The success rate for rediscovery can be improved significantly by performing the mating and mutation operations directly on the molecule (formally a graph with nodes and edges corresponding to atoms and bonds, respectively) rather than a string representation (Figure ). The success rate for tiotixene (38%) is noticeably lower than those for celecoxib (82%) and troglitazone (100%). The reason is that two of the fragments found in tiotixene are not found in the initial population, while the corresponding numbers for celecoxib and troglitazone are zero and one, respectively. The missing fragment for troglitazone relates to the connection between the chromane and benzene group (Figure ). Inspection of the initial population for the troglitazone GA searches shows that it contains several molecules with chromane and anisole groups, which can be combined relatively straightforwardly by a mating operation. The missing fragments for tiotixene relates to the thioxanthene moiety (Figure ). Inspection of the initial population for the tiotixene GA searches shows that the closest match is a single molecule containing a phenothiazine moiety. Constructing the thioxanthene moiety from the molecules in the initial popu-lation thus presents a significant challenge and accounts for the lower success rate for tiotixene rediscovery.