2165: Symmetric Pentamer Design with AlphaFold Predictions

Closed since over 3 years ago

Summary

• Created: June 24, 2022
• Expires: July 01, 2022 at 23:00 UTC
• Max points: 100

Description

Design a symmetric protein pentamer, with 5 identical chains of 80 residues each! This puzzle enables AlphaFold predictions for the monomer subunit of your design, so you can upload your solution for AlphaFold using the AlphaFold prediction tool. AlphaFold will predict the structure of your monomer subunit only (i.e. in the unbound state, in the absence of other symmetric copies). If you load this prediction, then Foldit will attempt to align the prediction with your solution. If you continue working off of the AlphaFold prediction, you may need to make adjustments at the interface where the monomer subunit interacts with symmetric copies.



This puzzle includes a Secondary Structure Objective, so no more than 50% of your design can form helices. 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. Contenders 100 pts. 23,604
• 2. Go Science 63 pts. 23,335
• 3. Anthropic Dreams 37 pts. 22,901
• 4. Gargleblasters 21 pts. 22,808
• 5. Marvin's bunch 11 pts. 19,674
• 6. Australia 5 pts. 17,584
• 7. Team China 2 pts. 17,523
• 8. L'Alliance Francophone 1 pt. 17,213
• 9. BOINC@Poland 1 pt. 15,860
• 10. Beta Folders 1 pt. 0

Top soloists

• 1. ichwilldiesennamen 100 pts. 23,303
• 2. spvincent 93 pts. 23,097
• 3. dcrwheeler 86 pts. 23,055
• 4. LociOiling 79 pts. 22,901
• 5. Galaxie 73 pts. 22,783
• 6. alcor29 67 pts. 22,584
• 7. Enzyme 62 pts. 22,492
• 8. Bruno Kestemont 57 pts. 22,332
• 9. HuubR 52 pts. 22,097
• 10. Punzi Baker 3 47 pts. 21,194

Comments

[bkoep]

Buried Unsats (max +500)
Penalizes polar atoms that cannot make hydrogen bonds, -250 points per atom (not including symmetric copies).

Core Existence: Monomer (max +2200)
Ensures that at least 22 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 +3000)
Rewards networks that comprise at least 2 H-bonds involving core residues.
Between 1 and 15 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.

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.

Secondary Structure (max +500)
No more than 50% of residues may form helices. Extra helices are penalized at 10 points per residue.

Neural Net (max +0)
Achieve an AlphaFold prediction confidence of 80% or more.

[Zhang Ruichong]

I'm getting 17434 points with the monomer being a single long helix (and 95% Alphafold confidence).

[bkoep]

Nice, 17k points is impressive! The reason for the 50% helix penalty is to encourage players to design diverse, non-helix folds.

A single long alpha helix (a.k.a. "megahelix") tends to have a very low energy, and is also a common fold for any hydrophilic sequences. For this reason, a megahelix design tends to have a good Foldit score and a high AlphaFold confidence.

However, megahelix designs tend to be poorly behaved in reality. The lack of long-range, tertiary interactions means that the helix can partially unfold without a large energy penalty. Most of the time, the protein exists in a partially-folded state.

In contrast, a compact and globular fold is held together with lots of tertiary interactions. Even partial unfolding will disrupt many of those interactions and incur a large energy penalty. This usually means the protein will be well-behaved, and is very stable in its completely-folded state.

[ichwilldiesennamen]

This bonus is actually 3000pts instead of the here written 2400pts. This should be expected sind we have now 5 units (monomer + 4 copies). Seems to be a copy&paste error from a Tetramer-Puzzle :)

[bkoep]

Good catch!