Foldit Puzzles

986b: Post-CASP TR774: Quest to the Native

Our preliminary analysis suggests that very few players were able to improve the starting model of this CASP11 refinement target from Puzzle 924. We'd like to see if you can reach the native structure for this CASP refinement target when it's provided as a guide. Players may NOT load in solutions from Puzzle 924, but they may load in solutions from the original Puzzle 986.

978: Revisiting Puzzle 134: Rice

This is a throwback puzzle to the early days of Foldit. This protein shuttles lipids between cell membranes in the rice plant. Players will receive a bonus for forming up to four disulfide bonds in this puzzle. We are revisiting old Foldit puzzles so we can see how useful the recent additions to the game have been. Players will NOT be able to load in any previous solutions for these puzzles.

976: Abeta binder full-length design

Due to CASP, it has been a while since we've posted an Alzheimer's disease puzzle. In this puzzle, we would like you to design a binder for the ABeta42 polypeptide that can bind to and stabilize the polypeptide in an alpha-helical conformation. You will get a bonus for forming up to three disulfide bonds.

977: Post-CASP Tc848: Server Model Contacts

This contact map puzzle is based on the same CASP11 target as Puzzle 965, and we want to see if you can improve a model from one of the competing servers. Instead of starting this puzzle with an extended chain, we've provided a model that satisfies a large number of contacts, but has some severe problems. Contacts are scored with the Contact Map filter in this puzzle, and there is an upper limit of 2775 possible points from the filter. Players will NOT be able to load solutions from Puzzle 965.

975: Ebola glycoprotein 30-residue inhibitory peptide design

Based on player feedback, we are posting a second anti-Ebola peptide design puzzle, this time with a slightly longer peptide. We would like you to design a small (30-residue) peptide that can bind to and block the Ebola glycoprotein. The glycoprotein is a viral surface protein that allows the Ebola virus to enter human cells. A small peptide inhibitor of this protein would therefore represent a candidate therapeutic for treating this deadly disease. We are starting you with a hotspot "stub" that was the top-scoring result from the earlier stub-finding puzzle, number 846 (congratulations to AnthropicDreams). We have extended this stub with twenty-seven additional residues that you can design.

974: Revisiting Puzzle 126: Ethanolamine Utilization

This is a throwback puzzle to the early days of Foldit. This protein allows bacteria to metabolize ethanolamine and use it in constructing cell walls and cell membranes. The C-terminus of this protein is disordered in the starting model, but the rest of the protein is fairly close to the correct answer. We are revisiting old Foldit puzzles so we can see how useful the recent additions to the game have been. Players will NOT be able to load in any previous solutions for these puzzles.

973: Post-CASP Tc853: Server Model Contacts

All CASP11 submission deadlines have passed, but our analysis of the results has just begun! This contact map puzzle is based on the same target as Puzzle 966, and we want to see if you can improve a model from one of the competing servers. Instead of starting this puzzle with an extended chain, we've provided a model that satisfies a large number of contacts. Contacts are scored with the Contact Map filter in this puzzle, and there is an upper limit of 2775 possible points from the filter. Players will NOT be able to load solutions from Puzzle 966.

972: 80 Residue Monomer Design: Pro Loops

In this design puzzle, we're encouraging players to incorporate PRO residues in the loops of their designs, so PRO residues will score more favorably than normal. Players will receive a 500 point bonus from the Secondary Structure filter if fewer than 50% of residues are in helices; penalties are incurred if more than 50% of residues form helices. The Residue IE Score monitors that all PHE, TYR, and TRP residues are scoring well; the Core Existence filter checks that at least 30% of the residues are buried in the core of your design; and the Fragment filter scans for parts of your design that are unlikely to fold up naturally. The Baker Lab will run folding predictions on your solutions for this puzzle, and those that perform well will be synthesized in the lab. Remember, you can use the Upload for Scientists button for up to 5 designs that you want us to look at, even if they are not the best-scoring solutions!

971: Ebola glycoprotein peptide inhibitor design (REPOSTED as 971c)

We would like you to design a small (25-residue) peptide that can bind to and block the Ebola glycoprotein. The glycoprotein is a viral surface protein that allows the Ebola virus to enter human cells. A small peptide inhibitor of this protein would therefore represent a candidate therapeutic for treating this deadly disease. We are starting you with a hotspot "stub" that was the top-scoring result from the earlier stub-finding puzzle, number 846. (Congratulations to AnthropicDreams!) We have extended this stub with twenty-two additional residues that you can design.

971c: Ebola glycoprotein peptide inhibitor design

We would like you to design a small (25-residue) peptide that can bind to and block the Ebola glycoprotein. The glycoprotein is a viral surface protein that allows the Ebola virus to enter human cells. A small peptide inhibitor of this protein would therefore represent a candidate therapeutic for treating this deadly disease. We are starting you with a hotspot "stub" that was the top-scoring result from the earlier stub-finding puzzle, number 846. (Congratulations to AnthropicDreams!) We have extended this stub with twenty-two additional residues that you can design. A small peptide in this size range probably won't fold the way a protein would. Some considerations -- good hydrophobic packing, lack of holes in the core, good hydrogen bonding, presence of secondary structure, etc. -- will be the same, but in addition, heavy disulfide cross-linking is often necessary for stability in this size range. You will get a considerable bonus for forming up to three disulfide bonds (for a total of five, counting the two disulfide bonds already present in the Ebola target protein). Many natural plant and animal toxins are small peptides, and it is common to see three disulfide bonds in a "leapfrog" pattern (i.e. cys1-cys4, cys2-cys5, cys3-cys6) for maximal stability. The starting point for this puzzle has three disulfides in this "leapfrog" pattern, but this might not be the optimal disulfide placement or backbone topology. Feel free to change the secondary structure, move the disulfides around, or otherwise improve on this!