Foldit Puzzles

1829: Aflatoxin Challenge: Round 16 Loop Prediction

Refold the loops in this Aflatoxin Challenge design! This is a followup to Round 14, this time starting with a completely unfolded loop. Previously, Foldit players had redesigned the binding loops of an oxidation enzyme, and testing at the Siegel Lab found that some designs had high oxidative activity for other molecules--but no activity against aflatoxin! We think the redesigned loops might be misfolding when aflatoxin is not in the binding pocket. Misfolded loops could prevent the enzyme from binding aflatoxin and catalyzing the oxidation reaction. We wonder if Foldit players can predict how these binding loops might misfold, by refolding the loops in ways that score better than the original design. If we can figure out how the binding loops misfold, then we might be able to fix them and recover activity against aflatoxin!

1828: Coronavirus Anti-inflammatory Design: Round 2

Note: This puzzle was closed early due to some problems with the protein backbone, and a corrected version was reposted as Puzzle 1828b. Players may load their saved solutions into the reposted puzzle.

1828b: Coronavirus Anti-inflammatory Design: Round 2

Note: This puzzle replaces Puzzle 1828, which had some errors in the protein backbone. Players may load solutions saved in Puzzle 1828.

1827: Revisiting Puzzle 112: Bovine

This is a throwback puzzle to the early days of Foldit. This particular protein is known as ubiquitin, and plays a prominent role in the protein degradation pathway. We are revisiting old Foldit puzzles so we can see how useful the recent additions to the game have been and to provide newer players with puzzles that are still scientifically relevant.

1826: Coronavirus Trimmed ORF8 Prediction

This is a follow-up to Puzzle 1823, but players noticed that the first 15 amino acids are highly predicted to be a signal peptide, so we have trimmed those residues from this puzzle. This protein is encoded in the viral genome of SARS-CoV-2, but the protein's structure is still unknown. If we knew how this protein folds, we might be able to figure out its exact function. Refold this different starting model to find higher-scoring solutions, which will tell us how this protein is most likely to fold!

1825: Coronavirus Binder Design: Round 7

Design a binder against coronavirus! We're challenging players to design an antiviral protein that could bind to the 2019 coronavirus spike protein and disrupt viral infection. The starting structure is a solution designed by Susume in our previous Round 3 puzzle. This solution makes an excellent interface with the target, but we're concerned that the binder may not fold properly, especially the loops connecting the three helices. We're asking Foldit players to try and improve this design so that it folds up correctly and can bind to the target! Players also have freedom to redesign an entirely new solution from scratch.

1824: Coronavirus Anti-inflammatory Design

Design an anti-inflammatory protein for COVID-19! Many COVID-19 complications are caused indirectly by the virus, and result from a severe over-stimulation of the human immune system. This kind of immune over-stimulation is commonly called a "cytokine storm." During a viral infection, immune cells normally release signaling proteins called cytokines, which inform the rest of the immune system about the infection and trigger inflammation. The inflammation is supposed to help the immune system fight off the infection, but too much inflammation can result in sepsis and organ failure.

1823: Coronavirus ORF8 Prediction Round 2

This is a follow-up to Puzzle 1820, but this time we are providing you with a starting model. Players may load in previous work from Puzzle 1820. This protein is encoded in the viral genome of SARS-CoV-2, but the protein's structure is still unknown. If we knew how this protein folds, we might be able to figure out its exact function. Refold this starting model to find higher-scoring solutions, which will tell us how this protein is most likely to fold!

1822: Revisiting Puzzle 111: Mouse

This is a throwback puzzle to the early days of Foldit. This protein is found in the nucleus of stem cells in mice, and is important for maintaining the pluripotency of the stem cell. The protein is modeled here as in a reduced environment, so no disulfide bonds are expected to form. We are revisiting old Foldit puzzles so we can see how useful the recent additions to the game have been and to provide newer players with puzzles that are still scientifically relevant.

1821: Coronavirus Binder Design: Round 6

Design a binder against coronavirus! We're challenging players to design an antiviral protein that could bind to the 2019 coronavirus spike protein and disrupt viral infection. The starting structure is a solution designed by Steven Pletsch in our previous Round 3 puzzle. This solution makes an excellent interface with the target, but we're concerned that the binder may not fold properly, especially the loops connecting the three helices. We're asking Foldit players to try and improve this design so that it folds up correctly and can bind to the target! Players also have freedom to redesign an entirely new solution from scratch.