Machine-learning repurposing of DrugBank compounds for opioid use disorder

• Main Authors: Feng, H. (Author), Jiang, J. (Author), Wei, G.-W (Author)
• Format: Article
• Language: English
• Published: Elsevier Ltd 2023
• Subjects: Absorption distribution; Absorption, distribution, metabolism, excretion, and toxicity; Adaptive boosting; ADMET; Binding affinities; Binding energy; Decision trees; Drug repurposing; Drugbank; DrugBank; Machine learning; Machine-learning; Natural language processing systems; Opioid receptors; Opioid use disorder; Opioids; Repurposing
• Online Access: View Fulltext in Publisher; View in Scopus
• ISBN: 00104825 (ISSN)
• DOI: 10.1016/j.compbiomed.2023.106921

Opioid use disorder (OUD) is a chronic and relapsing condition that involves the continued and compulsive use of opioids despite harmful consequences. The development of medications with improved efficacy and safety profiles for OUD treatment is urgently needed. Drug repurposing is a promising option for drug discovery due to its reduced cost and expedited approval procedures. Computational approaches based on machine learning enable the rapid screening of DrugBank compounds, identifying those with the potential to be repurposed for OUD treatment. We collected inhibitor data for four major opioid receptors and used advanced machine learning predictors of binding affinity that fuse the gradient boosting decision tree algorithm with two natural language processing (NLP)-based molecular fingerprints and one traditional 2D fingerprint. Using these predictors, we systematically analyzed the binding affinities of DrugBank compounds on four opioid receptors. Based on our machine learning predictions, we were able to discriminate DrugBank compounds with various binding affinity thresholds and selectivities for different receptors. The prediction results were further analyzed for ADMET (absorption, distribution, metabolism, excretion, and toxicity), which provided guidance on repurposing DrugBank compounds for the inhibition of selected opioid receptors. The pharmacological effects of these compounds for OUD treatment need to be tested in further experimental studies and clinical trials. Our machine learning studies provide a valuable platform for drug discovery in the context of OUD treatment. © 2023 Elsevier Ltd