Hybrid Diffusions for Stable Molecular Structure Generation via Explicit Energy-based Model

Generation of 3D molecules utilizing diffusion models often encounters difficulties in producing stable structures, primarily due to the emergence of unstable intermediate structures during diffusion steps. To account for this issue, we introduce a diffusion-based molecule generation model that incorporates an energy-based model (EBM), pretrained on density functional theory (DFT) data. Specifically, we propose three strategic use of EBM: 1) guided exploration using the EBM, 2) stability evaluation to accept the structure or to reject and restart the generation at the end of diffusion steps, and 3) performing post-relaxation refinement. With these three strategies, we demonstrate that the energy estimator significantly enhances the generated molecule’s stability.