Learning Flexible Forward Trajectories for Masked Molecular Diffusion

摘要

Masked diffusion models (MDMs) have achieved notable progress in modeling discrete data, while their potential in molecular generation remains underexplored. In this work, we explore their potential and introduce the surprising result that naively applying standards MDMs to molecules leads to severe performance degradation. We trace this critical issue to a *state-clashing problem*-where the forward diffusion trajectories of distinct molecules collapse into a common state, resulting in a mixture of reconstruction targets that cannot be learned with a typical reverse diffusion with unimodal predictions. To mitigate this, we propose **M**asked **E**lement-wise **L**earnable **D**iffusion (**MELD**) that orchestrates per-element corruption trajectories to avoid collisions between different molecular graphs. This is realized through a parameterized noise scheduling network that learns distinct corruption rates for individual graph elements, *i.e.*, atoms and bonds. Across extensive experiments, **MELD** achieves 100\% chemical validity in unconditional generation on QM9 and ZINC250K datasets, while markedly improving distributional and property alignment over standard MDMs on both conditional and unconditioned generation.