arXiv:2509.13294q-bio.BMcs.LG2025-09被引 8

用深度学习加速蛋白动力学模拟,实现千倍提速且保持精度。

Accelerating Protein Molecular Dynamics Simulation with DeepJump

  • 基于欧几里得等变流匹配模型,跨时标预测蛋白构象变化。
  • 在mdCATH数据集上实现约1000倍计算加速,准确恢复长期动态。
  • 适合需要高效蛋白折叠路径模拟的研究者使用。

解析生物分子的动态运动对连接其结构与功能至关重要,但仍是重大计算挑战。分子动力学(MD)模拟能详细刻画生物分子运动,但高时间分辨率带来巨大计算成本,限制了其在生物学相关时间尺度上的应用。深度学习方法通过学习长时序动力学,成为克服计算瓶颈的有前景方案。然而,通用的蛋白质动力学模型仍基本未被探索,且可实现加速程度与预测精度之间的权衡尚不明确。本文提出DeepJump,一种基于欧几里得等变流匹配的模型,用于跨多时间尺度预测蛋白质构象动力学。我们在mdCATH中多样化蛋白的轨迹上训练该模型,系统研究其在快速折叠蛋白长期动态泛化性能,并量化计算加速与预测精度间的权衡。实验表明,DeepJump可实现约1000倍的计算加速,有效恢复长期动态,并应用于从头折叠,成功预测折叠路径与天然构象。结果为实现蛋白质常规模拟提供了重要基础。

原文摘要 · Abstract (English)

Unraveling the dynamical motions of biomolecules is essential for bridging their structure and function, yet it remains a major computational challenge. Molecular dynamics (MD) simulation provides a detailed depiction of biomolecular motion, but its high-resolution temporal evolution comes at significant computational cost, limiting its applicability to timescales of biological relevance. Deep learning approaches have emerged as promising solutions to overcome these computational limitations by learning to predict long-timescale dynamics. However, generalizable kinetics models for proteins remain largely unexplored, and the fundamental limits of achievable acceleration while preserving dynamical accuracy are poorly understood. In this work, we fill this gap with DeepJump, an Euclidean-Equivariant Flow Matching-based model for predicting protein conformational dynamics across multiple temporal scales. We train DeepJump on trajectories of the diverse proteins of mdCATH, systematically studying our model's performance in generalizing to long-term dynamics of fast-folding proteins and characterizing the trade-off between computational acceleration and prediction accuracy. We demonstrate the application of DeepJump to ab initio folding, showcasing prediction of folding pathways and native states. Our results demonstrate that DeepJump achieves significant $\approx$1000$\times$ computational acceleration while effectively recovering long-timescale dynamics, providing a stepping stone for enabling routine simulation of proteins.

蛋白动力学深度学习分子模拟加速计算

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