Posts by jcorn

1) Message boards : Number crunching : minirosetta 2.05 (Message 65238)
Posted 8 Feb 2010 by jcorn
Hi Manuel and P.P.L.

The large memory requirements are a once-in-a-while occurrence, but not something entirely unexpected. These jobs occasionally find a very interesting possible solution and spend a lot of resources testing it. I had submitted these jobs with the requirement for 512 MB RAM allocated for boinc. But based on your observations, I'll increase that requirement to 1 GB in the future. Thanks very much for the reports!
2) Message boards : Rosetta@home Science : Design of protein-protein interfaces (Message 65207)
Posted 4 Feb 2010 by jcorn
For those who'd like more information on IGF-1, check out the wikipedia page
3) Message boards : Rosetta@home Science : Design of protein-protein interfaces (Message 65206)
Posted 4 Feb 2010 by jcorn
Hi boincers,
Since I last wrote, Tim Whitehead (username taw) and I have spent a lot of time testing the anti-IL23 designs that you made. So far we have a promising hit, but in science as in life, the results are somewhat ambiguous. I'll keep everyone updated when things are more concrete, but there's hope that your number-crunching has made a bona-fide binder for IL23!

I've also started designing against a new target, called Insulin-like Growth Factor 1 (IGF1). IGF is a central regulator of the speed of cell division: many tumors have been linked to having too much IGF around. Interestingly, the when an organism's cells are globally told to divide more slowly, by inhibiting IGF, the animal actually lives longer! As they say, the candle that burns twice as bright, burns half as long. In fact, since IGF is closely related to insulin and energy metabolism, some people have theorized that the increases in life span from caloric restriction are actually a side-effect of crosstalk with IGF signaling. So anti-IGF therapies hold promise as both anti-cancer agents and as anti-aging therapies.

I'm very excited to see what designs you can come up with, and everything is in place to test them in the lab. Look for workunits that start with "igf", eg - "igfhum" or "igffn3". Thanks for your help!
4) Message boards : Rosetta@home Science : Design of protein-protein interfaces (Message 56916)
Posted 13 Nov 2008 by jcorn
Hi everyone,
A quick update on computational design in general, and IL23 in particular.

As many people noticed, these design jobs are taking longer and using more memory than most R@H work units. This is because we are working with proteins that are much larger than what you normally fold during an abinitio run. For reference, imagine that abinitio runs are folding a steel chain with 1-inch links, and that the position of each link changes during the course of the workunit. Abinitio workunits then origami-fold about 8 feet of constant chain into a nice, pretty structure.

By contrast, our design workunits are dealing with two chains, each of which is twenty five to fifty feet long. Not only can the whole folded chain move, the positions of each link can shift slightly, *and* we're constantly swapping out links as the simulation progresses! We have twenty different links to play with, and each position on each chain could be any one of the twenty. Our challenge is to figure out how the two chains should lay on top of one another and what link should be at what position to make the the chains best fit together. As you can imagine, all of that takes a great deal of computing power, and about half a gigabyte of memory. We've put a temporary hold on future design workunits until we do a more benchmarking and fix the issues that you've brought up. For example, we are considering restricting design runs to machines with no less than 1GB of RAM.

Now the good news: Thanks to all of your work, the IL23 design project is moving at an incredible pace. Over the last 5 days, you generated half a million potential therapeutics for IL23! That's completely unprecedented for this kind of project, and would have taken me forever to do on our lab computers. So even though it was a somewhat rocky start, you have all made a very significant contribution towards creating an IL23 anti-inflammatory drug. I'm very much looking forward to sifting through all of the potential therapeutics you've designed, and I feel that R@H really holds the key to making this project work.
5) Message boards : Rosetta@home Science : Design of protein-protein interfaces (Message 56763)
Posted 7 Nov 2008 by jcorn
My name is Jacob Corn, and I'm a postdoc in the Baker Lab, working with Eva and Sarel on the design of protein-protein interfaces. As Sarel mentioned, this is an incredibly important problem, both for basic science and molecular medicine. But it is also an incredibly difficult problem. Without your support, we would never have enough computing power to work on these kinds of projects.

One target that I am attempting to design towards is interleukin 23 (aka IL23). Your body normally uses this protein to trigger the inflammatory response, which is a normal part of your body's immune system. However, if IL23 messages start to run out of control, they can cause serious autoimmune disorders, such as Chron's Disease. You can find more information on IL23 here
and Chron's Disease here

This week you may receive jobs with titles like "IL23p40_p40BrubYhbond_design_jecorn". These design simulations first dock two proteins against each other (one of which is IL23), then try to iteratively optimize the surface of one protein to better match the surface of IL23. Using the results of your calculations, I will the designed proteins and test them for binding to IL23, hopefully producing a new inhibitor to combat runaway diseases caused by runaway IL23 signals.

I'm very excited about this project, and look forward to your feedback.
6) Message boards : Rosetta@home Science : Energy vs rmsd plots (Message 56762)
Posted 7 Nov 2008 by jcorn

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