Molecular similarity is a fundamental concept in ligand-based compound discovery, owing to the hypothesis that two molecules exhibit similar properties and biological function if they are structurally similar. For small molecule drug discovery, similarly shaped molecules can fit into the same binding pocket, as complementarity between a drug molecule and its macromolecular receptor is crucial for effective binding. This similarity principle has been widely leveraged in virtual screening campaigns to efficiently filter large compound databases, narrowing them down to smaller, more manageable sets for pharmacological testing. Molecular similarity analysis involves two components: (1) structural representation and