The Objectives area in the Foldit app, showing several filters typically seen in design puzzles.
In Foldit, a Filter is a type of objective that affects a player's score, adding a bonus or subtracting a penalty. Filters are also referred to as conditions, but there are some important differences between filters and conditions.
In the Foldit app, each filters and its current bonus or penalty are shown in the Objectives area under the overall score. Each filter has an "Enable" option, which temporarily turns off the calculations that determine the bonus or penalty. Disabling a filter results in a "Conditions Up To Date" condition, and puts a red line through the overall score. The score is invalid until the filter is enabled again.
The "Toggle All" button in the objectives area turns off checking all filters, and also puts a red line through the score.
Each filter also has a "Show" option, which turns on some kind of visualization, and a "Run" button to recalculate the filter if it was disabled.
In Foldit, the basic score is calculated by the underlying Rosetta software suite. Filters change the Rosetta score, allowing the Foldit science team to direct players toward certain types of solutions. Design puzzles usually include several filters, but filters also appear in other types of puzzles.
Design puzzle with multiple filters.
Design Puzzle Filters[]
A Foldit design puzzle may include some or all of these filters.
Residue Count[]
Some Foldit design puzzles allow players to insert additional residues (segments). The Residue Count condition deducts a penalty if the number of residues exceeds the stated maximum. For example, the description for [Puzzle 1805b: Coronavirus Spike Protein Binder Design ] states:
Residue Count (max +550) Penalizes extra residues inserted beyond the starting 192, at a cost of 55 points per residue. Players may use up to 202 residues in total.
Core Existence[]
The Show option of the Ideal Loops filter adds red halos to segments in a non-ideal loop.
The Core Existence filter rewards a hydrophobic core.
In symmetry puzzles, there may be two core existence filters: "Core Existence: Monomer" and "Core Existence: Complex". The monomer filter also appears on non-symmetry design puzzle, which usually have "monomer" in their titles).
In a symmetry puzzle, the "Complex" core existence filter may reward the "interface" between the main chain and the symmetric chains . In many recent symmetry puzzles, the complex core filter doesn't give a penalty or bonus. Instead, the filter is included just for the "show" option, which allows players to see which segments are part of the complex core.
The Core Existence filter divides the protein into three layers: surface, core, and the boundary between surface and core. The "Show" option colors the segments in the surface layer blue, and core segments red. This is a lot like the "Hydro" coloring option, except it doesn't depend on whether a segment is hydrophobic or not. Boundary segments are shown in green, which is not found in Hydro coloring.
The Core Exists filter was described in a 2013 blog post. In the earliest versions, the "Core Exists" could apply to both the main chain and the symmetric chain in a symmetry puzzle. Later symmetry puzzles have two separate "Core Existence" filters, one for the monomer main chain, and one for the interface between the chains.
This follow-up to the 2013 blog post describes some considerations for refining the core of a monomer.
Ideal Loops[]
The ideal loops filter penalizes loops between sheets or helixes if they depart too far from ideal constraints. Several Foldit features, such as ABEGO coloring, the Rama map and the Blueprint tool are intended to help construct ideal loops. Also, puzzles with the Ideal Loops filter typically disallow use of the rebuild tool, in favor of the remix tool.
A 2016 blog post contrasts remix and rebuild, and describes the new user interface features which make the remix tool easier to use manually.
Secondary Structure[]
The Secondary Structure filter in a design puzzle places limits on how many residues are in a particular type secondary structure. Since helixes score well in Foldit, the Secondary Structure filter often requires that no more then 50% of residues are in a helix. This avoids designs which are mostly helixes. In several "More Sheets!" puzzles, the secondary structure filter was reversed, to require that at least 50% of residues are in sheets.
Secondary Structure Design[]
In design puzzles, the Secondary Structure Design filter limits which secondary structures can contain specific amino acids. This filter often disallows cysteine (CYS) entirely, while disallowing glycine, proline, and alanine in sheets and helixes.
Residue IE Score[]
Tyrosine with small interaction energy penalty.
Tyrosince with large interaction energy penalty.
The Residue IE (interaction energy) Score filter, found in design puzzles, typically monitors that the aromatic ring residues are scoring well. The aromatics are phenylalanine (PHE), tyrosine (TYR), and tryptophan (TRP). The filter applies a penalty if the interaction energy is too low.
The segments with penalties are highlighted with red halos if the "Show" option for the filter is checked. When there's a penalty, the segment's "Segment Information" window shows the current interaction energy and the required value. In this instance, smaller the score, the better, so a negative IE score is better than a positive score. (Normally, Foldit presents scores as positive values.)
The Residue IE Score filter was described in a 2012 blog post and a follow-up posting. The comments for Puzzle 640 describe how the filter was applied to the aromatic residues.
Hydrogen Bond Network[]
The Hydrogen Bond Network filter was described in a 2016 Foldit blog post. The Hydrogen Bond Network filter awards hydrogen bonds that link a series of hydrophobic residues on the surface of a protein. The filter usually includes a requirement that network bonds across monomer units in a symmetry puzzle. [Puzzle 1103] included an assymetric version of the filter, which required the network to cross multiple non-identical chains in the protein.
Other Conditions[]
Disulfide Count[]
The Disulfide Count filter is found on non-design puzzles. The filter rewards disulfide bridges. The filter is commonly used on "revisting" puzzles. When these puzzles were originally presented, there was no special reward for disulfide bridges.
Contact Map[]
The Contact Map filter is found on contact map puzzles, and awards bonuses for matching predicted contacts.
Layer Score / Layer Design[]
The related Layer Score and Layer Design filters were found in earlier Foldit design puzzles. They have been dropped in favor of the Core Existence filter in more recent puzzles.
The Layer Score filter was described in the comment for Puzzle 670: 30 Residue Symmetric Dimer of Dimers Freestyle Retry:
The Layer Score filter is a new filter designed to ensure proteins fold up into desirable shapes. It will categorize each backbone residue as either 'core', 'surface', or 'boundary'. If you think of the protein as being suspended in a liquid, the 'surface' residues are those most exposed to the liquid. Subsequently, the 'core' residues are those that are most protected and the 'boundary' residues are the ones that lie between the 'core' and the 'surface'. Most residues are categorized as either 'core' or 'surface'.
The successor Layer Design filter is described in the comments for Puzzle 682: 40 Residue Symmetric Trimer:
The "Layer Design" filter looks at the interactions of the residues based on the surface area of the protein. Residues can be either in the core, on the boundary or on the surface of the protein. Depending on the surroundings, the "Layer Design" filter will give you a bonus if your amino acid matches what it was expecting.
Both filters significantly slowed down game play. In particular, use of some long-running recipes became much less feasible. The ability to disable filters in a recipe led to recipes with "layers" or for layers in their titles, descriptions, or options. These recipes typically disabled filters during certain operations, but "for layers" also was used by recipes dealing with the Layer Design filter in other ways.
While the "layers" filters are gone, it's still common for Foldit recipes to offer an option to disable filters for the sake of performance.