Title: Scalable Spatio-Temporal SE(3) Diffusion for Long-Horizon Protein Dynamics
Primary area: applications to physical sciences (physics, chemistry, biology, etc.)
Keywords: Proteins, Molecular dynamics, Generative modeling, Diffusion models, Autoregressive modeling, SE(3)-equivariant diffusion, Spatiotemporal modeling

Abstract: Molecular dynamics (MD) simulations remain the gold standard for studying protein dynamics, but their computational cost limits access to biologically relevant timescales. Recent generative models have shown promise in accelerating simulations, yet they struggle with long-horizon generation due to architectural constraints, error accumulation, and inadequate modeling of spatiotemporal dynamics. We present STAR-MD (Spatio-Temporal Autoregressive Rollout for Molecular Dynamics), a scalable SE(3)-equivariant diffusion model that generates physically plausible protein trajectories over microsecond timescales. Our key innovation is a causal diffusion transformer with joint spatiotemporal attention that efficiently captures complex space-time dependencies while avoiding the memory bottlenecks of existing methods. On the standard ATLAS benchmark, STAR-MD achieves state-of-the-art performance across all metrics--substantially improving conformational coverage, structural validity, and dynamic fidelity compared to previous methods. STAR-MD successfully extrapolates to generate stable microsecond-scale trajectories where baseline methods fail catastrophically, maintaining high structural quality throughout the extended rollout. Our comprehensive evaluation reveals severe limitations in current models for long-horizon generation, while demonstrating that STAR-MD's joint spatiotemporal modeling enables robust dynamics simulation at biologically relevant timescales, paving the way for accelerated exploration of protein function.

TL;DR: A scalable spatiotemporal SE(3) diffusion model that generates long-horizon protein trajectories with state-of-the-art fidelity.