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A Seminar
report On

DNA Computing
Submitted in partial fulfillment of the requirement for the award of degree
of Bachelor of Technology in Computer Science

SUBMITTED TO:
SUBMITTED BY
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Acknowledgement

I would like to thank respected Mr…….. and Mr. ……..for giving me such a wonderful
opportunity to expand my knowledge for my own branch and giving me guidelines to
present a seminar report. It helped me a lot to realize of what we study for.

Secondly, I would like to thank my parents who patiently helped me as i went through
my work and helped to modify and eliminate some of the irrelevant or un-necessary
stuffs.

Thirdly, I would like to thank my friends who helped me to make my work more
organized and well-stacked till the end.

Next, I would thank Microsoft for developing such a wonderful tool like MS Word. It
helped my work a lot to remain error-free.

Last but clearly not the least, I would thank The Almighty for giving me strength to
complete my report on time.
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Preface
I have made this report file on the topic DNA Computing; I have tried my best to
elucidate all the relevant detail to the topic to be included in the report. While in the
beginning I have tried to give a general view about this topic.

My efforts and wholehearted co-corporation of each and everyone has ended on a

successful note. I express my sincere gratitude to …………..who assisting me throughout
the preparation of this topic. I thank him for providing me the reinforcement, confidence
and most importantly the track for the topic whenever I needed it.
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Contents

1. Introduction
2. History & Motivation
3. DNA Fundamentals
4. Principles of DNA Computing
5. Example of DNA Computing :
The Hamiltonian Path Problem
6. Present & Future DNA Computer
7. Advantages
8. Disadvantages
9. References
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An Introduction to DNA Computing

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

whose combinations 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, that is, performing
computations, simultaneously.
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History & Motivation:

"Computers in the future may weigh no more than 1.5 tons." So said Popular
Mechanics in 1949. 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 machinic components 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.
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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 in approximately 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 Fundamentals

DNA (deoxyribonucleic acid) is a double stranded sequence of four nucleotides;

the four nucleotides that compose a strand of DNA are as follows: adenine (A),
guanine (G), cytosine (C), and 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
a nitrogenous base.

The chemical structure of DNA consists of a particular bond of two linear

sequences of bases. This bond follows a property of Complementarity: adenine
bonds with thymine (A-T) and vice versa (T-A), cytosine bonds with guanine (C-
G) and vice versa (G-C). This is known as Watson-Crick complementarity.
The DNA monomers can link in two ways:
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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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The structure of DNA double helix

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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:

Synthesizing a desired polynomial-length strand used in all models.

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Mixing : combine the contents of two test tubes into a third one to achieve
union.
Annealing: bond together two single-stranded complementary DNA
sequences by cooling the solution. Annealing in vitro is known as
hybridization
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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Amplifying (copying): make copies of DNA strands by using the

Polymerase Chain Reaction PCR. 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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Separating the strands by length using a technique called gel

electrophoresis that makes possible the separation of strands by length.
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Extracting those strands that contain a given pattern as a substring

by using affinity purification.
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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.
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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.

Substituting: substitute, insert or delete DNA sequences by using

PCR site-specific oligonucleotide mutagenesis.
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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.

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 end inward, and exist with specificity to either
single-stranded or double-stranded form.)
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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.
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Example of DNA Computing : The Hamiltonian Path

Problem

In 1994 Leonard M. Adleman showed how to solve the Hamilton Path

Problem, using DNA computation.
Hamiltonian Path Problem:
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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Simplified graph

Hamiltonian path : Atlanta–Boston–Chicago–Detroit

Adleman´s Algorithm
Input: 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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City DNA Name Complement

Atlanta ACTTGCAG TGAACGTC
Boston TCGGACTG AGCCTGAC
Chicago GGCTATGT CCGATACA
Detroit CCGAGCAA GGCTCGTT
City DNA Flight Number
Atlanta - Boston GCAGTCGG
Atlanta - Detroit GCAGCCGA
Boston - Chicago ACTGGGCT
Boston - Detroit ACTGCCGA
Boston - Atlanta ACTGACTT
Chicago - Detroit ATGTCCGA
To implement step 2, the product of step 1 was amplified by PCR using
oligonucleotide primers representing vin and 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 CCGA
Atlanta → 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
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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.

Present & Future DNA Computer

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.
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Advantages

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.
The clear advantage is that we have a distinct memory block that
encodes bits.
Using one template strand as a memory block also allows us to use its
compliment. as another memory block, thus effectively doubling our
capacity to store information.

Disadvantages

Generating solution sets, even for some relatively simple problems, may
require 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.
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References

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,
Department of Computer Science University of Western Ontario
L.Adleman. On constructing a molecular computer. 1st DIMACS
workshop on DNA based computers, Princeton, 1995. In DIMACS
series, vol.27 (1996)
L.Adleman, P.Rothemund, S.Roweis, E.Winfree. On applying
molecular computation to the Data Encryption Standard. 2nd
DIMACS workshop on DNA based computers, Princeton, 1996