Calculating Non-Ideal Loops Penalty:

Case number:845813-2005262
Topic:Game: Tools
Opened by:jeff101
Status:Open
Type:Suggestion
Opened on:Saturday, May 19, 2018 - 16:51
Last modified:Monday, May 21, 2018 - 17:13

On Puzzle 1518, to calculate the Ideal Loops penalty,
it seemed like Foldit determined secondary structures
like the auto secondary structure button would find,
then it considered each continuous group of adjacent
loop residues as one loop.

For one structure (Je1b CW -2589.230 F -350) with the sequence below:

0000000001111111111222222222233333333334444444444555555555566666666667777777777888
1234567890123456789012345678901234567890123456789012345678901234567890123456789012
LLLLLLLLLLLLLLLLLLLELLLLLLLLLLLLEEEEEEELELLLLLLLLLLLLLLEEEEELLLLLLLLLLLLLLLLLLLLLL

showing the Ideal Loops filter gave a penalty of -500
for 5 non-ideal loops and put red blobs at segments
2-19 21-32 40 42-55 and 61-82 (all L positions above
except segment 1). Even the single-segment loop at
segment 40 counted as a non-ideal loop.

For another structure (Je1a CW 9826.952 F -456.8) with the sequence below:

0000000001111111111222222222233333333334444444444555555555566666666667777777777888
1234567890123456789012345678901234567890123456789012345678901234567890123456789012
LEEEELLLEELLLEEEEEEEEELLLEEEEEEEEEELLLLEEEELLLLEEEEEEEEEEELLEEEEEEEEEELLLEELLEEEEL

showing the Ideal Loops filter gave a penalty of -600
for 6 non-ideal loops and put red blobs at segments
6-8 11-13 23-25 36-39 71-73 and 76-77 (all L positions
above except segments 1 44-47 59-60 and 82). I took this
to mean that the loops at segments 44-47 and 59-60
passed the Ideal Loops filter and so were considered
as Ideal. Nevertheless, the colors within the Blueprint
Tool for segments 44-47 (brrb) and 59-60 (rr) did not
match any of the sheet-sheet loop Building Blocks within
the Blueprint Tool.

For a 3rd structure (Je1b CW 9827.220 -663.2) with the sequence below:

0000000001111111111222222222233333333334444444444555555555566666666667777777777888
1234567890123456789012345678901234567890123456789012345678901234567890123456789012
LEEEEELLEELLEEEEEEEEELLLEEELLLLEEELLLLEEEEELLLLEEEELLLLEEEEEEEEELLLEEELLEEEEELLLEL

showing the Ideal Loops filter gave a penalty of -800
for 8 non-ideal loops and put red blobs at segments
7-8 11-12 22-24 28-31 44-47 65-67 71-72 and 78-80
(all L positions above except segments 1 35-38 52-55 and 82).
I took this to mean that the Loops at segments 35-38 and 52-55
passed the Ideal Loops filter and so were considered as Ideal.
Nevertheless, the colors within the Blueprint Tool for
segments 35-38 and 52-55 were both brrb and did not match
any of the sheet-sheet loop Building Blocks within the
Blueprint Tool.

I am curious how Foldit decides which loops are ideal
and which ones are not. Does Foldit average the Ideality
subscores for all segments within a loop? Is there a cutoff
for this average Ideality subscore above which the loop is
considered Ideal and below which the loop is considered
Non-Ideal? I noticed that in the structures above, all
segments had either no Ideality subscore or negative ones.
I didn't see any segments with positive Ideality subscores.

(Sat, 05/19/2018 - 16:51  |  5 comments)


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

I think it would be useful when one opts to Show the
Ideal Loops Filter to have Foldit do the following:

(1) Put red blobs by Non-Ideal Loop segments
and green blobs by Ideal Loop segments in the
3D picture of the protein.

(2) Somehow mark Ideal & Non-Ideal Loop segments
in both the Blueprint Tool and Rama Map. Perhaps
use +'s for Ideal Loops and -'s for Non-Ideal Loops.

(3) In the Blueprint Tool, have another row showing
the secondary structure that the auto secondary
structure button would show. It does not always agree
with the secondary structure one has chosen for each
segment, but it seems to determine which segments get
grouped together & checked by the Ideal Loops filter.

(4) It would also be nice to be able to toggle the
Show Filter/Penalty boxes on/off while a Recipe is
running.

jeff101's picture
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Joined: 04/20/2012
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Below is an example of the Blueprint Tool
labeling proposed in (2) above:

For the structure Je1b CW 9827.220 -663.2 with the sequence below:

0000000001111111111222222222233333333334444444444555555555566666666667777777777888
1234567890123456789012345678901234567890123456789012345678901234567890123456789012
LEEEEELLEELLEEEEEEEEELLLEEELLLLEEELLLLEEEEELLLLEEEELLLLEEEEEEEEELLLEEELLEEEEELLLEL
?     --  --         ---   ----   ++++     ----    ++++         ---   --     --- ?

8 non-ideal loops marked with red blobs are at segments
7-8 11-12 22-24 28-31 44-47 65-67 71-72 and 78-80
while 2 ideal loops marked with green blobs are at segments
35-38 and 52-55. Segments 1 and 82 are marked with ? because
they are neither ideal nor non-ideal.

Susume's picture
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Joined: 10/02/2011

I am pretty sure the ideal loop filter looks first at hydrogen bonds to determine what is a loop, then looks at backbone torsion angles phi and psi (the two values that appear in the rama map) to determine whether it matches the list of allowed loops. It has to have some kind of allowed range of torsion angles for each allowed loop, which may or may not exactly match the colors shown in the rama map for the current AA. That is, a segment might be blue in the rama map but not within the allowed phi/psi range for a given ideal loop that has a blue in that spot, or may be within the allowed phi/psi range but not be quite within that colored rama area for the current AA.

You might look at the rama maps for your red-red and blue-red-red-blue loops that pass the filter, and see if the segment right after the second red is way up in the top left corner of the rama map. If so, it is very near to the bottom right corner (because the map wraps in both directions), which is yellow. If that is the case, you may be getting credit for a blue-red-red-yellow sheet-sheet loop, with leeway given in the allowed torsion angles for the yellow segment that lets them slop over into the adjacent corner of the blue area. The attached image shows the blueprint tool's suggested phi/psi angles for the BRRY loop; you can see that the yellow dot is way in the lower right corner, and therefore very close to the upper left corner. That said, I have also seen some red-red sheet-sheet loops pass the ideal loop filter. If they are not due to leeway in the BRRY loop allowed ranges, they may be a "hidden" allowed loop in their own right.

Auto structures uses DSSP, which relies on the presence or absence of hydrogen bonds, to decide what is a loop. This makes it a good approximation of the ideal loop filter's decision about what is a loop (since that also relies on hydrogen bonds), but may not be an exact match.

AFAIK the ideality subscore is completely unrelated to the torsion angles phi and psi, and therefore to the ideal loop filter - it just unfortunately has a similar name in foldit, so it is easy to confuse with ideal loops. I think the ideality subscore has to do with how much the lengths of the covalent bonds that hold the backbone together vary from expected values, and how much the omega dihedral angle (which unlike the phi and psi angles is not supposed to vary much) varies from expected values.

bkoep's picture
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This is correct.

The "Ideality" subscore (displayed in Segment Information) is completely unrelated to the "Ideal Loops Filter." The first corresponds to the lengths and angles of chemical bonds between atoms; the latter depends only on the phi and psi torsions of the protein backbone. Sorry for the confusion! This is an example of some very poor naming decisions on our part, and it ought to be corrected.

The red-red β-hairpin loop is indeed a special "hidden" allowed loop. It is actually a fairly common loop structure for β-hairpins, but it is not included in the Building Blocks for some technical reasons.* The Ideal Loop Filter does not allow for any "leeway"; the color boundaries in the Rama Map should correspond exactly to the phi and psi thresholds for the Ideal Loop Filter.

*The red-red (BRRB) β-hairpin induces some distortion in the adjacent β-strands, which makes this loop unsuitable as a drag-and-drop Building Block. To some extent, this is true of all the β-hairpins, and to account for this the Building Blocks are a little more complicated than you might think (see this blog post for details). For this particular β-hairpin, the distortion is so extensive that a BRRB Building Block was impractical.

bkoep's picture
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Thanks for the feedback, jeff101—these are great suggestions! I agree that there should be better distinctions in Foldit about player-defined and auto-defined secondary structure, and I definitely think there's room to improve the information content of the Blueprint panel and Ideal Loop Filter visualization.

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