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The ability of widely used sampling methods, such as molecular dynamics or Monte Carlo, to explore complex free energy landscapes is severely hampered by the presence of kinetic bottlenecks. A large number of solutions have been proposed to…

Statistical Mechanics · Physics 2014-08-29 Omar Valsson , Michele Parrinello

The ability to predict accurate thermodynamic and kinetic properties in biomolecular systems is of both scientific and practical utility. While both remain very difficult, predictions of kinetics are particularly difficult because rates, in…

Chemical Physics · Physics 2018-06-13 Yong Wang , Omar Valsson , Pratyush Tiwary , Michele Parrinello , Kresten Lindorff-Larsen

We introduce a novel enhanced sampling approach named OPES flooding for calculating the kinetics of rare events from atomistic molecular dynamics simulation. This method is derived from the On-the-fly-Probability-Enhanced-Sampling (OPES)…

Chemical Physics · Physics 2022-10-31 Dhiman Ray , Narjes Ansari , Valerio Rizzi , Michele Invernizzi , Michele Parrinello

Many enhanced sampling techniques rely on the identification of a number of collective variables that describe all the slow modes of the system. By constructing a bias potential in this reduced space one is then able to sample efficiently…

Computational Physics · Physics 2019-03-05 Michele Invernizzi , Michele Parrinello

We introduce a variational algorithm to estimate the likelihood of a rare event within a nonequilibrium molecular dynamics simulation through the evaluation of an optimal control force. Optimization of a control force within a chosen basis…

Statistical Mechanics · Physics 2021-01-14 Avishek Das , David T. Limmer

In this paper we combine two powerful computational techniques, well-tempered metadynamics and time lagged independent component analysis. The aim is to develop a new tool for studying rare events and exploring complex free energy…

Statistical Mechanics · Physics 2017-12-08 James McCarty , Michele Parrinello

Metadynamics is a commonly used and successful enhanced sampling method. By the introduction of a history dependent bias which depends on a restricted number of collective variables(CVs) it can explore complex free energy surfaces…

Statistical Mechanics · Physics 2013-12-06 Pratyush Tiwary , Michele Parrinello

Sampling complex free energy surfaces is one of the main challenges of modern atomistic simulation methods. The presence of kinetic bottlenecks in such surfaces often renders a direct approach useless. A popular strategy is to identify a…

Computational Physics · Physics 2019-09-25 Luigi Bonati , Yue-Yu Zhang , Michele Parrinello

A variational principle is derived for two-dimensional incompressible rotational fluid flow with a free surface in a moving vessel when both the vessel and fluid motion are to be determined. The fluid is represented by a stream function and…

Fluid Dynamics · Physics 2020-02-20 H. Alemi Ardakani , T. J. Bridges , F. Gay-Balmaz , Y. Huang , C. Tronci

We study by computer simulation the nucleation of a supersaturated Lennard-Jones vapor into the liquid phase. The large free energy barriers to transition make the time scale of this process impossible to study by ordinary molecular…

Statistical Mechanics · Physics 2018-08-15 Pablo M. Piaggi , Omar Valsson , Michele Parrinello

Given a set of inelastic material models, a microstructure, a macroscopic structural geometry, and a set of boundary conditions, one can in principle always solve the governing equations to determine the system's mechanical response.…

Computational Engineering, Finance, and Science · Computer Science 2023-06-27 Ghina Jezdan , Sanjay Govindjee , Klaus Hackl

Building on recent advances in scientific machine learning and generative modeling for computational fluid dynamics, we propose a conditional score-based diffusion model designed for multi-scenarios fluid flow prediction. Our model…

Machine Learning · Computer Science 2025-06-02 Wilfried Genuist , Éric Savin , Filippo Gatti , Didier Clouteau

Several recent methods have shown that it is possible to compute rate constants of very slow biomolecular processes using simulations where a time-dependent bias is added along one or several collective variables (CVs). We previously…

Chemical Physics · Physics 2026-05-01 Nicodemo Mazzaferro , Willmor J Pena Ccoa , Pilar Cossio , Glen M. Hocky

Extreme events are ubiquitous in a wide range of dynamical systems, including turbulent fluid flows, nonlinear waves, large scale networks and biological systems. Here, we propose a variational framework for probing conditions that trigger…

Fluid Dynamics · Physics 2018-07-10 Mohammad Farazmand , Themistoklis P. Sapsis

Active matter represents a broad class of systems that evolve far from equilibrium due to the local injection of energy. Like their passive analogues, transformations between distinct metastable states in active matter proceed through rare…

Statistical Mechanics · Physics 2022-01-17 Avishek Das , Benjamin Kuznets-Speck , David T. Limmer

The modeling of atomistic biomolecular simulations using kinetic models such as Markov state models (MSMs) has had many notable algorithmic advances in recent years. The variational principle has opened the door for a nearly fully automated…

Biological Physics · Physics 2019-11-26 Martin K. Scherer , Brooke E. Husic , Moritz Hoffmann , Fabian Paul , Hao Wu , Frank Noé

Estimating the free energy in molecular simulation requires, implicitly or explicitly, counting how many times the system is observed in a finite region. If the simulation is biased by an external potential, the weight of the configurations…

Chemical Physics · Physics 2021-12-22 Matteo Carli , Alessandro Laio

We present a method for performing multithermal-multibaric molecular dynamics simulations that sample entire regions of the temperature-pressure (TP) phase diagram. The method uses a variational principle [Valsson and Parrinello, Phys. Rev.…

Statistical Mechanics · Physics 2019-02-13 Pablo M. Piaggi , Michele Parrinello

Our ability to calculate rates of biochemical processes using molecular dynamics simulations is severely limited by the fact that the time scales for reactions, or changes in conformational state, scale exponentially with the relevant…

Chemical Physics · Physics 2024-03-19 Nicodemo Mazzaferro , Subarna Sasmal , Pilar Cossio , Glen M. Hocky

We develop a variational Bayes approach for dynamic variable selection in high-dimensional regression models with time-varying parameters and predictors that exhibit a predefined group structure. Through comprehensive simulation studies, we…

Methodology · Statistics 2025-04-16 Nicolas Bianco , Mauro Bernardi , Daniele Bianchi
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