Foldit Wiki

That's a protein! Blue and orange sidechains stick out of the green backbone.

Foldit is all about folding proteins. Design puzzles even let you create new proteins. Some Foldit player designs have been turned into real proteins by the Foldit lab.

Proteins are those weird squiggly things seen in the main Foldit window. If you can't see the weird squiggly thing, try typing "q" (minus the quotes) to move it back into view. Also, the "Home" key does the same thing, maybe better, on Windows.

Tryptophan's sidechain makes it stand out in a crowd.

Proteins in Foldit are made of chains of 20 different amino acids. Each amino acid has a standard backbone, which allows one amino acid to connect to the next one in the chain. The connections between amino acids are called peptide bonds. Foldit doesn't get involved in the part where the amino acids get chained together.

The sidechain is the part that makes each amino acid different. The sidechain sticks out from the backbone. Each sidechain has a different chemical formula. In some amino acids, like tryptophan, the sidechain has a distinctive shape that makes it easy to recognize. Other amino acids, like serine and cysteine, have sidechains with the same shape, just different atoms. You have use the correct view options to tell these amino acids apart.

Serine and cysteine can be hard to tell apart.

One amino acid, glycine, doesn't even have a sidechain, just a hydrogen atom. But it's not bitter. Glycine makes up for it by being flexible.

In Foldit, each amino acid in the chain is called a segment. Each segment is numbered, starting at one. Just to be confusing, segments are also called residues. It's a "residue" because technically, an amino acid stops being an amino acid when the peptide bond is made. But...the sidechain can still be acid. Let's just say this biochemistry stuff can be confusing.

The are three main goals for folding proteins in Foldit: eliminate clashes, pack the protein to fill in voids, and hide exposed hydrophobics. Your score depends on how well you meet these goals. The overall score has clashing, packing, and hiding components to match these goals.

Occasionally, some non-protein molecules appear in Foldit puzzle. Some puzzles have one or more ligands. Usually, the goal is to adapt the protein to bind with the ligand, but in small molecule design puzzles, the goal is change the ligand to bind with the protein.

At least one Foldit puzzle has been made entirely of RNA, and a couple of intro puzzles involve DNA, one even combining DNA and protein.

While there are differences, many Foldit tools also apply to ligands, RNA, and DNA. Instead of amino acids, DNA and RNA are chains of bases (more formally known as nucleobases, and each base has a segment number. Each ligand also has a segment number. Tools like shake and wiggle apply across the board as well. So when we talk about "the protein" in Foldit, it sometimes includes things that aren't made of amino acids.