arXiv:2508.07326physics.chem-phcs.LG2025-08

不依赖采样和标签,用历史轨迹建模罕见事件的演化路径。

Nonparametric Reaction Coordinate Optimization with Histories: A Framework for Rare Event Dynamics

  • 基于轨迹历史构建非参数化反应坐标,避免传统方法对损失函数的依赖。
  • 在蛋白质折叠中实现高精度通量估计与自由能图谱,验证通过严格测试。
  • 适用于不完整轨迹、稀疏数据的复杂系统,适合生物、气候等长期动态研究。

复杂系统中的罕见但关键事件(如蛋白质折叠、化学反应、疾病进展、极端天气或气候现象)由高维、随机、非平衡动力学驱动。准确识别刻画这些过程进展的最优反应坐标(RC)对理解与模拟至关重要。然而,由于缺乏真实标签、无通用非平衡动力学损失函数、神经网络架构难选且易过拟合、真实轨迹常不完整或不规则、采样有限及罕见事件严重数据失衡等问题,现有机器学习方法难以奏效。本文提出一种非参数化反应坐标优化框架,引入轨迹历史信息,克服上述挑战,可在不需大量采样情况下稳健分析不完整或不规则数据。该方法在蛋白质折叠动态中表现优异,生成通过严格验证的通量估计与高分辨率自由能剖面。其通用性还体现在相空间动力学、概念性海洋环流模型以及纵向临床数据集的应用中。结果表明,无需大规模构型空间采样即可准确刻画罕见事件动态,为复杂动力系统与纵向数据提供通用、灵活且鲁棒的分析框架。

原文摘要 · Abstract (English)

Rare but critical events in complex systems, such as protein folding, chemical reactions, disease progression, and extreme weather or climate phenomena, are governed by complex, high-dimensional, stochastic dynamics. Identifying an optimal reaction coordinate (RC) that accurately captures the progress of these dynamics is crucial for understanding and simulating such processes. However, determining an optimal RC for realistic systems is notoriously difficult, due to methodological challenges that limit the success of standard machine learning techniques. These challenges include the absence of ground truth, the lack of a loss function for general nonequilibrium dynamics, the difficulty of selecting expressive neural network architectures that avoid overfitting, the irregular and incomplete nature of many real world trajectories, limited sampling and the extreme data imbalance inherent in rare event problems. Here, we introduce a nonparametric RC optimization framework that incorporates trajectory histories and circumvents these challenges, enabling robust analysis of irregular or incomplete data without requiring extensive sampling. The power of the method is demonstrated through increasingly challenging analyses of protein folding dynamics, where it yields accurate committor estimates that pass stringent validation tests and produce high resolution free energy profiles. Its generality is further illustrated through applications to phase space dynamics, a conceptual ocean circulation model, and a longitudinal clinical dataset. These results demonstrate that rare event dynamics can be accurately characterized without extensive sampling of the configuration space, establishing a general, flexible, and robust framework for analyzing complex dynamical systems and longitudinal datasets.

反应坐标罕见事件轨迹建模动态系统

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