Puzzle 1855 Reaction Design panel

The Reaction Design panel from puzzle 1855.

A reaction design puzzle is similar to a small molecule design puzzle, allowing players to design a small molecule or ligand that binds to a protein target.

A described in a Foldit blog post, the Reaction Design Tool is much simpler than the collection of tools found in small molecule design puzzles.

A reaction design puzzle starts with an initial small ligand, known as the "reaction base". Players can add to the ligand by selecting "reactants" (also known as "fragments") from a predetermined list. The reactants bind to the base by "linking atoms".

In Puzzle 1855, the first reaction design puzzle, the starting ligand was a free-floating arginine molecule. (Although arginine is one of the 20 amino acids that make up protein in Foldit, the puzzle 1855 ligand was not linked to any other amino acids.)

The Reaction Design panel lets players customize the starting ligand. Some puzzles may offer multiple starting ligands, but in puzzle 1855, the only option was the arginine molecule.

Puzzle 1855 Reaction Design Panel Components

The options available in the puzzle 1855 reaction panel. The final ligand combines the selections in each of the four circled areas.

As an amino acid, the arginine ligand in puzzle 1855 had an N terminal and a C terminal, which became the linking atoms for the reactants. The leftmost column in the Reaction Design panel contained the reactants available to link to the N terminal nitrogen, and the center column contained the reactants for the C terminal. A third column allowed changing the "chirality" of arginine, offering either left-handed L-arginine or right-handed D-arginine.

As seen in the Building Block panel of the Blueprint feature, the images of the reaction base and the reactants can be rotated and zoomed. Black spheres highlight the linking atoms that attach the reactants to the base.

Puzzle 1855 Reaction Design Panel Defaults Highlighted

The Reaction Design panel with the hard-to-see default selections highlighted in red.

In the Reaction Design panel, clicking on an option selects it. In initial software release for reaction design, the selected item is surrounded by a blue-gray edge, which is hard to distinguish from other colors in the user interface.

With the Reaction Design panel open, the ligand shows a highlighted preview image of what the ligand will look like with the selected reactants. Clicking the unlabeled accept button at the bottom of the panel applies the changes.

In the initial release of reaction design, the same selections appear each time the panel is opened. The selections do not reflect any previous changes to the ligand. Also, the selections shown when the panel opens do not match the reactants and chirality displayed on the preview image. (Clicking the highlighted selections changes the preview image.)

See Puzzle 1855 reaction design for more on building a new ligand in the first reaction design puzzle.

While puzzle 1855 used an amino acid as the reaction base, future reaction design puzzles may use a different type of molecule. The amino acid offered two linking atoms, but other molecules may have more linking atoms or even just a single linking atom.

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