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Foldit time-lapse First hour of hand-folding de-novo puzzle 693

Madde hand folding de-novo

In a de-novo or "freestyle" puzzle, only the primary structure (the sequence of amino acids) is known.

In these puzzles, the protein starts as a straight extended chain, often with secondary structures assigned.

Unlike design puzzles, which also usually start as an extended change, players can't mutate (change) any of the amino acids in de-novo puzzle.

The beginner puzzle Easy Mini Freestyle is an example of a de-novo puzzle.

Players must look for clues to find the best shape for the protein. The clues include the:

The secondary structure predictions are often helpful, but usually not quite perfect. Players are free to try any of the secondary structure prediction tools found on the web.

Generally, hydrophobic segments should be hidden in the core of the protein as much as possible. Hydrophilic segments, especially long hydrophilics like arginine and lysine, are better candidates for the outside of the protein.

Segments with glycine and proline often indicate a spot where the protein bends or turns. They aren't usually found in the middle of a sheet or helix.


Over the years, several players have contributed strategies for folding a de-novo puzzle.