DNA Computing

Seminar Report

Submitted in partial fulfillment of degree of

Bachelor of Technology
In
Computer Science & Engineering
By

Mr. Hari Prakash Tiwari

Under the guidance of

Prof. Harender Singh

HOD(Computer Sc. & Engg.)

R. D. ENGINEERING COLLEGE
DUHAI GHAZIABAD
(Affiliated to Uttar Pradesh Technical University Lucknow)
2009-2010

i
 CERTIFICATE

This is to certify that the Seminar Report titled “DNA Computing” submitted by Hari Prakash
Tiwari student of B.Tech (CSE) Degree course from Uttar Pradesh Technical University, has
undergone study seminar work in R. D. Engineering College in partial fulfilment of the
requirements degree is a bona-fide record of the work done by his under my supervision.

His attendance, discipline and overall conduct are found good.

______________________ ______________________

Signature of the Co-ordinator Signature of the

HOD

Place: R. D. Engineering College

Date:

ii
 ACKNOWLEDGEMENT

It is my duty to acknowledge with gratitude the generous help that I have received from
Harender Singh,HOD CSE and Dr. B. Kumar Director of R. D. Engineering College,
Ghaziabad. They had provided us all the resources that are required for our project to be
operational.

We are greatful to Er. Harendra Singh, HOD of R. D. Engineering College, who has given me
methodology for my seminar report named “DNA Computing”. His infinite suggestions, ideas
and specific tasks given by him steered the study to the totality.

Also, I thank to my all faculty members those who have encorporated in this work.

Hari Prakash Tiwari

0623110020

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 ABSTRACT

Inroduction:

DNA computing, also known as molecular computing, is a new approach to massively parallel
computation based on groundbreaking work by Adleman . In November of 1994, Dr. Leonard
Adleman wrote the first paper on DNA computing. In this paper, he found a way to solve the
"Hamiltonian path problem," which involves finding all the possible paths between a certain
number of vertices. It is also known as the "traveling salesman problem." This name comes from
viewing each vertex as a city, with the problem to find all possible routes for a salesman passing
through each of these cities .

Computers today all use binary codes - 1's and 0's or on's and off's. These codes are the basis for
all possible calculations a computer is able to perform. Because the DNA molecule is also a
code, Adleman saw the possibility of employing DNA as a molecular computer. However, rather
than relying in the position of electronic switches in a microchip, Adleman relied on the much
faster reactions of DNA nucleotides binding with their complements, a brute force method that
would indeed work

A DNA computer is a collection of DNA strands that have been specially selected to aid in the
search of solutions for some problems. DNA computing results in parallelism, which means that
when enough DNA information is given, huge problems can be solved by invoking a parallel
search .

A nanocomputer that uses DNA (deoxyribonucleic acids) to store information and perform
complex calculations.

In 1994, University of Southern California computer scientist Leonard Adelman suggested that
DNA could be used to solve complex mathematical problems. Adelman found a way to harness
the power of DNA to solve the Hamiltonian path problem (the traveling salesman problem),
whose solution required finding a path from start to end going through all the points (cities) only
once.

Each city was encoded as its own DNA sequence (DNA sequence consists of a series of
nucleotides represented by the letters A, T, G, C).

The DNA sequences were set to replicate and create trillions of new sequences based on the
initial input sequences in a matter of seconds (called DNA hybridization). The theory holds that
the solution to the problem was one of the new sequence strands. By process of elimination, the
correct solution would be obtained.

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Adelman's experiment is regarded as the first example of true nanotechnology.

The main benefit of using DNA computers to solve complex problems is that different possible
solutions are created all at once. This is known as parallel processing. Humans and most
electronic computers must attempt to solve the problem one process at a time (linear processing).
DNA itself provides the added benefits of being a cheap, energy-efficient resource.

In a different perspective, more than 10 trillion DNA molecules can fit into an area no larger than
1 cubic centimeter. With this, a DNA computer could hold 10 terabytes of data and perform 10
trillion calculations at a time.

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 TABLE OF CONTENTS

CHAPTER NO. TITLE PAGE NO.

Cover Page i
Certificate ii
Acknowledgement iii
Abstract iv

1. Introduction………………………………………………………………vii

2. Why we need DNA computer………………………………………….....xv

3. Different form of computing.……………………………………………..xvi

3.1.Peptide Computing ………………………………………………..…xvi

3.2.Parellel Computing…………….……………………………………..xvi

3.3.Quantum Computer…..………………………………………………..xvi

4. How does DNA computer works…………………………………………xviii

5. Molecular Models of DNA ……………………………………………....xxi

6. Databases for DNA molecular models and sequences …………………..xxvii

7. Applications of DNA computing………………………………………….xxix

8. Drawbacks…………………………………………………………………..xxxi

9.Conclusion………………………………………………………………xxxii

10.References…………………………………………………………….xxxiii

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 Introduction

Contents

 Components of DNA
 Purine Bases

 Pyrimidine Bases

 Deoxyribose Sugar

 Nucleosides

 Nucleotides

 Base Pairs

 DNA Backbone

 DNA Double Helix

 DNA Helix Axis

Components of DNA

DNA is a polymer. The monomer units of DNA are nucleotides, and the polymer is known as a
"polynucleotide." Each nucleotide consists of a 5-carbon sugar (deoxyribose), a nitrogen
containing base attached to the sugar, and a phosphate group. There are four different types of
nucleotides found in DNA, differing only in the nitrogenous base. The four nucleotides are given
one letter abbreviations as shorthand for the four bases.

 A is for adenine

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  G is for guanine

 C is for cytosine

 T is for thymine

Purine Bases

Adenine and guanine are purines. Purines are the larger of the two types of bases found in DNA.
Structures are shown below:

Structure of A and G

The 9 atoms that make up the fused rings (5 carbon, 4 nitrogen) are numbered 1-9. All ring
atoms lie in the same plane.

Pyrimidine Bases

Cytosine and thymine are pyrimidines. The 6 stoms (4 carbon, 2 nitrogen) are numbered 1-6.
Like purines, all pyrimidine ring atoms lie in the same plane.

Structure of C and T

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Deoxyribose Sugar

The deoxyribose sugar of the DNA backbone has 5 carbons and 3 oxygens. The carbon atoms
are numbered 1', 2', 3', 4', and 5' to distinguish from the numbering of the atoms of the purine and
pyrmidine rings. The hydroxyl groups on the 5'- and 3'- carbons link to the phosphate groups to
form the DNA backbone. Deoxyribose lacks an hydroxyl group at the 2'-position when
compared to ribose, the sugar component of RNA.

Structure of deoxyribose

Nucleosides

A nucleoside is one of the four DNA bases covalently attached to the C1' position of a sugar. The
sugar in deoxynucleosides is 2'-deoxyribose. The sugar in ribonucleosides is ribose. Nucleosides
differ from nucleotides in that they lack phosphate groups. The four different nucleosides of

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DNA are deoxyadenosine (dA), deoxyguanosine (dG), deoxycytosine (dC), and
(deoxy)thymidine (dT, or T).

Structure of dA

In dA and dG, there is an "N-glycoside" bond between the sugar C1' and N9 of the purine.

Nucleotides

A nucleotide is a nucleoside with one or more phosphate groups covalently attached to the 3'-
and/or 5'-hydroxyl group(s).

DNA Backbone

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The DNA backbone is a polymer with an alternating sugar-phosphate sequence. The deoxyribose
sugars are joined at both the 3'-hydroxyl and 5'-hydroxyl groups to phosphate groups in ester
links, also known as "phosphodiester" bonds.

Example of DNA Backbone: 5'-d(CGAAT):

Features of the 5'-d(CGAAT) structure:

 Alternating backbone of deoxyribose and phosphodiester groups

 Chain has a direction (known as polarity), 5'- to 3'- from top to bottom
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  Oxygens (red atoms) of phosphates are polar and negatively charged

 A, G, C, and T bases can extend away from chain, and stack atop each other

 Bases are hydrophobic

DNA Double Helix

DNA is a normally double stranded macromolecule. Two polynucleotide chains, held together by
weak thermodynamic forces, form a DNA molecule.

Structure of DNA Double Helix

Features of the DNA Double Helix

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  Two DNA strands form a helical spiral, winding around a helix axis in a right-handed
spiral
 The two polynucleotide chains run in opposite directions

 The sugar-phosphate backbones of the two DNA strands wind around the helix axis like
the railing of a sprial staircase

 The bases of the individual nucleotides are on the inside of the helix, stacked on top of
each other like the steps of a spiral staircase.

Base Pairs

Within the DNA double helix, A forms 2 hydrogen bonds with T on the opposite strand, and G
forms 3 hyrdorgen bonds with C on the opposite strand.

Example of dA-dT base pair as found within DNA double helix

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Example of dG-dC base pair as found within DNA double helix

 dA-dT and dG-dC base pairs are the same length, and occupy the same space within a
DNA double helix. Therefore the DNA molecule has a uniform diameter.
 dA-dT and dG-dC base pairs can occur in any order within DNA molecules

DNA Helix Axis

The helix axis is most apparent from a view directly down the axis. The sugar-phosphate
backbone is on the outside of the helix where the polar phosphate groups (red and yellow atoms)
can interact with the polar environment. The nitrogen (blue atoms) containing bases are inside,
stacking perpendicular to the helix axis.

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 1. Why we need DNA computer

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 adenine 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).

xv
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

2. Different form of computing

1. 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 peptide sequences and antibodies have
been used by this model to solve a few NP-complete problems. Specifically, the
hamiltonian path problem (HPP) and some versions of the set cover problem are a
few NP-complete problems which have been solved using this computational model
so far. This model of computation has also been shown to be computationally
universal (or Turing complete).

This model of computation has some critical advantages over DNA computing. For
instance, while DNA is made of four building blocks, peptides are made of twenty
building blocks. The peptide-antibody interactions are also more flexible with respect
to recognition and affinity than an interaction between a DNA strand and its reverse
complement. However, unlike DNA computing, this model is yet to be practically
realized. The main limitation is the availability of specific monoclonal antibodies
required by the model.

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2. Parallel 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 peptide sequences and antibodies have been
used by this model to solve a few NP-complete problems. Specifically, the hamiltonian
path problem (HPP) and some versions of the set cover problem are a few NP-complete
problems which have been solved using this computational model so far. This model of
computation has also been shown to be computationally universal (or Turing complete).

This model of computation has some critical advantages over DNA computing. For
instance, while DNA is made of four building blocks, peptides are made of twenty
building blocks. The peptide-antibody interactions are also more flexible with respect
to recognition and affinity than an interaction between a DNA strand and its reverse
complement. However, unlike DNA computing, this model is yet to be practically
realized. The main limitation is the availability of specific monoclonal antibodies
required by the model.

3. Quantum Computer

A quantum computer is a device for computation that makes direct use of quantum
mechanical phenomena, such as superposition and entanglement, to perform operations
on data. The basic principle behind quantum computation is that quantum properties can
be used to represent data and perform operations on these data.[1]

Although quantum computing is still in its infancy, experiments have been carried out
in which quantum computational operations were executed on a very small number of
qubits (quantum bit). Both practical and theoretical research continues with interest,

and many national government and military funding

agencies support quantum computing research to develop quantum computers for
both civilian and national security purposes, such as cryptanalysis.[2]

If large-scale quantum computers can be built, they will be able to solve certain
problems much faster than any of our current classical computers (for example Shor's
algorithm). Quantum computers are different from other computers such as DNA

xvii
 computers and traditional computers based on transistors. Some computing
architectures such as optical computers[3] may use classical superposition of
electromagnetic waves. Without some specifically quantum mechanical resources
such as entanglement, it is conjectured that an exponential advantage over classical
computers is not possible.

3. How does DNA computer works

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
next generation 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.

xviii
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 city only
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
sticking together. 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.
Surpassing Silicon?
Although DNA computers haven't overtaken
silicon-based microprocessors, researchers
have made some progress in using genetic
code for computation. In 2003, Israeli
scientists demonstrated a limited, but
functioning, DNA computer. You can read
more about it at National Geographic.
The success of the Adleman DNA computer proves that DNA can be used to calculate complex
mathematical 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

xix
input signals from silicon transistors, and convert those signals into an output signal that allows
the computer to perform complex functions.
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 "And gate" 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.

Silicon vs. DNA Microprocessors

Silicon microprocessors have been the heart of the computing world for more than 40 years. In
that time, manufacturers have crammed more and more electronic devices onto their
microprocessors. In accordance with Moore's Law, the number of electronic devices put on a
microprocessor has doubled every 18 months. Moore's Law is named after Intel founder Gordon
Moore, who predicted in 1965 that microprocessors would double in complexity every two
years. Many have predicted that Moore's Law will soon reach its end, because of the physical
speed and miniaturization limitations of silicon microprocessors.
DNA computers have the potential to take computing to new levels, picking up where Moore's
Law leaves off. There are several advantages to using DNA instead of silicon:
 As long as there are cellular organisms, there will always be a supply of DNA.
 The large supply of DNA makes it a cheap resource.
 Unlike the toxic materials used to make traditional microprocessors, DNA biochips
can be made cleanly.
 DNA computers are many times smaller than today's computers.
DNA's key advantage is that it will make computers smaller than any computer that has come
before them, while at the same time holding more data. One pound of DNA has the capacity to
store more information than all the electronic computers ever built; and the computing power of
a teardrop-sized DNA computer, using the DNA logic gates, will be more powerful than the
world's most powerful supercomputer. More than 10 trillion DNA molecules can fit into an area
no larger than 1 cubic centimeter (0.06 cubic inches). With this small amount of DNA, a
computer would be able to hold 10 terabytes of data, and perform 10 trillion calculations at a
time. By adding more DNA, more calculations could be performed.
Unlike conventional computers, DNA computers perform calculations parallel to other
calculations. Conventional computers operate linearly, taking on tasks one at a time. It is parallel
computing that allows DNA to solve complex mathematical problems in hours, whereas it might
take electrical computers hundreds of years to complete them.
The first DNA computers are unlikely to feature word processing, e-mailing and solitaire
programs. Instead, their powerful computing power will be used by national governments for

xx
cracking secret codes, or by airlines wanting to map more efficient routes. Studying DNA
computers may also lead us to a better understanding of a more complex computer -- the human
brain.

4. Molecular Models of DNA

Molecular models of DNA structures are representations of the molecular geometry

and topology of Deoxyribonucleic acid (DNA) molecules using one of several means,
such as: closely packed spheres (CPK models) made of plastic, metal wires for 'skeletal
models', graphic computations and animations by computers, artistic rendering, and so
on, with the aim of simplifying and presenting the essential, physical and chemical,
properties of DNA molecular structures either in vivo or in vitro. Computer molecular
models also allow animations and molecular dynamics simulations that are very
important for understanding how DNA functions in vivo. Thus, an old standing dynamic
problem is how DNA "self-replication" takes place in living cells that should involve
transient uncoiling of supercoiled DNA fibers. Although DNA consists of relatively rigid,
very large elongated biopolymer molecules called "fibers" or chains (that are made of
repeating nucleotide units of four basic types, attached to deoxyribose and phosphate
groups), its molecular structure in vivo undergoes dynamic configuration changes that
involve dynamically attached water molecules and ions. Supercoiling, packing with
histones in chromosome structures, and other such supramolecular aspects also involve in
vivo DNA topology which is even more complex than DNA molecular geometry, thus
turning molecular modeling of DNA into an especially challenging problem for both
molecular biologists and biotechnologists. Like other large molecules and biopolymers,

xxi
 DNA often exists in multiple stable geometries (that is, it exhibits conformational
isomerism) and configurational, quantum states which are close to each other in energy
on the potential energy surface of the DNA molecule. Such geometries can also be
computed, at least in principle, by employing ab initio quantum chemistry methods that
have high accuracy for small molecules. Such quantum geometries define an important
class of ab initio molecular models of DNA whose exploration has barely started.

DNA computing biochip:3D

In an interesting twist of roles, the DNA molecule itself was proposed to be utilized for
quantum computing. Both DNA nanostructures as well as DNA 'computing' biochips
have been built (see biochip image at right).

The more advanced, computer-based molecular models of DNA involve molecular

dynamics simulations as well as quantum mechanical computations of vibro-rotations,
delocalized molecular orbitals (MOs), electric dipole moments, hydrogen-bonding, and
so on.

Examples of DNA molecular models

Animated molecular models allow one to visually explore the three-dimensional (3D) structure
of DNA. The first DNA model is a space-filling, or CPK, model of the DNA double-helix
whereas the third is an animated wire, or skeletal type, molecular model of DNA. The last two
DNA molecular models in this series depict quadruplex DNA that may be involved in certain
cancers[13][14]. The last figure on this panel is a molecular model of hydrogen bonds between
water molecules in ice that are similar to those found in DNA.

xxii
Images for DNA Structure Determination from X-Ray Patterns

The following images illustrate both the principles and the main steps involved in generating
structural information from X-ray diffraction studies of oriented DNA fibers with the help of
molecular models of DNA that are combined with crystallographic and mathematical analysis of
the X-ray patterns. From left to right the gallery of images shows:


o First row:

 1. Constructive X-ray interference, or diffraction, following Bragg's Law of X-ray

"reflection by the crystal planes";
 2. A comparison of A-DNA (crystalline) and highly hydrated B-DNA (paracrystalline)
X-ray diffraction, and respectively, X-ray scattering patterns (courtesy of Dr. Herbert R.
Wilson, FRS- see refs. list);
 3. Purified DNA precipitated in a water jug;
 4. The major steps involved in DNA structure determination by X-ray crystallography
showing the important role played by molecular models of DNA structure in this
iterative, structure--determination process;
o Second row:

 5. Photo of a modern X-ray diffractometer employed for recording X-ray patterns of

DNA with major components: X-ray source, goniometer, sample holder, X-ray detector
and/or plate holder;
 6. Illustrated animation of an X-ray goniometer;
 7. X-ray detector at the SLAC synchrotron facility;

xxiii
  8. Neutron scattering facility at ISIS in UK;
o Third and fourth rows: Molecular models of DNA structure at various scales;
figure #11 is an actual electron micrograph of a DNA fiber bundle, presumably of a single
bacterial chromosome loop.

Paracrystalline lattice models of B-DNA structures

xxiv
A paracrystalline lattice, or paracrystal, is a molecular or atomic lattice with significant amounts
(e.g., larger than a few percent) of partial disordering of molecular arranegements. Limiting
cases of the paracrystal model are nanostructures, such as glasses, liquids, etc., that may possess
only local ordering and no global order. Liquid crystals also have paracrystalline rather than
crystalline structures.

DNA Helix controversy in 1952

Highly hydrated B-DNA occurs naturally in living cells in such a paracrystalline state, which is a
dynamic one in spite of the relatively rigid DNA double-helix stabilized by parallel hydrogen
bonds between the nucleotide base-pairs in the two complementary, helical DNA chains (see
figures). For simplicity most DNA molecular models ommit both water and ions dynamically
bound to B-DNA, and are thus less useful for understanding the dynamic behaviors of B-DNA in
vivo. The physical and mathematical analysis of X-ray[15][16] and spectroscopic data for
paracrystalline B-DNA is therefore much more complicated than that of crystalline, A-DNA X-
ray diffraction patterns. The paracrystal model is also important for DNA technological
applications such as DNA nanotechnology. Novel techniques that combine X-ray diffraction of
DNA with X-ray microscopy in hydrated living cells are now also being developed (see, for
example, "Application of X-ray microscopy in the analysis of living hydrated cells"). Genomic
and Biotechnology Applications of DNA molecular modeling

The following gallery of images illustrates various uses of DNA molecular modeling in
Genomics and Biotechnology research applications from DNA repair to PCR and DNA
nanostructures; each slide contains its own explanation and/or details. The first slide presents an
overview of DNA applications, including DNA molecular models, with emphasis on Genomics
and Biotechnology.

xxv
Gallery: DNA Molecular modeling applications

xxvi
 6. Databases for DNA molecular models and sequences
X-ray diffraction

 NDB ID: UD0017 Database

 X-ray Atlas -database
 PDB files of coordinates for nucleic acid structures from X-ray diffraction by NA (incl.
DNA) crystals
 Structure factors dowloadable files in CIF format

Neutron scattering

 ISIS neutron source

 ISIS pulsed neutron source:A world centre for science with neutrons & muons at
Harwell, near Oxford, UK.

X-ray microscopy

 Application of X-ray microscopy in the analysis of living hydrated cells

xxvii
Electron microscopy

 DNA under electron microscope

Atomic Force Microscopy (AFM)

Two-dimensional DNA junction arrays have been visualized by Atomic Force Microscopy
(AFM)[17]. Other imaging resources for AFM/Scanning probe microscopy(SPM) can be freely
accessed at:

Gallery of AFM Images

Mass spectrometry--Maldi informatics

xxviii
 7. Applications of DNA computing

Computational Gene
A computational gene [1] [2] [3] is a molecular automaton consisting of a structural part and a
functional part; and its design is such that it might work in a cellular environment. The
structural part is a naturally occurring gene, which is used as a skeleton to encode the input
and the transitions of the automaton (Fig. 1A). The conserved features of a structural gene
(e.g., DNA polymerase binding site, start and stop codons, and splicing sites) serve as
constants of the computational gene, while the coding regions, the number of exons and
introns, the position of start and stop codon, and the automata theoretical variables (symbols,
states, and transitions) are the design parameters of the computational gene. The constants
and the design parameters are linked by several logical and biochemical constraints (e.g.,
encoded automata theoretic variables must not be recognized as splicing junctions). The
input of the automaton are molecular markers given by single stranded DNA (ssDNA)
molecules. These markers are signalling aberrant (e.g., carcinogenic) molecular phenotype
and turn on the self-assembly of the functional gene. If the input is accepted, the output
encodes a double stranded DNA (dsDNA) molecule, a functional gene which should be
successfully integrated into the cellular transcription and translation machinery producing a

xxix
 wild type protein or an anti-drug (Fig. 1B). Otherwise, a rejected input will assemble into a

partially dsDNA molecule which cannot be translated.

Challenges

Although mechanistically simple and quite robust on molecular level, several issues need to be
addressed before an in vivo implementation of computational genes can be considered. First, the
DNA material must be internalised into the cell, specifically into the nucleus. In fact, the transfer
of DNA or RNA through biological membranes is a key step in the drug delivery. Some results
show that nuclear localisation signals can be irreversibly linked to one end of the
oligonucleotides, forming an oligonucleotide-peptide conjugate that allows effective
internalisation of DNA into the nucleus [9].

In addition, the DNA complexes should have low immunogenicity to guarantee their integrity in
the cell and their resistance to cellular nucleases. Current strategies to eliminate nuclease
sensitivity include modifications of the oligonucleotide backbone such as methylphosphonate
and phosphorothioate (S-ODN) oligodeoxynucleotides, but along with their increased stability,
modified oligonucleotides often have altered pharmacologic properties.

Finally, similar to any other drug, DNA complexes could cause nonspecific and toxic side
effects. In vivo applications of antisense oligonucleotides showed that toxicity is largely due to
impurities in the oligonucleotide preparation and lack of specifity of the particular sequence used

Undoubtedly, progress on antisense biotechnology will also result in a direct benefit to the model
of computational genes

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 8. Drawbacks

 For small problems, computers can solve them easily. With increasing speed and
parallelism of CPU, more and more problems belong to this category.
 For larger problems, there are many issues.

1. Limited applicability of the method.

2. The mess of DNA which is needed to represent the problem can become prohibitively
large. The mess is not scalable.
3. Synthesizing such long base pairs and large amount of DNA becomes a very difficult
task. Such synthesis is not scalable.

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 4. The preparation and processing time are just too long to make it worth while even if it is
automated.
5. Experiments can fail due to many reasons such as DNA degradation, the secondary
structure of DNA, etc.

10. Conclusion

In conclusion, technology is always changing, and computer technology will soon take a drastic

change too. DNA Computing is very new concept which can be extended to achieve a very high

level of calculation.It can be used to medical field as well as in many fields and can be invoked

to reach high research.

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 Many issues to be overcome to produce a useful DNA computer.

 It will not replace the current computers because it is application specific, but has a

potential to replace the high-end research oriented computers in future.

 Nanotechnology?

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