KNIME-based Analysis of Off-Target Effect of Drugs Related to The Molecular 2D Fingerprint

Structurally similar molecules are likely to have similar biological activity. In this study, similarity searching based on molecular 2D fingerprint was performed to analyze off-target effects of drugs. The purpose of this study is to determine the correlation between the adverse effects and drug off-targets.

A workflow was built using KNIME to run dataset preparation of twenty-nine targets from ChEMBL, generate molecular 2D fingerprints of the ligands, calculate the similarity between ligand sets, and compute the statistical significance using similarity ensemble approach (SEA). Tanimoto coefficients (Tc) are used as a measure of chemical similarity in which the values between 0.2 and 0.4 are the most common for the majority of ligand pairs and considered to be insignificant similar.

The majority of ligand sets are unrelated, as is evidenced by the intrinsic chemical differences and the classification of statistical significance based on expectation value. The rank-ordered expectation value of inter-target similarity showed a correlation with off-target effects of the known drugs.

Similarity-searching using molecular 2D fingerprint can be applied to predict off-targets and correlate them to the adverse effects of the drugs. KNIME as an open-source data analytic platform is applicable to build a workflow for data mining of ChEMBL database and generating SEA statistical model.