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Theoretical and Experimental DNA Computation (Natural ...

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110 5 Physical Implementations<br />

not to provide definitive answers ...but rather to show that a number of seemingly<br />

disparate questions must be connected to each other in a fundamental<br />

way.” [46]<br />

In [45], Conrad exp<strong>and</strong>ed on this work, showing how the information processing<br />

capabilities of organic molecules may, in theory, be used in place of<br />

digital switching components (Fig. 5.1a). Enzymes may cleave specific substrates<br />

by severing covalent bonds within the target molecule. For example,<br />

as we have seen, restriction endonucleases cleave str<strong>and</strong>s of <strong>DNA</strong> at specific<br />

points known as restriction sites. In doing so, the enzyme switches the state of<br />

the substrate from one to another. Before this process can occur, a recognition<br />

process must take place, where the enzyme distinguishes the substrate from<br />

other, possibly similar molecules. This is achieved by virtue of what Conrad<br />

refers to as the “lock-key” mechanism, whereby the complementary structures<br />

of the enzyme <strong>and</strong> substrate fit together <strong>and</strong> the two molecules bind strongly<br />

(Fig. 5.1b). This process may, in turn, be affected by the presence or absence<br />

of lig<strong>and</strong>s. Allosteric enzymes can exist in more than one conformation (or<br />

“state”), depending on the presence or absence of a lig<strong>and</strong>. Therefore, in addition<br />

to the active site of an allosteric enzyme (the site where the substrate<br />

reaction takes place) there exists a lig<strong>and</strong> binding site which, when occupied,<br />

changes the conformation <strong>and</strong> hence the properties of the enzyme. This<br />

gives an additional degree of control over the switching behavior of the entire<br />

molecular complex.<br />

In [17], Arkin <strong>and</strong> Ross show how various logic gates may be constructed<br />

using the computational properties of enzymatic reaction mechanisms (also<br />

see [34] for a review of this work). In [34], Bray also describes work [79, 80]<br />

showing how chemical “neurons” may be constructed to form the building<br />

blocks of logic gates.<br />

5.3 Initial Set Construction Within Filtering Models<br />

All filtering models use the same basic method for generating the initial set<br />

of str<strong>and</strong>s. An essential difficulty in all filtering models is that initial multisets<br />

generally have a cardinality which is exponential in the problem size. It<br />

would be too costly in time, therefore, to generate these individually. What<br />

we do in practice is to construct an initial solution, or tube, containing a<br />

polynomial number of distinct str<strong>and</strong>s. The design of these str<strong>and</strong>s ensures<br />

that the exponentially large initial multi-sets of our model will be generated<br />

automatically. The following paragraph describes this process in detail.<br />

Consider an initial set of all elements of the form p1k1,p2k2,...,pnkn. This<br />

may be constructed as follows. We generate an oligonucleotide (commonly<br />

abbreviated to oligo) uniquely encoding each possible subsequence piki where<br />

1 ≤ i ≤ n <strong>and</strong> 1 ≤ ki ≤ k. Embedded within the sequence representing pi is<br />

our chosen restriction site. There are thus a polynomial number, nk,ofdistinct<br />

oligos of this form. The task now is how to combine these to form the desired

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