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Metrics 02

Binder metrics in the objectives area. The DDG, SASA, and shape complementarity metrics are available in this puzzle.

Binder metrics are special conditions which are available on binder puzzles.

Binder metrics include DDG, SASA, and shape complementarity. These metrics all evaluate the "interface" where a protein binder attaches to a different protein target.

(Note: the BUNS objective may also appear on binder puzzles, but it more general, and can appear on any design puzzle.

These metrics were first described in a March 2020 Foldit blog post titled Analysis of Protein Binder Designs. At one point, these metrics could not be calculated in Foldit. Separate external tools plus access to player solutions were required.

The metrics are now included as objectives in Foldit as of August 2020. For performance reasons, these metrics are treated differently than other objectives. At least initially, the metrics won't offer bonuses or penalties. They only provide information.

Metrics 03

In the objectives area, "Run All" calculates all binder metrics. Each metric can also be calculated separately using the corresponding "Run" button.

Also unlike many objectives, the binder metrics don't have an "enable" checkbox, only a "run" button. Players must click "run" to see the information for a single binder metric, or "run all" to see the information for all metrics. Calculating the metrics results in a pause of at least several seconds, which is the main reason they're treated separately for now.

Once calculated, the binder metrics are displayed in the objectives area. There is currently no way for a recipe to access the calculated values. The binder metrics remain displayed until part of the protein changes, when the metric values are replaced by the message "Disabled".

These metrics are not integrated into the underlying Rosetta software that provides the scores in Foldit. So it's possible a binder design with good metrics will have a relatively poor Foldit score, and vice versa.

DDGEdit

DDG 02

For DDG, a value of -40 kcal/mol is suggested. The lower the value, the better the fit between the binder and the target.

DDG measures the change in free energy when the binder is close to the target protein as opposed to when the target and the binder are free apart. A decrease in free energy when the binder is close to the target is desirable.

DDG is measured in kilocalories per mole, abbreviated as kcal/mol.

Hovering over the calculated DDG objective shows a suggested goal, which has been -40 kcal/mol in the early puzzles.

The displayed value of DDG uses the "E notation" version of scientific notation. A display value like "3.46e-10" means 3.46 times 10-10. This would be a very small positive value, where a much larger negative value is desirable.

See DDG for more detail.

SASAEdit

SASA 02

A target SASA of 1500 A2 is suggested. Unlike DDG, the higher the SASA, the better.

SASA is "solvent accessible surface area". As a binder metric, SASA refers to the surface area of the interface between the binder and the target. When the binder is close to the target, this area is actually inaccessible to the solvent.

The larger the SASA score, the better. SASA is measured in square Angstroms, or Å2.

Hovering over the calculated SASA objective shows a suggested goal, set at 1500 Å2 in the puzzles to date.

See SASA for more.

Shape complementarityEdit

Shape Complementarity 02

The suggested goal for shape complementarity is 0.6 or higher. A value of 1.0 indicates a perfect match, but may be hard to reach.

Like the DDG and SASA metrics, the shape complementarity binder metric looks at the interface between the binder and the target. As the names suggests, shape complementarity tries to determine how well the shape of the binder matches the shape of the target.

Unlike DDG and SASA, shape complementarity is a unitless value which can range from 0.0 to 1.0. The higher the shape complementarity value, the better.

A shape complementarity value of -1 is also possible, indicating the binder is too far from the target or the interface is too small for a meaningful calculation.

Hovering over the calculated shape complementarity shows a suggested target, which has been set to 0.6 in the initial puzzles.

See shape complementarity for more.

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