A disulfide bridge shown as a green-and-yellow spiral between the sulfur tips of two cysteine residues. (EnzDes coloring.)

A disulfide bridge is a strong bond that can form between two cysteines. The strength of disulfide bridges helps stabilize a protein.

Disulfide bridges are especially common in proteins that are secreted from cells. For example, disfulfide bridges are common in keratin, a type of protein found in skin, fingernails, hooves, and hair. Disulfide bridges contribute to curly hair.

Disulfide bridges are shown as yellow-and-green spirals in Foldit when the "Show bonds" option is selected in View Options. (In the advanced GUI, the "Show bonds (sidechain)" option shows disulfide bridges.)

Disulfide Bridge

Disulfide bridge formation. Each cysteine in the pair loses a hydrogen atom at the tip when a bridge forms, changing the atom count. (Stick+H view.)

A disulfide bridge is formed when a sulfur atom from one cysteine forms a single covalent bond with a sulfur atom from a second cysteine.

When a disulfide bridge forms, each cysteine loses one hydrogen atom. The atom count is 11 for a cysteine in mid-chain, but changes to 10 if the cysteine joins with another in a disulfide bridge. The atom count for other amino acids changes only at the N terminal and C terminal ends of the chain. See atom numbering for a complete discussion of atom numbering in Foldit.


Unlike hydrogen bonds, disulfide bridges were not shown in early versions of Foldit. Some users noticed that manipulating cysteine sidechains so that their ends pointed toward one another could yield points. The Foldit developers have confirmed that this effect was unrelated to the disulfide bridge. (See this discussion of a 2008 (?) visit to the Baker lab for more on early Foldit and its handling of disulfide bridges.)

Starting in January 2012, disulfide bridges were enabled in ALL puzzles by default.

In many more recent Foldit puzzles, a scoring filter adds a bonus, typically 250 points, for each disulfide bridge formed.


At least three Foldit recipes work with disulfide bridges.

The recipe Tvdl enhanced DRW 2.8.1 contains special bridge checking-logic. If the recipe detects disulfide bridges when it starts, it offers an option to preserve any bridges. If a rebuild breaks an existing bridge, the recipe discards the rebuild results in favor of keeping the bridge intact. This bridge-checking logic does not seem necessary in cases where there's a filter bonus for bridges. A broken bridge would mean a loss of 250 points from the filter bonus, which should cause the rebuild to be rejected. Similarly, a gain of 250 points from a newly formed bridge should ensure that a rebuild will be retained.

The recipe TvdL DRemixW 3.0.0 contains the same bridge-checking logic as the DRW version.

The recipe Bridge Wiggle v 1.2.1 - Brow42 checks the distances of all cysteine segments in the puzzle. The closest pairs of cysteines within 4 Angstroms of each other are proposed at possible bridges. The user can change proposed pairings with different combinations and add in more distant cysteines, although sulphur atom bands and backbone wiggling is often needed for them to work. The "More" button allows the user to test the proposed pairings. The "Start!" button repeatedly tries to band and wiggle the cysteine pairs to form bridges.

See alsoEdit

More information can be found in the wikipedia article "Disulfide".

Just for the sake of confusion, two cysteine molecules bonded together are also called cystine. "Cystine" often refers to pairing of two cysteines outside of a protein, but the term is also used in protein analysis.

The term "disulfide bond" is also common.

There are online services for biologists that predict which cystines likely from disulfbide bridges, a problem called "disulfide bond connectivity prediction". If you happen to stumble upon a puzzle that scores for bridges but does not tell you where they are, you can use services like DiaNNA and DISULFIND (allows generating alternatives) to make a quick educated guess.

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