Foldit Puzzles

1117: Ultra-compact 17-residue Marburg virus inhibitor

This is the third in our series of Marburg inhibitor peptide puzzles. We'd like you to design a 17-residue peptide that's able to inhibit the Marburg glycoprotein, a viral surface protein that allows the Marburg virus to infect cells. Seventeen residues might seem quite small, but smaller size can make it easier for a peptide to pass through barriers, such as the gut-blood barrier or the blood-brain barrier, and can also make it less likely to trigger an immune response. It's also quite easy to synthesize a peptide this small, which can mean both that we can make large amounts and that we can include unnatural amino acids or other chemical modifications that would not be possible in a protein that's expressed in bacteria or yeast, but which might aid function or stability. The flip side, though, is that it's more challenging to design something that folds well and binds with high affinity and specificity in this small size range -- but that's the challenge!

1116: Revisiting Puzzle 83: Cardiotoxin

This is a throwback puzzle to the early days of Foldit. This toxin, produced by the Chinese cobra N. atra, induces contracture in skeletal and cardiac muscle. This protein contains eight cysteine residues that oxidize to form four disulfide bonds. We are revisiting old Foldit puzzles so we can see how useful the recent additions to the game have been.

1115: 80 Residue Symmetric Trimer Design: HBNet

This puzzle combines the new HBNet filter with full-blown symmetric design. There are several other filters in effect; see the puzzle comments for details. 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!

1114: Unsolved De-novo Freestyle 53: Predicted Contacts

This is a follow-up puzzle for Puzzle 1111, now with Predicted Contacts to help guide your folding! See the blog for information on using the contact map. You can see the predicted contacts for this protein by clicking the Contact Map button in the Main menu (Selection Interface) or in the Actions tab (Classic Interface). You will notice that different contacts are shown in different shades of green, with brighter green contacts indicating stronger predictions. Players will be able to load in manual saves from Puzzle 1111 and use them as a starting point here.

1113: Revisiting Puzzle 82: Cytotoxin

This is a throwback puzzle to the early days of Foldit. This toxin, produced by the Mozambique spitting cobra, induces contracture in skeletal and cardiac muscle. We are revisiting old Foldit puzzles so we can see how useful the recent additions to the game have been.

1112: Compact 25-residue Marburg virus inhibitor

This is a continuation of our series of Marburg inhibitor peptide puzzles. We'd like you to design a 25-residue peptide that's able to inhibit the Marburg glycoprotein, a viral surface protein that allows the Marburg virus to infect cells. Smaller size can make it easier for a peptide to pass through barriers, such as the gut-blood barrier or the blood-brain barrier, and can also make it less likely to trigger an immune response. It also opens up the possibility of chemically synthesizing the peptide, which can mean both that it's easier to make large amounts and that we can include unnatural amino acids or other chemical modifications that would not be possible in a protein that's expressed in bacteria or yeast, but which might aid function or stability. The flip side, though, is that it's more challenging to design something that folds well and binds with high affinity and specificity in this small size range -- but that's the challenge!

1111: Unsolved De-novo Freestyle 53

This protein is known to activate cysteine desulferase, an enzyme that converts cysteine to alanine by transferring a sulfur atom. The structure of this protein is still unsolved. The PSIPRED secondary structure predictions are provided on the starting model.

1110: Revisiting Puzzle 81: Calcium Ion Binding Protein

This is a throwback puzzle to the early days of Foldit. This protein, which inhibits muscle contraction in the absence of calcium ions, changes conformation in the presence of calcium to allow muscle contraction. We are revisiting old Foldit puzzles so we can see how useful the recent additions to the game have been.

1109: 80 Residue Symmetric Dimer Design: HBNet

This puzzle combines the new HBNet filter with full-blown symmetric design. There are several other filters in effect; see the puzzle comments for details. 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!

1108: Compact 37-Residue Marburg Virus Inhibitor Design

Based on the results from Puzzle 1073: Marburg Binder Design with Disulfides (see the feedback on the Foldit blog for an idea of what we're looking for), we'd like to revisit this design target. The Marburg virus is a cousin of the Ebola virus, and causes a similarly deadly hemorrhagic fever. The largest outbreak, in 2004, had a 90% mortality rate. Understandably, we'd like an anti-viral agent to treat this disease.