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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

Simulating transition dynamics between metastable states is a fundamental challenge in dynamical systems and stochastic processes with wide real-world applications in understanding protein folding, chemical reactions and neural activities.…

Machine Learning · Computer Science 2024-10-22 Haibo Wang , Yuxuan Qiu , Yanze Wang , Rob Brekelmans , Yuanqi Du

We show that neural networks can be optimized to represent minimum energy paths as continuous functions, offering a flexible alternative to discrete path-search methods such as Nudged Elastic Band (NEB). Our approach parameterizes reaction…

Machine Learning · Computer Science 2025-07-10 Kalyan Ramakrishnan , Lars L. Schaaf , Chen Lin , Guangrun Wang , Philip Torr

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

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,…

Chemical reactions are often associated with an energy barrier along the reaction pathway which hinders the spontaneity of the reaction. Changing the energy barrier along the reaction pathway allows one to modulate the performance of a…

Computational Physics · Physics 2018-09-26 Sudipta Kundu , Satadeep Bhattacharjee , Seung-Cheol Lee , Manish Jain

The discovery of a minimum energy pathway (MEP) between metastable states is crucial for scientific tasks including catalyst and biomolecular design. However, the standard nudged elastic band (NEB) algorithm requires hundreds to tens of…

Materials Science · Physics 2025-12-18 Pranav Kakhandiki , Sathya Chitturi , Daniel Ratner , Sean Gasiorowski

We present a molecular simulation method to simultaneously find multiple transition pathways, and their associated free-energy profiles. The scheme extends path-metadynamics (PMD) [Phys. Rev. Lett. 109, 020601 (2012)] with multiple paths…

Statistical Mechanics · Physics 2025-06-23 Alberto Pérez de Alba Ortíz , Bernd Ensing

Stochastic electronic structure theories, e.g., Quantum Monte Carlo methods, enable highly accurate total energy calculations which in principle can be used to construct highly accurate potential energy surfaces. However, their stochastic…

We introduce a method of exploring potential energy contours in complex dynamical systems based on potentiostatic kinematics wherein the systems are evolved with minimal changes to their potential energy. We construct a simple iterative…

Computational Physics · Physics 2022-04-13 Michael J. Waters , James M. Rondinelli

Many algorithms for finding reaction pathways require an initial estimate of the minimum energy path (MEP). Most estimation methods use a variational approach and thus must be seeded from an even simpler path, such as one generated by…

Chemical Physics · Physics 2020-11-16 Mark C Palenik

Many biological, chemical, and physical systems are underpinned by stochastic transitions between equilibrium states in a potential energy. Here, we consider such transitions in a minimal model with two possible competing pathways, both…

Statistical Mechanics · Physics 2025-12-17 Gulzar Ahmad , Sergey Saveliev , Steven P Fitzgerald , Marco G Mazza , Andrew J Archer

In the last few decades, several novel algorithms have been designed for finding critical points on PES and the minimum energy paths connecting them. This has led to considerably improve our understanding of reaction mechanisms and kinetics…

Computational Engineering, Finance, and Science · Computer Science 2024-10-30 Sandra Liz Simon , Nitin Kaistha , Vishal Agarwal

We report a new algorithm for constructing pathways between local minima that involve a large number of intervening transition states on the potential energy surface. A significant improvement in efficiency has been achieved by changing the…

Other Condensed Matter · Physics 2009-11-11 Joanne M. Carr , Semen A. Trygubenko , David J. Wales

A central goal of protein-folding theory is to predict the stochastic dynamics of transition paths --- the rare trajectories that transit between the folded and unfolded ensembles --- using only thermodynamic information, such as a…

Biomolecules · Quantitative Biology 2018-08-09 William M. Jacobs , Eugene I. Shakhnovich

We describe a robust and efficient chain-of-states method for computing Minimum Energy Paths~(MEPs) associated to barrier-crossing events in poly-atomic systems. The path is parametrized in terms of a continuous variable $t \in [0,1]$ that…

Chemical Physics · Physics 2015-10-26 E. R. Hernandez , C. P. Herrero , J. M. Soler

We demonstrate a new algorithm for finding protein conformations that minimize a non-bonded energy function. The new algorithm, called the difference map, seeks to find an atomic configuration that is simultaneously in two constraint…

Biomolecules · Quantitative Biology 2007-06-13 Ivan C. Rankenburg , Veit Elser

The folding pathway and rate coefficients of the folding of a knotted protein are calculated for a potential energy function with minimal energetic frustration. A kinetic transition network is constructed using the discrete path sampling…

Biomolecules · Quantitative Biology 2010-07-05 Michael C. Prentiss , David J. Wales , Peter G. Wolynes

Protein folding processes are generally described statistically with the help of multidimensional free energy landscape, typically reduced to a 1-D free energy profile along good reaction co-ordinate. There are many physical parameters…

Biological Physics · Physics 2017-05-04 Debajyoti De , Anurag Singh , Amar Nath Gupta

The minimum energy path (MEP) describes the mechanism of reaction, and the energy barrier along the path can be used to calculate the reaction rate in thermal systems. The nudged elastic band (NEB) method is one of the most commonly used…

Numerical Analysis · Mathematics 2025-03-24 Xuanyu Liu , Huajie Chen , Christoph Ortner