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The ability of widely used sampling methods, such as molecular dynamics or Monte Carlo, to explore complex free energy landscapes is severely hampered by the presence of kinetic bottlenecks. A large number of solutions have been proposed to…

Statistical Mechanics · Physics 2014-08-29 Omar Valsson , Michele Parrinello

Existing adaptive bias techniques, which seek to estimate free energies and physical properties from molecular simulations, are limited by their reliance on fixed kernels or basis sets which hinder their ability to efficiently conform to…

Statistical Mechanics · Physics 2018-04-04 Hythem Sidky , Jonathan K. Whitmer

A popular way to accelerate the sampling of rare events in molecular dynamics simulations is to introduce a potential that increases the fluctuations of selected collective variables. For this strategy to be successful, it is critical to…

Computational Physics · Physics 2021-01-19 Luigi Bonati

A new approach for efficiently exploring the configuration space and computing the free energy of large atomic and molecular systems is proposed, motivated by an analogy with reinforcement learning. There are two major components in this…

Chemical Physics · Physics 2018-04-18 Linfeng Zhang , Han Wang , Weinan E

Collective variable (CV) or order parameter based enhanced sampling algorithms have achieved great success due to their ability to efficiently explore the rough potential energy landscapes of complex systems. However, the degeneracy of…

Chemical Physics · Physics 2018-07-11 Jing Zhang , Ming Chen

While variable selection is essential to optimize the learning complexity by prioritizing features, automating the selection process is preferred since it requires laborious efforts with intensive analysis otherwise. However, it is not an…

Machine Learning · Computer Science 2019-10-29 Makiya Nakashima , Alex Sim , Youngsoo Kim , Jonghyun Kim , Jinoh Kim

Monte Carlo methods are widely used importance sampling techniques for studying complex physical systems. Integrating these methods with deep learning has significantly improved efficiency and accuracy in high-dimensional problems and…

Disordered Systems and Neural Networks · Physics 2024-12-24 Yixiong Ren , Jianhui Zhou

The development of enhanced sampling methods has greatly extended the scope of atomistic simulations, allowing long-time phenomena to be studied with accessible computational resources. Many such methods rely on the identification of an…

Computational Physics · Physics 2022-06-08 Luigi Bonati , GiovanniMaria Piccini , Michele Parrinello

Progressive Neural Network Learning is a class of algorithms that incrementally construct the network's topology and optimize its parameters based on the training data. While this approach exempts the users from the manual task of designing…

Machine Learning · Computer Science 2020-05-26 Dat Thanh Tran , Moncef Gabbouj , Alexandros Iosifidis

In this work, we present Enhanced Representation-Based Sampling (ERBS), a novel enhanced sampling method designed to generate structurally diverse training datasets for machine-learned interatomic potentials. ERBS automatically identifies…

Chemical Physics · Physics 2026-01-23 Moritz René Schäfer , Johannes Kästner

Macromolecular and biomolecular folding landscapes typically contain high free energy barriers that impede efficient sampling of configurational space by standard molecular dynamics simulation. Biased sampling can artificially drive the…

Biological Physics · Physics 2018-11-01 Wei Chen , Andrew L Ferguson

The determination of efficient collective variables is crucial to the success of many enhanced sampling methods. As inspired by previous discrimination approaches, we first collect a set of data from the different metastable basins. The…

Computational Physics · Physics 2026-03-03 Enrico Trizio , Michele Parrinello

The free energy landscapes of several fundamental processes are characterized by high barriers separating long-lived metastable states. In order to explore these type of landscapes enhanced sampling methods are used. While many such methods…

Chemical Physics · Physics 2019-04-12 Jayashrita Debnath , Michele Invernizzi , Michele Parrinello

Enhanced sampling methods are indispensable in computational physics and chemistry, where atomistic simulations cannot exhaustively sample the high-dimensional configuration space of dynamical systems due to the sampling problem. A class of…

Chemical Physics · Physics 2024-04-04 Jakub Rydzewski , Ming Chen , Tushar K. Ghosh , Omar Valsson

Neural network (NN) interatomic potentials provide fast prediction of potential energy surfaces, closely matching the accuracy of the electronic structure methods used to produce the training data. However, NN predictions are only reliable…

Machine Learning · Computer Science 2021-08-31 Daniel Schwalbe-Koda , Aik Rui Tan , Rafael Gómez-Bombarelli

Many important challenges in science and technology can be cast as optimization problems. When viewed in a statistical physics framework, these can be tackled by simulated annealing, where a gradual cooling procedure helps search for…

Disordered Systems and Neural Networks · Physics 2024-01-17 Mohamed Hibat-Allah , Estelle M. Inack , Roeland Wiersema , Roger G. Melko , Juan Carrasquilla

Machine learning methods provide a general framework for automatically finding and representing the essential characteristics of simulation data. This task is particularly crucial in enhanced sampling simulations. There we seek a few…

Chemical Physics · Physics 2021-07-07 Jakub Rydzewski , Omar Valsson

Many enhanced sampling techniques rely on the identification of a number of collective variables that describe all the slow modes of the system. By constructing a bias potential in this reduced space one is then able to sample efficiently…

Computational Physics · Physics 2019-03-05 Michele Invernizzi , Michele Parrinello

The use of external restraints is ubiquitous in advanced molecular simulation techniques. In general, restraints serve to reduce the configurational space that is available for sampling, thereby reducing the computational demands associated…

Diffusion-based samplers learn to sample complex, high-dimensional distributions using energies or log densities alone, without training data. Yet, they remain impractical for molecular sampling because they are often slower than molecular…

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