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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

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

We consider the problem of sampling transition paths between two given metastable states of a molecular system, e.g. a folded and unfolded protein or products and reactants of a chemical reaction. Due to the existence of high energy…

Biomolecules · Quantitative Biology 2023-07-19 Lars Holdijk , Yuanqi Du , Ferry Hooft , Priyank Jaini , Bernd Ensing , Max Welling

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 increasing use of machine-learning (ML) enabled systems in critical tasks fuels the quest for novel verification and validation techniques yet grounded in accepted system assurance principles. In traditional system development,…

Machine Learning · Computer Science 2020-02-11 Taejoon Byun , Sanjai Rayadurgam

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

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 (MD) simulations are fundamental computational tools for the study of proteins and their free energy landscapes. However, sampling protein conformational changes through MD simulations is challenging due to the relatively…

Biomolecules · Quantitative Biology 2023-07-20 Diego E. Kleiman , Hassan Nadeem , Diwakar Shukla

A generative modeling framework is proposed that combines diffusion models and manifold learning to efficiently sample data densities on manifolds. The approach utilizes Diffusion Maps to uncover possible low-dimensional underlying (latent)…

Machine Learning · Computer Science 2025-04-22 Dimitris G. Giovanis , Ellis Crabtree , Roger G. Ghanem , Ioannis G. Kevrekidis

Deep learning models with a large number of parameters, often referred to as over-parameterized models, have achieved exceptional performance across various tasks. Despite concerns about overfitting, these models frequently generalize well…

Machine Learning · Computer Science 2025-06-10 Ilya Kaufman Sirot , Omri Azencot

Sampling from high-dimensional Gibbs measures poses a challenge when the energy landscape consists of multiple metastable states. Enhanced-sampling methods mitigate this difficulty by introducing adaptive biasing potentials to facilitate…

Numerical Analysis · Mathematics 2026-05-06 Liyao Lyu , Siyu Guo , Huan Lei

Manifold models provide low-dimensional representations that are useful for processing and analyzing data in a transformation-invariant way. In this paper, we study the problem of learning smooth pattern transformation manifolds from image…

Computer Vision and Pattern Recognition · Computer Science 2013-05-20 Elif Vural , Pascal Frossard

We introduce manifold-learning flows (M-flows), a new class of generative models that simultaneously learn the data manifold as well as a tractable probability density on that manifold. Combining aspects of normalizing flows, GANs,…

Machine Learning · Statistics 2020-11-16 Johann Brehmer , Kyle Cranmer

Understanding the behavior of complex molecular systems is a fundamental problem in physical chemistry. To describe the long-time dynamics of such systems, which is responsible for their most informative characteristics, we can identify a…

Chemical Physics · Physics 2024-09-11 Jakub Rydzewski

Metadynamics (MTD) is a very powerful technique to sample high-dimensional free energy landscapes, and due to its self-guiding property, the method has been successful in studying complex reactions and conformational changes. MTD sampling…

Computational Physics · Physics 2016-02-05 Shalini Awasthi , Venkat Kapil , Nisanth N. Nair

System identification has greatly benefited from deep learning techniques, particularly for modeling complex, nonlinear dynamical systems with partially unknown physics where traditional approaches may not be feasible. However, deep…

Machine Learning · Computer Science 2025-04-17 Marco Forgione , Ankush Chakrabarty , Dario Piga , Matteo Rufolo , Alberto Bemporad

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

Manifold learning flows are a class of generative modelling techniques that assume a low-dimensional manifold description of the data. The embedding of such a manifold into the high-dimensional space of the data is achieved via learnable…

Machine Learning · Statistics 2025-03-07 Kyriakos Flouris , Ender Konukoglu

Manifold learning aims to discover and represent low-dimensional structures underlying high-dimensional data while preserving critical topological and geometric properties. Existing methods often fail to capture local details with global…

Machine Learning · Computer Science 2025-05-08 Ren Wang , Pengcheng Zhou