W4_Similarity_search

In virtual screening (VS), compounds similar to known ligands of a target under investigation often build the starting point for drug development. This approach follows the similar property principle stating that structurally similar compounds are more likely to exhibit similar biological activities (exceptions are so-called activity cliffs). For computational representation and processing, compound properties can be encoded in form of bit arrays, so-called molecular fingerprints, e.g. MACCS and Morgan fingerprints. Compound similarity can be assessed by fingerprint comparison measures, such as the Tanimoto and Dice similarity. Using these encoding and comparison methods, VS is here conducted based on a similarity search with the following steps:

1.Calculate MACC/Morgan fingerprints and Tanimoto/Dice similarity for dataset
2.Split Dataset into active & inactive compounds (pIC50 cutoff > 6.3)
3.VS of query Gefitinib against dataset based on a similarity search
4.Evaluate screening with enrichment plots

Author:
Dominique Sydow, Michele Wichmann, Jaime Rodríguez-Guerra, Daria Goldmann, Gregory Landrum, and Andrea Volkamer