MolFilterGAN: a progressively augmented generative adversarial network for triaging AI-designed molecules

Artificial intelligence (AI)-based molecular design methods, especially deep generative models for generating novel molecule structures, have gratified our imagination to explore unknown chemical space without relying on brute-force exploration. However, whether designed by AI or human experts, the molecules need to be accessibly synthesized and biologically evaluated, and the trial-and-error process remains a resources-intensive endeavor. Therefore, AI-based drug design methods face a major challenge of how to prioritize the molecular structures with potential for subsequent drug development. This study indicates that common filtering approaches based on traditional screening metrics fail to differentiate AI-designed molecules. To address this issue, we propose a novel molecular filtering method, MolFilterGAN, based on a progressively augmented generative adversarial network. Comparative analysis shows that MolFilterGAN outperforms conventional screening approaches based on drug-likeness or synthetic ability metrics. Retrospective analysis of AI-designed discoidin domain receptor 1 (DDR1) inhibitors shows that MolFilterGAN significantly increases the efficiency of molecular triaging. Further evaluation of MolFilterGAN on eight external ligand sets suggests that MolFilterGAN is useful in triaging or enriching bioactive compounds across a wide range of target types. These results highlighted the importance of MolFilterGAN in evaluating molecules integrally and further accelerating molecular discovery especially combined with advanced AI generative models.

Automated summary

Artificial intelligence (AI)-based molecular design methods, particularly deep generative models, have allowed us to explore unknown chemical space without brute-force exploration. However, the challenge lies in synthesizing and evaluating the designed molecules efficiently. This study proposes MolFilterGAN, a novel molecular filtering method, which surpasses conventional screening approaches. The evaluation of MolFilterGAN on DDR1 inhibitors and external ligand sets proves its effectiveness in triaging bioactive compounds and accelerating molecular discovery.