MALAVIYA NATIONAL INSTITUTE OF TECHNOLOGY

DNA COMPUTING

Submitted By
Shubham Aggarwal 2009UCP893

10 April, 2012 Department of Computer Engineering MNIT Jaipur

Declaration
I, Shubham Aggarwal, declare the following regarding the work presented in this Seminar titled DNA Computing.

This work is done wholly or mainly while in candidature for a B.Tech Degree. Where any part of this report has previously been submitted for a degree or any other qualification at MNIT Jaipur or any other institution, this has been clearly stated. Where I have consulted the published work of others, this is always clearly attributed. Where I have quoted from the work of others, the source is always given. I have acknowledged all sources of help No part of the report is plagiarized and the report does not suffer from any acts of plagiarism.

Signature

Date

ACKNOWLEDGMENT
I am really thankful to many of the people who really helped me to create my seminar report. My deepest thank to Mrs. Meenakshi Tripathi the guide of my seminar report for guiding and correcting various documents of me with attention, care and constantly encouraging me with their valuable suggestions and enthused thought me seminar work. A special mention needs to be made to our friends who have helped us with their valuable suggestions.

Shubham Aggarwal 2009UCP893 B.Tech, 3rd Year Computer Engineering Deptt.

ABSTRACT
In this paper I intend to present the computing technology that has a great future - DNA COMPUTING. DNA computing can be viewed as a manifestation of an emerging new area of science made possible by our rapidly developing ability to control the molecular world. DNA computing is in its infancy and its implications are only beginning to be explored.

The paper begins with a brief description of DNA and its structure. An introduction to DNA COMPUTING and its origin have been given .Various operations performed on DNA is discussed in detail.

The salient features of DNA Computer (one that uses dna computing as its basic method of problem solving) have been mentioned. An insight into the advantages, disadvantages, applications and limitations of dna-computing has been made. Finally, the paper discusses the various stages in its path of development at present and the expectations in the near future

Contents
1. INTRODUCTION .......................................................................................................... 5 1.1 1.2 2.1 Beginning of DNA computing ............................................................................. 5 Concepts of DNA computing ............................................................................... 6 Basics of DNA ..................................................................................................... 7

2. DNA Characteristics:- ..................................................................................................... 7 2.2. Structure of DNA:- .................................................................................................. 8 3. DNA OPERATIONS ...................................................................................................... 9 3.1 Synthesis ................................................................................................................... 9 3.2 Denaturing, annealing and ligation ......................................................................... 10 3.3 Hybridization separation ......................................................................................... 11 3.4 Gel-Electrophoresis................................................................................................. 11 4 Nature of DNA computing............................................................................................. 12 4.1 General working aspects ......................................................................................... 12 4.2 Information storage and processing capabilities ..................................................... 13 5. Comparison of DNA and Electronic Computers ......................................................... 15 5.1. Similarities ............................................................................................................. 15 5.2. Differences ............................................................................................................. 16 6. Applications of DNA Computing ................................................................................. 18 6.1 Advantages .............................................................................................................. 18 6.2 Drawbacks............................................................................................................... 19 7. FUTURE OF DNA COMPUTER ................................................................................ 19 8. CONCLUSION ............................................................................................................. 20 9. Bibliography ................................................................................................................. 21

1. INTRODUCTION
DNA computing is a nascent technology that seeks to capitalize on the enormous informational capacity of DNA, biological molecules that can store huge amounts of information and are able to perform operations similar to a computer's through the deployment of enzymes, biological catalysts that act like software to execute desired operations. A new version of a biomolecular computer developed at the Israel Institute of Technology composed entirely of DNA molecules and enzymes. It can perform as many as a billion different programs simultaneously. Previous biomolecular computers, such as the one built by Institute of Science three years ago, were limited to just 765 simultaneous programs. A DNA-based computer has solved a logic problem that no person could complete by hand, setting a new milestone for this infant technology that could someday surpass the electronic digital computer in certain areas. 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. DNA computing is an alternative to the way computers work today. While this technology is not readily available, or being mass produced, the theory behind it is quite old and the development is on going and catching more speed. Companies like IBM are attempting to use DNA to produce the next generation of processors. Before discussing how DNA can be used in computers, it's important to first understand the basic structure of a DNA molecule.

1.1 Beginning of DNA computing

DNA computing began in 1994 when Leonard Adleman has first shown that computing can be done using DNA also, without using usual machine but using test tubes etc. in a biological laboratory. For this, he has chosen Hamiltonian path problem (HPP) known to us as the Traveling salesman problem (TSP) and obtained solution using DNA experiments. Things would not have gone further if the problem he has chosen is simple 5

but as he has taken HPP, which is an NP-Complete problem for which there is no polynomial time algorithm using conventional computer, it created an exciting and made people to think more about DNA computing. The power of the method proposed by Adleman is in the fact that tremendous parallelism can be introduced using DNA operations and that helped Adleman to solve an NP-Complete problem. Also during the same time Charles Bennetts has done some work on DNA computing.[2] Adleman, now considered the father of DNA computing, is a professor at the University of Southern California and spawned the field with his paper, Molecular Computation of Solutions of Combinatorial Problems. Since then, Adleman has demonstrated how the massive parallelism of a trillion DNA strands can simultaneously attack different aspects of a computation to crack even the toughest combinatorial problems, such as the governments supposedly uncrackable Data Encryption Standard.

1.2 Concepts of DNA computing

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. The promise of DNA computing is massive parallelism: with a given setup and enough DNA, one can potentially solve huge problems by parallel search. This can be much faster than a conventional computer, for which massive parallelism would require large amounts of hardware, not simply more DNA. Since Adlemans original experiment researchers have developed several different models to solve other mathematical and computational problems using molecular techniques. Lipton who showed that formula SAT can be solved on a DNA computer generalized Adelmans techniques. These algorithms essentially use a brute force approach to solve hard combinatorial problems. This approach is interesting due to the massive parallelism available in DNA computers. Also there are classes of algorithms which can be implemented on a DNA computer, namely some algorithms based on dynamic programming. Graph connectivity and knapsack are classical problems solvable in this

way. These problems are solvable by conventional computers in polynomial time, but only so long as they are small enough to fit in memory. DNA computers using dynamic programming could solve substantially larger instances because their large memory capacity than either conventional computers or previous brute force algorithms on DNA computers. The reason dynamic programming algorithms are suitable for DNA computers are that the sub problems can be solved in parallel.

2. DNA Characteristics:2.1 Basics of DNA

Deoxyribonucleic acid (DNA) is the master molecule of every cell. It contains vital information that gets passed on to each successive generation. It coordinates the making of itself as well as other molecules (proteins). If it is changed slightly, serious consequences may result. If it is destroyed beyond repair, the cell dies. Changes in the DNA of cells in multicellular organisms produce variations in the characteristics of a species. Over long periods of time, natural selection acts on these variations to evolve or change the species. DNA is one of the nucleic acids, information-containing molecules in the cell (ribonucleic acid, or RNA, is the other nucleic acid). DNA is found in the nucleus of every human cell. The information in DNA: guides the cell (along with RNA) in making new proteins that determine all of our biological traits gets passed (copied) from one generation to the next

The key to all of these functions is found in the molecular structure of DNA, as described by Watson and Crick. .

2.2. Structure of DNA: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. The chemical structure of DNA (the famous double- helix) was discovered by James Watson and Francis Crick in 1953. It 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 (CG) and vice versa (G-C). This is known as Watson-Crick complementarity.

Figure 2.2: Structure 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.

3. DNA OPERATIONS
All models of DNA computation apply a specific sequence of biological operations to a set of strands. These operations are commonly used by molecular biologists. Some operations are specific to certain models of DNA computation.

3.1 Synthesis
A desired strand of DNA can be synthesized in lab. This is possible for strands up to a certain length. Longer random strands are available. They consist of DNA sequences that have been cloned from many different organisms. The synthesizer is supplied with the four nucleotide bases in solution, which are combined according to a sequence entered by the user. The instrument makes millions of copies of the required oligonucleotides and places them in solution in a small vial. Information stored in DNA duplex as CG or AT base pairs. Maximum information density of 2 bits per DNA base location

3-CAACGTTG-5

5-GTTGCAAC-3

Figure 3.1: Information storage in DNA

3.2 Denaturing, annealing and ligation

Double-stranded DNA may be dissolved into single strands (or denatured) by heating the solution to a temperature determined by the composition of the strand. Heating breaks the hydrogen bonds between complementary strands. Since the hydrogen bonds between strands are much weaker than the covalent bonds within strands, the strands remain undamaged by this process. Since a G-C pair is joined by three hydrogen bonds, the temperature required to break it is slightly higher than that for an A-T pair, joined by only two hydrogen bonds. This factor was taken into account when designing sequences to represent computational elements. Annealing is the reverse of melting, whereby a solution of single strands is cooled, and allowing complementary strands to bind together. In double-stranded DNA, if one of the single strands contains a discontinuity, then this may be repaired by DNA ligase, which is an enzyme which helps in joining two DNA strands or pairs of nucleotides.

Figure 3.2: Process of Ligation 10

3.3 Hybridization separation

Separation by hybridization is an operation often used in DNA computation, and involves the extraction from a test tube of any single strands containing a specific short sequence (e.g., extract all strands containing the sequence TAGACT). If we want to extract single strands containing the sequence X, we first create many copies of its complement. We attach to these oligonucleotides a biotin molecule which binds in turn to a fixed matrix. If we pour the contents of the test tube over this matrix, strands containing X will anneal to the anchored complementary strands. Washing the matrix removes all strands that do not anneal, leaving only strands containing X. These may then be removed from the matrix.

3.4 Gel-Electrophoresis
Gel electrophoresis is an important technique for sorting DNA strands by size. Electrophoresis is the movement of charged molecules in an electric field. Since DNA molecules carry negative charge, when placed in an electrical field they tend to migrate towards the positive pole. The rate of migration of a molecule in an aqueous solution depends on its shape and electrical charge. Since DNA molecules have the same charge per unit length, they all migrate at the same speed in an aqueous solution. However, if electrophoresis is carried out in a gel (usually made of agarose, polyacrylamide or a combination of the two) the migration rate of a molecule is also affected by its size. This is due to the fact that the gel is a dense network of pores through which the molecules must travel. Smaller molecules therefore migrate faster through the gel, thus sorting them according to size. The DNA will be placed in a well cut out of the gel, and a charge applied. Once the gel has been run (usually overnight), it is necessary to visualize the results. This is achieved by staining the DNA with the fluorescent dye ethidium bromide and then viewing the gel under ultraviolet light. At this stage the gel is usually photographed for convenience. One such photograph is depicted in Fig.3.3 Gels are interpreted as follows; each lane corresponds to one particular sample of DNA

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Figure 3.4: Gel electrophoresis photograph

4 Nature of DNA computing

4.1 General working aspects
Bio-molecular computers work at the molecular level. Because biological and mathematical operations have some similarities, DNA, the genetic material that encodes for living organisms, is stable and predictable in its reactions and can be used to encode information for mathematical systems. Our computers, with more and more packed onto their silicon chips are approaching the limits of miniaturization. Molecular computing may be a way around this limitation. 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.[1] 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

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manufacture of enzymes, which are biological catalysts that could be called the software, used to execute the desired calculation. DNA computers use deoxyribonucleic acids A (adenine), C (cytosine), G (guanine) and T (thymine) as the memory units and recombinant DNA techniques already in existence carry out the fundamental operations. 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. Their potential power underscores how nature could be capable of crunching number better and faster than the most advanced silicon chips.

4.2 Information storage and processing capabilities

Nucleic Acids are used because of density, efficiency and speed. DNA molecules can store far more information than any existing computer memory chip. This means that DNA computing is a far denser packing of molecular information compared with siliconbased computers. A single bacterium cell measures just a micron square - about the same size as a single silicon transistor - but holds more than a megabyte of DNA memory and has all the computational structures to sense and respond to its environment. To try to put this in some understandable perspective, it has been estimated that a gram of DNA can hold as much information as a trillion CDs.

4.3 Efficiency In both the solid-surface glass-plate approach and the test tube approach, each DNA strand represents one possible answer to the problem that the computer is trying to solve. The strands have been synthesized by combining the building blocks of DNA, called nucleotides, with one another, using techniques developed for biotechnology. The set of DNA strands is manufactured so that all conceivable answers

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are included. Because a set of strands is tailored to a specific problem, a new set would have to be made for each new problem. Most electronic computers operate linearly and they manipulate one block of data after another, biochemical reactions are highly in parallel: a single step of biochemical operations can be set up so that it affects trillions of DNA strands. While a DNA computer takes much longer than a normal computer to perform each individual calculation, it performs an enormous number of operations at a time and requires less energy and space than normal computers. 1000 liters of water could contain DNA with more memory than all the computers ever made, and a pound of DNA would have more computing power than all the computers ever made. The only fundamental difference between conventional computers and DNA computers is the capacity of memory units: electronic computers have two positions (on or off), whereas DNA has four (C, G, A or T). The study of bacteria has shown that restriction enzymes can be employed to cut DNA at a specific word (W). Many restriction enzymes cut the two strands of double-stranded DNA at different positions leaving overhangs of single-stranded DNA. Two pieces of DNA may be rejoined if their terminal overhangs are complementary. Complements are referred to as sticky ends. Using these operations, fragments of DNA may be inserted or deleted from the DNA. Information is stored in DNA as CG or AT base pairs with maximum information density of 2bits per DNA base location. Information on a solid surface is stored in a NON-ADDRESSED array of DNA words of a fixed length (16mers). DNA Words are linked together to form large combinatorial sets of molecules. DNA computers are massively parallel, while electronic computers would require additional hardware; DNA computers just need more DNA. This could make the DNA computer more efficient, as well as more easily programmable.

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5. Comparison of DNA and Electronic Computers

As we have seen the concepts and characteristics of DNA Computer, we can now compare the DNA Computers with Conventional Electronic Computers.

5.1. Similarities
Transformation of Data: Both DNA computers and electronic computers use Boolean logic (AND, OR, NAND, NOR) to transform data. The logical command AND is performed by separating DNA strands according to their sequences, and the command OR is done by pouring together DNA solutions containing specific sequences. For example, the logical statement X or Y is true if X is true or if Y is true. To simulate that, the scientists would pour the DNA strands corresponding to X together with those corresponding to Y.

Manipulation of Data: Electronic computers and DNA computers both store information in strings, which are manipulated to do processes. Vast quantities of information can be stored in a test tube. The information could be encoded into DNA sequences and the DNA could be stored. To retrieve data, it would only be necessary to search for a small part of it - a key word, for example, by adding a DNA strand designed so that its sequence sticks to the key word wherever it appears on the DNA.

Computation Ability: All computers manipulate data by addition and subtraction. A DNA computer should be able to solve a satisfiability problem with 70 variables and 1,000 AND-OR connections. To solve it, assign various DNA sequences to represent 0s and 1s at the various positions of a 70 digit binary number. Vast numbers of these sequences would be mixed together, generating longer molecules corresponding to every possible 70- digit sequence.

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5.2. Differences

Size: Conventional computers are about 1 square foot for the desktop and another square foot for the monitor. One new proposal is for a memory bank containing more than a pound of DNA molecules suspended in about 1,000 quarts of fluid, in a bank about a yard square. Such a bank would be more capacious than all the memories of all the computers ever made. The first ever-electronic computer took up a large room whereas the first DNA computer (Adleman) was 100 micro liters. Adleman dubbed his DNA computer the TT-100, for test tube filled with 100 micro liters, or about one-fiftieth of a teaspoon of fluid, which is all it took for the reactions to occur.

Speed: Conventional computers can perform approximately 100 MIPS (millions of instruction per second). Combining DNA strands as demonstrated by Adleman, made computations equivalent to 109 or better, arguably over 100 times faster than the fastest computer. The inherent parallelism of DNA computing was staggering.

Minimal Storage Requirements: DNA stores memory at a density of about 1 bit per cubic nanometer where conventional storage media requires 1012 cubic nanometers to store 1 bit. In essence, mankinds collective knowledge could theoretically be stored in a small bucket of DNA solution.

Minimal Power Requirements: There is no power required for DNA computing while the computation is taking place. The chemical bonds that are the building blocks of DNA happen without any outside power source. There is no comparison to the power requirements of conventional computers.

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Table: Comparison of a DNA computer and a Conventional Computer DNA Computers Conventional Computers

Storage Media

Nucleic acids

Semiconductors

Nature of Operations

Parallel

Sequential

Type of Operations

Biochemical Operations

Logical Operations

Speed of each Operation

Slow Ultra-High (one bit per cubic nanometer) One million Gbits per square inch More powerful than any supercomputer Smaller than any computer High

Fast (10^12 cubic nanometers to store one bit) 7 Gbits per square inch

Memory Capacity

Data Density

Computational Power

Less powerful

Computer Size

Larger size

power requirements

Not required

Required

Cost

Cheaper

Expensive

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6. Applications of DNA Computing

As far as applications are concerned, this can be quite useful in figuring out how to route telephone calls, plane trips, and basically any problem that can be turned into a Hamiltonian problem. It is also been claimed that DNA can be used to solve optimization problems involving business management. This would involve optimizing the routing of raw materials. It is even said that DNA can be used in devising the wiring schematics for circuits. Applications making use of classic DNA computing schemes where the use of massive parallelism holds an advantage over traditional computing schemes, including potential polynomial time solutions to hard computational problems. Applications making use of the natural capabilities of DNA, including those that make use of informational storage abilities and those that interact with existing and emerging biotechnology. Contributions to fundamental research within both computer science and the physical sciences, especially concerning exploring the limitations of computability and to understanding and manipulating bimolecular chemistry. By the DNA methods, the DNA models are much more flexible, potent, and cost effective

6.1 Advantages
1) Perform millions of operations simultaneously. 2) Generate a complete set of potential solutions. 3) Conduct large parallel searches. 4) Efficiently handle massive amounts of working memory. 5) The clear advantage is that we have a distinct memory block that encodes bits. 6) The differentiation between sub sequences denoting individual bits allows a natural border between encoding sub-strands. 7) 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 18

6.2 Drawbacks
1) Generating solution sets, even for some relatively simple problems, may require impractically large amounts of memory (lots and lots of DNA strands are required) 2) Many empirical uncertainties, including those involving: actual error rates, the generation of optimal encoding techniques, and the ability to perform necessary biooperations conveniently in vitro (for every correct answer there are millions of incorrect paths generated that are worthless). 3) This is a rather good encoding, however, as we increase the size of our memory, we have to ensure that our sub-strands have distinct complements in order to be able to set and clear specific bits in our Memory.

7. FUTURE OF DNA COMPUTER

Some centers of research in this area are at the University of Southern California at Los Angeles, with Dr. Adleman, Princeton, with Dr. Richard Lipton and his graduate students Dan Boneh and Eric Baum, and the NEC Research Institute in Princeton, NJ. With others elsewhere, they are developing new branches in this young field. Advancements are being made in cryptography. Researchers are working on decreasing error in and damage to the DNA during the computations/reactions. The Princeton contingent has published papers on models for universal DNA computers, while others have described methods for doing addition and matrix multiplication with these computers. Currently, molecular computing is a field with a great deal of potential, but few suits of practical value. In the wake of Adleman's solution of the Hamiltonian path problem, there came a host of other articles on computation with DNA; however, most of them were purely theoretical. Currently, a functional DNA "computer" of the type most people are familiar with lies many years in the future. But work continues: in his article Speeding Up Computation via Molecular Biology Lipton shows how 19

DNA can be used to construct a Turing machine, a universal computer capable of performing any calculation. The field of DNA computing is truly exciting for the revolution it implies will occur within the next few years. It also demonstrates the current trend of merging and lack of distinction between the sciences, where a computer scientist can mess around with biology equipment and come up with something new and valuable.

8. CONCLUSION
The research in DNA computing is in a primary level. High information density of DNA molecules and massive parallelism involved in the DNA reactions make DNA computing a powerful tool. Tackling problems with DNA computing would be more appropriate when the problems are computationally intractable in nature .Because the DNA Computing due to its high degree of parallelism, can overcome the difficulties that may cause the problem intractable on silicon computers. However using DNA computing principles for solving simple problems may not be suggestible. It has been proved by many research accomplishments that any procedure that can be programmed in a silicon computer can be realized as a DNA computing procedure. Due to its incredible applications in Cryptography, research in DNA computing is gaining some pace and there is a wide scope for the researchers to make use of this powerful computing tool.

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Bibliography
[1] Adleman L. M., Molecular computation of solutions to combinatorial problems, 1994. [2] Diana Roo Recent Developments in DNA-Computing Lehrstuhl fur Theoretische Informatik UniversitatWurzburg Am Exerzierplatz 3, 97072 Wurzburg, Germany. [3] W. B. Langdon Comparison of DNA chip and Computer Vision Data Computer Science, University College, London Gower Street, London.

[4] External Links::

www.howstuffworks.com www.ieee.org
en.wikipedia.org/wiki/DNA_computing

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