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1992: Symmetric D2 Tetramer Design: H-bond Networks
Status: Closed


Name: 1992: Symmetric D2 Tetramer Design: H-bond Networks
Status: Closed
Created: 05/12/2021
Points: 100
Expired: 05/19/2021 - 23:00
Difficulty: Intermediate
Description: Design a D2 symmetric protein tetramer, with 4 identical chains that assemble together! Unlike the cyclical C4 symmetry that we are used to, the proteins in this puzzle will come together as a "dimer of dimers" with D2 symmetry. The H-bond Network Objective encourages players to build buried, satisfied H-bond networks at the interface between symmetric chains. H-bond networks are a great way to introduce polar residues at the interface, but it's important that all of the bondable atoms make hydrogen bonds! We've also adjusted the H-bond Network Objective so that poor-scoring H-bonds may not contribute to networks; poor-scoring H-bonds will be displayed in red. This puzzle uses the Buried Unsats Objective, with a large penalty for buried polar atoms that can't make H-bonds. In this puzzle, there are no limits on the Complex Core, but we've included the Complex Core objective so players can see the core residues that can be incorporated into H-bond Networks.
Categories: Design, Overall, Symmetry

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bkoep's picture
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Buried Unsats (max +500)
Penalizes polar atoms that cannot make hydrogen bonds, -200 points per atom (not including symmetric copies).

Core Existence: Monomer (max +1600)
Ensures that at least 16 residues are buried in the core of the monomer unit.

Core: Complex (max +0)
Awards no bonuses or penalties. Click Show to see which residues count as "Core" for the H-bond Network objective.

H-bond Network (max +2400)
Rewards networks that comprise at least 2 H-bonds involving core residues.
Between 1 and 12 H-bonds should cross the interface between symmetric units.
Networks must be at least 75% satisfied (i.e. 75% of all bondable atoms in a network must make a H-bond).

Interaction Energy (max +500)
Monitors that all large PHE, TYR, and TRP residues are scoring well.

SS Design (max +500)
Penalizes all CYS residues. Penalizes GLY, ALA residues in sheets. Penalizes GLY, ALA in helices.

Ideal Loops (max +500)
Penalizes any loop region that does not match one of the Building Blocks in the Blueprint tool. Use "Auto Structures" to see which regions of your protein count as loops.

alcor29's picture
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Immediate crash

Immediate crash on 1992. After making three helices crash occurred when clicked on idealize structure. See discord vet chat for log.

jeff101's picture
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Groups: Go Science
How many segments per monomer?

Please list the # of segments per monomer on 
the pages for puzzles like this. This would 
help me decide which puzzles to attempt next.
I asked in Vet Chat and was told this one has
60 segments per monomer. Is that correct?


HMK's picture
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Number of segments? Examples for D2-Symmetry

That's a good idea to list the number of segments, Jeff1010.

Another suggestion: are there any examples how this D2-Symmetry of Dimers looks like in naturally occuring proteins?
Or are we automatically led by the mechanics of the puzzle to this kind of symmetry?

Many thanks in advance

HuubR's picture
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Four times "yes!"

Yes, jeff101, this puzzle has indeed 60 residues per monomer.

Yes, HMK, I fully agree with you and jeff101 that it would be helpful to mention the number of residues in the puzzle description.

Yes, HMK, there are examples of these proteins in nature. I came across one in the second picture in the Wikipedia entry for Tetrameric protein, which shows Beta-glucuronidase. I'm sure there are many more examples.

And the fourth yes: the puzzle setup will indeed assure that the four monomers are arranged in the right way, just like it does with a Trimer or a "regular" (C4) Tetramer. But just as it took me a bit of "getting used to" when I opened my first Trimer puzzle last year, it may not be obvious right away how this D2 symmetry works, or maybe better phrased: how it behaves. Let me try to describe my experience.

First a little disclaimer: I have no background in molecular biology, nor in chemistry in general; I am just describing how all of this appears to a layperson like me. I hope it helps other players who are in a similar position.

In all Symmetry puzzles, you have one "original" chain of residues that you can work on, and a number (2 or 3) of less colourful "copies" that have exactly the same shape, but a different position and orientation in 3D space.
In a Trimer or a C4 Tetramer, there is one symmetry axis. The copies are created by rotating the original over a certain angle. For a Trimer, these angles are 120° and 240°, for a C4 Tetramer they are 90°, 180°, and 270°. After some getting used to, it is not so difficult to spot the symmetry axis, and to predict what will happen to the copies when you move the original in a certain way.

For a D2 Tetramer, it is an entirely different ball game! This symmetry does not have just one symmetry axis, but three, and they are not easy to spot.

You could describe it as follows. The first copy is created by rotating the original around, let's say, the X axis, over 180°. Likewise, the second copy is formed by rotating the original around the Y axis, also over 180°, and the third copy is the original rotated around the Z axis. But you could equally well say that the second rotation (180° around the Y axis) not only creates the second copy (from the original) but also the third copy, from the first copy! That is why this symmetry is often calle "Dimer of Dimers: the first rotation creates a dimer (original and first copy), and the second rotation makes a copy of that dimer (second and third copy), so it creates a dimer consisting of these two dimers.

The beauty is, that (mathematically) a 180° rotation around one axis, followed by 180° around another axis (perpendicular to the first), is equivalent to a single 180° rotation around the third perpendicular axis. As a consequence, and contrary to what the name "Dimer of Dimers" might suggest, there is no specific pairing of the original with one of the copies. All monomers have equal status in this puzzle, except that you cannot work on the copies, of course.

But to avoid all that math, it is much easier to just fold your favourite monomer shape, preferably with a part sticking out on one side so you can recognise it from a distance, and then play with it!
Zoom out far enough to see all four monomers, hit Q to center the lot on your screen, use the Move tool and watch what happens.

Hope you enjoy it as much as I do!

grogar7's picture
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No Crashing :-)

This 60x4 residue D2 symmetry puzzle has not crashed even once for me! That is in stark contrast to the last 90x4 C4 symmetry tetramer, which was very crashy!

I am wondering if changes were made to the coding that account for the improvement?

Joined: 03/28/2020
Groups: Go Science
Crashing scales with residues

For me the likelihood of crashes increases with the number of residues. The 60s are very well playable. 90s are a nightmare.
Try this workaround: https://fold.it/portal/node/2011479
This makes things MUCH more stable for me on every puzzle.
Crashes seem to be related on the amount of data stored for undo.
I sincirely hope this gets looked at by the developers soon and fixed. THAT would REALLY be an improvement to gameplay and attract more players.

grogar7's picture
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Thanks for the reply, ichwilldiesennamen :) I will try this the next time I have problems!

HMK's picture
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thanks to HuubR

Thank you so much for your in-depth-explanation about the D2-tetramers, HuubR

robgee's picture
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Monomer length

To get the length of the monomer/protein:

Just use SS edit 2.01

Chain A for normal proteins.
Chain B for binders(usually).


frood66's picture
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weird bond lines

showing Bond shows weird bonds.....very long ones....clearly of no value. glitch I guess

Joined: 12/06/2008
Groups: Contenders
(Sorry, Frood... went to hit

(Sorry, Frood... went to hit the "reply" button and hit the "downvote" button by mistake... and the site won't let me fix it.)

I am also seeing strange bonds forming between residues on opposite sides of the tetramer, clearly physically impossible. See link for a photo.


beta_helix's picture
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I upvoted for you

I upvoted to cancel your downvote, Boots :-)

Joined: 12/06/2008
Groups: Contenders
Not a random thing.

Since posting, I have tried re-aligning the monomers into another orientation, to see if this was a one-off.

*Every* time I run a script to make H-bonds, I get these impossible bonds forming. This is a bug. Will file a feedback.

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