TABLE 8.

Alignment check (Step 4) for a top-rated (TR) CURA statement showing that the ability statement was supported by Steps 1–3 and each step added greater insight into the finalized CURA statement: Determine using computational software whether and where a ligand may be binding to a protein

PICURA components	Supporting outputs
Step 1: Content analysis	Concepts detected: Protein motifs Protein homology Structure–function relationships Intermolecular forces: protein–ligand interactions Representations detected: Various computer-generated protein structures (e.g., LigPlot+ and ProMOL representations)
Step 2: Open-ended survey	“We use protein sequence alignment to find similar proteins with known function, we use domain analysis to find proteins with similar domain composition, we use structure alignment to find similar structures with known functions, we use docking to simulate interactions between enzyme and possible substrate to try to choose more likely substrate. Each type of computational evidence does not generate one answer, but rather a list that can be ordered.”
Step 3: Interview	“[A student] could look at the binding of two ligands to a protein that the ligands are almost identical, they’re slightly different and see that you know, let’s say, one ligand has a benzene ring attached to it and the other one doesn’t, and the one with the benzene ring binds with 2 kilocalories per mole better than one without it, and so I would hope that they would look at that and say I need to find out where that benzene ring interacts to cause that much better binding. And that sort of thing, so by having them look at the results they obtained… computationally in one program but then test that in either another program or [run an assay in the lab].”