Repurformer: Transformers for Repurposing-Aware Molecule Generation

Abstract

Generating as diverse molecules as possible with desired properties is crucial for drug discovery research, which invokes many approaches based on deep generative models today. Despite recent advancements in these models, particularly in variational autoencoders (VAEs), generative adversarial networks (GANs), Transformers, and diffusion models, a significant challenge known as \textit{the sample bias problem} remains. This problem occurs when generated molecules targeting the same protein tend to be structurally similar, reducing the diversity of generation. To address this, we propose leveraging multi-hop relationships among proteins and compounds. Our model, Repurformer, integrates bi-directional pretraining with Fast Fourier Transform (FFT) and low-pass filtering (LPF) to capture complex interactions and generate diverse molecules. A series of experiments on BindingDB dataset confirm that Repurformer successfully creates substitutes for anchor compounds that resemble positive compounds, increasing diversity between the anchor and generated compounds.