1897: Symmetric Trimer Design: H-bond Networks

Closed since over 5 years ago

Summary

• Created: October 01, 2020
• Expires: October 07, 2020 at 23:00 UTC
• Max points: 100

Description

Design a symmetric protein trimer, with 3 identical chains that assemble together! 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. 19,197
• 2. Gargleblasters 73 pts. 19,146
• 3. Go Science 52 pts. 19,031
• 4. Anthropic Dreams 36 pts. 18,892
• 5. Beta Folders 24 pts. 18,531
• 6. Void Crushers 16 pts. 18,054
• 7. L'Alliance Francophone 10 pts. 17,392
• 8. Marvin's bunch 6 pts. 17,180
• 9. Russian team 4 pts. 16,688
• 10. Hold My Beer 2 pts. 16,130

Top soloists

• 1. Enzyme 100 pts. 19,142
• 2. fiendish_ghoul 97 pts. 18,742
• 3. silent gene 93 pts. 18,734
• 4. NinjaGreg 89 pts. 18,731
• 5. ichwilldiesennamen 85 pts. 18,593
• 6. LociOiling 82 pts. 18,531
• 7. Bruno Kestemont 79 pts. 18,477
• 8. BootsMcGraw 75 pts. 18,461
• 9. g_b 72 pts. 18,452
• 10. mirp 69 pts. 18,385

Comments

[bkoep]

Buried Unsats (max +500)
Penalizes polar atoms that cannot make hydrogen bonds, -150 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 +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.

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

[infjamc]

If the idea behind the "Secondary Structure" objective is to discourage 3-helix designs, the 10-point-per-residue penalty seems a bit light…

[BootsMcGraw]

Agreed. In a 90-residue puzzle, which typically can score over 20,000 points, having a 3-helix would only penalize the score 450 points, or about 2%.

You guys penalize 55 points per extra residue, 50 points for alanine in helices (when is this going to change?), and hundreds of points for a badly placed aromatic. Why not increase the penalty for too many helices accordingly? Fifty points per helix residue over 50% sounds reasonable. It deters, but doesn't prevent players from using the 3-helix bundle conformation.

[bkoep]

Looking at previous puzzle results, we actually don't see much of a score discrepancy between helical bundles and helix/sheet folds.

Helical bundles are certainly more popular. But it is not uncommon to find a couple of helix/sheet folds in the top #3 solutions to a puzzle.

My guess is that helical bundles just take less work to design in Foldit (this is certainly the case in for other non-Foldit design methods). But, at the end of the day, a well-folded helix/sheet fold is a fair match for a helical bundle on the scoreboards.

The small bonus in this puzzle is just a nudge, but still it should be more than enough to outpace helical bundles in the top-scoring structures.