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The committor functions are central to investigating rare but important events in molecular simulations. It is known that computing the committor function suffers from the curse of dimensionality. Recently, using neural networks to estimate…

Machine Learning · Statistics 2025-01-28 Yueyang Wang , Kejun Tang , Xili Wang , Xiaoliang Wan , Weiqing Ren , Chao Yang

We analyze the efficiency of different methods for the calculation of reaction rates in the case of two simple analytical benchmark systems. Two classes of methods are considered: the first are based on the free energy calculation along a…

Statistical Mechanics · Physics 2009-11-11 Titus S. van Erp

Rare events such as conformational changes in biomolecules, phase transitions, and chemical reactions are central to the behavior of many physical systems, yet they are extremely difficult to study computationally because unbiased…

Machine Learning · Statistics 2026-04-16 Yuanqi Du , Jiajun He , Dinghuai Zhang , Eric Vanden-Eijnden , Carles Domingo-Enrich

In complex molecular systems, the reaction coordinate (RC) that characterizes transition pathways is essential to understand underlying molecular mechanisms. This review surveys a framework for identifying the RC by applying deep learning…

Chemical Physics · Physics 2026-03-27 Toshifumi Mori , Kei-ichi Okazaki , Kang Kim , Nobuyuki Matubayasi

Due to the time scale problem, rare events are not accessible by straight forward molecular dynamics. The presence of multiple reaction channels complicates the problem even further. The feasibility of the standard free energy based methods…

Statistical Mechanics · Physics 2009-11-13 Titus S. van Erp

The thermal cis-trans isomerization around the C$_{13}$=C$_{14}$ double bond of retinal is a prototypical high-barrier reaction whose mechanism hinges on subtle out-of-plane bending motions. We apply Artificial Intelligence for Molecular…

Finding optimal reaction coordinates and predicting accurate kinetic rates for activated processes are two of the foremost challenges of molecular simulations. We introduce an algorithm that tackles the two problems at once: starting from a…

Statistical Mechanics · Physics 2023-10-30 Line Mouaffac , Karen Palacio-Rodriguez , Fabio Pietrucci

Rare events in molecular dynamics are often related to noise-induced transitions between different macroscopic states (e.g., in protein folding). A common feature of these rare transitions is that they happen on timescales that are on…

Probability · Mathematics 2026-01-06 Carsten Hartmann , Annika Jöster , Christof Schütte , Alexander Sikorski , Marcus Weber

A central object in the computational studies of rare events is the committor function. Though costly to compute, the committor function encodes complete mechanistic information of the processes involving rare events, including reaction…

Statistical Mechanics · Physics 2022-11-23 Muhammad R. Hasyim , Clay H. Batton , Kranthi K. Mandadapu

Searching for reaction pathways describing rare events in large systems presents a long-standing challenge in chemistry and physics. Incorrectly computed reaction pathways result in the degeneracy of microscopic configurations and inability…

Chemical Physics · Physics 2019-06-18 J. Rydzewski , O. Valsson

The construction of a reaction network containing all relevant intermediates and elementary reactions is necessary for the accurate description of chemical processes. In the case of a complex chemical reaction (involving, for instance, many…

Chemical Physics · Physics 2017-12-19 Gregor N. Simm , Markus Reiher

Transition path theory (TPT) offers a powerful formalism for extracting the rate and mechanism of rare dynamical transitions between metastable states. Most applications of TPT either focus on systems with modestly sized state spaces or use…

Statistical Mechanics · Physics 2026-01-14 Nils E. Strand , Schuyler B. Nicholson , Hadrien Vroylandt , Todd R. Gingrich

Sampled structure sequences obtained, for instance, from real-time reactivity explorations or first-principles molecular dynamics simulations contain valuable information about chemical reactivity. Eventually, such sequences allow for the…

Chemical Physics · Physics 2018-04-25 Michael A. Heuer , Alain C. Vaucher , Moritz P. Haag , Markus Reiher

Molecular transitions -- such as protein folding, allostery, and membrane transport -- are central to biology yet remain notoriously difficult to simulate. Their intrinsic rarity pushes them beyond reach of standard molecular dynamics,…

Finding representative reaction pathways is necessary for understanding mechanisms of molecular processes, but is considered to be extremely challenging. We propose a new method to construct reaction paths based on mean first-passage times.…

Chemical Physics · Physics 2015-06-26 Sanghyun Park , Klaus Schulten

Mapping the chemical reaction pathways and their corresponding activation barriers is a significant challenge in molecular simulation. Given the inherent complexities of 3D atomic geometries, even generating an initial guess of these paths…

Computational Physics · Physics 2025-01-24 Akihide Hayashi , So Takamoto , Ju Li , Yuta Tsuboi , Daisuke Okanohara

Biological organisms are open, adaptve systems that can respond to changes in environment in specific ways. Adaptation and response can be posed as an optimization problem, with a tradeoff between the benefit obtained from a response and…

Statistical Mechanics · Physics 2018-10-17 Suman G. Das , Madan Rao , Garud Iyengar

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…

Chemical Physics · Physics 2026-03-04 Polina V. Banushkina , Sergei V. Krivov

We propose a general theory to describe the distribution of protein-folding transition paths. We show that transition paths follow a predictable sequence of high-free-energy transient states that are separated by free-energy barriers. Each…

Biomolecules · Quantitative Biology 2016-09-21 William M. Jacobs , Eugene I. Shakhnovich

Adaptive multilevel splitting algorithms have been introduced rather recently for estimating tail distributions in a fast and efficient way. In particular, they can be used for computing the so-called reactive trajectories corresponding to…

Numerical Analysis · Mathematics 2014-12-25 Joran Rolland , Eric Simonnet