4.5. Generating Clusters. We formed clusters based on the 3D Tanimoto combo score of building blocks at each position. First, we transformed 3D Tanimoto combo scores into distances by subtracting each similarity score from 2, the maximum value for the Tanimoto combo. Due to slight variations in the con-former overlay process, distance matrices were not perfectly symmetric and some diagonal elements (a compound to itself) had distances slightly greater than zero. To symmetrize the distance matrix, we averaged it with its transpose and set the diagonal elements to zero.