl group (OH) attached to 3´ carbon
a phosphate group
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DNA Computing 10
The DNA monomers can link in two ways:
Phosphodiester bond Hydrogen bond
The four nucleotides adenine (A), guanine (G), cytosine (C), and thymine (T) compose a strand
of DNA. Each DNA strand has two different ends that determine its polarity: the 3’end, and the
5’end. The double helix is an anti-parallel (two strands of opposite polarity) bonding of two
complementary strands.
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DNA Computing 11
The structure of DNA double helix
Principles of DNA Computing
DNA is the major information storage molecule in living cells, and billions of years of evolution
have tested and refined both this wonderful informational molecule and highly specific enzymes
that can either duplicate the information in DNA molecules or transmit this information to other
DNA molecules. Instead of using electrical impulses to represent bits of information, the DNA
computer uses the chemical properties of these molecules by examining the patterns of
combination or growth of the molecules or strings. DNA can do this through the manufacture of
enzymes, which are biological catalysts that could be called the ’software’, used to execute the
desired calculation.
A single strand of DNA is similar to a string consisting of a combination of four different
symbols A G C T. Mathematically this means we have at our disposal a letter alphabet, Σ = {A
GC T} to encode information which is more than enough considering that an electronic
computer needs only two digits and for the same purpose. In a DNA computer, computation
takes place in test tubes or on a glass slide coated in 24K gold. The input and output are both
strands of DNA, whose genetic sequences encode certain information. A program on a DNA
computer is executed as a series of biochemical operations, which have the effect of
synthesizing, extracting, modifying and cloning the DNA strands.
As concerning the operations that can be performed on DNA strands the proposed models of
DNA computation are based on various combinations of the following primitive bio-operations:
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DNA Computing 12
Synthesizing
Mixing : combine the contents of two test tubes into a third one to achieve union. a
desired polynomial-length strand used in all models.
Annealing:
bond together two single-stranded complementary DNA sequences by cooling the solution.Annealing in vitro is known as hybridization
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DNA Computing 13
Melting:
break apart a double-stranded DNA into its single-stranded complementary components by
heating the solution. Melting in vitro is also known under the name of denaturation.
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DNA Computing 14
Amplifying (copying):
ake copies of DNA strands by using the Polymerase Chain Reaction PCRm. The DNA
polymerase enzymes perform several functions including replication of DNA. The
replication reaction requires a guiding DNA single-strand called template, and a shorter
oligonucleotide called a primer, that is annealed to it.
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DNA Computing 15
Separating:-
the strands by length using a technique called gel electrophoresis that makes possible theseparation of strands by length.
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DNA Computing 16
Extracting
those strands that contain a given pattern as a substring by using affinity purification.
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DNA Computing 17
Cutting
DNA double-strands at specific sites by using commercially available restriction enzymes.
One class of enzymes, called restriction endonucleases, will recognize a specific short
sequence of DNA, known as a restriction site. Any double-stranded DNA that contains the
restriction site within its sequence is cut by the enzyme at that location.
Ligating:
paste DNA strands with compatible sticky ends by using DNA ligases. Indeed, another
enzyme called DNA ligase, will bond together, or ``ligate'', the end of a DNA strand to
another strand.
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DNA Computing 18
Substituting:
substitute, insert or delete DNA sequences by using PCR site-specific oligonucleotide
mutagenesis.
Marking single strands by hybridization: complementary sequences are attached to the strands,
making them double-stranded. The reverse operation is unmarking of the double-strands
by denaturing, that is, by detaching the complementary strands. The marked sequences
will be double-stranded while the unmarked ones will be single-stranded.
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DNA Computing 19
Destroying
the marked strands by using exonucleases, or by cutting all the marked strands with a
restriction enzyme and removing all the intact strands by gel electrophoresis. (By using
enzymes called exonucleases, either double-stranded or single-stranded DNA molecules
may be selectively destroyed. The exonucleases chew up DNA molecules from the endinward, and exist with specificity to either single-stranded or double-stranded form.)
Detecting and Reading:
given the contents of a tube, say ``yes'' if it contains at least one DNA strand, and ``no''
otherwise. PCR may be used to amplify the result and then a process called sequencing is used
to actually read the solution.
In Short, DNA computers work by encoding the problem to be solved in the language of DNA:
the base-four values A, T, C and G. Using this base four number system, the solution to any
conceivable problem can be encoded along a DNA strand like in a Turing machine tape. Every
possible sequence can be chemically created in a test tube on trillions of different DNA strands,
and the correct sequences can be filtered out using genetic engineering tools.
Algorithm
Turing machine:
A Turing machine is, as described in theoretical informatics, a machine which may
easily be described by a band, able to store information and a few operations on it. Each rule is
stated in the form: "In state n, if the head is reading symbol x, write symbol y, then move left or right one cell on the tape, and change the state to m." It was shown by Dr. Adleman that the
Turing machine has more computing power than every other deterministic machine especially
the computer itself. A Turing machine is an all-purpose machine, which may be used for every
computation.
One example of a Turing machine.
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DNA Computing 20
The goal of the computer, which works with DNA, is to develop an all-purpose
computer like the Turing machine. As a matter of fact this is rather difficult. Every command
should be possible in every state of the machine and it should be readable (extractable) at every
point of time. Great efforts in research are necessary to implement this.
Recent experiments on DNA computing have shown that it is more efficient to use the power of DNA computing in specific algorithms where the mapping in DNA is easy and the
parallel computing power of DNA’s are useable. Specifically, problems which are hard to solve
with Turing machines may work better (in terms of speed and efficiency) with DNA
computing. These problems referred to, as NP-complete problems are not solvable in
polynomial time with Turing machines. This means that the number of steps to solve the
problems increase exponentially with the number of the input data.
NP-complete problems are common in the real world. Examples are the Hamiltonian path or
the Shortest-Path in a graph.
Example of DNA Computing :
The Hamiltonian Path Problem;-
In 1994 Leonard M. Adleman showed how to solve the Hamilton
Path Problem, using DNA computation.
A directed graph G with designated nodes vin and vout is said to
have a Hamiltonian path if and only if there exists a sequence of compatible one-way edges e1,e2, ...en that begins at vin, ends at vout and enters every other node exactly once. A simplified
version of this problem, known as the traveling salesman problem, poses the following question:given an arbitrary collection of cities through which a salesman must travel, what is the shortest
route linking those cities? This problem is difficult for conventional computers to solve because
it is a ”non-deterministic polynomial time problem”. These problems, when the instance size is
large, are intractable with conventional computers, but can be solved using massively parallel
computers like DNA computers. NP problems are intractable with deterministic
(conventional/serial) computers, but can be solved using non-deterministic (massively parallel)
computers. A DNA computer is a type of non-deterministic computer. The Hamiltonian Path
problem was chosen by Adleman because it is known as ”NP-complete”.
Directed graph with node 0 as source (Vin)
and node 6 as destination (Vout)
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DNA Computing 21
Simplified graph
Hamiltonian path : Atlanta–Boston–Chicago–Detroit
Adleman´s AlgorithmInput: A directed graph G with n vertices, and designated vertices vin and vout.
Step 1:
Generate paths in G randomly in large quantities.
Step 2:
Reject all paths that
do not begin with vin and
do not end in vout.
Step 3:
Reject all paths that do not involve exactly n vertices.
Step 4:
For each of the n vertices v: reject all paths that do not involve v.
Output:
YES, if any path remains; NO, otherwise.
To implement step 1,
each node of the graph was encoded as a random 20-base strand of DNA. Then, for each edge
of the graph, a different 20-base oligonucleotide was generated that contains the second half of
the source code plus the first half of the target node.
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DNA Computing 22
City DNA Name Complement Atlanta ACTTGCAG TGAACGTC Boston TCGGACTG AGCCTGACChicago GGCTATGT CCGATACA Detroit CCGAGCAA GGCTCGTT
City DNA Flight Number
Atlanta – Boston GCAGTCGGAtlanta – Detroit GCAGCCGA
Boston – Chicago ACTGGGCTBoston – Detroit ACTGCCGABoston – Atlanta ACTGACTTChicago – Detroit ATGTCCGA
To implement step 2, The product of step 1 was amplified by PCR using oligonucleotide primers representing vinand vout and ligase enzyme. This amplified and thus retained only those molecules encoding
paths that begin with vin and end with vout. ~1014 computations are carried out in a single
second.
For implementing step 3, Agarose gel electrophoresis allowed separation and recovery of DNA strands of the correct
length. The desired path, if it exists, would pass through all seven nodes, each of which was
assigned a length of 20 bases. Thus PCR products encoding the desired path would have to be
140 bp.
Step 4, was accomplished by successive use of affinity purification for each node other than the start
and end nodes. The solution strand has to be filtered from the test tube:
GCAG TCGG ACTG GGCT ATGT CCGAAtlanta → Boston → Chicago → Detroit
Thus we see in a graph with n vertices, there are a possible (n-1)! permutations of the
vertices between beginning and ending vertex.
To explore each permutation, a traditional computer must perform O(n!) operations to explore
all possible cycles. However, the DNA computing model only requires the representative oligos.
Once placed in solution, those oligos will anneal in parallel, providing all possible paths in the
graph at roughly the same time. That is equivalent to O(1) operations, or constant time. In
addition, no more space than what was originally provided is needed to contain the constructed paths.
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DNA Computing 23
DNA Computing Technology:
DNA computers can't be found at your local electronics store yet. The technology is still in
development, and didn't even exist as a concept a decade ago. In 1994, Leonard Adleman
introduced the idea of using DNA to solve complex mathematical problems. Adleman, a
computer scientist at the University of Southern California, came to the conclusion that DNA
had computational potential after reading the book "Molecular Biology of the Gene," written by
James Watson, who co-discovered the structure of DNA in 1953. In fact, DNA is very similar to
a computer hard drive in how it stores permanent information about your genes.
Adleman is often called the inventor of DNA computers. His article in a 1994 issue of the
journal Science outlined how to use DNA to solve a well-known mathematical problem, called
the directed Hamilton Path problem, also known as the "traveling salesman" problem. The goal
of the problem is to find the shortest route between a number of cities, going through each cityonly once. As you add more cities to the problem, the problem becomes more difficult. Adleman
chose to find the shortest route between seven cities.
You could probably draw this problem out on paper and come to a solution faster than Adleman
did using his DNA test-tube computer. Here are the steps taken in the Adleman DNA computer
experiment:
1. Strands of DNA represent the seven cities. In genes, genetic coding is represented by the
letters A, T, C and G. Some sequence of these four letters represented each city and
possible flight path.
2. These molecules are then mixed in a test tube, with some of these DNA strands stickingtogether. A chain of these strands represents a possible answer.
3. Within a few seconds, all of the possible combinations of DNA strands, which represent
answers, are created in the test tube.
4. Adleman eliminates the wrong molecules through chemical reactions, which leaves
behind only the flight paths that connect all seven cities.
The success of the Adleman DNA computer proves that DNA can be used to calculate complexmathematical problems. However, this early DNA computer is far from challenging silicon-
based computers in terms of speed. The Adleman DNA computer created a group of possible
answers very quickly, but it took days for Adleman to narrow down the possibilities. Another
drawback of his DNA computer is that it requires human assistance. The goal of the DNA
computing field is to create a device that can work independent of human involvement.
Three years after Adleman's experiment, researchers at the University of Rochester developed
logic gates made of DNA. Logic gates are a vital part of how your computer carries out
functions that you command it to do. These gates convert binary code moving through the
computer into a series of signals that the computer uses to perform operations. Currently, logic
gates interpret input signals from silicon transistors, and convert those signals into an output
signal that allows the computer to perform complex functions.
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DNA Computing 24
The Rochester team's DNA logic gates are the first step toward creating a computer that has a
structure similar to
that of an electronic PC. Instead of using electrical signals to perform logical operations, these
DNA logic gates rely on DNA code. They detect fragments of genetic material as input, splice
together these fragments and form a single output. For instance, a genetic gate called the "Andgate" links two DNA inputs by chemically binding them so they're locked in an end-to-end
structure, similar to the way two Legos might be fastened by a third Lego between them. The
researchers believe that these logic gates might be combined with DNA microchips to create a
breakthrough in DNA computing.
DNA computer components -- logic gates and biochips -- will take years to develop into a
practical, workable DNA computer. If such a computer is ever built, scientists say that it will be
more compact, accurate and efficient than conventional computers. In the next section, we'll
look at how DNA computers could surpass their silicon-based predecessors, and what tasks
these computers would perform.
How DNA Computers Will Work:
Even as you read this article, computer chip manufacturers are furiously racing to make the next
microprocessor that will topple speed records. Sooner or later, though, this competition is bound
to hit a wall. Microprocessors made of silicon will eventually reach their limits of speed and
miniaturization. Chip makers need a new material to produce faster computing speeds.
You won't believe where scientists have found the new material they need to build the nextgeneration of microprocessors. Millions of natural supercomputers exist inside living organisms,
including your body. DNA (deoxyribonucleic acid) molecules, the material our genes are made
of, have the potential to perform calculations many times faster than the world's most powerful
human-built computers. DNA might one day be integrated into a computer chip to create a so-
called biochip that will push computers even faster. DNA molecules have already been
harnessed to perform complex mathematical problems.
While still in their infancy, DNA computers will be capable of storing billions of times more
data than your personal computer. In this article, you'll learn how scientists are using genetic
material to create nano-computers that might take the place of silicon-based computers in the
next decade
Silicon vs. DNA Microprocessors:
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DNA Computing 26
A year ago, 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. "This re-designed device uses its DNA input as its source of
fuel," said Ehud Shapiro, who led the Israeli research team. This computer can perform 330
trillion operations per second, more than 100,000 times the speed of the fastest PC.
While a desktop PC is designed to perform one calculation very fast, DNA strands produce
billions of potential answers simultaneously. This makes the DNA computer suitable for
solving "fuzzy logic" problems that have many possible solutions rather than the either/or
logic of binary computers. In the future, some speculate, there may be hybrid machines that
use traditional silicon for normal processing tasks but have DNA co-processors that can take
over specific tasks they would be more suitable for.
ADVANTAGES
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DNA Computing 27
Perform millions of operations simultaneously.
Generate a complete set of potential solutions and conduct large parallel
searches.
Efficiently handle massive amounts of working memory.
They are inexpensive to build, being made of common biological materials.
block, thus effectively doubling our capacity to The clear advantage is that we have a
distinct memory block that encodes bits.
DNA computers show promise because they do not have the limitations of silicon-based
chips. For one, DNA based chip manufacturers will always have an ample supply of raw
materials as DNA exists in all living things; this means generally lower overhead costs.
Secondly, the DNA chip manufacture does not produce toxic by-products. Last but not the least,
DNA computers will be much smaller than silicon-based computers as one pound of DNA chips
can hold all the information stored in all the computers in the world.
With the use of DNA logic gates, a DNA computer the size of a teardrop will be more
powerful than today's most powerful supercomputer. A DNA chip less than the size of
a dime will have the capacity to perform 10 trillion parallel calculations at one time aswell as hold ten terabytes of data. The capacity to perform parallel calculations, much
more trillions of parallel calculations, is something silicon-based computers are not
able to do. As such, a complex mathematical problem that could take silicon-based
computers thousands of years to solve can be done by DNA computers in hours. For
this reason, the first use of DNA computers will most probably be cracking of codes,
route planning and complex simulations for the government.
DISADVANTAGES
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DNA Computing 28
Generating solution sets, even for some relatively simple problems, mayrequire impractically large amounts of memory (lots and lots of DNA strands
are required)
Many empirical uncertainties, including those involving: actual error rates, the
generation of optimal encoding techniques, and the ability to perform necessary
bio-operations conveniently in vitro (for every correct answer there are millions
of incorrect paths generated that are worthless).
DNA computers could not (at this point) replace traditional computers. They are
not programmable and the average dunce can not sit down at a familiar keyboard
and get to work.
CONCLUSION
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DNA Computing 29
DNA computers will work through the use of DNA-based logic gates. These logic gates are very
much similar to what is used in our computers today with the only difference being the
composition of the input and output signals. In the current technology of logic gates, binary
codes from the silicon transistors are converted into instructions that can be carried out by the
computer. DNA computers, on the other hand, use DNA codes in place of electrical signals as
inputs to the DNA logic gates. DNA computers are, however, still in its infancy and though it
may be very fast in providing possible answers, narrowing these answers down still takes days.
The idea of DNA Based computing is to subvert the mechanisms produced by
evolution and use them to do data processing we want to do.
References
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Paun, G., Rozenberg, G., and Salomaa, A., DNA Computing,Springer,1998.
DNA COMPUTING-GRAPH ALGORITHMS [lec-12.pdf] G. P. Raja Sekhar,Dept. of Mathematics, IIT, Kharagpur
Leonard M. Adleman, Computing with DNA, Scientific American,August 1998.
From Microsoft to Biosoft Computing with DNA, Lila Kari, Departmentof Computer Science University of Western Ontario
L.Adleman. On constructing a molecular computer. 1st DIMACSworkshop on DNA based computers, Princeton, 1995. In DIMACSseries, vol.27 (1996)
L.Adleman, P.Rothemund, S.Roweis, E.Winfree. On applying molecularcomputation to the Data Encryption Standard. 2nd DIMACS workshopon DNA based computers, Princeton, 1996