1667: "Too Much Density!" Freestyle puzzle

Closed since almost 7 years ago

Summary

• Created: April 25, 2019
• Expires: May 06, 2019 at 07:00 UTC
• Max points: 100

Description

This Electron Density puzzle is different than anything we've ever posted before! The extended chain is 187 residues long, but we are giving you a lot more density than that. You'll need to find where to fit this chain in the giant blob of density. (The "Trim Density" tool will be your friend)

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• 10. vakobo 74 pts. 20,076

Comments

[horowsah]

Just wanted to address a few questions from above- this density comes from cryo-EM. In EM, the resolution is typically low (in this case, around 4 angstrom resolution), and often it's of a multi-protein complex. One major challenge is figuring out which parts of the density correspond to which of the proteins in the multi-protein complex, or even which parts of the density might be noise. So having "spare" density like this is a hard but important scientific puzzle that microscopists frequently encounter.

[Susume]

I have found at least ten helices in the cloud (you can mark them with one dot, two dots, three dots etc to number them so you can tell them apart), but it's fairly impossible to tell which ones to use because the resolution on the sidechains is so poor. Without visible aromatics to use as landmarks, placing the protein is pretty much guesswork. Is it possible to recalculate the cloud from the data in a way that favors sidechains more?

[Bautho]

I actually took Chain K :D

[LociOiling]

There are three PDBs that match:

• 5MRW, chains C, G, K; offset 0
• 6HRA, chain C, offset 3
• 6HRB, chain C, offset 3

For 6HRA and 6HRB, the "offset 3" means segment 1 in Foldit is segment 4 in the PDB model.

Both 6HRA and 6HRB show a complex of four proteins.

5MRW has the same four proteins, give or take a few segments, but they're repeated three times. So it's kind of a trimer of tetramers, with 12 protein chains overall.

5MRW has 4,335 segments, where 6HRB has only 1,458.

I'm guessing the density contains all or part of the four proteins.

[jeff101]

Apparently in previous puzzles, the Foldit team trimmed the density so it only contained the protein of interest. In practice, how do microscopists & the Foldit team know which parts to trim and which parts to keep?

[frood66]

oops1 I accidentally down voted - sorry Sus.

Truth is - the definition is rather too low for an extremely mind boggling puzzle…..
there are some aromatic markers (but they are oft in areas of loop)
The majority of the cloud is of no use since this cloud contains more than one chain.
Once the superfluous are removed - that helps a bit. But I would still like to see an eraser to remove these - they are are pointless
As for completing the puzzle? I know some of it (and have it) Will I bother to try to complete? - prob not. Too much is loop and too much is disordered (invisible)

[frood66]

It has been 'de rigour' for puzzle pages to give the sequence for some time - so what has happened?

It has also been requested (and followed by FC) to state the definition (Angstrom) on ED puzzles.

I (and others) find it very curious that huge ED is posted - and neither 'usual' info has been given.

Just saying! :)

[frood66]

All vets know that trim density is of little value in early game.

If players cannot get past early game - then it becomes doubly useless. It is generally only of value in mid/late game and only then with reasonable definition (which this puzzle does not have)

We all know this - strange that the setters do not. :(

Come on guys - give us something to work with! Or are U just using us as lab rats?

[Bletchley Park]

What exactly is the point of these puzzles if people lookup the structure and from all the info deduce which protein it is and how it should look like ? Wasn't the idea that we would train ourselves to recognize features and map those to a model that fits reality without prior knowledge ?

[jeff101]

I for one have not yet looked at the pdb files or my team's
shares for this puzzle. I am trying to do this puzzle as if its
results are unknown (and perhaps they are unknown, perhaps
this is a new structure for the same sequence, but maybe this
one is when bound to a new drug, for example). I am using the
PsiPred secondary structure listed above and relying a lot on
recipes so far. I had a solo rank 17 when last I checked, and
I have some more ideas to pursue regarding this puzzle.

Nevertheless, I haven't yet found a good starting position
(a terminal end or a recognizable sequence of residues in the
middle of the protein chain). My best solutions so far sort of
follow one chain over here and another chain over there. There
are many places where my solutions clearly jump from one chain
to another. I am still hopeful I can make more progress on this
puzzle. If nothing else, it is good practice. If we can do this
type of puzzle, it opens the door for more puzzles like this,
and the scientists won't have to spend as much time
processing their data before giving it to us to solve.

Finally, if this is a new structure for an old sequence,
scientists in the real world would certainly look at the pdb
files for the old structures. They would use whatever data
they could find to get insight into how this new structure
folds.