Just a thought. Could be used as a model system for evolution research. I just saw Susan Blackmore's TED talk - she summarizes Darwin's Origin of the Species as:
If you have
- variation
- selection
- heredity
Then you *must* have
- evolution
It would be interesting to speculate how those three factors could be introduced.
I've definitely experienced this problem - my laptop loves to sabotage the local NPR station and slight changes in the angle of the screen seem to have large effects. What impresses me is that the detector can select output from one screen over all others. In the New Scientist article, Kuhn pulls a screen from 25 meters away at a public conference. How many other screens were around and how was this selection achieved? Would a possible countermeasure be to have a second screen playing white noise (or some other noise generator) nearby?
This is admittedly off topic, but does the word symmetrical bug anyone else besides me? Doesn't symmetric work just as well? Sure its commonly used, but what about the word dynamical? That's been popping up in scientific journals for at least the last decade or so. And orientated? wtf?
Just a tiny factual correction to the above post. For those searching for this article, its in the May 8th issue of Nature. The remainder of the above reference is accurate.
What makes this success deserve the superlative 'humongous', imho, is twofold. One, as Bowling Moses refers, the size of sequence space is 10^15 to 10^23. However, you combine this with the number of possible rotameric conformations certain sidechains can adopt, and your search space climbs to 10^50 to 10^70 in size. Make things even more formidable by thinking about the rotational and translational degrees of freedom within an active site pocket and you're trying to find the best solution from among 10^110 states!! Only because of novel improvements to Dead End Elimination, which were outlined in an earlier article by Looger and Hellinga in the Journal of Molecular Biology, are such huge problems able to be solved in 3 days. The second major triumph of this paper is the design of polar specificity. While not the first example of designing polar interactions, a strict rule of satisfying all possible hydrogen bonds has greatly improved both Dead End Elimination selection and the specificity of the resulting active site. Up until now, the best designed small molecule binders were shape matching grease with grease.
When using a higher resolution search scheme (e.g. more states), Looger and colleagues were able to design a TNT binding protein with nanomolar binding, while preserving specificity. It seems possible that Hellinga may be at the top of the pack in designing useful enzymes. If the proteins are designed to target a substrate transition state, it may be possible to design artificial biocatalysts.
While plenty of TNT degrading enzymes have been developed either by natural evolution or by artificially directed processes, the advantages of an in silico approach are obvious. Hellinga could make one design in 3 days... and computers will only get faster.
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Just a thought. Could be used as a model system for evolution research. I just saw Susan Blackmore's TED talk - she summarizes Darwin's Origin of the Species as: If you have - variation - selection - heredity Then you *must* have - evolution It would be interesting to speculate how those three factors could be introduced.
I saw this episode of Bananas in Pyjamas. Very sad.
Number of people with brain cancer equals half the human population.
I've definitely experienced this problem - my laptop loves to sabotage the local NPR station and slight changes in the angle of the screen seem to have large effects. What impresses me is that the detector can select output from one screen over all others. In the New Scientist article, Kuhn pulls a screen from 25 meters away at a public conference. How many other screens were around and how was this selection achieved? Would a possible countermeasure be to have a second screen playing white noise (or some other noise generator) nearby?
This is admittedly off topic, but does the word symmetrical bug anyone else besides me? Doesn't symmetric work just as well? Sure its commonly used, but what about the word dynamical? That's been popping up in scientific journals for at least the last decade or so. And orientated? wtf?
Just a tiny factual correction to the above post. For those searching for this article, its in the May 8th issue of Nature. The remainder of the above reference is accurate.
... and computers will only get faster.
What makes this success deserve the superlative 'humongous', imho, is twofold. One, as Bowling Moses refers, the size of sequence space is 10^15 to 10^23. However, you combine this with the number of possible rotameric conformations certain sidechains can adopt, and your search space climbs to 10^50 to 10^70 in size. Make things even more formidable by thinking about the rotational and translational degrees of freedom within an active site pocket and you're trying to find the best solution from among 10^110 states!! Only because of novel improvements to Dead End Elimination, which were outlined in an earlier article by Looger and Hellinga in the Journal of Molecular Biology, are such huge problems able to be solved in 3 days. The second major triumph of this paper is the design of polar specificity. While not the first example of designing polar interactions, a strict rule of satisfying all possible hydrogen bonds has greatly improved both Dead End Elimination selection and the specificity of the resulting active site. Up until now, the best designed small molecule binders were shape matching grease with grease.
When using a higher resolution search scheme (e.g. more states), Looger and colleagues were able to design a TNT binding protein with nanomolar binding, while preserving specificity. It seems possible that Hellinga may be at the top of the pack in designing useful enzymes. If the proteins are designed to target a substrate transition state, it may be possible to design artificial biocatalysts.
While plenty of TNT degrading enzymes have been developed either by natural evolution or by artificially directed processes, the advantages of an in silico approach are obvious. Hellinga could make one design in 3 days