Investigating the behavior of diffusion models for accelerating electronic structure calculations

Abstract

We present an investigation of diffusion models for molecular generation, with the aim of better understanding how their predictions compare to the results of physics-based calculations. The investigation into these models is driven by their potential to significantly accelerate electronic structure calculations using machine learning, without requiring expensive first-principles datasets for training interatomic potentials. We find that the inference process of a popular diffusion model for de novo molecular generation is divided into an exploration phase, where the model chooses the atomic species, and a relaxation phase, where it adjusts the atomic coordinates to find a low-energy geometry. As training proceeds, we show that the model initially learns about the first-order structure of the potential energy surface, and then later learns about higher-order structure. We also find that the relaxation phase of the diffusion model can be re-purposed to sample the Boltzmann distribution over conformations and to carry out structure relaxations. For structure relaxations, the model finds geometries with ∼10× lower energy than those produced by a classical force field for small organic molecules. Initializing a density functional theory (DFT) relaxation at the diffusion-produced structures yields a >2× speedup to the DFT relaxation when compared to initializing at structures relaxed with a classical force field.