TeachOpenCADD_​Workflow4_​Similarity_​search

4. Ligand-based screening: compound similarity

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 measures such as the Tanimoto and Dice similarity. The following steps show how to use these encodings and comparison methods. VS is here conducted based on a similarity search.

Step 2
Similarity search of query compound (example: gefitinib)
against full dataset using Tanimoto/Dice similarity

Step 1
Calculate fingerprints for dataset and query compound

Step 3
Evaluate performance with enrichment plots (split dataset into active and inactive compounds at pIC50 = 6.3)

MACC fingerprints

Morgan fingerprints