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2187: Two-Sided Strand Binder Design: Round 3

Closed since about 1 month ago

Intermediate Overall Design

Summary


Created
August 16, 2022
Expires
Max points
100
Description

Design a beta strand and a separate protein that can bind to it! This puzzle has added an H-bond Network Objective, to reward sidechain H-bonds between the binder and strand target. For maximum effect, the H-bond network should be buried away from solvent. Similar to Round 2, a Secondary Structure Objective will penalize designs with >50% helices. We think it will be important to design a binder that forms a strong beta sheet around the target strand.



This is a two-sided design problem, where we can design the sequence of both binding partners. The goal is to design a pair of proteins that will self-associate in solution. This is especially useful for bioengineering applications where we might want to use a short peptide as a "signal" that can be recognized by its binding partner. Although the short peptide may be flexible in solution, we would like to bind it in the shape of beta strand, so the target backbone has been frozen as a beta strand. However, you may still change the sidechains of the strand target to any amino acid you want!



AlphaFold predictions are enabled for the designed binder. Once you've designed a binder for the strand target, upload your solution for AlphaFold using the AlphaFold prediction tool. AlphaFold will predict the structure of your binder chain only (i.e. in the unbound state, in the absence of the strand target). If you load this prediction, then Foldit will attempt to align the prediction with your solution (i.e. in the bound state, making an interface with the strand target). If you continue working off of the AlphaFold prediction, you may need to make adjustments at the interface where the binder interacts with the target. See the puzzle comments for additional Objectives.

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Comments


bkoep Staff Lv 1

DDG Metric (max +2000)
The predicted binding energy of your design. The goal DDG is -40.0 or less.

Contact Surface (max +2000)
Measures how much of your binder surface is in close contact with the target strand. The goal Contact Surface is 500 or more.

Buried Unsats (max +500)
Penalizes 20 points for each polar atom that cannot make any hydrogen bonds.

Core Existence (max +1500)
Ensures that at least 20 percent of all residues are buried in the core, when the binder is bound to the target.

H-bond Network (max +800)
Rewards networks that comprise at least 2 H-bonds involving core residues.
Between 1 and 4 H-bonds should cross the interface between target and binder.
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)
Disabled use of CYS residues.

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.

LociOiling Lv 1

As Enzyme first noted in #veteran, this puzzle has an H-bond Network objective. The previous two rounds didn't have this objective.

I'm guessing that this objective was included by mistake, since it isn't mentioned in the puzzle comments.

It'll be interesting to see if anyone succeeds in getting an H-bond network in this non-symmetry puzzle.

bkoep Staff Lv 1

The H-Bond Network objective is no mistake! We would like to have sidechain H-bonds between the strand target and the binder to increase binding specificity.

The HBNet Objective is mentioned briefly in the puzzle description and detailed in the puzzle comments. If you are not seeing these, please let me know – there could be a problem with the website or app.