An Objective guides work on a puzzle.
Objectives often add or subtract points, going beyond the normal Score calculations. Many objectives have a "show" option, which often highlights areas that need improvement.
Some objectives don't change the score, but their "show" option can reveal information that's not available elsewhere.
In puzzles with one or more objectives, the Objectives area shows the current status of each objective, along with the total score change for all objectives.
Small molecule design puzzles typically have eight or more objects. Some revisiting puzzles have a single objective, one that rewards disulfide bridges.
Previously, protein design puzzles usually had several objectives, similar to small molecule design puzzles. Protein design puzzles were once common, but none have appeared in Foldit recently.
Objectives can be temporarily disabled to improve performance. The Objectives dropdown shows total bonus or penalty from all objectives. The Objectives dropdown can also enable or disable objectives, either individually or in total. The puzzle's score valid if any objectives are disabled. A redline indicates an invalid score.
Common objectives found on a small molecule design puzzle include:
- Similarity rewards a bonus based on the similarity to the starting compound.
- Compound Library awards a large bonus when the current small molecule can be found in a library of untested compounds which can like be synthesized. The current small molecule must be submitted for a search using the Compound Library panel.
- Torsion Quality rewards small molecules based on the position of rotatable bounds.
- Number of Rotatable Bonds rewards ligands with a smaller number of rotatable bonds. The "show" option highlights the rotatable bonds in the ligand.
- Ligand TPSA rewards ligands with a low TPSA, or "topological polar surface area". The "show" option highlights polar atoms in the ligand, which contribute to TPSA.
- Ligand cLogP rewards ligands with a low cLogP, which are less hydrophobic. The "show" option highlights hydrophobic atoms in the ligand.
- Ligand Hydrogen Bond Donors rewards ligands which don't exceed a certain number of atoms which can act as hydrogen bond donors. The "show" option highlights potential donor atoms.
- Bad Groups rewards ligands for avoiding specific chemical groups. The "show" option highlights any bad groups.
- Molecular Weight rewards ligands where the molecular weight is low. This objective does not have a "show" option.
- Synthetic Accessibility rewards ligands which can actually be made in a lab. The "show" option identifies areas that would be difficult to synthesize.
Some small molecule objectives have been used in the past, but haven't been seen in more recent puzzles. These include:
- Alter Core rewards changing a specific structure in the starting ligand. The "show" option highlights the structure that needs to change.
- HBond rewards making a specific number of hydrogen bonds between the ligand and the protein. The "show" option highlights the atoms on protein that can form hydrogen bonds with the ligand.
- Ligand Substructures rewards ligands which are more "drug-like". The "show" option highlights problematic substructures.
Common objectives found on a design puzzle include:
- Buried Unsats, which deducts points if BUNs (buried unsatisfied polar atoms) are present. The "show" option highlights the BUNs.
- Core Existence: Monomer, in a symmetry puzzle, this objective deducts points if the main chain has a weak core. The "show" option colors the segments to indicate which are in the core, which are on the surface, and which are on the boundary in between the core and surface.
- Core: Complex, in a symmetry puzzle, this objective doesn't change the score. Instead, the "show" option colors segment to indicate which are core, surface, or boundary. Unlike Core Existence: Monomer, the coloring indicates the core formed by the main chain and the symmetric chains when they are close together, forming a complex.
- Interaction Energy looks at how certain amino acids are contributing to the score, and deducts points for underachievers. The "show" option reveals which segments are disappointing.
- Hydrogen Bond Network, rewards hydrogen bond networks. The "show" option highlights bonds which contribute to a hydrogen bond network. "Show" also indicates bonds which are close, but not quite, to being in a network.
- SS Design, penalizes certain amino acids when they appear in certain secondary structures. Commonly, glycine and alanine aren't allowed in helices or sheets. The "show" option highlights any offending segments.
- Ideal Loops penalizes any non-ideal loops found. See Ideal Loops for more on this complex topic. The "show" option highlights any bad loops.
- Secondary Structure limits how many segments can have a specific secondary structure. Typically, only 50% of segments are allowed to form helices.
- Neural net works with the AlphaFold tool, highlighting portions of the protein which are far away from where AlphaFold predicts they should be.
A binder puzzle may have additonal objectives, including:
- DDG rewards designs with negative DDG (the more negative, the better). This objective does not have a "show" option.
- Contact Surface rewards contact between the binder and its target. This objective does not have a "show" option.
See also[]
- Wikipedia:Lipinski's rule of five, for an explanation of the many SMD objectives