A novel molecule generative model of VAE combined with Transformer for unseen structure generation

Abstract: Recently, molecule generation using deep learning has been actively investigated in drug discovery. In this field, Transformer and VAE are widely used as powerful models, but they are rarely used in combination due to structural and performance mismatch of them. This study proposes a model that combines these two models through structural and parameter optimization in handling diverse molecules. The proposed model shows comparable performance to existing models in generating molecules, and showed by far superior performance in generating molecules with unseen structures. Another advantage of this VAE model is that it generates molecules from latent representation, and therefore properties of molecules can be easily predicted or conditioned with it, and indeed, we show that the latent representation of the model successfully predicts molecular properties. Ablation study suggested the advantage of VAE over other generative models like LLM in generating novel molecules. It also indicated that the latent representation can be shortened to ~32 dimensional variables without loss of reconstruction, suggesting the possibility of a much smaller molecular descriptor or model than existing ones. This study is expected to provide a virtual chemical library containing a wide variety of compounds for virtual screening and to enable efficient screening.