A widely used example being LOMAP a rule-based algorithm developed around the requirements that, first, each node needs to be present in at least one cycle, and second, a network should require only a relatively small number of calculations connecting each ligand with each other. Recently HIMAP 36 was proposed, which is an algorithm that uses a density-based clustering step and an additional optimization phase for building up a network around these design concepts: n n log(n) desired number of edges, and a certain number of graph cycles. These more sophisticated methods demonstrate the interest in approaches that plann free energy calculation networks, while optimizing multiple features of networks.