We begin by defining the idea of "productivity" for individual building blocks, which we use to assess the overall activity of compounds. A key question we address here is whether building block analysis produces a sufficient signal for a predictive model. Using the findings from these studies, we then develop a method to estimate the productivity of untested building blocks. Finally, to guide subsequent DEL screens on a target, we design a method to (1) identify new and likely productive building blocks and (2) predict the activity of compounds containing the identified building blocks.