TEMPO: Temporal Multi-scale Autoregressive Generation of Protein Conformational Ensembles

TL;DR

This paper introduces TEMPO, a hierarchical autoregressive model that captures multi-scale protein dynamics, enabling realistic and temporally coherent simulation of conformational trajectories by combining biophysical principles with advanced generative modeling.

Contribution

The paper presents a novel hierarchical autoregressive framework that models protein dynamics across multiple scales, preserving causal dependencies and improving trajectory realism.

Findings

Successfully generates temporally coherent protein trajectories.

Balances computational efficiency with physical accuracy.

Captures both large-scale motions and local fluctuations.

Abstract

Understanding the dynamic behavior of proteins is critical to elucidating their functional mechanisms, yet generating realistic, temporally coherent trajectories of protein ensembles remains a significant challenge. In this work, we introduce a novel hierarchical autoregressive framework for modeling protein dynamics that leverages the intrinsic multi-scale organization of molecular motions. Unlike existing methods that focus on generating static conformational ensembles or treat dynamic sampling as an independent process, our approach characterizes protein dynamics as a Markovian process. The framework employs a two-scale architecture: a low-resolution model captures slow, collective motions driving major conformational transitions, while a high-resolution model generates detailed local fluctuations conditioned on these large-scale movements. This hierarchical design ensures that the causal dependencies inherent in protein dynamics are preserved, enabling the generation of temporally coherent and physically realistic trajectories. By bridging high-level biophysical principles with state-of-the-art generative modeling, our approach provides an efficient framework for simulating protein dynamics that balances computational efficiency with physical accuracy.