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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

We propose an efficient novel path sampling-based framework designed to accelerate the investigation of rare events in complex molecular systems. A key innovation is the shift from sampling restricted path ensemble distributions, as in…

Chemical Physics · Physics 2025-03-28 Gianmarco Lazzeri , Peter G. Bolhuis , Roberto Covino

Accurate phase diagram calculation from molecular dynamics requires systematic treatment and convergence of statistical averages. In this work we propose a Gaussian process regression based framework for reconstructing the free energy…

Computational Physics · Physics 2021-11-02 V. Ladygin , I. Beniya , E. Makarov , A. Shapeev

Molecule synthesis through machine learning is one of the fundamental problems in drug discovery. Current data-driven strategies employ one-step retrosynthesis models and search algorithms to predict synthetic routes in a top-bottom manner.…

Machine Learning · Computer Science 2024-06-05 Songtao Liu , Hanjun Dai , Yue Zhao , Peng Liu

The mechanical unfolding of an engineered protein composed of eight domains of Ig27 is investigated by using atomic force microscopy. Exploiting a fluctuation relation, the equilibrium free energy as a function of the molecule elongation is…

Soft Condensed Matter · Physics 2008-05-29 A. Imparato , F. Sbrana , M. Vassalli

We propose a new method to obtain kinetic properties of infrequent events from molecular dynamics simulation. The procedure employs a recently introduced variational approach [Valsson and Parrinello, Phys. Rev. Lett. 113, 090601 (2014)] to…

Statistical Mechanics · Physics 2015-08-19 James McCarty , Omar Valsson , Pratyush Tiwary , Michele Parrinello

This paper investigates the problem of estimating the spectral power parameters of random analog sources using numerical measurements acquired with minimum digitization complexity. Therefore, spectral analysis has to be performed with…

Signal Processing · Electrical Eng. & Systems 2019-10-29 Manuel S. Stein

Molecular dynamics is a powerful tool for studying the thermodynamics and kinetics of complex molecular events. However, these simulations can rarely sample the required time scales in practice. Transition path sampling overcomes this…

Chemical Physics · Physics 2023-07-31 Gianmarco Lazzeri , Hendrik Jung , Peter G. Bolhuis , Roberto Covino

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 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

Alchemical free energy calculations are a useful tool for predicting free energy differences associated with the transfer of molecules from one environment to another. The hallmark of these methods is the use of "bridging" potential energy…

A new scheme for the numerical evaluation of the one-loop self-energy correction to all orders in Z \alpha is presented. The scheme proposed inherits the attractive features of the standard potential-expansion method but yields a…

Atomic Physics · Physics 2009-11-11 Vladimir A. Yerokhin , Krzysztof Pachucki , Vladimir M. Shabaev

Free energies as a function of a selected set of collective variables are commonly computed in molecular simulation and of significant value in understanding and engineering molecular behavior. These free energy surfaces are most commonly…

Statistical Mechanics · Physics 2022-11-15 Michael R. Shirts , Andrew L. Ferguson

Weighted average sampling is more practical and numerically more stable than sampling at single points as in the classical Shannon sampling framework. Using the frame theory, one can completely reconstruct a bandlimited function from its…

Information Theory · Computer Science 2014-07-04 Haizhang Zhang

Recent developments in statistical mechanics have allowed the estimation of equilibrium free energies from the statistics of work measurements during processes that drive the system out of equilibrium. Here a different class of processes is…

Statistical Mechanics · Physics 2009-11-11 Artur B. Adib

We introduce a new class of Sequential Monte Carlo (SMC) methods, which we call free energy SMC. This class is inspired by free energy methods, which originate from Physics, and where one samples from a biased distribution such that a given…

Computation · Statistics 2010-06-16 Nicolas Chopin , Pierre Jacob

Weighted ensemble (WE) is an enhanced path-sampling method that is conceptually simple, widely applicable, and statistically exact. In a WE simulation, an ensemble of trajectories is periodically pruned or replicated to enhance sampling of…

A theoretical framework is proposed for an energy decomposition scheme along the reaction coordinate, in which the ensemble average of the potential energy weighted with reactive flux intensity is decomposed into energy components at the…

Chemical Physics · Physics 2022-03-04 Wenjin Li

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

Computing averages over a target probability density by statistical re-weighting of a set of samples with a different distribution is a strategy which is commonly adopted in fields as diverse as atomistic simulation and finance. Here we…

Chemical Physics · Physics 2012-02-21 Michele Ceriotti , Guy A. R. Brain , Oliver Riordan , David E. Manolopoulos