Auxiliary Discrminator Sequence Generative Adversarial Networks (ADSeqGAN) for Few Sample Molecule Generation

원문 초록

In this work, we introduce Auxiliary Discriminator Sequence Generative Adversarial Networks (ADSeqGAN), a novel approach for molecular generation in small-sample datasets. Traditional generative models often struggle with limited training data, particularly in drug discovery, where molecular datasets for specific therapeutic targets, such as nucleic acids binders and central nervous system (CNS) drugs, are scarce. ADSeqGAN addresses this challenge by integrating an auxiliary random forest classifier as an additional discriminator into the GAN framework, significantly improves molecular generation quality and class specificity. Our method incorporates pretrained generator and Wasserstein distance to enhance training stability and diversity. We evaluate ADSeqGAN on a dataset comprising nucleic acid-targeting and protein-targeting small molecules, demonstrating its superior ability to generate nucleic acid binders compared to baseline models such as SeqGAN, ORGAN, and MolGPT. Through an oversampling strategy, ADSeqGAN also significantly improves CNS drug generation, achieving a higher yield than traditional de novo models. Critical assessments, including docking simulations and molecular property analysis, confirm that ADSeqGAN-generated molecules exhibit strong binding affinities, enhanced chemical diversity, and improved synthetic feasibility. Overall, ADSeqGAN presents a novel framework for generative molecular design in data-scarce scenarios, offering potential applications in computational drug discovery. We have demonstrated the successful applications of ADSeqGAN in generating synthetic nucleic acid-targeting and CNS drugs in this work.