1963: Two-sided Interface Design

Closed since about 5 years ago

Summary

• Created: March 03, 2021
• Expires: March 10, 2021 at 23:00 UTC
• Max points: 100

Description

Design an interface between two protein chains! This puzzle starts with a fully-folded interface, but you will need to refold it in order to get credit. The Exploration Objective checks how closely your solution matches the starting structure, and any solution with RMSD < 3.0 A will not receive credit! We're hoping that Foldit players can find high-scoring variations on this starting structure. See the blog for more details.



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. Contenders 100 pts. 17,859
• 2. Go Science 65 pts. 17,579
• 3. Anthropic Dreams 41 pts. 17,069
• 4. Gargleblasters 24 pts. 16,735
• 5. Beta Folders 14 pts. 16,709
• 6. Marvin's bunch 7 pts. 16,450
• 7. BOINC@Poland 4 pts. 16,408
• 8. Australia 2 pts. 15,836
• 9. Void Crushers 1 pt. 15,724
• 10. L'Alliance Francophone 1 pt. 15,648

Top soloists

• 1. ichwilldiesennamen 100 pts. 17,579
• 2. CharlieFortsConscience 94 pts. 17,310
• 3. Galaxie 87 pts. 17,069
• 4. Bruno Kestemont 81 pts. 16,942
• 5. HuubR 76 pts. 16,735
• 6. LociOiling 70 pts. 16,709
• 7. drumpeter18yrs9yrs 65 pts. 16,693
• 8. WBarme1234 60 pts. 16,662
• 9. g_b 56 pts. 16,650
• 10. dcrwheeler 52 pts. 16,591

Comments

[bkoep]

Exploration
Compares the backbone of your solution with the starting structure. Solutions will only gain credit if they are different from the starting structure with RMSD > 3 A.

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.