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Many biological processes occur on time scales longer than those accessible to molecular dynamics simulations. Identifying collective variables (CVs) and introducing an external potential to accelerate them is a popular approach to address…

Computational Physics · Physics 2024-10-24 Enrico Trizio , Andrea Rizzi , Pablo M. Piaggi , Michele Invernizzi , Luigi Bonati

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

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

Enhanced sampling simulations make the computational study of rare events feasible. A large family of such methods crucially depends on the definition of some collective variables (CVs) that could provide a low-dimensional representation of…

Computational Physics · Physics 2026-03-03 Jintu Zhang , Luigi Bonati , Enrico Trizio , Odin Zhang , Yu Kang , TingJun Hou , Michele Parrinello

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

A variety of enhanced sampling methods predict multidimensional free energy landscapes associated with biological and other molecular processes as a function of a few selected collective variables (CVs). The accuracy of these methods is…

Computational Physics · Physics 2024-04-09 Lukas Müllender , Andrea Rizzi , Michele Parrinello , Paolo Carloni , Davide Mandelli

Generating a data set that is representative of the accessible configuration space of a molecular system is crucial for the robustness of machine learned interatomic potentials (MLIP). However, the complexity of molecular systems,…

Machine Learning · Computer Science 2025-01-28 Aik Rui Tan , Johannes C. B. Dietschreit , Rafael Gomez-Bombarelli

We introduce a method for elucidating and modifying the functionality of systems dominated by rare events that relies on the automated tuning of their underlying free energy surface. The proposed approach seeks to construct collective…

Computational Physics · Physics 2021-08-31 Dan Mendels , Juan J. de Pablo

Understanding the long-time dynamics of complex physical processes depends on our ability to recognize patterns. To simplify the description of these processes, we often introduce a set of reaction coordinates, customarily referred to as…

Chemical Physics · Physics 2024-12-31 Tuğçe Gökdemir , Jakub Rydzewski

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

Free energy biasing methods have proven to be powerful tools to accelerate the simulation of important conformational changes of molecules by modifying the sampling measure. However, most of these methods rely on the prior knowledge of…

Biological Physics · Physics 2021-10-20 Zineb Belkacemi , Paraskevi Gkeka , Tony Lelièvre , Gabriel Stoltz

Designing an appropriate set of collective variables is crucial to the success of several enhanced sampling methods. Here we focus on how to obtain such variables from information limited to the metastable states. We characterize these…

Chemical Physics · Physics 2020-04-08 Luigi Bonati , Valerio Rizzi , Michele Parrinello

The dynamics of physical systems that require high-dimensional representation can often be captured in a few meaningful degrees of freedom called collective variables (CVs). However, identifying CVs is challenging and constitutes a…

Chemical Physics · Physics 2024-04-03 Jakub Rydzewski

Collective variables (CVs) are low-dimensional projections of high-dimensional system states. They are used to gain insights into complex emergent dynamical behaviors of processes on networks. The relation between CVs and network measures…

Physics and Society · Physics 2026-03-19 Marvin Lücke , Stefanie Winkelmann , Jobst Heitzig , Nora Molkenthin , Péter Koltai

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…

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

High-dimensional metastable molecular system can often be characterised by a few features of the system, i.e. collective variables (CVs). Thanks to the rapid advance in the area of machine learning and deep learning, various deep…

Machine Learning · Computer Science 2023-08-10 Wei Zhang , Christof Schütte

Several enhanced sampling techniques rely on the definition of collective variables to effectively explore free energy landscapes. Existing variables that describe the progression along a reactive pathway offer an elegant solution but face…

Chemical Physics · Physics 2024-02-05 Thorben Fröhlking , Luigi Bonati , Valerio Rizzi , Francesco Luigi Gervasio

While recent advances in AI have transformed protein structure prediction, protein function is also strongly influenced by the thermodynamic and kinetic features encoded in its underlying free-energy surface. Here, we propose a…

Biological Physics · Physics 2026-04-29 Alexander Zhilkin , Muralika Medaparambath , Dan Mendels

Conformational sampling of biomolecules using molecular dynamics simulations often produces large amount of high dimensional data that makes it difficult to interpret using conventional analysis techniques. Dimensionality reduction methods…

Biomolecules · Quantitative Biology 2021-12-08 Mahdi Ghorbani , Samarjeet Prasad , Jeffery B. Klauda , Bernard R. Brooks
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