1959: Two-sided Interface Design

Closed since about 5 years ago

Summary

• Created: February 20, 2021
• Expires: February 26, 2021 at 23:00 UTC
• Max points: 100

Description

Design an interface between two protein chains! This puzzle is much like Puzzle 1950 but we've piled on some more Objectives to reward a H-bond Network at the interface, as well as a single disulfide bond at the interface. In this two-sided design puzzle, you can mutate the interface residues of both chains A and B, but you may only shape the backbone of chain A. The goal is to create a binding interface between the two protein chains so that they will stick together in solution. However, the starting position of the two chains is important, so the locked regions are held in place by strong constraints. The only way to make the two chains bind will be to fold up a brand new interface between them.



As you build on chain A, it will be important to make a strong core so that it folds up correctly. It will also be important to have good hydrophobic packing at the interface where the two chains come together, so that they bind each other tightly. Players may add up to 40 additional residues at a cost of 55 points per residue. See the puzzle comments for Objective details.

Top groups

• 1. Go Science 100 pts. 24,589
• 2. Gargleblasters 68 pts. 24,069
• 3. Anthropic Dreams 44 pts. 23,875
• 4. Contenders 27 pts. 23,460
• 5. L'Alliance Francophone 16 pts. 23,345
• 6. Marvin's bunch 9 pts. 23,290
• 7. Beta Folders 5 pts. 23,121
• 8. BOINC@Poland 3 pts. 22,766
• 9. Australia 1 pt. 22,309
• 10. Olsztynek 1 pt. 21,822

Top soloists

• 1. ichwilldiesennamen 100 pts. 24,524
• 2. Bruno Kestemont 95 pts. 24,197
• 3. Enzyme 90 pts. 23,989
• 4. Galaxie 85 pts. 23,874
• 5. grogar7 81 pts. 23,868
• 6. mirp 76 pts. 23,854
• 7. akaaka 72 pts. 23,704
• 8. ZeroLeak7 68 pts. 23,533
• 9. ucad 64 pts. 23,509
• 10. johnmitch 61 pts. 23,473

Comments

[bkoep]

Contact Surface (max +1000)
Measures how much of your binder surface is in close contact with the target protein. The goal Contact Surface is 400 or more.

Core Existence: Chain A (max +5000)
Ensures that at least 24% of residues are buried in the core of the entire solution.

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 +2000)
Rewards networks that comprise at least 2 H-bonds involving core residues.
Networks must be at least 75% satisfied (i.e. 75% of all bondable atoms in a network must make a H-bond).

Buried Unsats (max +500)
Penalizes polar atoms that cannot make hydrogen bonds, -50 points per atom.

Residue Count (max +2200)
Penalizes added residues at a cost of 55 pts per residue. Players may add up to 40 residues, for a total of 220.

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

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.

Disulfide Count (max +250)
Rewards a single disulfide bond that spans the interface. Place two CYS residues close to one another to form a disulfide bond.

[ichwilldiesennamen]

Isn't an H-Bond Network Bonus target of 2000 unrealistically high for this puzzle? Because compared to previous symmetry-puzzles with H-Bond-Bonus we do not get the additional bonus of the symmetric copies with this one! I already have a massive HBnet but it scores only 675pts bonus. And in order to get the 2000 the whole interface would have to be crammed with HBnets :) (and a disulfide bridge as addon). Was this intended or is it just a copy-and-paste mistake from previous symmetry-puzzles?

[bkoep]

Ten buried H-bonds is probably excessive, and also would be pretty difficult to accomplish. We do still want there to be some orange-orange hydrophobic contacts at the interface.

We won't close this puzzle early, but may follow up with another puzzle if the top scoring solutions look too polar at the interface.

[ichwilldiesennamen]

Thanks bkoep for your answer. Then I will leave it at that. My solution still has quite some hydrophobic contact at the interface between A and B which could be substituted with HBnets. But since this would reduce hydrophobic contact I will spare me the effort to do this.

[Bautho]

My hydrogen bonded residues actually got mutated to hydrophobic ones because they score better then the HBNet Bonus…