26 December 2011

RNA computer-aided design system

The Americans have created a constructor program for assembling RNA moleculesRIA News

American biologists have developed a complex of computer programs that allows you to assemble virtual RNA molecules with specified properties, test them in a virtual laboratory and use mockups to assemble real RNA chains, according to an article published in the journal Science (Carothers et al., Model-Driven Engineering of RNA Devices to Quantitatively Program Gene Expression – VM).

In the last few years, biologists and computer engineers have been actively developing systems that facilitate the "reprogramming" of bacteria and other living organisms. So, in July 2011, biologists from South Korea and the United States developed a genetic editor that allows you to cut, copy and paste large and small sections of DNA directly into the Escherichia coli cell.

A group of biologists led by Jay Keasling from the University of California at Berkeley (USA) has created, as they call their technology, a "computer-aided design system" (CAD) for assembling RNA molecules with specified properties.
This technique of RNA assembly involves creating and studying the properties of a virtual "layout" of an RNA molecule using a special computer program and assembling a finished product without having to check every step of this process.

"We had to develop models that would be complex enough to accurately display the subtleties necessary for an adequate simulation of the system's function, and at the same time simple enough to be designed in the form of measurable and controlled variables. We imagined these variables as parts of a system that could be changed with predictable results – in much the same way as a chemical engineer controls a chemical factory by moving the handles from the valves. The models were needed in order to predict how a combination of the positions of different handles would affect the operation of the entire system," explained one of the group members James Carothers from the University of California at Berkeley.

The system of Kiesling and his colleagues is designed to assemble some of the most complex RNA molecules – the so-called ribozymes (ribonucleic acid + en-zim, RNA molecules capable, like enzyme proteins, of catalyzing molecular biological reactions – VM) and aptazims (apta mer + en-zim, i.e. ribozymes associated with An aptamer is a chain of several nucleotides or amino acids capable of specifically binding to a specific site of biomolecules; due to this, aptazymes control many different processes in the cell. The figure from the article in Science shows several aptazymes synthesized according to preliminary calculations (VM).

The authors of the article studied the mechanical and chemical laws governing the parameters of the assembly of the RNA molecule and affecting its properties, and designed them in the form of computer algorithms. Based on these algorithms, the scientists developed a computer program that allowed them to collect virtual RNA molecules and observe its interaction with other substances and other RNA chains. A proven version of the molecule can be assembled already in real conditions, without spending effort on additional checks.

To test the operation of this system, scientists collected 24 different versions of ribozyme RNA and compared how the programmed functions of the molecule would correspond to the actual results of its work in Escherichia coli cells.

According to the idea of Kisling and his colleagues, each RNA molecule was supposed to make bacteria produce a certain amount of red fluorescent protein (RFP). In general, all the molecules worked as scientists intended – their overall "accuracy" is approaching 94%.

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26.12.2011

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