March 18: Fold on, fold on
Hey folders!
Dev Josh here with your weekly Foldit update. This week has been tough for me, I hope it’s been easier for you. But we press on! We fold in the face of adversity, in the name of science!
Solutions from This Week's Puzzles
(Disclaimer: This is not scientific feedback; these solutions are not officially endorsed by the Foldit scientists.)
Puzzle 2117: Symmetric Tetramer Design with AlphaFold Predictions
Puzzle 2118: TGF Receptor Binder Design: Round 16
Today’s Master Folding Tips
Don’t fear the Rama map! It can be a useful tool for figuring out which residues are not ideal. Simply click on dots that don’t seem clustered up with the rest of them. Then, if that dot isn’t in a colored region (the ideal space for it), you can drag it into a colored region to fix the ideality. Be careful that this might tear apart the rest of your fold — it’s important to look at the Rama map early before you start refining your draft!
Have you mastered the Revisiting puzzles? If so, please try the design puzzles! Now that AlphaFold has been shown to work excellently, Revisiting puzzles are posted primarily for practice and to benchmark Foldit. But the real scientific work happens in the design challenges and Electron Density challenges!
Until next time, happy folding!
Newsletter March 25: System 2 Folding
Hey folders!
Dev Josh here with your weekly Foldit update.
Solutions from This Week's Puzzles
(Disclaimer: This is not scientific feedback; these solutions are not officially endorsed by the Foldit scientists.)
Puzzle 2120: Electron Density Reconstruction 6
Puzzle 2121: Symmetric Tetramer Design with AlphaFold Predictions
Today’s Master Folding Tips
In his bestselling book, “Thinking, Fast and Slow,” Daniel Kahneman says there are two kinds of thinking: System 1, the fast and unconscious thinking, the kind you play action games or catch a baseball with; and System 2, the slow and deliberate thinking you use for planning and tough decisions. Foldit is a System 2 game. Half of Foldit — the design half — is played in your head. What kind of design do you want to make? What do you imagine the shape looks like? Every puzzle has a goal, and in biology form follows function, so the shape is the solution to reaching that goal. What shape binds best, or fits the data best, or would be the most stable structure? The second half of Foldit is making that shape using the tools available to you. Even then, this requires thought: is your shape working out how you expected it to? If not, what can you learn about how amino acids interact, or how Foldit tools work, from this new experience? Why does it want to bend that way? And why, oh why, don’t these sheets want to stay lined up?
Slow down, folders, give it some thought. You’re doing great, and because of your efforts, scientific research is making quicker steps toward some incredibly useful outcomes.
Until next time, happy folding!
Newsletter April 1: Pulling Is For Fools
Hey folders!
Dev Josh here with your weekly Foldit update. Congratulations to Boots McGraw for his Design of the Month! Check it out in this month’s Lab Report!
Solutions from This Week's Puzzles
(Disclaimer: This is not scientific feedback; these solutions are not officially endorsed by the Foldit scientists.)
Puzzle 2123: CD47 Binder Design: Round 7
Puzzle 2124: Symmetric Tetramer Design with AlphaFold Predictions
Today’s Master Folding Tips
This week, try folding without using the Pull tool at all! Between Blueprint, Rebuild, and Pick Sidechains, I think you could design a protein without ever nudging it. Prove me right or prove me wrong, then let me know how it goes!
Don’t forget to check out the Successful Binder Design Sandbox so you can see what great binders look like!
Until next time, happy folding!
Newsletter April 8: Visualize Success!
Hey folders!
Dev Josh here with your weekly Foldit update.
Solutions from This Week's Puzzles
(Disclaimer: This is not scientific feedback; these solutions are not officially endorsed by the Foldit scientists.)
Puzzle 2126: CD22 Binder Design
Puzzle 2127: Symmetric Trimer Design with AlphaFold Predictions
Upcoming Updates
One of the coolest things we're working on lately is better integration of neural networks into Foldit. What this means is that you'll be able to leverage the powers of cutting-edge machine learning to take better folding actions! More details coming soon!
Today’s Master Folding Tips
Be sure to check out these successful designs from the recent publication from the Baker lab!
Until next time, happy folding!
Newsletter April 15: Titles are Hard
Hey folders!
Dev Josh here with your weekly Foldit update.
Solutions from This Week's Puzzles
(Disclaimer: This is not scientific feedback; these solutions are not officially endorsed by the Foldit scientists.)
Puzzle 2129: Tie2 Binder Design: Round 5
Puzzle 2130: Symmetric Trimer Design with AlphaFold Predictions
Today’s Master Folding Tips
Are you paying attention to which structures your AAs prefer to be in? It's not a hard-and-fast rule, but check out the wiki for AA structure preferences. I find this especially helpful for getting started by mutating my isoleucines away into something more suitable for the structure I'm designing, like asparagines for loops, valines for sheets, and MALEK for helices.
Until next time, happy folding!
Newsletter April 22: Zoom, Enhance!
Hey folders!
Dev Josh here with your weekly Foldit update.
Solutions from This Week's Puzzles
(Disclaimer: This is not scientific feedback; these solutions are not officially endorsed by the Foldit scientists.)
Puzzle 2132: CD47 Binder Design
Puzzle 2133: Symmetric Trimer Design with AlphaFold Predictions
A Closer Look
This week, let’s take a closer look at this binder design by alcor29 that manages to score an impressive +7245.4 bonus points from Objectives!
Alcor gets 2000 points from DDG, which measures how much more the designed binder wants to be bound to the target compared to not bound. Those carefully placed oranges and blues mean that this binder folds up okay, but is much happier when attached to the binding target that complements it well.
Alcor gets 1805.4 points from Contact Surface: look how much space the binder takes up when sitting on the binding site. A large contact surface is useful for a strong connection.
Lastly, these hydrogen bonds will help the protein bind very specifically to the target. If only this one polar atom was satisfied! Alas, it’s buried between the two proteins without a bond.
Today’s Master Folding Tips
Did you know you can fix un-ideal loops with Remix too? LociOiling made a video about it here!
Have a question about Foldit? Ask on our Discord!
Until next time, happy folding!
Newsletter April 29: A Ton of Solutions
Hey folders!
Dev Josh here with your weekly Foldit update.
Solutions from This Week's Puzzles
(Disclaimer: This is not scientific feedback; these solutions are not officially endorsed by the Foldit scientists.)
Puzzle 2135: TGF Receptor Binder Design: Round 17
Puzzle 2136: KLHDC2 ligand design
Puzzle 2137: Electron Density Reconstruction 7
Today’s Master Folding Tips
If you’re tackling the latest set of Electron Density puzzles, here’s a tip for you: you can make notes on the electron density cloud with Tab! Use this to remind yourself where you think each amino acid should go — like working through a Sudoku puzzle — or even just use the note dots to draw out the shape of the protein so you can see it clearer!
Don’t forget to upload your solutions using the “Share with Scientists” button for any solutions you really want the scientists to check out!
Until next time, happy folding!
Newsletter May 6: The Future of Small Molecule Design (Is Here)
Hey folders!
Dev Josh here with your weekly Foldit update.
Solutions from This Week's Puzzles
(Disclaimer: This is not scientific feedback; these solutions are not officially endorsed by the Foldit scientists.)
Puzzle 2138: 2138: Symmetric Trimer Design with AlphaFold Predictions
Puzzle 2139: 2139: KLHDC2 ligand design: Round 2
Today’s Master Folding Tips
Let’s look at a new tool shown off in the latest lab report! The Tweak Ligand tool lets you tweak rotatable bonds in your small molecules. Use it to reduce the strain on bond angles — check the Torsion Quality objective to see how you’re doing!
What do players have to say about this?
“Very nice” - cas0362
“Wow, now I can optimize my ligand better!” - cjddig
You heard it here first, folks, this new tool opens a whole new future for ligand design!
Try it out for yourself in Puzzle 2142!
Until next time, happy folding!
Newsletter May 13: Happy 14th Birthday, Foldit!
Hey folders!
Dev Josh here with your weekly Foldit update. This Sunday, we celebrated Foldit’s 14th birthday! Now that Foldit is an angsty teenager, we’ve had to spend more time cleaning up after its code and reminding it not to crash so much when it gets upset. We’ve got some exciting updates in the works, but nothing I can talk about just yet. So here’s to many more years to come for citizen science protein folding!
Solutions from This Week's Puzzles
(Disclaimer: This is not scientific feedback; these solutions are not officially endorsed by the Foldit scientists.)
Puzzle 2141: CD22 Binder Design: Round 4
Puzzle 2142: KLHDC2 ligand design: Round 3
Today’s Master Folding Tips
How well do you know your Koga & Koga design rules? Be sure to check out their supplements for SS design principles to help make sure your designs are scientifically valid!
What are you doing for Foldit’s birthday week? Tweet us @Foldit!
Until next time, happy folding!
Newsletter August 18: What Did I Miss?
Hey folders!
Dev Josh here with your weekly Foldit update. I’m back from my internship and eager to fold again! What big news have I missed this summer? Let me know on Discord!
Solutions from This Week's Puzzles
(Disclaimer: This is not scientific feedback; these solutions are not officially endorsed by the Foldit scientists.)
Puzzle 2183: CD22 Binder Design: Round 8
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Puzzle 2184: Symmetric Hexamer Design with AlphaFold Predictions
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Science Corner
This week we talked to horowsah about the recent Electron Density Reconstruction puzzles. In these puzzles, scientists are probing different types of problems that can happen when solving crystal structures in order to see if Foldit players can solve these crystal structures better than professional crystallographers. The answer is… yes! Foldit players are really good at solving crystal structures in interesting ways. If you’d like to really help the scientists on Reconstruction puzzles, horowsah says this: “Sometimes try prioritizing the electron density, and then try prioritizing geometrical criteria, as it’s not easy to tell early on which one will be more important.”
Today’s Master Folding Tips
Having trouble getting started on design puzzles? Those extended chains can be intimidating when your protein is just one straight line. Bruno's Design Models recipe is a great way to start drafting your fold early on! Run this recipe, then use Ideal SS on each structure and you'll be halfway to having something foldable!
If you’ve tried our developer preview (“devprev”), please let us know what you think by submitting feedback!
Until next time, happy folding!
