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ignasi
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Message 17932 - Posted: 12 Jul 2010 | 12:49:18 UTC

Dear crunchers,
In the past months you crunched a set of WUs that aimed at observing a free ligand binding to a protein (*IBUCH_esrever*). At least 1 of the 750 simulations has reached destination! http://youtu.be/a3IsIQiEjeQ
Congratulations for this amazing result. However, we lack a bit of statistics for this event and we need to get more of these. We are extending the experiment (*IBUCH_freebind*). They're sitting in the queue, get yours!

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Message 17942 - Posted: 13 Jul 2010 | 12:15:46 UTC - in response to Message 17932.

What ligand was it?

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Message 17948 - Posted: 14 Jul 2010 | 10:31:47 UTC - in response to Message 17942.
Last modified: 14 Jul 2010 | 10:33:59 UTC

The ligand is pYEEI (phosphorilated-Tyrosine, Glutamic Acid x2 and Isoleucine). It is the shortest to bind to and SH2 domain.
We haven't performed any freeligand binding experiment of larger peptides. However we do have tryied to compute binding free energies for them: PQpYEEIPI,...

cheers,

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Message 17950 - Posted: 14 Jul 2010 | 11:55:41 UTC - in response to Message 17932.

So, these are those very long workunits.
Give me more :)
http://youtu.be/a3IsIQiEjeQ

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Message 17953 - Posted: 14 Jul 2010 | 13:12:41 UTC - in response to Message 17948.

The pTyr seems to be behaving like an anchor, allowing for some serious changes in the rest of the peptide; at one stage it flips over (about 34sec). After being snapped into place it looks more at ease. Would be nice to see a big energy change at that point.

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Message 17995 - Posted: 16 Jul 2010 | 9:38:18 UTC - in response to Message 17950.

So, these are those very long workunits.
Give me more :)


Nope, they are not. These are *GCY* not *freebind*.

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Message 17996 - Posted: 16 Jul 2010 | 9:43:29 UTC - in response to Message 17953.

The pTyr seems to be behaving like an anchor, allowing for some serious changes in the rest of the peptide; at one stage it flips over (about 34sec). After being snapped into place it looks more at ease. Would be nice to see a big energy change at that point.


Exactly.
pTyr is the principal residue establishing the first contacts with the SH2 domain. Once it does, it doesn't detach (at the timescale we're looking at) and reduces the number of conformations that it needs to explore before binding. It is falling down to an energetic well--it likes to be there.

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Message 18001 - Posted: 16 Jul 2010 | 15:58:15 UTC - in response to Message 17995.


Nope, they are not. These are *GCY* not *freebind*.


Thank you for pointing out my mistake....

I got a lot of *freebind* too.
But I like the *GCY* more, because these are more gainful in a view of the credit/time ratio :)

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Message boards : News : Free ligand binding success & continuation