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The study of the rare transitions that take place between long lived metastable states is a major challenge in molecular dynamics simulations. Many of the methods suggested to address this problem rely on the identification of the slow…

Chemical Physics · Physics 2023-06-07 Dhiman Ray , Enrico Trizio , Michele Parrinello

Collective variables (CVs) play a crucial role in capturing rare events in high-dimensional systems, motivating the continual search for principled approaches to their design. In this work, we revisit the framework of quantitative coarse…

Numerical Analysis · Mathematics 2025-06-06 Shashank Sule , Arnav Mehta , Maria K. Cameron

In molecular dynamics simulations, rare events, such as protein folding, are typically studied using enhanced sampling techniques, most of which are based on the definition of a collective variable (CV) along which acceleration occurs.…

Chemical Physics · Physics 2024-07-22 Soojung Yang , Juno Nam , Johannes C. B. Dietschreit , Rafael Gómez-Bombarelli

Mini-proteins and peptides manifest dynamic conformational fluctuation and involve mutual interconversion among metastable states. A robust mapping of the conformational landscape underlying mini-proteins and peptides often requires…

Chemical Physics · Physics 2021-09-29 Satyabrata Bandyopadhyay , Jagannath Mondal

Enhanced sampling methods typically require predefined collective variables (CVs) that presuppose knowledge of reaction coordinates, restricting the discovery of unanticipated transition mechanisms or intermediates. Here, we show that a…

Chemical Physics · Physics 2026-04-08 Xiangrui Li , Daniel Schwalbe-Koda

Selection of appropriate collective variables for enhancing sampling of molecular simulations remains an unsolved problem in computational biophysics. In particular, picking initial collective variables (CVs) is particularly challenging in…

Machine Learning · Statistics 2018-05-15 Mohammad M. Sultan , Vijay S. Pande

Extending spatio-temporal scale limitations of models for complex atomistic systems considered in biochemistry and materials science necessitates the development of enhanced sampling methods. The potential acceleration in exploring the…

Machine Learning · Statistics 2019-01-18 Markus Schöberl , Nicholas Zabaras , Phaedon-Stelios Koutsourelakis

The large number of spectral variables in most data sets encountered in spectral chemometrics often renders the prediction of a dependent variable uneasy. The number of variables hopefully can be reduced, by using either projection…

Machine Learning · Computer Science 2007-09-26 Fabrice Rossi , Damien François , Vincent Wertz , Marc Meurens , Michel Verleysen

In graph learning, maps between graphs and their subgraphs frequently arise. For instance, when coarsening or rewiring operations are present along the pipeline, one needs to keep track of the corresponding nodes between the original and…

Machine Learning · Computer Science 2023-02-01 Marco Pegoraro , Riccardo Marin , Arianna Rampini , Simone Melzi , Luca Cosmo , Emanuele Rodolà

These notes offer a unified introduction to spectral methods for the study of complex systems. They are intended as an operative manual rather than a theorem-proof textbook: the emphasis is on tools, identities, and perspectives that can be…

Statistical Mechanics · Physics 2025-09-10 Francesco Caravelli

Finding a reduction of complex, high-dimensional dynamics to its essential, low-dimensional "heart" remains a challenging yet necessary prerequisite for designing efficient numerical approaches. Machine learning methods have the potential…

Dynamical Systems · Mathematics 2022-06-15 Przemyslaw Zielinski , Jan S. Hesthaven

Many real-analytic flows, e.g. in chemical kinetics, share a multiple time scale spectral structure. The trajectories of the corresponding dynamical systems are observed to bundle near so-called slow invariant manifolds (SIMs), which are…

Dynamical Systems · Mathematics 2019-12-04 Jörn Dietrich , Dirk Lebiedz

Slow-fast dynamical systems, i.e., singularly or non-singularly perturbed dynamical systems possess slow invariant manifolds on which trajectories evolve slowly. Since the last century various methods have been developed for approximating…

Chaotic Dynamics · Physics 2021-06-30 Jean-Marc Ginoux

Understanding protein conformational dynamics is essential for elucidating biological function but remains challenging due to the wide range of timescales and the complexity of collective motions. Enhanced sampling methods overcome…

Statistical Mechanics · Physics 2026-05-11 Souvik Mondal , Michael A. Sauer , Matthias Heyden

Controlling polymorphism in molecular crystals is crucial in the pharmaceutical, dye, and pesticide industries. However, its theoretical description is extremely challenging, due to the associated long timescales ($ > 1 \, \mu s$). We…

Chemical Physics · Physics 2023-02-09 Oren Elishav , Roy Podgaetsky , Olga Meikler , Barak Hirshberg

We develop a model reduction technique for non-smooth dynamical systems using spectral submanifolds. Specifically, we construct low-dimensional, sparse, nonlinear and non-smooth models on unions of slow and attracting spectral submanifolds…

Dynamical Systems · Mathematics 2023-12-25 Leonardo Bettini , Mattia Cenedese , George Haller

Monte Carlo simulations are widely used to simulate complex molecular systems, but standard approaches suffer from metastability. Lately, the use of non-local proposal updates in a collective-variable (CV) space has been proposed in several…

Statistical Mechanics · Physics 2026-04-20 Christoph Schönle , Davide Carbone , Marylou Gabrié , Tony Lelièvre , Gabriel Stoltz

Complex systems often show macroscopic coherent behavior due to the interactions of microscopic agents like molecules, cells, or individuals in a population with their environment. However, simulating such systems poses several…

Distributed, Parallel, and Cluster Computing · Computer Science 2026-03-11 Asif Hamid , Danish Rafiq , Shahkar Ahmad Nahvi , Mohammad Abid Bazaz

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

Molecular dynamics is crucial for understanding molecular systems but its applicability is often limited by the vast timescales of rare events like protein folding. Enhanced sampling techniques overcome this by accelerating the simulation…

Machine Learning · Computer Science 2026-02-24 Seonghyun Park , Kiyoung Seong , Soojung Yang , Rafael Gómez-Bombarelli , Sungsoo Ahn