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Secondary Structure

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Three sheets. Sheets form hydrogen bonds with each other along their edges.


A helix. A helix forms hydrogen bonds with itself, drawing the backbone into a spiral pattern.

Secondary Structure refers to repeating patterns that help shape the protein. The patterns are the result of hydrogen bonds that form between atoms in the protein's backbone.

Sheets and helixes are the types of secondary structure which have a specific pattern of bonds. Parts of the protein that aren't in a sheet or a helix are called loop. Loop sections don't have any definitive pattern to their hydrogen bonds.

In Foldit, players can change the secondary assigned to a specific segment. (Any locked segments are an exception.) Changing the secondary structure doesn't change the shape of the protein immediately, but it may influence how some Foldit tools operate.

Foldit also has an auto structures tool that assigns the correct secondary structure based on the current hydrogen bonds.

In contrast to the secondary structure, the primary structure of a protein is the sequence of amino acids that make up the protein.

Helix, Sheet, Loop, LigandEdit

The amino acids in a protein form hydrogen bonds with each other. The bonds help stabilize the protein. The bonds often occur in two predictable patterns, called helixes and sheets. Segments which aren't bonded in one of these patterns are called "loop".

The helixes, sheets, and loops are called the "secondary structure" of the protein.


A helix is a spiral. In an ideal helix, each amino acid bonds to the fourth amino acid following it. So segment is bonded to segment 6, segment 3 is bonded to segment 7, and so on. Real helixes may not follow this bonding pattern perfectly.

Ideal Helix 0001

Helix created using Idealize Secondary Structure tool.


Compared to a helix, a sheet is flat, although they often twist. Sheets don't bond to themselves, they bond to other sheets. Sheets are shown as a flat ribbon. The bondable donor and acceptor atoms form a zigzag pattern on the edges of the ribbon. The donor atom on a "zig" on one sheet can bond to the acceptor atom in a "zag" in the another sheet.

Ideal Sheets 0001

Sheets created using Idealize Secondary Structure, then aligned manually.


The parts of a protein that aren't in helixes or sheets are called "loop". Sometimes, a relatively short section of loop connects helixes and sheets that are close to each other; in other cases, long meandering sections of loop connect more distant structures.


In addition, some Foldit puzzles have an atom or molecule that's not part of the protein, but interacts with the protein. These extra pieces are called "ligands". Ligands are normally represented by a single segment at the end of the protein. (In a few puzzles, ligands have been more than one segment, located in the middle of a protein.)

Working with secondary structure in FolditEdit

Foldit uses the following secondary structure abbreviations:

  • H for helix
  • E for sheet
  • L for loop
  • M for molecule, used for ligands

Some Foldit recipes print out the secondary structure using one of these codes for each segment. So you might see something like:


for the secondary structure.

Changing secondary structureEdit

In Foldit, you can always change the secondary structure of a segment, as long as the puzzle designers have left the segment unlocked. There's also an "auto structures" tool that will assign secondary structures as Foldit sees them.

There's an "idealize secondary structure" tool that changes the shape of a sheet or helix to its perfect form. An ideal helix is a straight spiral, an ideal sheet is a slightly twisted flat structure. Real helixes are often bent, and real sheets can bend and twist severely.

In the original interface, right click on a segment in the structure you want idealized, and select "Idealize SS" from the menu.

Idealize SS original 0001

Idealize Secondary Structure in the original interface.

In the selection interface, select the segments that you want idealize, and click on the idealize icon or use the "5" hotkey.

Idealize SS selection 0001

Idealize Secondary Structure in the selection interface.

Predicting secondary structureEdit

Foldit "de-novo" puzzles involve proteins that don't have published solutions. The goal is for Foldit players to figure out the correct shape for the protein. De-novo puzzles start with a straight "extended chain". Most de-novo puzzles start with a predicted secondary structure generated based on the primary structure (amino acid sequence). There are several Secondary structure prediction tools available online that may different predictions. These tools often use H for helix and S for sheet just as seen in Foldit. Instead of "L" for loop, some tools use "-", some use a space, and some use "C" for "coil".


Screenshot - Foldit Glossary showing Secondary Structure

How does Foldit deal with Secondary Structure?Edit

In Foldit, the assigned secondary structures are mainly mainly help players see the structure of the protein. There's always been a question of how much the assigned secondary structure affects Foldit tools like shake, wiggle, and rebuild.

When you change a section from one structure type to another, nothing moves. All the segments are in the same positions as they were before. In scientific terms, the energy of the molecule is the same, so the score shouldn’t and doesn’t change.

When you Rebuild that section, loop sections will be flexible and wiggly because that’s how loops are. Helix sections will be stiff because helices have internal hydrogen bonds that stabilize that shape. The same argument goes for sheets.

If you Rebuild a section in loop form, it goes all over the place. If you Rebuild in helix form, there’s still some flopping, but the Rebuild is seeking possible helical formations, and you see more helix-like structures than you do just random structures.

Many Foldit recipes offer an option to convert the entire protein to loop before starting. Especially when using rebuild, the flexibility of loop form is believed to give better results.

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