Align Your Structures: Generating Trajectories with Structure Pretraining for Molecular Dynamics

Aniketh Iyengar, Jiaqi Han, Pengwei Sun, Mingjian Jiang, Jianwen Xie, Stefano Ermon

Keywords: diffusion models, molecular dynamics

Abstract: Generating molecular dynamics (MD) trajectories using deep generative models has attracted increasing attention, yet remains inherently challenging due to the limited availability of MD data and the complexities involved in modeling high-dimensional MD distributions. To overcome these challenges, we propose a novel framework that leverages structure pretraining for MD trajectory generation. Specifically, we first train a diffusion-based structure generation model on a large-scale conformer dataset, on top of which we introduce an interpolator module trained on MD trajectory data, designed to enforce temporal consistency among generated structures. Our approach effectively harnesses abundant conformer data to mitigate the scarcity of MD trajectory data and effectively decomposes the intricate MD modeling task into two manageable subproblems: structural generation and temporal alignment. We comprehensively evaluate our method on QM9 and DRUGS datasets across various tasks, including unconditional generation, forward simulation, and interpolation. Experimental results confirm that our approach excels in generating chemically realistic MD trajectories, as evidenced by remarkable improvements of accuracy in bond length, bond angle, and torsion angle distributions.

Submission Number: 51