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Homework Title / No. : _____1__________Course Code : _BTY889____ Course Instructor : ___VIPIN GUPTA___ Course Tutor (if applicable) : _VIPIN GUPTA Date of Allotment : __19/02/2012______ Date of submission : 27/02/2012____________ Students Roll No.___ ROE117A40 ______ Section No. : ___OE117_______________ Declaration: I declare that this assignment is my individual work. I have not copied from any other students work or from any other source except where due acknowledgment is made explicitly in the text, nor has any part been written for me by another person. Students Signature PRAKASH KUMAR KOTWAL Evaluators comments: _____________________________________________________________________ Marks obtained : ___________ out of ______________________ Content of Homework should start from this page only:

[x=0] DNA Computing:

Q.(i) In 1994, Leonard Adleman demonstrated a proof-of-concept use of DNA in a form of computation which solved the seven-point Hamiltonian path problem. What did he do? Ans:The directed Hamiltonian path (DHP) problem is one of the hard computational problems for which there is no practical algorithm on a conventional computer available. Many problems, including the traveling sales person problem and the longest path problem, can be translated into the DHP problem, which implies that an algorithm for DHP can also solve all the translated problems. To study the robustness of the laboratory protocol of the pioneering DNA computing for the DHP problem performed by Leonard Adleman (1994), we investigated how the graph size, multiplicity of the Hamiltonian paths, and the size of oligonucleotides that encode the vertices would affect the laboratory procedures.

Hamiltonian path problem

A Hamiltonian path through a directed graph G = (V, E) with V = {v1, v2, . . . vn} and E V V is a path that passes through every vertex of a directed graph exactly once and begins at a designated vertex vin V and ends at vout V . Finding such a path is an NP-complete problem. No polynomial time algorithm is known for this problem and it is unlikely that such an algorithm exists. Since the search for a Hamiltonian path can be done in parallel, this problem is very well suited for DNA computing. Figure shows a graph which has a (unique) Hamiltonian path for vin = 1 and vout = 6 given by the edges (01), (12), (23), (34), (45), (56). The molecular algorithm presented in Section solves the problem for this graph.

4 3 1

Algorithm given by Leonard Adleman

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In 1994 Leonard M. Adleman presented the following algorithm to solve the directed Hamiltonian path problem using DNA to encode the graph and standard protocols and enzymes from biochemistry to process it: 1.
2.

Generate random paths through the graph. Keep only those paths that begin with vin and end with vout. If the graph has n vertices, then keep only those paths that enter exactly n vertices. Keep only those paths that enter all of the vertices of the graph at least once.

3. 4.

5. If any paths remain, say Yes; otherwise, say No.

Q.(ii) Draw a flow diagram depicting the various parts of a hypothetical DNA computer and their interoperability. Ans:-

Q.(iii) How is the memory stored in a DNA computing device? Describe the mechanism. Which components function as the hardware, software and the power source? Ans:Even as some scientists and engineers develop improved versions of current computing technology, others are looking into drastically different approaches. DNA computing offers the potential of massively parallel calculations with low power consumption and at small sizes. Research in this area has been limited to relatively small systems, but a group from Caltech recently constructed DNA logic gates using over 130 different molecules and used the system to calculate the square roots of numbers. Now, the same group published a paper in Nature that shows an artificial neural network, consisting of four neurons, created using the same DNA circuits. The artificial neural network approach taken here is based on the perceptron model, also known as a linear threshold gate. This models the neuron as having many inputs, each with its own weight (or significance). The neuron is fired (or the gate is turned on) when the sum of each input times its weight exceeds a set threshold. These gates can be used to construct compact Boolean logical circuits, and other circuits can be constructed to store memory. As we described in the last article on this approach to DNA computing, the authors represent their implementation with an abstraction called "seesaw" gates. This allows them to design circuits where each element is composed of two base-paired DNA strands, and the interactions between circuit elements occurs as new combinations of DNA strands pair up. The ability of strands to displace each other at a gate (based on things like concentration) creates the seesaw effect that gives the system its name. In order to construct a linear threshold gate, three basic seesaw gates are needed to perform different operations. Multiplying gates combine a signal and a set weight in a seesaw reaction that uses up fuel molecules as it converts the input signal into output signal. Integrating gates combine multiple inputs into a single summed output, while thresholding gates (which also require fuel) send an output signal only if the input exceeds a designated threshold value. Results are read using reporter gates that fluoresce when given a certain input signal. To test their designs with a simple configuration, the authors first constructed a single linear threshold circuit with three inputs and four outputsit compared the value of a three-bit binary number to four numbers. The circuit output the correct answer in each case. For the primary demonstration on their setup, the authors had their linear threshold circuit play a computer game that tests memory. They used their approach to construct a four-neuron Hopfield network, where all the neurons are connected to the others and, after training (tuning the weights and thresholds) patterns can be stored or remembered. The memory game consists of three steps: 1) the human chooses a scientist from four options (in this case, Rosalind Franklin, Alan Turing, Claude

Shannon, and Santiago Ramon y Cajal); 2) the human tells the memory network the answers to one or more of four yes/no (binary) questions used to identify the scientist (such as, Did the scientist study neural networks? or "Was the scientist British?"); and 3) after eight hours of thinking, the DNA memory guesses the answer and reports it through fluorescent signals. They played this game 27 total times, for a total of 81 possible question/answer combinations (34). You may be wondering why there are three options to a yes/no questionthe state of the answers is actually stored using two bits, so that the neuron can be unsure about answers (those that the human hasn't provided, for example) using a third state. Out of the 27 experimental cases, the neural network was able to correctly guess all but six, and these were all cases where two or more answers were not given. In the best cases, the neural network was able to correctly guess with only one answer and, in general, it was successful when two or more answers were given. Like the human brain, this network was able to recall memory using incomplete information (and, as with humans, that may have been a lucky guess). The network was also able to determine when inconsistent answers were given (i.e. answers that dont match any of the scientists). These results are excitingsimulating the brain using biological computing. Unlike traditional electronics, DNA computing components can easily interact and cooperate with our bodies or other cellswho doesnt dream of being able to download information into your brain (or anywhere in your body, in this case)? Even the authors admit that its difficult to predict how this approach might scale up, but I would expect to see a larger demonstration from this group or another in the near future.

Q.(iV) What is the source of processing power of a DNA computer? Describe the process mechanism and contrast it with that of an electronic computer, aspect by aspect. AnsNeed for DNA Computing
1. Conventional or traditional silicon based computers have a limited speed

beyond a point cannot be miniaturize.

2. Information storage capacity of DNA molecule is much higher than the silicon

chips.One cubic nano meter of DNA is sufficient to store 1 bit information.

3. Operations on DNA Computing are parallel, test tube of DNA may contain

around trillions of strands.

4. 1 gram of DNA can store a huge amount of data such as 1024 MB of data; to

listen to the same amount of data stored in a CD will require 163,000 centuries.
5. With the bases spaced at a distance of 0.35 nm in a DNA molecule, data

density is around million Gbits/inch in a DNA computer. Where ad data density is around 7 Gbits/inch in a typical high performance HDD.

Difference between electronic computer and dna computer:1) 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." Following is an example of how a Bio Chemical Inverter works. Bio-chemical Inverter: The characteristics of natural gene regulation systems can be exploited to design in vivo logic circuits (Weiss et al., 1999). How a biochemical inverter achieves the two states in digital inversion using genetic regulatory elements? Here, the concentration of a particular messenger RNA (mRNA) molecule represents a logic signal. In the first case, the input mRNA is absent and the cell transcribes the gene for the output mRNA using RNA polymerase (RNAp) molecules. In the second case, the input mRNA is present and the cell translates the input mRNA into the input protein using ribosomes. A digital inverter that consists of a gene encoding the instructions for protein B and containing a region (P) to which protein A binds. When A is absent (left)a situation representing the input bit 0the gene is active and B is formedcorresponding to an output bit 1. When A is produced (right)making the input bit 1it binds to P and blocks the action of the genepreventing B from being formed and making the output bit 0. The input protein then binds specifically to the gene at the promoter site (labeled \P") and prevents the cell from synthesizing the output mRNA. Now more complete picture that explains the role of transcription and translation cellular processes in inversion is explained here.

Biochemical inversion uses the transcription and translation cellular processes. Ribosomal RNA translates the input mRNA into an amino acid chain, which then folds into a three-dimensional protein structure. When the protein binds an operator of the gene's promoter, it prevents transcription of the gene by RNA polymerase (RNAp). In the absence of the repressor protein, RNAp transcribes the gene into the output mRNA. It depicts a functional model of the inverter derived from its biochemical reaction phases. The first phase in inversion is the translation stage, denoted as L. The input signal to this stage, and thus the inverter, corresponds to the concentration level of the input mRNA, A. Ribosomal RNA (rRNA) translates the input mRNA into the input repressor protein, A , where L represents the steady state mapping between the mRNA and protein concentrations. The relationship between the input mRNA and repressor protein is initially linear, with increases in A corresponding to increases in A, until an asymptotic boundary is reached. The properties of this boundary are determined by characteristics of the cell such as amino acid synthesis capabilities, the efficiency of the ribosome-binding site, and mRNA stability. Since cells degrade mRNA as well as protein molecules, constant synthesis of the input mRNA is needed to maintain a steady level of the input repressor protein. In the second phase, input protein monomers combine to form polymers that bind the operator, and subsequently repress the transcription of the output gene. The Functional composition of the inversion stages: the translation stage maps input mRNA levels (A) to input protein levels (A), the cooperative binding stage maps input protein levels to bound operator levels (A), and the transcription stage maps bound operator levels to output mRNA levels (Z). The degradation of the mRNA and protein molecules is represented with the electrical ground symbol. The degradation of mRNA is part of the translation stage, while the degradation of proteins is part of the cooperative binding stage. The graphs illustrate the steady-state relationships for each of these stages and the overall inversion function that results from combining these stages. This cooperative binding, which ensures that only dimerized proteins can bind the DNA, decreases the digital noise. Let us define the concentration of operator that is bound to the repressor, or the strength of the repression, as A. In addition, denote the cooperative binding stage that occurs between A and A as C. In steady state, the relationship between A and A is sigmoidal. At low levels of A, the strength of repression does not increase significantly for increases in A because these concentrations are too low for appreciable dimerization. At higher concentrations of A, however, considerable dimerization occurs, resulting in a nonlinear increase in repression activity. For values of A approaching saturation, the operator is mostly bound, and repressor activity is close to maximal. At this point, increasing the concentration of A does not increase repression, and instead causes the A/A curve to move toward an asymptotic boundary. In this way, the cooperative binding stage performs signal restoration in which the analog output signal better represents the

appropriate digital meaning than the corresponding analog input signal. Because each stage of the computation reduces the noise in the system through signal restoration, multiple inverters can be combined into more complex circuits, while still maintaining or even increasing the overall reliability of the system. In the final stage of the inverter, the transcription stage, RNA polymerase (RNAp) transcribes the regulated gene and the input signal is inverted. Let us define Z to be the output signal of the inverter and Z to be its corresponding mRNA concentration. The transcription stage, with input A and output Z, has a steady state relationship in which increases in A correspond to monotonic decreases in Z. During periods of minimal repression, transcription progresses at rapid rates resulting in maximal concentrations of Z. However, for high levels of repression, the transcriptional activity declines and the level of Z drops. Overall, the three stages combine to form a system that behaves as an inverter, negating the input mRNA signal, A, to yield the output mRNA signal, Z. Furthermore, with efficient signal restoration during the cooperative binding stage of inversion, complex but reliable digital logic circuits are attainable.

2) 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 3) 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 70digit sequence

Q.(V) What are the kinds of computing problems that can be solved using a DNA computer? What are its limitations ? ANS:COMPUTING PROBLEMS THAT CAN BE SOLVED BY DNA COMPUTER:1. A 20-variable instance of the NP-complete three-satisfiability (3-SAT) problem was solved on a simple DNA computer. The unique answer was found after an exhaustive search of more than 1 million (220) possibilities. This computational problem may be the largest yet solved by nonelectronic means. Problems of this size appear to be beyond the normal range of unaided human computation. 2. Suitable for Combinatorial Problems From the first day that DNA Computation is developed, Scientists used it to solve combinatorial Problems. In 1994, Leonard Adleman used DNA to solve one of Hamiltonian Path problem -Traveling Salesman problem. After that Lipton used DNA Computer to break Data Encryption Standard (DES) [Bon1995]. And then much of the work on DNA computing has continued to focus on solving NP-complete and other hard computational problems. In fact, experiments have proved that DNA Computers are suitable for solving complex combinatorial problems, even until now, it costs still several days to solve the problems like Hamiltonian Path problems. But the key point is that Adleman's original and subsequent works demonstrated the ability of DNA Computers to obtain tractable solutions to NP-complete and other hard computational problems, while these are unimaginable using conventional computers.

LIMITATIONS OF DNA COMPUTER:1. IT INVOLVES A RELATIVELY LARGE AMOUNT OF ERROR. 2. REQUIRES HUMAN ASSISTANCE. 3. TIME CONSUMING LABORATORY PROCEDURES. 4. NO UNIVERSAL METHOD OF DATA REPRESENTATION

Q.(vi) What unanswered questions does your analysis leave behind. Where do you find a scope for improvement in the current technology? Which of the constituent operations can be performed differently with similar or better results? Ans: Questions that are not answered according to my analysis:1. Storage and Associative Memory - large content addressable memory using DNA 2. Massively Parallel Processing - handle millions of operations in parallel 3. Hamiltonians problem 4. Cryptography

I find these area for improvement in the current technology: SELF POWERED DNA COMPUTER UNVEILED IN 2003 FIRST PROGRAMMABLE AUTONOMOUS COMPUTING MACHINE WITH INPUT,OUTPUT,SOFTWARE AND HARDWARE ALL MADE OF DNA MOLOCULES. CAN PERFORM A BILLION OPERATIONS PER SECOND WITH 99.8% ACCURACY BIOLOGICAL COMPUTERS DEVELOPED USED TO FIGHT CANCERS DESIGNER DNAIDENTIFIES ABNORMAL AND IS ATTRACTED TO IT,RELEASES CHEMICALS TO INHIBIT GROWTH.SUCCESSFULY TESTED ON ANIMALS.

These constituent operations can be performed differently with similar or better results: IT INVOLVES A RELATIVELY LARGE AMOUNT OF ERROR. REQUIRES HUMAN ASSISTANCE. TIME CONSUMING LABORATORY PROCEDURES.
NO UNIVERSAL METHOD OF DATA REPRESENTATION.