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For sampling multiple pathways in a rugged energy landscape, we propose a novel action-based path sampling method using the Onsager-Machlup action functional. Inspired by the Fourier-path integral simulation of a quantum mechanical system,…

Biological Physics · Physics 2015-05-18 Hiroshi Fujisaki , Motoyuki Shiga , Akinori Kidera

We present a new efficient transition pathway search method based on the least action principle and the Gaussian process regression method. Most pathway search methods developed so far rely on string representations, which approximate a…

Computational Physics · Physics 2022-09-13 JaeHwan Shim , Juyong Lee , Jaejun Yu

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

We propose a new modularity optimization method, Mod-CSA, based on stochastic global optimization algorithm, conformational space annealing (CSA). Our method outperforms simulated annealing in terms of both efficiency and accuracy, finding…

Computational Physics · Physics 2012-04-26 Juyong Lee , Steven P. Gross , Jooyoung Lee

We propose a novel path sampling method based on the Onsager-Machlup (OM) action by generalizing the multiscale enhanced sampling (MSES) technique suggested by Moritsugu and coworkers (J. Chem. Phys. 133, 224105 (2010)). The basic idea of…

Biological Physics · Physics 2015-06-15 Hiroshi Fujisaki , Motoyuki Shiga , Kei Moritsugu , Akinori Kidera

We apply the conformational space annealing (CSA) method to the Lennard-Jones clusters and find all known lowest energy configurations up to 201 atoms, without using extra information of the problem such as the structures of the known…

Statistical Mechanics · Physics 2009-11-10 Julian Lee , In-Ho Lee , Jooyoung Lee

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

The minimum action method (MAM) is to calculate the most probable transition path in randomly perturbed stochastic dynamics, based on the idea of action minimization in the path space. The accuracy of the numerical path between different…

Computational Physics · Physics 2017-05-26 Y Sun , X Zhou

Characterizing conformational transitions in physical systems remains a fundamental challenge, as traditional sampling methods struggle with the high-dimensional nature of molecular systems and high-energy barriers between stable states.…

Chemical Physics · Physics 2025-09-22 Magnus Petersen , Gemma Roig , Roberto Covino

Molecular dynamics (MD) simulations are useful in obtaining thermodynamic and kinetic properties of bio-molecules but are limited by the timescale barrier, i.e., we may be unable to efficiently obtain properties because we need to run…

Chemical Physics · Physics 2017-08-23 Surl-Hee Ahn , Jay W. Grate , Eric F. Darve

Interest in equilibrium-based sampling methods has grown with recent advances in computational hardware and Markov state modeling (MSM) methods, yet outstanding questions remain that hinder widespread adoption. Namely, how do sampling…

Biomolecules · Quantitative Biology 2018-05-15 Maxwell I. Zimmerman , Justin R. Porter , Xianqiang Sun , Roseane R. Silva , Gregory R. Bowman

Characterizing thermally activated transitions in high-dimensional rugged energy surfaces is a very challenging task for classical computers. Here, we develop a quantum annealing scheme to solve this problem. First, the task of finding the…

Quantum Physics · Physics 2021-01-18 Philipp Hauke , Giovanni Mattiotti , Pietro Faccioli

Simulation of surface processes is a key part of computational chemistry that offers atomic-scale insights into mechanisms of heterogeneous catalysis, diffusion dynamics, as well as quantum tunneling phenomena. The most common theoretical…

Chemical Physics · Physics 2023-05-01 Wei Fang , Yu-Cheng Zhu , Yi-Han Cheng , Yi-Ping Hao , Jeremy O. Richardson

We address the problem of sampling double-ended diffusive paths. The ensemble of paths is expressed using a symmetric version of the Onsager-Machlup formula, which only requires evaluation of the force field and which, upon direct time…

Statistical Mechanics · Physics 2011-07-27 Thomas F. Miller , Cristian Predescu

A global optimization method, conformational space annealing (CSA), is applied to study a 46-residue protein with the sequence B_9N_3(LB)_4N_3B_9N_3(LB)_5L, where B, L and N designate hydrophobic, hydrophilic, and neutral residues,…

Statistical Mechanics · Physics 2009-11-10 Seung-Yeon Kim , Sung Jong Lee , Jooyoung Lee

We propose a new generalized-ensemble algorithm, which we refer to as the multicanonical-multioverlap algorithm. By utilizing a non-Boltzmann weight factor, this method realizes a random walk in the multi-dimensional, energy-overlap space…

Statistical Mechanics · Physics 2009-11-11 Satoru G. Itoh , Yuko Okamoto

We introduce a variational approximation to the microscopic dynamics of rare conformational transitions of macromolecules. Within this framework it is possible to simulate on a small computer cluster reactions as complex as protein folding,…

Soft Condensed Matter · Physics 2015-02-19 S. a Beccara , L. Fant , P. Faccioli

The Minima Hopping global optimization method uses physically realizable molecular dynamics moves in combination with an energy feedback that guarantees the escape from any potential energy funnel. For the purpose of finding reactions…

Materials Science · Physics 2014-06-05 Bastian Schaefer , Stephan Mohr , Maximilian Amsler , Stefan Goedecker

We present a method to sample reactive pathways via biased molecular dynamics simulations in trajectory space. We show that the use of enhanced sampling techniques enables unconstrained exploration of multiple reaction routes. Time…

Computational Physics · Physics 2020-07-15 Davide Mandelli , Barak Hirshberg , Michele Parrinello

Spontaneous structural rearrangements play a central role in the organization and function of complex biomolecular systems. In principle, physics-based computer simulations like Molecular Dynamics (MD) enable us to investigate these…

Quantum Physics · Physics 2026-03-19 Danial Ghamari , Philipp Hauke , Roberto Covino , Pietro Faccioli
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