Newsletter January 7: Rama-what now?
Hey folders!
Dev Josh here with your weekly Foldit update. I'm personally recovering from a booster vaccine for COVID-19, so this newsletter might be a little light. Make sure you get vaccinated to stop the spread and save lives!
Solutions from This Week's Puzzles
(Disclaimer: This is not scientific feedback; these solutions are not officially endorsed by the Foldit scientists.)
Puzzle 2087: TGF Receptor Binder Design
Puzzle 2088: VHL Ligand Design
Today’s Master Folding Tips
The Rama Map might seem scary, but it’s actually pretty simple and useful! Every amino acid has a preferred range of angles, and the Rama Map shows that preferred range as a smear of color. When you click on an amino acid (the dots on the map), it will highlight what that amino acid’s preferred range is. If that dot isn’t in a colored zone: bad news! You can drag the dot into a colored zone to instantly change its angle, or place a Blueprint block on that amino acid and give it a wiggle: Blueprint constraints will help it move naturally into its ideal angle.
Have you seen the latest Lab Report? Be sure to subscribe and hit that bell icon so you get notified when our lab reports go live!
Until next time, happy folding!
Newsletter January 14: A Visit From Foldie
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 2090: CD47 Binder Design
Puzzle 2091: VHL Ligand Design
Art of the Week
Take a look at this lovely drawing by chaperoneKaty on our Discord! Meet Foldie the peptide and Nat the native guide!
Today’s Master Folding Tips
New to Foldit? Check out this comprehensive guide on how to play, as well as S0ckrates’s lightning fast tutorial guide!
For the experts: check out these de-novo design tips from the Rocklin lab, courtesy of Susume for sharing!
Still folding on your own? Join a group today!
Until next time, happy folding!
Newsletter January 21: Raising Their Championship Belt
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 2093: Symmetric Tetramer Design with AlphaFold Predictions
Puzzle 2094: Olivetolic Acid Ligand Binder Design
Community News
A belated congratulations to Cyberkashi and infjamc of the Contenders for getting the #1 solution to Puzzle 2091: VHL Ligand Design Round 10! This week another Contenders member, Bletchley Park, took the lead as the best evolver on Puzzle 2094: Olivetolic Acid Ligand Binder Design: Round 4. It’s looking like a great time to be a Contender! Congratulations to the whole group!
Today’s Master Folding Tips
Here’s a hidden trick: when using the Move tool, hold shift and left click + drag on the move arrows to move your protein forward and backward relative to the camera! Thanks Susume for this tip!
I’ll leave you with a conundrum: if you ate yourself, would you become twice as big or disappear completely? Let me know on our Discord!
Until next time, happy folding!
Newsletter January 28: A Niche Subject
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 2096: Symmetric Trimer Design with AlphaFold Predictions
Puzzle 2097: TGF Receptor Binder Design
Today’s Master Folding Tips
If you’re new to protein folding, check out this video by the Amoeba Sisters, courtesy of chaperoneKaty on our Discord!
For the expert folders, consider this niche protein motif: the Niche! Niches are the most common design motif for ligand design. Next time you’re making a pocket for a ligand or trying to design a ligand to a pocket, think about how they fit together. How will the electrical charges help it sit in the pocket or not?
Want to read more about motifs? Check out this fantastic resource.
Until next time, happy folding!
Newsletter February 4: Wham! Bam! Goodbye Spam!
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 2099: Symmetric Trimer Design with AlphaFold Predictions
Puzzle 2100: Electron Density Reconstruction 3
Recipe of the Week
Still trying to figure out the selection interface? Try LociOiling’s SelectoPro! This tool helps you select residues by whether they are mutable, frozen, locked, hydrophobic, hydrophilic, or by their layer in the protein (core, boundary, or surface).
Community Updates
With the help of player moderator LociOiling, over 14,000 spam accounts have been banned from Foldit this week. We are also working on features of the upcoming website re-design to automatically detect and prevent spam. We will continue our vigilance to prevent and remove spam, harassment, and other community violations in order to maintain a safe and positive space for our players. For more information, see our community rules.
Today’s Master Folding Tips
There’s an old saying in computer science: garbage in, garbage out. If your fold isn’t looking good, no amount of wiggling or recipe-running will save it. Start with a shape that looks good using the Blueprint tool — take your time figuring out how long each secondary structure should be and which loop to use — and only start refining once your fold looks reasonable.
Not sure what a “good” fold is? Ask in our Discord! We’re always happy to answer questions.
Until next time, happy folding!
Newsletter February 11: Insights On the Big-To-Small Folding Strategy
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 2102: Symmetric Trimer Design with AlphaFold Predictions
Puzzle 2103: Olivetolic Acid Ligand Binder Design
Today’s Master Folding Tips
Try folding from tertiary structure to atoms: first, decide on what your overall shape looks like (your tertiary structure). Then form your helices and sheets (your secondary structure) and arrange them into that overall shape. Once that looks good, run auto-mutate to set the amino acid sequence (your primary structure). After stabilizing with a shake and wiggle, take a closer look at every atom: are some hydrophobic carbons exposed? Are some hydrophilic polars buried? This final phase might require manually mutating amino acids and picking sidechains to satisfy all of the objectives: your tools have a hard time seeing the bigger picture on their own.
Try this out with the new Neural Net Objective, out now in Puzzle 2106!
Until next time, happy folding!
Newsletter February 18: The Trick to Winning Foldit
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 2105: Symmetric Trimer Design with AlphaFold Predictions
Puzzle 2106: Design with Neural Net Objective
Today’s Master Folding Tips
I’ll be honest folks, after writing these newsletters for over 85 weeks, I’m running out of tips! What questions do you still have about Foldit? What puzzles or parts of the puzzles still challenge you? Send in your questions to mail.fold.it@gmail.com and I’ll answer them in future newsletters! Let me know what would be helpful to read about!
In the meantime, I asked co-creator Seth Cooper if he had any tips for Foldit players. He says: “The trick to winning Foldit is earning the most points.” So that’s it folks! It’s that easy. Just earn points. :)
Until next time, happy folding
Newsletter February 25: A Brief Interlude for Hexaflexafolding
Hey folders!
Dev Josh here with your weekly Foldit update.
Do you love folding? Try some folding in real-life with hexaflexagons! These fun shapes have very curious mathematical properties. Read more about flexagons here (or for advanced mathematicians, here) or try folding your own with this guide!
Solutions from This Week's Puzzles
(Disclaimer: This is not scientific feedback; these solutions are not officially endorsed by the Foldit scientists.)
Puzzle 2108: Electron Density Reconstruction 4
Puzzle 2109: Symmetric Tetramer Design with AlphaFold Predictions
Puzzle 2110: Revisiting Puzzle 114: Black Mamba
Until next time, happy folding!
Newsletter March 4th and Conquer!
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 2111: CD22 Binder Design
Puzzle 2112: Symmetric Tetramer Design with AlphaFold Predictions
Today’s Master Folding Tips
So your fold is looking good, but it’s still not good enough, and nothing stands out as being “bad” about your fold. What do you do? There’s a few things you could try, including:
- Make some mutations by hand, then wiggle and shake
- Change the edges of your secondary structures: make loops longer or shorter, then mutate, wiggle, and shake
- Apply a different ideal loop Building Block to a loop, then re-fold the protein in a new shape
Want to get a sneak peak at the latest features and bug fixes? Try out the developer preview here!
Until next time, happy folding!
Newsletter March 11: Electron DONEsity
Hey folders!
Dev Josh here with your weekly Foldit update. In our last couple of developer meetings, we’ve talked about the results of the latest electron density reconstruction puzzles. And y’all are CRUSHING it! Thank you so much for your help! These puzzles help us better understand the structure of known proteins, and your folds are making big improvements to our understanding of these structures!
Solutions from This Week's Puzzles
(Disclaimer: This is not scientific feedback; these solutions are not officially endorsed by the Foldit scientists.)
Puzzle 2114: Electron Density Reconstruction 5
Puzzle 2115: CD22 Binder Design: Round 2
Today’s Master Folding Tips
When doing electron density puzzles, there are a few tricks that can help you out. First, get to know the tools in your Electron Density panel. This can help you view the density cloud in different ways. You can also watch some guide videos linked on the wiki. For the experts, check out this course from real protein crystallographers on fitting and refinement.
That’s all for this week! Keep an eye out for the next Electron Density Reconstruction puzzle!
Until next time, happy folding!
