To illustrate the scaling of the design space, for a map that connects 20 ligands (𝑛 = 20) by 95 edges (𝑘 = 𝑘 𝑓 𝑢𝑙𝑙 ∕2), there are ≈10 55 designs to select from. These values apply to an undirected graph, meaning that the calculation is equivalent in each direction. Heuristics and intuition are unlikely to produce statistically optimal designs at this scale; we instead need an information-driven model to steer the design process. Thus, to decide what edges to simulate, we should design experiments that logically allocate resources to preserve precision.