Gas station without pumps

2012 January 25

Another success for FoldIt

Filed under: Uncategorized — gasstationwithoutpumps @ 20:20
Tags: , , , ,

David Baker‘s group has had another success for FoldIt, their computer game for folding proteins.  As reported in Nature News, Victory for crowdsourced biomolecule design, FoldIt players managed to improve the computer-designed enzyme that catalyzes Diels-Alder reactions.  I’ve not read the paper itself (Increased Diels-Alderase activity through backbone remodeling guided by FoldIt players), which is hidden behind a paywall (though UC has a library subscription, so I do have access).

The initial impressive feat from Baker’s group was that they designed an enzyme de novo using Rosetta design (this was reported in 2010).  The FoldIt addition was an 18-fold increase in activity, which came from targeted redesign (redesigning a loop to increase contact between the protein and one of the reactants, stabilizing the new loop, and so forth).  The FoldIt players were not not choosing the goals of the redesign (that was done by postdocs in Baker’s group), but they were exploring the protein space in ways that conventional optimization programs do not (such as adding 13 amino acids).

This is not the first success for FoldIt.  They had a Nature paper in 2010, which reported on the success of FoldIt players at predicting protein structure on a target that had eluded automatic methods for a few years.

So far as I know, FoldIt is the only computer game so far to have made any real advances in molecular engineering. (The main other contender, EteRNA, though fun to play, does not capture enough in its scoring function for EteRNA play to do anything very useful.)

Disclaimer: my former PhD student, Firas Khatib, was an author on both the FoldIt papers mentioned here, though he was not part of the original enzyme design team.

2011 June 3

Cyberslug t-shirt designs

Filed under: Uncategorized — gasstationwithoutpumps @ 20:05
Tags: , , ,

Last year I started a “tradition” of designing a T-shirt for one of my classes.
Last year, it was for the Banana Slug Genomics class:

slug dreaming of double helices

This was the 2010 design. Slug reproduction does involve them curling around each other, but in a planar spiral, not in a helix.

Although I taught the Banana Slug Genomics course again this year, I had few students in it, and I did not want to repeat last year’s shirt. So I designed a shirt for my other class, in which I was teaching about computational protein design. The protein image is an SH3 barrel (PDB id 1jo8A), which we had used as an example in class. It turned out that there were two other courses also doing protein work this quarter: an undergraduate course in protein engineering and the lab part of an undergraduate course in molecular biomechanics. My students did the same lab as the undergrads (but a day earlier). The lab consisted of transfecting E. coli with a plasmid, growing the cells, expressing the protein, lysing the cells, purifying the protein on a cobalt column using the HIS tag, and using SUMO protease to cleave off the HIS and SUMO tag.

We had hoped to be able to get genes synthesized for proteins of our own design, but the 10-week quarter was too short—we did not have any computational plausible designs until about 8 weeks into the quarter.

I’m hoping that enough of the undergrads will like the t-shirt design to amortize the setup charges for the two silk screens needed for the design:

Cyberslug dreaming of protein structure

This is the design for this year's t-shirt. I'm taking orders (from people affiliated with the Jack Baskin School of Engineering, since JBSoE has the rights to the cyberslug—for UCSC people the affiliation can be pretty loose) until Monday 6 June 2011.

%d bloggers like this: