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Accurate free-energy estimation is essential in molecular simulation, yet the periodic boundary conditions (PBC) commonly used in computer simulations have rarely been explicitly exploited. Equilibrium methods such as umbrella sampling,…

Statistical Mechanics · Physics 2025-11-03 Daniel Nagel , Tristan Bereau

In this paper, we develop a novel mesh-free framework, termed physics-informed neural networks with invariant measure score matching (PINN-IMSM), for reconstructing dynamical systems from unlabeled point-cloud data that capture the system's…

Numerical Analysis · Mathematics 2026-01-21 Yongsheng Chen , Suddhasattwa Das , Wei Guo , Xinghui Zhong

The present paper proposes an adaptive biasing potential for the computation of free energy landscapes. It is motivated by statistical learning arguments and unifies the tasks of biasing the molecular dynamics to escape free energy wells…

Mathematical Physics · Physics 2018-03-05 I. Bilionis , P. S. Koutsourelakis

Energy landscapes play a crucial role in shaping dynamics of many real-world complex systems. System evolution is often modeled as particles moving on a landscape under the combined effect of energy-driven drift and noise-induced diffusion,…

Computational Engineering, Finance, and Science · Computer Science 2025-03-04 Ruikun Li , Huandong Wang , Qingmin Liao , Yong Li

Free energy landscapes encode the kinetics, intermediates, and transition states that govern molecular processes and are thus a key target of single biomolecule research. Typical approaches to deriving optimal, error-minimizing,…

Biological Physics · Physics 2025-11-25 Oliver Cheng , Zosia Adamska , Michael P. Brenner , Megan C. Engel

Recently, nanofluidics experiments have been used to characterize the behavior of single DNA molecules confined to narrow slits etched with arrays of nanopits. Analysis of the experimental data relies on analytical estimates of the…

Soft Condensed Matter · Physics 2024-09-09 James M. Polson , Matthew Kozma

We address the problem of constructing accurate mathematical models of the dynamics of complex systems projected on a collective variable. To this aim we introduce a conceptually simple yet effective algorithm for estimating the parameters…

Statistical Mechanics · Physics 2022-09-28 Karen Palacio-Rodriguez , Fabio Pietrucci

We present a differentiable formalism for learning free energies that is capable of capturing arbitrarily complex model dependencies on coarse-grained coordinates and finite-temperature response to variation of general system parameters.…

Computational Physics · Physics 2024-05-31 Blake R. Duschatko , Xiang Fu , Cameron Owen , Yu Xie , Albert Musaelian , Tommi Jaakkola , Boris Kozinsky

Free energies govern the behavior of soft and liquid matter, and improving their predictions could have a large impact on the development of drugs, electrolytes or homogeneous catalysts. Unfortunately, it is challenging to devise an…

Chemical Physics · Physics 2021-04-14 Jan Weinreich , Nicholas J. Browning , O. Anatole von Lilienfeld

Various methods achieving importance sampling in ensembles of nonequilibrium trajectories enable to estimate free energy differences and, by maximum-likelihood post-processing, to reconstruct free energy landscapes. Here, based on Bayes…

Statistical Mechanics · Physics 2010-07-02 Manuel Athènes , Mihai-Cosmin Marinica

A family of fast sampling methods is introduced here for molecular simulations of systems having rugged free energy landscapes. The methods represent a generalization of a strategy consisting of adjusting a model for the free energy as a…

Computational Physics · Physics 2022-02-07 Pablo F. Zubieta Rico , Juan J. de Pablo

Data-Free Meta-Learning (DFML) aims to extract knowledge from a collection of pre-trained models without requiring the original data, presenting practical benefits in contexts constrained by data privacy concerns. Current DFML methods…

Machine Learning · Computer Science 2024-12-10 Yongxian Wei , Zixuan Hu , Zhenyi Wang , Li Shen , Chun Yuan , Dacheng Tao

We demonstrate how a prior assumption of smoothness can be used to enhance the reconstruction of free energy profiles from multiple umbrella sampling simulations using the Bayesian Gaussian process regression approach. The method we derive…

Statistical Mechanics · Physics 2014-07-25 Noam Bernstein , Thomas Stecher , Gábor Csányi

The equilibrium free energy landscape of off-lattice model heteropolymers as a function of an internal coordinate, namely the end-to-end distance, is reconstructed from out-of-equilibrium steered molecular dynamics data. This task is…

Statistical Mechanics · Physics 2008-09-17 Stefano Luccioli , Alberto Imparato , Alessandro Torcini

Many important multi-component crystalline solids undergo mechanochemical spinodal decomposition: a phase transformation in which the compositional redistribution is coupled with structural changes of the crystal, resulting in dynamically…

Computational Engineering, Finance, and Science · Computer Science 2023-07-19 Xiaoxuan Zhang , Krishna Garikipati

We introduce an innovative approach for solving high-dimensional Fokker-Planck-L\'evy (FPL) equations in modeling non-Brownian processes across disciplines such as physics, finance, and ecology. We utilize a fractional score function and…

Machine Learning · Computer Science 2024-06-18 Zheyuan Hu , Zhongqiang Zhang , George Em Karniadakis , Kenji Kawaguchi

Free energy perturbation (FEP) is frequently used to evaluate the free energy change of a biological process, e.g. the drug binding free energy or the ligand solvation free energy. Due to the sampling inefficiency, FEP is often employed…

Chemical Physics · Physics 2017-01-31 Ying-Chih Chiang , Frank Otto

Describing the complex landscape of infinite-dimensional free energy is generally a challenging problem. This difficulty arises from the existence of numerous minimizers and, consequently, a vast number of saddle points. These factors make…

Soft Condensed Matter · Physics 2025-07-15 Keiichiro Kagawa , Takeshi Watanabe , Yasumasa Nishiura

Particles interacting with short-ranged potentials have attracted increasing interest, partly for their ability to model mesoscale systems such as colloids interacting via DNA or depletion. We consider the free energy landscape of such…

Mathematical Physics · Physics 2015-06-11 Miranda Holmes-Cerfon , Steven J. Gortler , Michael P. Brenner

We present a method to explore the free energy landscapes of chemical reactions with post-transition-state bifurcations using an enhanced sampling method based on well-tempered metadynamics. Obviating the need for computationally expensive…

Chemical Physics · Physics 2023-04-18 Juno Nam , YounJoon Jung
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