1932: Symmetric Tetramer Design: H-bond Networks

Closed since about 5 years ago

Summary

• Created: December 18, 2020
• Expires: December 25, 2020 at 23:00 UTC
• Max points: 100

Description

Design a symmetric protein tetramer, with 4 identical chains that assemble together! 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.

Top groups

• 1. Go Science 100 pts. 21,072
• 2. Gargleblasters 65 pts. 20,277
• 3. Contenders 41 pts. 20,236
• 4. Anthropic Dreams 24 pts. 19,655
• 5. Beta Folders 14 pts. 19,427
• 6. L'Alliance Francophone 7 pts. 18,687
• 7. Marvin's bunch 4 pts. 17,679
• 8. Void Crushers 2 pts. 16,640
• 9. Australia 1 pt. 15,300
• 10. BOINC@Poland 1 pt. 13,299

Top soloists

• 11. LociOiling 63 pts. 19,427
• 12. silent gene 60 pts. 19,378
• 13. NinjaGreg 57 pts. 19,297
• 14. hpaege 54 pts. 19,050
• 15. Galaxie 51 pts. 18,990
• 16. Bautho 49 pts. 18,930
• 17. Mike Lewis 46 pts. 18,895
• 18. g_b 44 pts. 18,886
• 19. Ashrai 41 pts. 18,793
• 20. BootsMcGraw 39 pts. 18,792

Comments

[bkoep]

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

Core Existence: Monomer (max +2000)
Ensures that at least 20 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 +1800)
Rewards networks that comprise at least 2 H-bonds involving core residues.
Between 1 and 9 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.

[grogar7]

For a symmetric trimer, this bonus accepts a maximum of 9 h-bonds. Shouldn't it be set for 12 h-bonds for a tetramer??

[BootsMcGraw]

Dimers and trimers align with planar symmetry. In these puzzles, the tetramers also align in a plane. Why wouldn't they align in a tetrahedron, since that conformation is the most efficient way to cram four of something into a given sphere?

[grogar7]

addendum to the above: it seems that one would have to make 12 inter-unit bonds to get credit for 9 !!

[bkoep]

That's an oversight in the puzzle set up; we'll be sure to fix it in future tetramer puzzles!

[bkoep]

We could certainly design tetramers with tetrahedral (T) or dihedral (D2) symmetry instead of cyclic (C4) symmetry! The symmetry operators are different, of course, so those would require a different puzzle setup. But we have run D2 design puzzles in the past, and we will surely run more in the future.

A tetrahedral assembly does require a more extensive interface, since each subunit must make contact with all 3 of its partners. For this reason, I suspect it may be a more difficult design target than a C4 assembly (we've seen that large designed interfaces can jeopardize protein solubility).

Edit: Actually, I don't think we could design a true tetrahedron with only 4 protein subunits. A tetrahedron has 4x C3 symmetry axes. Each of your "subunits" would need to have perfect C3 symmetry, which is practically impossible for a single protein chain. Natural tetrahedral assemblies include at least 12 protein chains.