Papers › Non-Parametric Analysis of Non-Equilibrium Simulations

Non-Parametric Analysis of Non-Equilibrium Simulations

7 Feb 2021arXiv:2102.03950links table onlyarchive 2025-07-28

Sergei V. Krivov

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We extend the non-parametric framework of reaction coordinate optimization to non-equilibrium ensembles of (short) trajectories. For example, we show how, starting from such an ensemble, one can obtain an equilibrium free energy profile along the committor, which can be used to determine important properties of the dynamics exactly. New adaptive sampling approach, the transition state ensemble enrichment, is suggested, which samples the configuration space by "growing" committor segments towards each other starting from the boundary states. This framework is suggested as a general tool, alternative to the Markov state models, for a rigorous and accurate analysis of simulations of large biomolecular systems, as it has the following attractive properties. It is immune to the curse of dimensionality, it does not require system specific information, it can approximate arbitrary reaction coordinates with high accuracy and it has sensitive and rigorous criteria to test optimality and convergence. The approaches are illustrated on a 50-dimensional model system and a realistic protein folding trajectory.

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