Hi Matt, I'll try to answer your questions ...

Hi Vanita, I wanted to say thanks for all your posts; I seem to learn something new from each one of them ...

Ok. Some stuff is cleared up there. But what I'm still wondering is back to my first question. How does one get a snapshot of the viral proteins? You say it's "large and squishy". I see in court cases these guys bringing in this big white sheet of something that has a whole ton of light and dark marks on it, a DNA sample from somebody. If they do that with that, is there something similar with HIV? I can see where a person getting all these "snapshots" would soon see the weak points and know what to target so that question is answered. And so, if we have these "snapshots" and know where the weak points are "from year to year, and strain to strain", what exactly are we crunching and how does it benefit in making a vaccine?

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Hi Matt,

a DNA sample from somebody. If they do that with that, is there something similar with HIV?

Yes, exactly. The same DNA sequencing technologies used in forensics are also used for basic molecular biology research on things like HIV (in fact, basic researchers developed these techniques long before forensic scientists began using them).

... see the weak points and know what to target ...

Yes, the constant parts of the DNA sequence are what we want to target. But from the DNA sequence alone, we don't know how to target those constant, weak points.

what exactly are we crunching and how does it benefit in making a vaccine?

And now we get to the crux of the matter. But the answer to this last bit is multi-part.
1) Right now the numbers you are crunching are test cases of protein structure prediction, that will help us improve our prediction algorithm
2) Our algorithm can take a DNA sequence and convert it into a protein structure - in other words, if you have a protein you want to target for vaccine design, or other drug, you need to know the structure (shape) of that protein. By helping us improve the algorithm, you are helping us make more accurate structure predictions, which will help drug designers make more effective drugs. (See Disease Related Research and this thread).
3) In the case of HIV vaccine, we don't need to predict the structure of the constant regions (the weak points), because someone else has already solved these structures experimentally. What we can do is figure out how to use our design program (which is closely related to our prediction program) to take the HIV protein structure and make a vaccine.
4) By improving our prediction program, you improve our energy function, which improves our design program
5) Specifically, another post-doc here (Bill, who will soon start his own lab) is using the design program to find scaffolds that will present pieces of the HIV weak points to the immune system.
6) The reason a scaffold is necessary is because you can't just give a small piece of the HIV protein alone as a vaccine - it's too small and unstable, it needs a scaffold that will stabilize it, and basically shout to the immune system "here! look at this!". The scaffold has to hold the piece of HIV in a rigid conformation, the same conformation that it has in the context of the whole virus. There are also other considerations - the scaffold itself needs to be non-immunogenic. Bill is designing all these desirable properties into the vaccine candidates and his collaborators are testing the candidates.

There have been great breakthroughs in protein structure prediction and protein design in the last few years, but these are still non-trivial methods. We need your number crunching to help us improve the accuracy of the prediction and design program, so that it can run in a more automated fashion with less human intervention, and so that it produces fewer bad results and more good ones.

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And suddenly it all makes sense. That's really cool stuff to know. It makes a person feel like it's really close to happening. Thanks for the explainations and stuff. It's nice to know what's going on behind the scenes sometimes. Hope all our numbers help quick.

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Sir David Baker ... :)

I want to swipe most of your initial Post to put into the Wiki at the "spot" of the Rosetta@Home project for the topic What are the differences... as you are going to be doing more than just Rosetta development ...

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Sir David Baker ... :)

I want to swipe most of your initial Post to put into the Wiki at the "spot" of the Rosetta@Home project for the topic What are the differences... as you are going to be doing more than just Rosetta development ...

sounds good to me, Sir Paul!

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Sir David Baker ... :)

I want to swipe most of your initial Post to put into the Wiki at the "spot" of the Rosetta@Home project for the topic What are the differences... as you are going to be doing more than just Rosetta development ...

sounds good to me, Sir Paul!

Thanks, Minor, minor changes ... for one thing I made the links work ...

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For those INTERESTED, we have been updating the "papers" page and trying to make it relevant ... at the moment we now have reference materials and papers about BOINC and the projects, or a start at least, in one place ...

Check it out ... Papers on the BOINC System

One of the reasons I have long argued for centralized information about BOINC and the projects it rode in on ...

I know, more important things to do ... but that is the advantage of collaborative editing ... the minor changes build UP ... Chris made some yesteday, me today ... :)

Anyway, interesting material if ya'll are interested in what the projects are doing ...

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