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This protein from puzzle 1297 has been grown, crystallized, and solved by the Foldit science team. Anthropic Dreams players Waya, Galaxie, and Susume contributed to this design. Waya provided this image.

One of the major goals of Foldit design puzzles is creating artificial proteins that fold up on their own the way natural ones do.

The Foldit science team has been testing player designs in various ways, and refining the game to produce more realistic proteins.

Players have produced at least one protein that has passed all the science tests. The protein has been grown in bacteria, extracted and crystallized, then "solved" using X-ray diffraction. The same process is used to analyze natural proteins.

The first successful player design was produced for Puzzle 1297 by Anthropic Dreams, with Waya, Galaxie, and Susume contributing.

The successful protein was then presented in Puzzle 1381 as a de-novo. The science team finally shared the good news, and presented the protein yet again in Puzzle 1384 with the electron density included.

Testing processEdit

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Graph of Rosetta@home results for a protein designed by a Foldit player. The red dots have a "funnel" shape, converging toward the lower left-hand corner. This shape indicates the protein is likely to fold up on its own. An image of the protein has been superimposed on the plot.

The Foldit blog post The Baker Lab tests Foldit player-designed proteins describes the basic process, which involves testing promising solutions using Rosetta@home and other tools as a first step.

Designs which pass initial tests move on to "wet lab" testing, which involves growing the protein in E. coli bacteria. The blog post The story of a Foldit design details the steps involved in growing, extracting, and purifying a protein.

Protein designs which make it through all the stages of wet lab testing go on to crystallization trials. Proteins don't form crystals easily, so this phase usually involves automated testing of many different methods and conditions. As described in the Foldit blog post Foldit design update - Part 2, "protein crystallization is a lottery".

The Foldit blog post protein crystallization showed an example of a protein that appeared on its way to growing a good crystal.

Once a suitable crystal is grown, the next step is X-ray crystallography to produce an electron density of the protein. The electron density information allows the three-dimensional structure of the protein to be determined, meaning the protein has been "solved".

The Foldit blog post X-ray Diffraction covers this step, and describes the successful solution of the Anthropic Dreams protein from Puzzle 1297.

As was done from the successful protein from Puzzle 1297, proteins designed by Foldit players may be presented de-novo puzzles, in part to supplement Rosetta@home testing.

Successful designs may also appear as electron density puzzles, again as was the case for the Puzzle 1297 protein.

Foldit blog posts on design puzzle resultsEdit

These blog posts from bkoep (Brian Koepnick) and beta_helix (Firas Khatib) describe the results of various Foldit design and electron density puzzles.

Foldit trophy!Edit

In 2009, Puzzle 187 challenged players to redesign human fibronectin (RCSB 1FNF). Based on initial testing, one player design was selected for the "web lab". Things didn't work out quite as hoped, but the player, Boots McGraw, got a unique souvenir.

The following blog posts detail the process:

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