1752: Symmetric Trimer Design: 70 Residues

Closed since over 6 years ago

Summary

• Created: October 28, 2019
• Expires: November 04, 2019 at 23:00 UTC
• Max points: 100

Description

This symmetric design puzzle has C3 symmetry, with three symmetric chains. This puzzle is a little different from other symmetry puzzles, in that we want players to focus on building a smaller interface between the chains. The "Core Limit: Complex" objective will incur penalties if there are too many buried residues in the total assembly. See the puzzle comments for Objective details. The Baker Lab will run folding predictions on your solutions for this puzzle, and those that perform well will be synthesized in the lab. Remember, you can use the Upload for Scientists button for up to 5 designs that you want us to look at, even if they are not the best-scoring solutions!

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• 10. neon_fuzz 63 pts. 18,707

Comments

[bkoep]

Core Existence: Monomer (max +1900)
Ensures that at least 19 residues are buried in the core of the monomer unit.

Core Limit: Complex (max +500)
Checks that no more than 75 residues are buried in the symmetric complex, including the interface between monomer units.

SS Design (max +500)
Penalizes all CYS residues. Penalizes GLY, ALA residues in sheets. Penalizes GLY, ALA, SER, THR 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.

[LociOiling]

OK, let's recap. With have 70 residues to work with, no more than 50% may be in helixes, and the Secondary Structure condition says I have 70 too many residues in helixes. Seems like a problem.

[LociOiling]

The previous odd message occurred with a triple helix design.

I'm not seeing a problem in a design with two smaller helixes and some sheets, conforming to the "secondary structure" condition.

I'll try something intermediate just to see what happens.

[LociOiling]

This time, made two helixes of 23 segments each, with three loop segments between them, and one end cap. Left the rest of the protein in the start position. Idealized the helixes.

Now the message says "you have 28 too many residues in helixes".

Clicking the "show" box highlights each of the 46 newly created helix segments.

Seems like the limit should be 35 segments in helixes, so this case is only 11 over the limit. Not clear to me where the 28 count comes from.

[LociOiling]

Tried two helixes, with 18 and 19 segments. The message complains about "1 too many residues in helixes". Seems like the limit should be 35, so maybe one free helix segment, I'll take it.

Added another 3-segment helix, but the message didn't change. Added a fourth segment to the new helix and idealized. Now the message says "13 too many residues in helixes".

So it's a little non-linear.

[bkoep]

It sounds like there are some inconsistencies in the Objective tool-tips, and we can probably make the messaging clearer. But I think everything may be working correctly under the hood.

The Secondary Structure Objective is non-linear, so I'm not surprised it jumped when you added the fourth segment.

This is because the Objective recognizes an α-helix by H-bonding patterns, the same as Auto Structures. The objective does not care about what the user assigns as "helix" (e.g. using the Assign Secondary Structure tool).

That means your 3-segment helix doesn't really count as an α-helix until you add the 4th segment, which completes one full turn of the α-helix and makes an H-bond between residues 1 and 4. In other words, you can't have an α-helix with less than 4 segments.

(This is not a Foldit bug, α-helices really behave this way! The helix is stabilized by the H-bonds between each turn; a 3-segment turn is incomplete, and doesn't make any stabilizing H-bonds!)

I recommend using Auto Structures to see which parts of your protein actually count as α-helix!

[LociOiling]

My technique was to take the starting pose, mark some helixes, and use the idealize tool (hotkey 5) to coil them.

The part about the 3-segment helix being incomplete makes sense, but idealize does coil the segments into an almost-helix.

I'll try some additional experiments, and use share with scientists for the interesting results.

[LociOiling]

It may have something to do with multiples of 4, but I don't have a good handle on how the penalty is calculated yet.

I should also note that the penalty is only 10 points per extra helix segment, but the non-linear nature of the penalty makes up for the low value.

In all of these cases, the helixes were marked with the secondary structure tool, then idealized with hotkey 5, "idealize secondary structure". I left three loop segments between each helix, at least initially.

Share V1 starts with three 12-segment helixes, no penalty.

Share V2 changes adds one segment to the middle helix in V1, and idealizes the middle helix. The penalty is now 1 segment.

Share V3 adds one segment to the third helix in V2. The penalty jumps to 4 segments.

Share V4 is a different setup, with four 9-segment helixes marked and idealized, and a fifth 5-segment helix marked but not idealized. No penalty.

Share V5 idealizes the fifth helix in V4. The penalty is now 13 segments.