rmoretti Staff Lv 1
Objectives
Maximum bonus: +1 000
Torsion Quality (max +1000)
Keeps bond rotations in a good range. Using Wiggle or Tweak Ligand can fix bad torsions. (Show highlights torsions to be rotated.)
2455: CASP16 Ligand Puzzle L2000
Closed since almost 2 years ago
Intermediate Overall Small Molecule DesignSummary
- Created
- May 10, 2024
- Expires
- Max points
- 100
Use the Ligand Queue (default hotkey 7) to explore how different ligand bind to the protein.
This puzzle is part of the CASP16 competition. Foldit players are participating to see how well they can predict how small molecules can bind to proteins. Note that in contrast to prior drug design puzzles, we're not just interested in the top scoring small molecule, but instead are interested in getting good structures for each of the provided ligand compounds. Its worth dividing your time across all the compounds, rather than concentrating on a particular one.
The protein target is human Cathepsin G There are a number of structures of human Cathepsin G bound to ligands as well as other proteins at the PDB. There are 2 ligand structures of interest in this competition. The starting small molecule is a substrate mimic from a known crystal structure, and is provided just to indicate the likely binding site. It's not one of the molecules in the competition - you'll need to use the Ligand Queue tool in order to load one of the other ligands.
Since the goal is to predict the structure of the protein ligand complex, we've allowed full backbone and sidechain flexibility on this puzzle. -- That said, all of the bound structures are highly similar to each other (and thus to the starting structure). The backbone is very unlikely to change at all from the starting conformation.
- Sequence
- MQPLLLLLAFLLPTGAEAGEIIGGRESRPHSRPYMAYLQIQSPAGQSRCGGFLVREDFVLTAAHCWGSNINVTLGAHNIQRRENTQQHITARRAIRHPQYNQRTIQNDIMLLQLSRRVRRNRNVNPVALPRAQEGLRPGTLCTVAGWGRVSMRRGTDTLREVQLRVQRDRQCLRIFGSYDPRRQICVGDRRERKAAFKGDSGGPLLCNNVAHGIVSYGKSSGVPPEVFTRVSSFLPWIRTTMRSFKLLDQMETPL
Top groups
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1. Go Science100 pts. 23,225
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1. BootsMcGraw Lv 1100 pts. 21,503 -
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Comments
jeff101 Lv 1
The backbone is very unlikely to change at all from the starting conformation.
Why do you let us vary the position of the backbone in this puzzle? What if we get a much higher score with a different protein backbone conformation? Would our result be more correct than if we kept the backbone's starting conformation?
jeff101 Lv 1
The following post is also related to this puzzle: https://fold.it/forum/suggestions/how-in-lua-to-wiggle-the-ligand-and-sidechains-without-wiggling-the-backbone
BootsMcGraw Lv 1
Wiggle function doesn't work. Protein lurches once or twice, then stops. Doesn't matter if on "low", "medium", "high", or "auto" Wiggle Power. Ligand doesn't move at all. Please fix, or throw out this puzzle and replace with one that works properly.