SpaceLight is a much faster tool than FTrees, and accordingly, most of the time SpaceHASTEN spends in similarity searches of non-enumerated chemical spaces is due to FTrees calculations. However, the extra computational costs were justified as SpaceLight and FTrees retrieved different compounds from the non-enumerated chemical spaces (Figures and) and both tools contributed to the final lists of virtual hits as well (Table ). The virtual hits from the three screening campaigns were analyzed with respect to their number, their diversity, and their novelty. The key result of this study is presented in Figure : SpaceHASTEN pulled out a large number of high scoring compounds (virtual hits) from approximately 48 billion non-enumerated chemical space after docking only three million compounds. The difference to the baseline of random docking is striking. For example, by docking randomly 3 million compounds from the Enamine REAL diverse set, one would expect to get 6 virtual hits whereas SpaceHASTEN delivered 38,149 virtual hits (Table ). The structures and docking scores of the retrieved virtual hits are available in Supporting Information S1-S3.