In order to improve over the application of any one particular problem variant or algorithm, SynRBL resorts to the heuristics implemented in RDKit and computes several alternative variants: MCISis addressed using the Fragment Matching and Compound Similarity (FMCS) , while the Rascal algorithm , as implemented in the RDKit library, is used to solve the MCES problem. Moreover, an ensemble method that amalgamates outcomes from five distinct configurations, detailed in In order to deal with alternative embeddings of the MCS, we enumerate all maximal solutions of MCS(X i , Y ) and identify the solutions that minimize the number of fragments resulting from the removal of the common subgraph. In the example in Fig. , one isomorphism corresponds to the disruption of the amide bond CO -N, thereby producing one additional fragment. The alternative embedding of the same common subgraph implies breaking bonds containing the amine bond CH 3 -N, resulting in three additional fragments. Hence, we choose the former embedding.