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jeff101's picture
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Joined: 04/20/2012
Groups: Go Science

Cree Leukoencephalopathy (CLE) is a neurological disease
synonymous with several other diseases described in [1] below:

[1] https://en.wikipedia.org/wiki/Leukoencephalopathy_with_vanishing_white_matter

At the heart of these diseases are mutations in eIF2 and/or eIF2B complexes.

jeff101's picture
User offline. Last seen 8 hours 7 min ago. Offline
Joined: 04/20/2012
Groups: Go Science
Can Foldit help cure Cree Leukoencephalopathy?

A search of http://www.rcsb.org gave a number of known structures for
eIF2B complexes and led to the following 2 articles (among others):

[2] http://onlinelibrary.wiley.com/doi/10.1111/febs.13896/epdf

[3] https://academic.oup.com/nar/article-pdf/43/20/9994/5983580/gkv930.pdf

[2] and [3] are by 2 different crystallography groups and give the sense that
eIF2 and eIF2B are large complexes, probably larger than most proteins we study
with Foldit.

I was hoping fellow Foldit players and the Foldit team could brainstorm ways
Foldit could help tackle CLE and related diseases. Perhaps we could use known
structures for certain subunits to determine the structures for mutated versions
of these subunits. Also, when Foldit's drug design tools become available, perhaps
we could design drugs to fill in parts of the eIF2 or eIF2B complexes that are
mutated in common diseased versions of these complexes. [1] lists mutations like
R113H, G584A, and R195H, for example.

If you have the time, please explore the above articles and the pdb files available.
If you have any suggestions for puzzles, articles to read, structures to explore, etc.
please post them here.

Thanks!
Jeff

Joined: 09/24/2012
Groups: Go Science
What about a contest-type chalenge without points ?

If the protein is such large, many players won't find it fair competition.
In the Contest, we have such large proteins and we have a plenty of time to try them.
What about a special competition for such an useful protein beyond the limits of Foldit?
With a huge amount of time (say 1 months), no point? (or 3 months for points).

I would find it challenging, and the longer period of time for same points would make it fair enough.

Whatever the suggestions, with or without points, I'm willing to work on Cree Leukoencephalopathy.

jeff101's picture
User offline. Last seen 8 hours 7 min ago. Offline
Joined: 04/20/2012
Groups: Go Science
Imitate Puzzle 1000?

In Puzzle 1000: Breach Ebola's Defences!
https://fold.it/portal/node/1998572
https://fold.it/portal/node/2000209
we designed a small peptide to bind to
a much larger protein complex.

Perhaps we could do similar things
with the mutated complexes in CLE.

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