Enhancing Opioid Bioactivity Predictions through Integration of Ligand-Based and Structure-Based Drug Discovery Strategies with Transfer and Deep Learning Techniques.

The opioid epidemic has cast a shadow over public health, necessitating immediate action to address its devastating consequences. To effectively combat this crisis, it is crucial to discover better opioid drugs with reduced addiction potential. Artificial intelligence-based and other machine learning tools, particularly deep learning models, have garnered significant attention in recent years for their potential to advance drug discovery. However, using these tools poses challenges, especially when training samples are insufficient to achieve adequate prediction performance. In this study, we investigate the effectiveness of transfer learning in building robust deep learning models to enhance ligand bioactivity prediction for each individual opioid receptor (OR) subtype. This is achieved by leveraging knowledge obtained from pretraining a model using supervised learning on a larger data set of bioactivity data combined with ligand-based and structure-based molecular descriptors related to the entire OR subfamily. Our studies hold the potential to advance opioid research by enabling the rapid identification of novel chemical probes with specific bioactivities, which can aid in the study of receptor function and contribute to the future development of improved opioid therapeutics.