Overall, while both LOMAP and the simple radial approach yield maps of planned simulations, these approaches do little to quantify anticipated performance and may yield higher error predictions in the free energy change relative to more statistically optimal designs. Planning an ideal map of RBFE calculations is challenging because the number of possible designs grows rapidly. We will denote a design with 𝑛 number of nodes and 𝑘 number of edges as 𝒢 (𝑛, 𝑘). The number of possible edges, 𝑘 𝑓 𝑢𝑙𝑙 , that we pick between to form a design is