Figure 1. Similarity Ensemble Approach (SEA).

SEA compares groups of ligands based upon bond topology. Example ligand sets include the thymidylate synthase reaction set, composed of the reaction substrates and products, and the nucleotide reverse transcriptase inhibitor (NRTI) drug set, which includes known inhibitors of the nucleoside reverse transcriptase enzyme. Fingerprints representing the bond topology of each molecule are generated. Raw scores between sets are calculated based upon Tanimoto coefficients between fingerprints for all molecule pairs. Finally, the raw scores are compared to a background distribution to determine the expectation value (E) representing the chemical similarity between sets. See Methods for further details.