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2202: Two-sided Strand Binder Design: Round 6

Closed since 9 days ago

Intermediate Overall Design


September 21, 2022
Max points

Design a beta strand and a separate protein that can bind to it! We've adjusted the H-bond Network Objective to encourage small but well-satisfied networks. We think the target strand needs just one buried, polar sidechain to achieve highly-specific binding. This puzzle allows 110 residues for the binder, and a Secondary Structure Objective will penalize designs with >50% helices. 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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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 25 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 2 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.