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2111: CD22 Binder Design: Round 1

Closed since 7 months ago

Intermediate

Summary


Created
February 18, 2022
Expires
Max points
100
Description

Note: This puzzle was closed early due to an error that allowed parts of the target chain to move. This puzzle has been reposted as Puzzle 2111b.



Design a protein that can bind to CD22! This puzzle enables AlphaFold predictions for your designed binder. Once you've designed a binder for the 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 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 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.



CD22 is a receptor protein found on the surface of human B cells. In some kinds of blood cancer, these B cells become malignant and proliferate throughout the body, making them difficult to treat with targeted therapy. CD22 is a helpful marker that distinguishes these B cells from other types of tissue in the body. A binder for CD22 could be useful as a kind of homing device for chemotherapy, specifically targeting the cancerous cells and leaving healthy cells unaffected by toxic chemotherapy drugs.



In this puzzle, we've presented a section of the CD22 target that we think is an appropriate binding site. The backbone and most of the sidechains are frozen, except at the binding site, where flexible sidechains are shown in color. Players should design a new protein that can tightly bind to these sidechains and recognize CD22. In order to bind the CD22 target, designs will need to make lots of hydrophobic contacts and satisfy any polar atoms that are buried at the interface. But designs will also need to have lots of secondary structure (helices or sheets) and a large core, so that they fold up correctly! Note that the frozen target already contains one BUNS atom at residue 7; the BUNS Objective will penalize this atom, but players may not be able to satisfy the atom with a binder and should ignore it. See the puzzle comments for Objective details.

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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 protein. The goal Contact Surface is 500 or more.

Buried Unsats (max +500)
Penalizes 100 points for each polar atom that cannot make any hydrogen bonds.

Core Existence (max +1500)
Ensures that at least 25 percent of residues are buried in the core of the monomer unit.

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

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.

SS Design (max +500)
Disabled use of CYS residues.

Neural Net (max +0)
Achieve an AlphaFold prediction confidence of 80% or more.

jacob_n Lv 1

The target protein seems to be movable, it comes apart when I run wiggle.

alcor29 Lv 1

If wiggle, the target and the design fly apart and distort. Only option is to run a script that does not wiggle. Is this deliberate?