Closed since about 3 years ago
Intermediate Overall DesignDesign a binding pocket for the cAMP ligand! Neural Net Objective awards a 2000 pt. bonus for AlphaFold predictions with both high confidence and high similarity to the current solution. After an AlphaFold prediction is complete, load the original or predicted structure from the AlphaFold panel to receive the bonus. You can continue to work on this solution, but the bonus will disappear if the similarity drops. Note that the table in the AlphaFold panel only displays the similarity of the original solution; the true similarity of your current solution is recalculated by the Neural Net Objective as you change its structure.
Once you've designed a binder for the target ligand, upload your solution for AlphaFold using the AlphaFold prediction tool. AlphaFold will predict the structure of your binder only (i.e. in the absence of the ligand). If you load this prediction, then Foldit will attempt to align the prediction with your solution. We are looking for designs where the raw AlphaFold prediction has a binding pocket that fits the ligand!
Cyclic AMP (cAMP) is a secondary signaling molecule found within the cell. We typically think of signaling molecules as things that bind to surface receptors on the outside of the cell. Often these surface receptors produce secondary signals inside the cell membrane; these spread throughout the cell so that interior machinery can respond to the original surface signal. cAMP is extremely polar, which makes it a very difficult binding target! A good binder will need to make lots of H-bonds with the cAMP ligand in order to satisfy all of the polar atoms.
This puzzle starts with the backbone from a natural cAMP binder, with the ligand placed roughly in the correct position in the binding pocket. However, players may completely redesign the protein or reposition the ligand within the binding pocket. Try to design a binding pocket with high Contact Surface and zero BUNS! See the puzzle comments for Objective details.
Contact Surface Metric (max +2000)
Measures how much of your binder surface is in close contact with the target protein. The goal Contact Surface is 200 or more.
Buried Unsats (max +1000)
Penalizes 200 points for each polar atom that cannot make any hydrogen bonds.
Neural Net (max +2000)
Achieve an AlphaFold prediction confidence of 80% or more, and similarity to current solution is 80% or more.
It seems the title is wrong!
I recommend:
"2251: cAMP Ligand Binder Design: Round 7"
Oof you're right! We had meant to post an FMN binder puzzle but it looks like the wrong files were used. Anyway it is still good to have more cAMP binder designs!
I've changed the puzzle title and description to match the actual puzzle (cAMP binder design).
