Foldit Newsletters

[agcohn821]

August 26: Together We Can Figure Out Monkeypox

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 2186: CD47 Binder Design: Round 13

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Puzzle 2187: Two-Sided Strand Binder Design: Round 3

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From the Scientists

Let’s research monkeypox! In the latest puzzle series, we’re hoping you can design a binder protein to attach to the monkeypox H3 protein to help diagnose or even prevent the monkeypox virus! Here’s what the scientists have to say about this:

“The monkeypox H3 protein is displayed on the surface of the virus. The complete role of H3 is still unclear, but it seems to be involved in the recognition of human cells. A binder for H3 could be useful for detecting monkeypox, and might even help to block infection. Scientists have yet to solve the structure of the monkeypox H3 protein, although we do have a crystal structure of a related protein from Vaccinia virus. The structure of the target in this puzzle comes from an AlphaFold prediction of monkeypox H3.”

Today’s Master Folding Tips

How do you decide what amino acids should go in your loops? This paper by Lin et al. found some correlations between amino acids and loop types. Check it out!

Until next time, happy folding!

[agcohn821]

Newsletter September 6: Foldit’s 100th Newsletter: Our Biggest Update in YEARS!

Hey folders!

Dev Josh here with some very exciting updates! But first, I’ve been told that this is the 100th newsletter!

Okay, back to the exciting news! Next week, we will finally be launching the NEW WEBSITE! This update comes with a bunch of changes. I’ll summarize them here, and you can keep an eye out for a blog post coming today that describes everything in more detail.

Goodbye Old, Hello New

One of the big reasons we needed a new website is that our old website is running on code that’s 15 years old, with web design that’s aged just as much. The new website is sleek, modern, and much cleaner on the backend.
Here are just some of the website changes that come with that:

• Posts and comments now support markdown formatting
• You can attach images, .pdb, and text files with your posts and comments
• You can fine-tune your notification settings for specific forum activity, privacy settings, and even subscribing to this newsletter

Maybe most excitingly, you can view solutions online!

That’s right! The new website supports interactive 3D molecular viewer technology where you can share and discuss solutions right in the website!

An Online Cookbook

As mentioned a while back when we were first preparing for the new website, we are no longer supporting Lua V1 and GUI recipes. Now that we’re focusing just on Lua V2, we cooked up these awesome updates for you:

• Write and edit recipes from the website — updates are automatically sent to anyone who has that recipe in their cookbook
• Your cookbook is now managed online — add, remove, and sort recipes on the site and changes will be automatically synced with the Foldit app
• The Foldit app can now launch raw .lua files as recipes

Shinier Points

Foldit’s gamification needed some polish, so here’s what we’ve updated:

• Global scores are being retired in favor of Category scores — become master of Electron Density or the Symmetry savant!
• Levels and Experience Points (XP) are coming soon! Unlike leaderboard scores, XP will reflect your specific contributions to Foldit’s scientific goals, and you’ll be able to earn XP for your dedication to the gameplay and your contributions to the science of Foldit.

Code Cleanup

We took this opportunity to make a ton of improvements to our codebase and backend. Not only will this make development smoother, here are some benefits you can appreciate as well:

• The Windows app will use 64-bit machine code, instead of 32-bit
• The Foldit app can now securely remember your login credentials
• You can now import preferences from other installations of Foldit

Boost your Play with Neural Networks!

Last but definitely not least, with this new website comes a very incredible, brand new protein design tool! The Neural Net Mutate lets you use an AI algorithm to predict what sequence will fold into the structure you’ve designed. Not only does this outperform traditional Mutate, it’s way faster. Neural Net Mutate can mutate an entire protein in 1-2 seconds! Talk about an upgrade!!

Keep an eye out for the blog post today and upcoming news with more details on all of this and what you need to do to switch over to the new technology.

What’s your favorite update? Let me know on the Discord!

Until next time, happy folding!

[agcohn821]

Newsletter September 9: New Website, New Foldit!

Hey folders!

Dev Josh here with your weekly Foldit update. Our new website is now live! Check it out at the usual place, here.

We’re experiencing a few technical difficulties as we get everything up and running, so if you can’t connect, try again in a few hours. Thanks for your patience!

Today’s Master Folding Tips

Having trouble fixing an unideal loop? Try temporarily re-assigning an adjacent helix/sheet segment to a loop so that a local wiggle can try different angles! Don't forget to freeze the first segment of each secondary structure on either side so that you're not wiggling everything.

Let us know what you think of our new website on Discord!

Until next time, happy folding!

[agcohn821]

Foldit News, September 16

Hey folders!

Dev Josh here with your weekly Foldit update.

This Week's Puzzles

Puzzle 2198: Protein Design with Neural Net Mutate</h3>

In this puzzle, your goal is to try out the new Neural Net Mutate tool! This tool uses an AI algorithm to predict a protein sequence that will fold into a given structure. Read more on our blog! Keep in mind that the algorithm has a bit of randomness, so if you don’t like your results, try running it again!

Puzzle 2199: Two-sided Strand Binder Design: Round 5

In this puzzle, our scientists want to understand how to bind to a strand from both sides. Why? Well, sometimes in bioengineering, researchers want to make a strand ‘signal’ another protein, and that requires a strong bond between a strand and the binder. This puzzle is all about small but well-satisfied hydrogen bond networks.

Today’s Master Folding Tips

You might know that the Blueprint tool adds torsional constraints, which is why you want to take them off during the late game. But did you know that those constraints are different from the ones the Blueprint starts in? Each Blueprint block has "adjusted" torsions so that things lock into place nicely when you're constructing a backbone from scratch. Then the torsional constraints help bring things back into ideality the next time you wiggle. For example, if you made two ideal helices in Foldit and used an un-adjusted ideal AGBBA loop, the ideal helices would not align parallel to one another – they would flare off at a skew angle. Usually we want the helices to be parallel to each other, but this requires some tiny adjustments to "perfect ideality".

For more on the Blueprint tool, check out this blog post!

Until next time, happy folding!

[agcohn821]

Foldit News, September 23

Hey folders!

Dev Josh here with your weekly Foldit update.

This Week's Puzzles

Puzzle 2201: Monkeypox H3 Binder Design: Round 4

In this puzzle, scientists want to design a protein that can bind to the monkeypox H3 protein. H3 is a protein on the surface of the virus that seems to be involved in the recognition of human cells. If we can make a binder to H3, we might be able to detect or even block monkeypox!

Puzzle 2203: Electron Density Reconstruction 13

In this puzzle, scientists have data from an electron microscope about the structure of this protein, and some researchers have published what they think the structure of this protein is. But we think Foldit players can do a better job of reconstructing the structure from the electron density data!

Today’s Master Folding Tips

Use the "Show bondable atoms" and "Show bondable hydrogens" visualization options to see what you can line up to form new bonds!

Until next time, happy folding!

[agcohn821]

Foldit News, September 30

Hey folders!

Dev Josh here with your weekly Foldit update.

This Week's Puzzles

Puzzle 2204: SARS-CoV-2 helicase CACHE Challenge: Round 1

This puzzle is part of Foldit's participation in the CACHE Challenge to design a drug targeting the SARS-CoV-2 helicase. Helicase inhibition is an anti-viral strategy that would work on the current and future outbreaks of SARS-CoV-2. Your participation in this challenge can help accelerate the discovery of a coronavirus antiviral that complements existing therapies.

Puzzle 2205: BMPR Binder Design: Round 1

In this puzzle, you’re trying to design a protein to bind to the BMPR target: the Bone Morphogenic Protein Receptor. This receptor is on the surface of bone-producing osteoblast cells. When molecules bind to BMPR, it triggers the cell to generate new bone tissue. Synthetic BMPs are already used in medicine to stimulate bone growth for special procedures like spinal fusions, but they also bind to other things and can cause unintended side effects. If Foldit players can design a protein to bind specifically to BMPR and nothing else, we would be able to more effectively help patients regrow bone tissue!

Today’s Master Folding Tips

Given a particular sheet length, the helix length to cover it in a sheet-helix-sheet motif doesn't vary much. The chirality stays the same, too. No need to play with these designs, sheet-helix-sheet motifs are pretty consistent!

Until next time, happy folding!