The virtual library set can be further broken down into libraries designed using a 'combinatorial' approach, and a broader set of reactions using more 'bespoke' chemistry, which covers the reaction space more extensively. This enabled consideration of domain dependency with respect to template library size. We found that virtual libraries designed using a combinatorial approach benefited marginally from increasing the template library size. With the 1,064 most frequently occurring templates in the USPTO dataset, routes could be found for 65 % of the compounds in the virtual libraries designed using a combinatorial approach. This increased to a maximum of 72 % when the 25,126 most frequently occurring templates were used. This is in line with what would be expected, as combinatorial libraries employ frequently used and robust reactions in their design.