Enzyme-based computers

Israeli researchers have built a molecular computer using enzymes as logical gates. But don't rush to your computer store: this kind of computers is not designed for speed. Instead, it could be 'implanted' inside your body for intelligent drug delivery or to complex drug therapies.

Israeli researchers have built a molecular computer using enzymes as logical gates, according to New Scientist. the scientists used "two enzymes -- glucose dehydrogenase (GDH) and horseradish peroxidase (HRP) -- to trigger two interconnected chemical reactions." And the enzyme-based computer was able to perform computations using these chemical logic functions. But don't rush to your computer store: this kind of computers is not designed for speed. Instead, it could be 'implanted' inside your body for intelligent drug delivery or to complex drug therapies.

Here is a short description of the molecular computer built by a team led by Professor Itamar Willner of the Hebrew University of Jerusalem.

The team built their computer using two enzymes - glucose dehydrogenase (GDH) and horseradish peroxidase (HRP) - to trigger two interconnected chemical reactions. Two chemical components - hydrogen peroxide and glucose - were used to represent input values (A and B). The presence of each chemical corresponded to a binary 1, while the absence represented a binary 0. The chemical result of the enzyme-powered reaction was determined optically.
The enzyme computer was used to perform two fundamental logic computations known as AND (where A and B must both equal one) and XOR (where A and B must have different values). The addition of two further enzymes - glucose oxidase and catalase - connected the two logical operations, making it possible to add together binary digits using the logic functions.

Below is a diagram showing endonuclease-based logic gates described in a previous work, "Endonuclease-based logic gates and sensors using magnetic force-amplified read out of DNA scission on cantilevers" (Credit: Itamar Willner et al.).

Endonuclease-based logic gates

Here is a short explanation available from Moldynlogic (Molecular Logic Machines by Electronic Excitations and Inter- and Intra- Molecular Quantum Dynamics), a EU project, which helped to fund the research described here today.

The endonuclease scission of magnetic particles functionalized with sequence-specific DNAs, which are associated on cantilevers, is followed by the magnetic force-amplified readout of the reactions by the nano-mechanical deflection/retraction of the cantilevers. The systems are employed to develop AND or OR logic gates and to detect single base mismatch specificity of the endonucleases. The two endonucleases EcoRI (EA) and AscI (EB) are used as inputs.

But don't confuse these enzyme-based computers with their chemical cousins that are DNA computers. Those can potentially be faster than today's computers because of their intrinsic parallelism capabilities. On the contrary, computing with enzymes is very slow as reports New Scientist.

But Willner says his enzyme computer is not designed for speed – it can take several minutes to perform a calculation. Rather, he envisages it eventually being incorporated into bio-sensing equipment and used, for example, to monitor and react to a patient's response to particular dosages of a drug.

For more information, this research work has been published by the journal Angewandte Chemie International Edition under the title "Elementary Arithmetic Operations by Enzymes: A Model for Metabolic Pathway Based Computing" (Volume 45, Issue 10, Pages 1572-1576, February 27, 2006). Here is how access to this article. And here is a link to a summary of this paper (via PhysOrg.com). Here is the introduction.

Computers are really very simply put together. They only understand two responses: yes or no, expressed as 1 or 0 in binary. Using logic operations, this can be used to program calculations and their results. Biological systems behave in a similar way: a stimulus acts on an ensemble of molecules, setting off defined chemical reactions. This analogy inspired I. Willner and his co-workers to use a combination of coupled enzymes to construct a simple circuit in which enzymatic reactions correspond to logic operations.

If you want to learn more about these enzyme-based computers, you can check this page from Yissum, the Technology Transfer Company of the Hebrew University of Jerusalem about a patented method to build "Enzyme-Electrodes for Biosensor Applications." Here is a short introduction.

A general method has been developed that assembles enzyme-electrodes, which attains electrical contact between the enzyme and electrode. The enzyme electrodes yield an amperometric (current) response proportional to the concentration of the respective analyte in the sample. The method of preparation of the enzyme electrodes is based on the organization of a covalently-linked enzyme monolayer or multilayers on the electrode surfaces. Enzyme electrodes for the sensing of glucose, lactate and other substrates, were developed. This generic method was further developed by tailoring of enzyme-electrodes by the reconstitution of apo-flavoenzymes onto relay-FAD monolayers. The resulting enzyme-electrodes yield unprecedented current densities.

But what will these enzyme-based computers useful for? They might be used as "as implantable devices that respond to metabolic pathways or follow complex drug therapies," a view shared by Martyn Amos from University of Exeter, UK, who said to New Scientist that these devices have a great potential.

"If such counters could be engineered inside living cells, then we can imagine them playing a role in applications such as intelligent drug delivery, where a therapeutic agent is generated at the site of a problem," Amos says. "Counters would also offer a biological 'safety valve', to prevent engineered cells proliferating in an uncontrolled fashion."

Sources: Will Knight, New Scientist, February 23, 2006; and various web sites

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