We find additional evidence that the building block in position 3 has the greatest effect on trisynthon activity. When the building block in position 3 has P(active) value in the range [0.80, 1.00] (bin 4), the probability of forming an active compound is never less than 93% (Fig- ure 4B, C, Table , S3). Building blocks in positions 1 and 2 exhibit far less influence over the overall activity of the compound and subsequently do not rescue activity to the same extent that building blocks in position 3 can (Figure , Table ).