Figure 4. Analysis of FDA Drug-Target Association.

Frequency histogram depicting the number of protein target hits (y-axis) for each FDA drug (x-axis). Targets are considered hits for a particular molecule if the final ranking (Z-score) of the molecule places it in the Top 1 position, or somewhere in the Top 40 positions. (A) Frequency histogram depicting the number of protein targets hit y-aixs for each FDA drugs (x-axis) in the Top 1 position. The 2D structure of staurosporine, the drug with the most hits, is also displayed. (B) Frequency histogram depicting the number of protein target hits (y-axis) for each FDA drug (x-axis) in the Top 40 position. The Top 40 provides a more relaxed criterion for protein targets to be considered as hits. As such, for those molecules that survive the final cut-offs and are found in the Top 40 rank list for a particular protein, we predict that they have a good potential to bind to that given target. DB02197, DB03376 and DB02916, drugs with the most predicted hits, are depicted. (C) To further enrich our prediction paradigm, we included one more term corresponding to ligand shape. The value for this term is the RMSD of the docked ligand compared to the active conformation of the co-crystallized ligand for a particular protein crystal structure, which is derived from a set of 100 protein targets. The histogram portrays the frequency of hits of each FDA drug along with the 2D structure of the drug with most target hits (Indomethacin).