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.)
2467: CASP16 Ligand Puzzle L3000 Round 2
Closed since over 1 year ago
Intermediate Overall Small Molecule DesignSummary
- Created
- June 06, 2024
- Expires
- Max points
- 100
Use the Reaction Design Panel (no default hotkey) and the Compound Library (default hotkey H) to explore how different ligands 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 rat autotaxin There are several dozen structures of this protein in the Protein Databank, many of them bound to ligands. There are 219 ligand structures of interest in this competition. The starting small molecule is one of the co-crystalized ligands, 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 and Compound Library tools 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, and there a restraints (unchangeable bands) to the starting conformation -- these will show up as red lines if you move the backbone too far. It should also be noted that we haven't given you the full 846 amino acid long protein the CASP organizers are looking for, but just the ligand binding domain.
In contrast with the first round, we're starting with a different protein backbone and ligand structure. We've also enabled the Reaction Design panel as an alternate way of navigating the various compounds available. The Reaction Design panel is set up for "single component" reactions: The "reactions" across the top are a selection of common substructures, and the reagents below are the various compounds you can select. All the ligands to test should be accessible directly from the Reaction Design panel.
For people who prefer it, the Ligand Queue is also enabled, with a set of compounds which is different than Round 1.,
Top groups
-
100 pts. 26,292
-
-
-
-
-
-
-
-
-
Comments
LociOiling Lv 1
The list of CASP 16 L3000 compounds has been expanded to include the ligand queue compounds from round 2. There are several holdovers from round 1 still in the queue.
Round 2 also offers the reaction design tool, as an alternate path to all 219 ligands. Reaction design has only been seen in a limited number of Foldit puzzles to date. See Reaction Design puzzle on the wiki for an overview of how the tool works. The Foldit blog post Reaction design tool gives additional background.