Chemical & Engineering News published a brief news story today on Ashworth et al., which appeared in the June 1st issue of Nature. In that paper, the authors showed that computational protein design could be used to alter the specificity of the homing endonuclease I-MsoI. The redesigned enzyme was highly active and it cleaved the new recognition sequence about 10,000 times more effectively (in vitro) than the wild-type enzyme.

Earlier this year, David Liu’s laboratory demonstrated that it was possible to use directed evolution to modify the specificity of another homing endonuclease (I-SceI), but Ashworth et al. is the first paper in which computational protein design was successfully used to modify the specificity of a homing endonuclease.

The authors say that “the method should be generalizable to any protein–DNA interface redesign problem: for example, the reprogramming of transcription factor binding specificity” and they believe that “[t]he use and refinement of the computational modelling and design strategies described here should … [enable them to design] novel proteins [that are] able to recognize and cleave any desired DNA site with high specificity for targeted genomics applications.”

Joshua

Joshua Finkelstein (Associate Editor, Nature)

Ask people what they associate with Finland and the one thing everyone mentions is they’ve heard the language is fiendishly difficult. It certainly is—especially, if, like me, you are trying to get an uncooperative ( and non-English speaking) ticket machine to sell you a train ticket back to your hotel after a long day at the Human Genome Meeting in Helsinki. Still, the experience does make me sympathise with the scientists who are trying to decode the information encrypted in our DNA. Because if my Berlitz pocket phrasebook is anything to go by, it seems as though the human genome is written in Finnish.

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