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We have analyzed dynamics on the complex free energy landscape of protein folding in the FOLD-X model, by calculating for each state of the system the mean first passage time to the folded state. The resulting kinetic map of the folding…

Statistical Mechanics · Physics 2009-11-10 M. A. Micheelsen , C. Rischel , J. Ferkinghoff-Borg , R. Guerois , L. Serrano

In this paper, we present a novel reinforcement learning framework designed to optimize molecular dynamics by focusing on the entire trajectory rather than just the final molecular configuration. Leveraging a stochastic version of…

Optimization and Control · Mathematics 2024-10-22 Chandrajit Bajaj , Minh Nguyen , Conrad Li

It is often difficult to quantitatively determine if a new molecular simulation algorithm or software properly implements sampling of the desired thermodynamic ensemble. We present some simple statistical analysis procedures to allow…

Statistical Mechanics · Physics 2013-03-04 Michael R. Shirts

Machine learning (ML) is transforming all areas of science. The complex and time-consuming calculations in molecular simulations are particularly suitable for a machine learning revolution and have already been profoundly impacted by the…

Chemical Physics · Physics 2019-11-11 Frank Noé , Alexandre Tkatchenko , Klaus-Robert Müller , Cecilia Clementi

Molecular dynamics (MD) is a widely-used tool for simulating the molecular and materials properties. It is a common wisdom that molecular dynamics simulations should obey physical laws and, hence, lots of effort is put into ensuring that…

Chemical Physics · Physics 2023-08-23 Lina Zhang , Yi-Fan Hou , Fuchun Ge , Pavlo O. Dral

Boltzmann Generators have emerged as a promising machine learning tool for generating samples from equilibrium distributions of molecular systems using Normalizing Flows and importance weighting. Recently, Flow Matching has helped speed up…

Machine Learning · Statistics 2025-10-21 Lorenz Vaitl , Leon Klein

Due to the time scale problem, rare events are not accessible by straight forward molecular dynamics. The presence of multiple reaction channels complicates the problem even further. The feasibility of the standard free energy based methods…

Statistical Mechanics · Physics 2009-11-13 Titus S. van Erp

Emergent phenomena share the fascinating property of not being obvious consequences of the design of the system in which they appear. This characteristic is no less relevant when attempting to simulate such phenomena, given that the outcome…

Soft Condensed Matter · Physics 2014-11-26 D. C. Rapaport

We present a molecular simulation method to simultaneously find multiple transition pathways, and their associated free-energy profiles. The scheme extends path-metadynamics (PMD) [Phys. Rev. Lett. 109, 020601 (2012)] with multiple paths…

Statistical Mechanics · Physics 2025-06-23 Alberto Pérez de Alba Ortíz , Bernd Ensing

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

The dynamic of complex ordering systems with active rotational degrees of freedom exemplified by protein self-assembly is explored using a machine learning workflow that combines deep learning-based semantic segmentation and rotationally…

Soft Condensed Matter · Physics 2021-04-26 Sergei V. Kalinin , Shuai Zhang , Mani Valleti , Harley Pyles , David Baker , James J. De Yoreo , Maxim Ziatdinov

Many processes of scientific importance are characterized by time scales that extend far beyond the reach of standard simulation techniques. To circumvent this impediment a plethora of enhanced sampling methods has been developed. One…

Computational Physics · Physics 2018-12-05 Dan Mendels , Giovannimaria Piccini , Z. Faidon Brotzakis , Yi I. Yang , Michele Parrinello

The equations of classical mechanics can be used to model the time evolution of countless physical systems, from the astrophysical to the atomic scale. Accurate numerical integration requires small time steps, which limits the computational…

Chemical Physics · Physics 2026-03-09 Filippo Bigi , Johannes Spies , Michele Ceriotti

Estimating free energy differences, an important problem in computational drug discovery and in a wide range of other application areas, commonly involves a computationally intensive process of sampling a family of high-dimensional…

A central endeavor of thermodynamics is the measurement of free energy changes. Regrettably, although we can measure the free energy of a system in thermodynamic equilibrium, typically all we can say about the free energy of a…

Statistical Mechanics · Physics 2012-04-10 David A. Sivak , Gavin E. Crooks

Recently discovered identities in statistical mechanics have enabled the calculation of equilibrium ensemble averages from realizations of driven nonequilibrium processes, including single-molecule pulling experiments and analogous computer…

Statistical Mechanics · Physics 2011-11-21 David D. L. Minh , John D. Chodera

We present a detailed comparison of computational efficiency and precision for several free energy difference ($\Delta F$) methods. The analysis includes both equilibrium and non-equilibrium approaches, and distinguishes between…

Biological Physics · Physics 2009-11-11 F. Marty Ytreberg , Robert H. Swendsen , Daniel M. Zuckerman

In molecular dynamics (MD) simulations, transitions between states are often rare events due to energy barriers that exceed the thermal temperature. Because of their infrequent occurrence and the huge number of degrees of freedom in…

Chemical Physics · Physics 2024-12-06 Tuğçe Gökdemir , Jakub Rydzewski

Molecular dynamics (MD) simulation is a widely used technique to simulate molecular systems, most commonly at the all-atom resolution where equations of motion are integrated with timesteps on the order of femtoseconds…

Molecular dynamics (MD) simulation is essential for various scientific domains but computationally expensive. Learning-based force fields have made significant progress in accelerating ab-initio MD simulation but are not fast enough for…

Machine Learning · Computer Science 2023-08-29 Xiang Fu , Tian Xie , Nathan J. Rebello , Bradley D. Olsen , Tommi Jaakkola
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