Here you can see the original instructions of the intro puzzles.

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The information below is intended to provide basic tips and guidelines for the tutorial puzzles. If you have additional questions, you may either:

• Leave a comment below or

• Ask online in Fold.it chat either in the game client or using an external IRC client.

Tip: Try to complete the tuorials without help first. Experience has shown this results in deeper understanding of the game mechanics.

Tip: On the tutorials follow the instructions closely, don't overthink and do too much. Don't be afraid to reset and start again. Don't be in a rush to finish the level and move on, this is your opportunity to have a play with the tools and find out how they work.

Tip : read carefully the texts, press on button "tell me more", reset the puzzle after a few try and redo.

First puzzles video : http://www.youtube.com/watch?v=JW_Fd6blrLM

Contents 1 Sidechains 2 Backbone packing 3 Hydrogen Bonding 4 Hydrophobics and Hydrophilics 5 Tools and Types 6 Sequences 7 Protein Design 8 More molecules 9 Comments

Sidechains Edit

Level 1-1: One Small Clash

This is a protein. We need your help to fold it into the right shape!

You can drag SIDECHAINS with the mouse. Get rid of the clash by clicking and dragging one of the sidechains away from the other.

Level 1-2: Swing It Around

You can't see the sidechains from this angle! Click and drag on the white background to rotate the view. You can also move or zoom by holding ctrl or shift while you drag. Watch your score! It tells you how well the protein is folded.

Level 1-3 : Shake

You've earned the SHAKE tool! You can use shake to fix clashes for you! When you think SHAKE has done a good enough job, you can press it again to Stop.

Backbone packing Edit

Level 2-1: When Backbones Collide

This is the BACKBONE of the protein. Sometimes the backbone is too close together. Click and drag the backbone to pull it appart!

You can always Undo.

Shake will adjust the sidechains for you."

Level 2-2: Close the Gap

Ot

her times the backbone is too far apart. VOIDS are an indicator that there is empty space that needs to be filled. Try getting rid of some of the voids by dragging the backbone together! Remember to use SHAKE to get rid of the clashes! Oops, the helices are too far apart. Want to reset?"

Madde's video: http://www.youtube.com/watch?v=WVJoyRfPbic Tips ; drag one helice closer to the other, theyhave to be paralell

Level 2-3: Wiggle

You now have access to a VERY powerful tool: the WIGGLE tool! Just like SHAKE tries to take care of sidechains, WIGGLE tries to let Foldit improve the backbone. WIGGLE gets stuck if it cannot increase the score. Click this button again to stop the tool.

Hydrogen Bonding Edit

Level 3-1: Sheets Together

Its time to learn about the best things for improving your score in Foldit - Hydrogen bonds! Try pressing Wiggle. Those blue and white bands are Hydrogen Bonds. They form when these zig-zaggy sheets line up together like this.

Level 3-2: Lonely Sheets

Time to matc

h up some sheets! Wiggle doesn't always work by itself. You can connect these sheets with RUBBER BANDS . Hold shift (or click on middle button) and drag from one to the other. Try it with this sheet! Hold shift and drag. Rubber Bands pull together when you Wiggle. Don't worry about individual sidechains. Try connecting the sheets with a Rubber Band.

Tip : put rubber bands between to two little sheets, wiggle, remove bands, shake and wiggle

Level 3-3: Sheets and Ladders

Thre

e sheets have been torn apart! Rubber Bands are free! Make as many as you want. You can move the view around and drag the background. When you're close, you can remove the bands and Wiggle again.

Tip : put a rubber band at each end of the sheet with the end of the sheet above, wiggle, remove the bands, shake and wiggle. The step ladder are the sheets and the side the bands

Madde's video: http://www.youtube.com/watch?v=47Qco7fYa2k

Level 3-4: Lock and Lower

</gallery>One of the sheets is out of place! Sheets like to be alongside each other. Remember, hydrogen bonds are great for your score. You can Freeze the sheets already in place. Hold shift and double click.

Tip : one sheet is over the row, freeze the 2 sheets on each side of it, double click on them, put the sheet between this two, rotate to see if the protein is flat, shake and wiggle,

Madde's video: http://www.youtube.com/watch?v=X7DPcTvz4Ns

Level 3-5: Rebuild

You might have guessed by now, but color is used to show how well part of the protein is folded.

This loop appears to be a problem. You can deal with problematic segments by using the REBUILD tool. Rebuild tests out different shapes for the protein. Right click (for windows) on the backbone to start a Rebuild. You can stop when Rebuild finds the shape you want. Shake and Wiggle will take care of clashes. This looks like a good shape! Try a Shake and Wiggle to clean it up. You can Wiggle a single section. Right click and choose Wiggle

Madde's video: http://www.youtube.com/watch?v=V-AiFAO_xgo

Hydrophobics and Hydrophilics Edit

Level 4-1: Hide the Hydrophobics

Orange sidechains are HYDROPHOBIC . They want to be buried inside the protein. These bubbles are called EXPOSEDS. EXPOSEDS may appear on unburied hydrophobics! (yellow ball moving).

Blue sidechains need plenty of space. They should point outward.

Orange sidechains should be kept surrounded. Hide it in the empty space in the protein's interior and move the blue hydrophilic away outside. Your score measures not only clashes, but also how well hydrophobics are hidden.

Tip : move the orange sidechain in the center.

Level 4-2: Turn It Down

Sometimes you need to rotate to bury the hydrophobics. You can rotate with the TWEAK tool. Right click the helix to find it. Click and hold the purple arrows to rotate. Click stop to finish the Tweak.

The helix has turned and exposed a hydrophobic!

Madde's video : http://www.youtube.com/watch?v=rafK-Z0dZs8

Level 4-3: Flippin' Sheets

One of these sheets has unburied hydrophobics. You can easily flip a sheet with Tweak. The straight (purple) arrows turn the sheet 180 degrees and shift it to maintain hydrogen bonds.

Look for the sheet with the exposed hydrophobics, and click the new straight arrows on the Tweak tool to shift and flip it.

You're almost there! Try a Wiggle to finish up.

Shake and wiggle before then flip the sheet with oranges out in the right direction

LennStar's guide: This is one puzzle that really dislikes being mishandled. It took me at least 5 tries. This is how to do it: If you already have done anything to it, reset the puzzle. (Hint: You propably have to move the 4 sheets to the foreground, the one with the arrow pointing on with the short end to the left. You can also go back to puzzle menu to get the right view.)
Now right click on the one sheet where the arrow from the text points to. Click tweak. Now click one time on the straight arrow to the right. Now the sheet should flip. use shake and wiggle it. That should raise your score to the needed points.

Madde's video : http://www.youtube.com/watch?v=RDLNivggADE

Level 4-4: The Right Rotation

Orange pointing in, blue pointing out. Right click a helix to Tweak it.

Madde's video : http://www.youtube.com/watch?v=LX3qVcE4hlI

Level 4-5: Changing the structure

Changing the structure of the protein can help you see a solution better, and also affects Rebuild and Tweak. These three segments should be sheets. To enter Structure mode, click the Modes tab and choose Structure, or press 2. Right click a section of the protein while in structure mode to asign its structure from the three secondary structure types. Once you've done that, try using tweak to flip the sheet down. Use Shake and Wiggle to finish up. If the protein starts coming apart, you can use reset or undo.

Tip : click on pull mode, flip the sheet with the left arrow or rebuild the last part of the sheet.

Madde's video : http://www.youtube.com/watch?v=TfXeSc4AyA8

This puzzle is replaced in devprev by Structure and rebuild 4-5 Structure and Rebuild: http://youtu.be/x-l1aSl8QKg

Tools and Types Edit

Level 5-1: Quest to the native (QTTN)

In this puzzle, the correct solution, called a NATIVE, is known. To align the guide with a specific section of the protein, Right click any segment and click ALIGN GUIDE. Use the tools available to match the protein with the guide. If you haven't discovered it yet, you can attach a rubber band from the protein to a point in empty space. Rubber bands also affect the pull tool, not just wiggle. Remember to freeze parts of the protein that you don't want warped by wiggle or pull.

Level 5-2: Movin' along

Sometimes you can MOVE whole pieces of the protein. Click on a piece to bring up the

MOVE tool. Then press and hold down RIGHT BUTTON (CTRL on Mac) anywhere on the tool to drag the piece around. You can't pull on the backbone of this puzzle.

Tip : Click on the helix, then in the middle of the purple cross with the right button of your mouse (crtl on mac), then drag the helix on the shadow (if the helix rotates, you have not choose the right button), rotate the view to check then shake and wiggle. Dont use Align tools, if you have use it, go to intro puzzle menu then to movin along to refresh the view.

Madde's video : http://www.youtube.com/watch?v=Q2x03y6e4Kk

Level 5-3: Electron density

In an Electron Density puzzle, we only have data on the rough shape of the protein. You are given this data as a 3D surface that predicts the general areas where parts of the protein are located. The backbone of the protein will fit neatly inside the 3D region, but it's up to you to work out how it fits.

Click on the ELECTRON DENSITY button. These options let you control how the density surface is drawn. Adjust the THRESHOLD to change the thickness of the density region. At a good threshold, you can see shapes in the region that match parts of the protein. After moving the protein press ALIGN PROTEIN TO DENSITY to line up the surface with the protein. The alignment usually takes a few seconds to complete. Use Shake, Wiggle, and careful moving to fold the protein into the best possible shape that fits inside the predicted region.

Tip : wiggle, shake, wiggle, shake, then drag the end of protein inside the cloud with caution, skahe, wiggle. vidoe : http://www.youtube.com/watch?v=jDOY1QIGkog

Level 5-4: Exploration

In exploration puzzles like this one, your goal is to find a solution that is different from the starting structure. Your calculated score will be the protein's base score times an exploration multiplier for finding new configurations. You can use the Contact Map to help you find new configurations for the protein. The rows and columns in Contact Map correspond to segments of the backbone. A black mark indicates that the segments corresponding to that row and column are in contact. The red areas are contacts present in the starting structure. White areas are new contacts, which increase your score multiplier. You can click on TUTORIAL to learn more about Exploration puzzles. Use all the tools you have learned to fold this protein into a new shape. Don't be afraid to break some connections to make new ones. Try lining up all 4 sheets.

Madde's video :http://www.youtube.com/watch?v=AAh3ThsxohQ

Level 5-5: Control over clashing

You may have noticed that using Wiggle when there are many clashes causes the protein to come apart. To avoid this, lower the CLASHING IMPORTANCE . This lets Wiggle keep making small adjustments even if the protein is packed too tight. A lower Clashing Importance also lets you make moves that add clashes without unravelling the protein, like pulling on a tangled strand. Try setting Clashing Importance to 0.1, then Wiggle while slowly increasing it.

Madde's video: http://www.youtube.com/watch?v=TdC-9fmXdjY

Sequences Edit

Level 6-1: Basic Threading

These levels will introduce the powerful ALIGNMENT tool! It will let you use the structures of real proteins, called TEMPLATES, by THREADING. Click on the smiley button to bring up the ALIGNMENT tool. This 3D strcutures shows the backbone of the template. The bottom row of the letters is the TEMPLATE SEQUENCE. you can see it in 3D as spheres connected by lines. The top row of letters is the sequence of your protein. The cylinders in 3D show how its backbones lines up with the template.

When you THREAD, your protein will try to fit onto the 3D template where the cylinders are. Click the little smiley to try threading. Now that you've threaded it, try a shake and wiggle!

In this puzzle, you'll just need to use the ALIGNMENT tool to thread, then wiggle and shake. Don't worry about making manual adjustments. In this puzzle, you'll just need to use the ALIGNMENT tool to thread, then shake and wiggle.

Level 6-2 : Cut and paste

This blue band is a CUT. A CUT appears when the backbone of the protein has been cut. You need to close the CUT to complete the puzzle! To close the CUT, left click on one segment to bring up the MOVE tool, and then move the pieces together until the CUT turns yellow. Then click the CUT. Now SHAKE and WIGGLE to finish up!

Level 6-3: Alignin' Sequences

Bring up the alignment tool again. This time the letters and colors in the sequences are not lined up well.This middle row shows how well each letter matches; a bigger white bar means a better match. And this score (on the right) shows how the sequences match overall . You can click and drag or use the arrow keys to move the letters around. Try to line up the colors. It's okay if there are spaces, but fewer spaces is better. Enabling THREADING will let you see the changes to the protein now, or you can wait until you're done to THREAD. When there's a gap in the aligment, a CUT is inserted. When you're done aligning, move the two pieces together, then WIGGLE and click when the band turns yellow to close the cut. Good, now SHAKE and WIGGLE to finish up!"

Video: http://youtu.be/TNi1b1HxEKE

Protein Design Edit

Level 7-1: Intro to Design

Welcome to the design puzzles. In these challenges you will have the power to design new proteins! Segments with brighter colors can be designed! Some of these sidechains are too large. You can change them in Design Mode. To enter Design Mode, click the Modes tab and choose Design, or press 4. Select the segments you want to mutate. Click the Mutate Button from the menu. Then click the picture of the sidechain you want to mutate to Try to find better fits for both designable sidechains. If you're stuck, it may be easier to restart from the beginning.

Level 7-2: Swapping Side Chains

Now some sidechains are too small, causing voids! Try replacing them with some large ringed hydrophobics.

You'll need to change to Design Mode.

Level 7-3: Mass Mutate

This helix has lot of unburied orange hydrophobics.You can change them to blue hydrophilics in Design Mode. You've earned a new tool! Mutate Sidechains is like Shake, but may mutate designable sidechains. Stop the Mutate Sidechains by pressing the space bar.

Dont reset on this puzzle, go to menu/ intro puzzle and click on mass mutate.

Level 7-4: Insertion and Deletion

This red line is a CONSTRAINT, indicating that the segments it connects should be closer together. You can change the length of the helix by inserting or deleting segments. Right click a segment of the helix and use Insert Between. The blue blinking segments will show you where it will appear. The protein seems a little short now. You may want to undo or insert a segment. You can use wiggle and mutate sidechains to finish up. The protein seems a little long now. You may want to undo or delete a segment.

More molecules Edit

Level 8-1: Ligand debut

These levels contain molecules other than proteins! This small molecule is a LIGAND. Proteins can be designed to bind ligands. Hydrogen bonds are important for binding ligands. Connect red atoms with blue atoms to form bonds between the ligand and sidechains! Left click on the ligand to bring up MOVE tool. RIGHT-button-drag to move left, right, up, and down, LEFT-button-drag to rotate and SHIFT-LEFT (or MIDDLE) -button-drag to move ligand Into/Out of screen. When the ligand is in a good place, try a wiggle!

Level 8-2: Ligand constraints

These are CONSTRAINTS. Red constraints are violated. Make the constraints become green! After moving the ligand closer, use WIGGLE SIDECHAINS to wiggle the sidechains and the ligand at the same time. Try and compare it to Shake Sidechains.

Level 8-3: DNA Pairing

Use Design Mode to find the correct match for the incorrectly paired sidechains. DNA sidechains pair according to color and size. Match sidechains of same color and opposite sizes to make lots of bonds!

Match sidechains of the same color and opposite sizes to form lots of hydrogen bonds! Look at this big yellow sidechain with a small yellow sidechain. Use Design Mode to find the right match for the incorrectly paired purple sidechains!

Level 8-4: DNA and Protein

DNA can hydrogen bond to protein. Mutate the proteins to form better bonds. Try adding a long hydrophilic here. Try a shorter, forked hydrophilic here