Molecular Docking for Prediction and Interpretation of Adverse Drug Reactions

Title:Molecular Docking for Prediction and Interpretation of Adverse Drug Reactions

Volume: 21 Issue: 5

Author(s): Heng Luo, Achille Fokoue-Nkoutche, Nalini Singh, Lun Yang, Jianying Hu and Ping Zhang*

Affiliation:

• Center for Computational Health, IBM T.J. Watson Research Center, Yorktown Heights, NY 10598,United States

Keywords: Molecular docking, chemical-protein interactome, machine learning, prediction, side effects, adverse drug reactions.

Abstract: Aim and Objective: Adverse drug reactions (ADRs) present a major burden for patients and the healthcare industry. Various computational methods have been developed to predict ADRs for drug molecules. However, many of these methods require experimental or surveillance data and cannot be used when only structural information is available.

Materials and Methods: We collected 1,231 small molecule drugs and 600 human proteins and utilized molecular docking to generate binding features among them. We developed machine learning models that use these docking features to make predictions for 1,533 ADRs.

Results: These models obtain an overall area under the receiver operating characteristic curve (AUROC) of 0.843 and an overall area under the precision-recall curve (AUPR) of 0.395, outperforming seven structural fingerprint-based prediction models. Using the method, we predicted skin striae for fluticasone propionate, dermatitis acneiform for mometasone, and decreased libido for irinotecan, as demonstrations. Furthermore, we analyzed the top binding proteins associated with some of the ADRs, which can help to understand and/or generate hypotheses for underlying mechanisms of ADRs.

Conclusion: Machine learning combined with molecular docking can help to predict ADRs for drug molecules and provide possible explanations for the ADR mechanisms.

Cite this article as:

Luo Heng, Fokoue-Nkoutche Achille , Singh Nalini , Yang Lun , Hu Jianying and Zhang Ping*, Molecular Docking for Prediction and Interpretation of Adverse Drug Reactions, Combinatorial Chemistry & High Throughput Screening 2018; 21(5) . https://dx.doi.org/10.2174/1386207321666180524110013