The first time you log in to Foldit, the Campaign puzzles are recommended, starting with One Small Clash. The puzzles menu lets you play science puzzles and access other features of Foldit.
Foldit is complicated, but getting started is quick and easy. Many of the steps involve a visit to the main Foldit website, fold.it.
Get Registered
The Download page at fold.it first suggests that you create an account, then download and install.
Consider the Foldit Community Rules when selecting a user name. Moderators will change offensive names to something like "Pretty Little Pony 456".
Download and install
Foldit runs on Windows, Mac, and Linux. Foldit needs a lot of computer power, so it's unlikely to appear on mobile platforms anytime soon.
Use the Bugs forum on fold.it to report install problems.
On Windows, one common problem is that the Foldit installer is not signed. Windows Defender or other security packages may require you to click through warnings to complete the install. It's OK to trust the installer, as long as you downloaded from fold.it.
Running Foldit
Assuming the install step goes smoothly, the first thing Foldit does when it starts is to download the latest updates. This can take a while, but after the first time, big downloads happen only a few times a year.
After it updates itself, the Foldit client restarts and asks you to log in. You'll need to have created an account on fold.it to log in.
Campaign
The Campaign menu starts with One Small Clash, but then lets you branch off on multiple tracks.
The first time you start Foldit, the Campaign section is highlighted, and "Continue in One Small Clash" appears right above the "Quit" button.
The Campaign puzzles are recommended for all most users. (For classroom use, instructors may prefer the more technical Education puzzles instead.)
Just clicking "Continue in One Small Clash" gets you started with the Campaign. Clicking "Campaign" on the main puzzles menu gives you the full Campaign menu, which shows the branching tracks through the Campaign after the first puzzle.
Most of the Campaign puzzles can be completed quickly, but some are a lot more challenging. If you get stuck, the best advice is to reset the puzzle (control + r) and try again.
While you don't have to complete the entire Campaign, you'll probably find the rest of game a little less confusing if you do as many as possible
After the Campaign
Beginner puzzles appear when "Show beginner puzzles" is checked.
Foldit usually offers three numbered science puzzles each week.
You can start playing Foldit science puzzles at any time, even if you haven't completed Campaign. They're available under "Science Puzzles" on the main puzzle menu.
There are normally three numbered science puzzles available. Science puzzles usually run for a one week.
There are also several beginner puzzles, which appear when "Show beginner puzzles" is checked on the science puzzle menu.
Most of the beginner puzzles run for six weeks at a time, and then start as a new puzzle when they expire. There's also the beginner puzzle "Protein Design Sandbox", which runs for years at a time.
Both beginner puzzles and the numbered science puzzles award global points when they expire, which contribute to player ranking. Only new players receive global points for beginner puzzles.
Aside from the beginner puzzles, there's almost always a revisiting puzzle running. Revisiting puzzles were originally presented in the early days of Foldit, and have been revisited many times since then. Revisiting puzzles are mainly a way for the Foldit science team to evaluate the impact of changes to the game, but they're still fought over as intensely as any other puzzle.
Electron density puzzles, particularly the Electron Density Reconstruction series, generally appear weekly as well.
A Small molecule design puzzle is usually the third numbered puzzle each week. These puzzles involve designing a non-protein small molecule (or ligand that can stick to a particular protein target.
Filling your Cookbook
As seen in the game, a Cookbook with a few recipes.
The My Cookbook page lets you organize your recipes.
Recipes are one of the most important parts of Foldit.
Recipes are available in the Cookbook. The Cookbook is available in the game, but it's managed on the Foldit website, fold.it.
New players start out with an empty cookbook, so here are some suggested starter recipes. The full list of available recipes is available on the Recipes page at fold.it. You current Cookbook is at My Cookbook on fold.it.
One of the most powerful and most useful recipes in Foldit is Timo van der Laan's Tvdl enhanced DRW 3.1.1, better known as EDRW, which applies the Rebuild tool to the worst-scoring sections of the protein. EDRW can be useful on revisiting puzzles and electron density puzzles, but it's not helpful on small molecule design puzzles.
In the early phases of folding, you may want to have a "fuse" (sometimes spelled "fuze") recipe, which stabilizes the protein by varying the Clashing Importance setting (CI) while wiggling and shaking. The recipe Rav3n_pl Fuzes v1.5.1 is a useful one, but there are many others. Many other recipes do fusing as part of a larger process.
Toward the end of a puzzle, many players use a variation of the Local Wiggle Strategy to make small improvements to the protein. Banded Worm Pairs Inf Filt 3.4.10 is one example of a local wiggle recipe, which uses bands to help keep things moving.
Recipes are written in the Lua scripting language, which is also used in Angry Birds and World of Warcraft. The wiki has Lua Scripting Tutorial (Beginner 1) and other pages showing how to get started with Lua.