A comprehensive review of molecular optimization in artificial intelligence‐based drug discovery

Abstract Drug discovery is aimed to design novel molecules with specific chemical properties for the treatment of targeting diseases. Generally, molecular optimization is one important step in drug discovery, which optimizes the physical and chemical properties of a molecule. Currently, artificial intelligence techniques have shown excellent success in drug discovery, which has emerged as a new strategy to address the challenges of drug design including molecular optimization, and drastically reduce the costs and time for drug discovery. We review the latest advances of molecular optimization in artificial intelligence‐based drug discovery, including data resources, molecular properties, optimization methodologies, and assessment criteria for molecular optimization. Specifically, we classify the optimization methodologies into molecular mapping‐based, molecular distribution matching‐based, and guided search‐based methods, respectively, and discuss the principles of these methods as well as their pros and cons. Moreover, we highlight the current challenges in molecular optimization and offer a variety of perspectives, including interpretability, multidimensional optimization, and model generalization, on potential new lines of research to pursue in future. This study provides a comprehensive review of molecular optimization in artificial intelligence‐based drug discovery, which points out the challenges as well as the new prospects. This review will guide researchers who are interested in artificial intelligence molecular optimization.