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2050: Symmetric D2 Tetramer Design with AlphaFold Predictions

Closed since 12 months ago

Intermediate Overall Design Symmetry

Summary


Created
September 30, 2021
Expires
Max points
100
Description

Design a D2 symmetric protein tetramer, with 4 identical chains of 60 residues each! Unlike the cyclical C4 symmetry that we are used to, the proteins in this puzzle will come together as a "dimer of dimers" with D2 symmetry. 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.

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Comments


bkoep Staff Lv 1

Buried Unsats (max +500)
Penalizes polar atoms that cannot make hydrogen bonds, -200 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.

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

H-bond Network (max +2400)
Rewards networks that comprise at least 2 H-bonds involving core residues.
Between 1 and 12 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).

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.

bkoep Staff Lv 1

That was an error in the puzzle description; this puzzle should permit as much alpha helix as you want! I've corrected the puzzle description.

HuubR Lv 1

My initial reaction was:  Wow, another D2 Symmetry puzzle.  Nice!

But then I thought, before I spend a lot of work on a new design, let me have a look at the way bands between the chains work now. As I pointed out in a feedback item last June, this was a bug in the previous D2 symmetry puzzles.

This quick test was a bitter disappointment:  the bug has not been resolved.   :-(

I would like to hear from Foldit Staff what has been done in the past three and a half months to address this (as milkshake announced in this comment), and also: when can we expect a fix?

For now, all we can do is avoid any bands to chain 1 (purple) and chain 3 (brown), or, if you need a band to one of these chains, use this workaround.

bkoep Staff Lv 1

I had thought this bug was fixed when we addressed the HBNetwork issues with D2 symmetry. We'll have to dig back into it, but it looks like a potentially hairy bug, so may be difficult to track down.