Generating molecules with desired chemical properties presents a critical challenge in fields such as chemical synthesis and drug discovery. Recent advancements in artificial intelligence (AI) and deep learning have significantly contributed to data-driven molecular generation. However, challenges persist due to the inherent sensitivity of simplified molecular input line entry system (SMILES) representations and the difficulties in applying generative adversarial networks (GANs) to discrete data. This study introduces RL-MolGAN, a novel Transformer-based discrete GAN framework designed to address these challenges. Unlike traditional Transformer architectures, RL-MolGAN utilizes a first-decoder-then-encoder structure, facilitating the generation of drug-like molecules from both $de~novo$ and scaffold-based designs. In addition, RL-MolGAN integrates reinforcement learning (RL) and Monte Carlo tree search (MCTS) techniques to enhance the stability of GAN training and optimize the chemical properties of the generated molecules. To further improve the model's performance, RL-MolWGAN, an extension of RL-MolGAN, incorporates Wasserstein distance and mini-batch discrimination, which together enhance the stability of the GAN. Experimental results on two widely used molecular datasets, QM9 and ZINC, validate the effectiveness of our models in generating high-quality molecular structures with diverse and desirable chemical properties.

Deep generative models, such as generative adversarial networks (GANs), are pivotal in discovering novel drug-like candidates via de novo molecular generation. However, traditional character-wise tokenizers often struggle with identifying novel and complex sub-structures in molecular data. In contrast, alternative tokenization methods have demonstrated superior performance. This study introduces a molecular GAN that integrates a byte level byte-pair encoding tokenizer and employs reinforcement learning to enhance de novo molecular generation. Specifically, the generator functions as an actor, producing SMILES strings, while the discriminator acts as a critic, evaluating their quality. Our molecular GAN also integrates innovative reward mechanisms aimed at improving computational efficiency. Experimental results assessing validity, uniqueness, novelty, and diversity, complemented by detailed visualization analysis, robustly demonstrate the effectiveness of our GAN.

Generating novel drug molecules with desired biological properties is a time consuming and complex task. Conditional generative adversarial models have recently been proposed as promising approaches for de novo drug design. In this paper, we propose a new generative model which extends an existing adversarial autoencoder (AAE) based model by stacking two models together. Our stacked approach generates more valid molecules, as well as molecules that are more similar to known drugs. We break down this challenging task into two sub-problems. A first stage model to learn primitive features from the molecules and gene expression data. A second stage model then takes these features to learn properties of the molecules and refine more valid molecules. Experiments and comparison to baseline methods on the LINCS L1000 dataset demonstrate that our proposed model has promising performance for molecular generation.