Alternatively, de novo generative methods and those that operate directly on molecular building blocks and reactions sidestep the enumeration problem. While de novo generative methods may explore a larger or complementary chemical space, generated molecules are frequently impossible to synthesize. Likewise, methods that screen unenumerated libraries explore a large chemical space using fragment-based screening, but docking scoring functions may not accurately determine fragment binding modes and rank their typically low affinities. Furthermore, to our knowledge, no benchmark datasets enable a comprehensive comparison between enumerated and unenumerated methods. Given these considerations, we focus on exploring enumerated chemical space.