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Given a multidimensional free-energy or potential-energy landscape, finding reaction paths that connect an initial (or reactant) state and a final (or product) state is important for biophysics and materials science. The likelihood of a…

Statistical Mechanics · Physics 2024-12-12 Tetsuro Nagai , Koji Yoshida

We consider the problem of sampling transition paths between two given metastable states of a molecular system, e.g. a folded and unfolded protein or products and reactants of a chemical reaction. Due to the existence of high energy…

Biomolecules · Quantitative Biology 2023-07-19 Lars Holdijk , Yuanqi Du , Ferry Hooft , Priyank Jaini , Bernd Ensing , Max Welling

Understanding the dynamics of complex molecular processes is often linked to the study of infrequent transitions between long-lived stable states. The standard approach to the sampling of such rare events is to generate an ensemble of…

Computational Physics · Physics 2023-05-22 Sebastian Falkner , Alessandro Coretti , Salvatore Romano , Phillip Geissler , Christoph Dellago

Transition path sampling (TPS), which involves finding probable paths connecting two points on an energy landscape, remains a challenge due to the complexity of real-world atomistic systems. Current machine learning approaches use…

Machine Learning · Computer Science 2025-06-27 Sanjeev Raja , Martin Šípka , Michael Psenka , Tobias Kreiman , Michal Pavelka , Aditi S. Krishnapriyan

In comparison to numerous enhanced sampling methods for equilbrium thermodynamics, accelerating simulations for kinetics and nonequilibrium statistics are relatively rare and less effective. Here we derive a time-reversal path sampling…

Chemical Physics · Physics 2023-11-10 Zhirong Liu

Molecular systems often remain trapped for long times around some local minimum of the potential energy function, before switching to another one -- a behavior known as metastability. Simulating transition paths linking one metastable state…

Machine Learning · Statistics 2023-02-02 Tony Lelièvre , Geneviève Robin , Inass Sekkat , Gabriel Stoltz , Gabriel Victorino Cardoso

Stochastic systems often exhibit multiple viable metastable states that are long-lived. Over very long timescales, fluctuations may push the system to transition between them, drastically changing its macroscopic configuration. In realistic…

Statistical Mechanics · Physics 2023-04-14 Tobias Grafke , Alessandro Laio

In this paper, we present criteria for non-exponential ergodicity of continuous-time Markov chains on a countable state space. These criteria can be verified by examining the ratio of transition rates over certain paths. We applied this…

Probability · Mathematics 2024-02-09 Minjoon Kim , Jinsu Kim

Sampling all possible transition paths between two 3D states of a molecular system has various applications ranging from catalyst design to drug discovery. Current approaches to sample transition paths use Markov chain Monte Carlo and rely…

Quantitative Methods · Quantitative Biology 2024-05-29 Michael Plainer , Hannes Stärk , Charlotte Bunne , Stephan Günnemann

We describe an adaptive importance sampling algorithm for rare events that is based on a dual stochastic control formulation of a path sampling problem. Specifically, we focus on path functionals that have the form of cumulate generating…

Dynamical Systems · Mathematics 2019-01-30 Omar Kebiri , Lara Neureither , Carsten Hartmann

The time evolution of many physical, chemical, and biological systems can be modelled by stochastic transitions between the minima of the potential energy surface describing the system of interest. We show that in cases where there are two…

Statistical Mechanics · Physics 2024-09-11 S. P. Fitzgerald , A. Bailey Hass , G. Díaz Leines , A. J. Archer

In the study of rare events in complex systems with many degrees of freedom, a key element is to identify the reaction coordinates of a given process. Over recent years, a number of methods and protocols have been developed to extract the…

Chemical Physics · Physics 2015-10-27 Wenjin Li , Ao Ma

Models of reaction chemistry based on the stochastic simulation algorithm (SSA) have become a crucial tool for simulating complicated biological reaction networks due to their ability to handle extremely complicated reaction networks and to…

Quantitative Methods · Quantitative Biology 2009-11-13 Navodit Misra , Russell Schwartz

An analysis of the network defined by the potential energy minima of multi-atomic systems and their connectivity via reaction pathways that go through transition states allows to understand important characteristics like thermodynamic,…

Materials Science · Physics 2016-08-03 Bastian Schaefer , Stefan Goedecker

In many systems, the time scales of the microscopic dynamics and macroscopic dynamics of interest are separated by many orders of magnitude. Examples abound, for instance nucleation, protein folding, and chemical reactions. For these…

Other Condensed Matter · Physics 2009-11-13 J. Kuipers , G. T. Barkema

We introduce a rigorous method to microscopically compute the observables which characterize the thermodynamics and kinetics of rare macromolecular transitions for which it is possible to identify a priori a slow reaction coordinate. In…

Biomolecules · Quantitative Biology 2015-06-05 P. Faccioli , F. Pederiva

Understanding transition pathways between two meta-stable states of a molecular system is crucial to advance drug discovery and material design. However, unbiased molecular dynamics (MD) simulations are computationally infeasible because of…

Machine Learning · Computer Science 2025-01-28 Kiyoung Seong , Seonghyun Park , Seonghwan Kim , Woo Youn Kim , Sungsoo Ahn

We discuss the ``soft-ratcheting'' algorithm which generates targeted stochastic trajectories in molecular systems with scores corresponding to their probabilities. The procedure, which requires no initial pathway guess, is capable of…

Chemical Physics · Physics 2007-05-23 Daniel M. Zuckerman , Thomas B. Woolf

Many processes in chemistry, physics, and biology involve rare events in which the system escapes from a metastable state by surmounting an activation barrier. Examples range from chemical reactions, protein folding, and nucleation events…

Chemical Physics · Physics 2020-10-07 Niels Zijlstra , Daniel Nettels , Rohit Satija , Dmitrii E. Makarov , Benjamin Schuler

Probabilistic sampling methods have become very popular to solve single-shot path planning problems. Rapidly-exploring Random Trees (RRTs) in particular have been shown to be efficient in solving high dimensional problems. Even though…

Artificial Intelligence · Computer Science 2009-12-02 Nicolas A. Barriga , Mauricio Araya-López