Nonparametric Reaction Coordinate Optimization with Histories: A Framework for Rare Event Dynamics
This provides a general framework for analyzing rare events in domains like protein folding and climate modeling, though it appears incremental as it builds on existing RC optimization methods by adding history incorporation.
The paper tackles the problem of identifying optimal reaction coordinates for rare event dynamics in complex systems by introducing a nonparametric framework that incorporates trajectory histories, achieving accurate committor estimates and high-resolution free energy profiles in protein folding analyses.
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. This work introduces a nonparametric RC optimization framework that incorporates trajectory histories, enabling robust analysis even for irregular or incomplete data. The power of the method is demonstrated through increasingly challenging analyses of protein folding dynamics, where it provides accurate committor estimates that pass a stringent validation test and yield high-resolution free energy profiles. Its generality is further illustrated through applications to dynamics in phase space, a conceptual ocean circulation model, and a longitudinal clinical dataset. These results demonstrate that rare event dynamics can be accurately characterized without exhaustive sampling of the configuration space, establishing a general, flexible, and robust framework for analyzing complex dynamical systems and longitudinal datasets.