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The free energy profile of a reaction can be estimated in a molecular-dynamics approach by imposing a mechanical constraint along a reaction coordinate (RC). Many recent studies have shown that the temperature can greatly influence the path…

Chemical Physics · Physics 2009-11-11 P. Fleurat-Lessard , T. Ziegler

The Free Energy Principle (FEP) states that under suitable conditions of weak coupling, random dynamical systems with sufficient degrees of freedom will behave so as to minimize an upper bound, formalized as a variational free energy, on…

Quantum Physics · Physics 2022-07-21 Chris Fields , Karl Friston , James F. Glazebrook , Michael Levin

Reaction probabilities as a function of total angular momentum and the resulting reaction cross-sections for the collision of open shell S($^1$D) atoms with para-hydrogen have been calculated in the kinetic energy range 0.09--10 meV (1--120…

Chemical Physics · Physics 2015-05-28 Manuel Lara , P. G. Jambrina , A. J. C. Varandas , J. -M. Launay , F. J. Aoiz

The reaction dynamics for the H + HeH$^+$ $\rightarrow$ He + H$_2^+$ reaction in its electronic ground state is investigated using two different representations of the potential energy surface (PES). The first uses a combined kernel and…

Chemical Physics · Physics 2025-03-28 Meenu Upadhyay , Silvan Käser , Jayakrushna Sahoo , Yohann Scribano , Markus Meuwly

The free energy principle (FEP) states that any dynamical system can be interpreted as performing Bayesian inference upon its surrounding environment. In this work, we examine in depth the assumptions required to derive the FEP in the…

Neurons and Cognition · Quantitative Biology 2022-05-23 Miguel Aguilera , Beren Millidge , Alexander Tschantz , Christopher L. Buckley

Free energy perturbation (FEP) is considered the gold-standard simulation method for estimating small molecule binding affinity, a quantity of vital importance to drug discovery. The accuracy of FEP critically depends on an accurate model…

The concept of a protein diffusing in its free energy folding landscape has been fruitful for both theory and experiment. Yet the choice of the reaction coordinate (RC) introduces an undesirable degree of arbitrariness into the problem. We…

Biological Physics · Physics 2015-05-19 Michael Hinczewski , Yann von Hansen , Joachim Dzubiella , Roland R. Netz

The description of chemical processes at the molecular level is often facilitated by use of reaction coordinates, or collective variables (CVs). The CV measures the progress of the reaction and allows the construction of profiles that track…

Chemical Physics · Physics 2023-04-26 Johannes C. B. Dietschreit , Dennis J. Diestler , Rafael Gómez-Bombarelli

High-temperature reactions widely exist in nature. However, they are difficult to be characterized either experimentally or computationally. The routinely used minimum energy path (MEP) model in computational modeling of chemical reactions…

Chemical Physics · Physics 2020-05-13 Xiongzhi Zeng , Zongyang Qiu , Pai Li , Zhenyu Li , Jinlong Yang

We present an approach that extends the theory of targeted free energy perturbation (TFEP) to calculate free energy differences and free energy surfaces at an accurate quantum mechanical level of theory from a cheaper reference potential.…

Computational Physics · Physics 2021-11-15 Andrea Rizzi , Paolo Carloni , Michele Parrinello

Free energy profile (FE Profile) is an essential quantity for the estimation of reaction rate and the validation of reaction mechanism. For chemical reactions in condensed phase or enzymatic reactions, the computation of FE profile at ab…

Computational Physics · Physics 2018-11-15 Pengfei Li , Xiangyu Jia , Xiaoliang Pan , Yihan Shao , Ye Mei

The Free-Energy Principle (FEP) [1-3] has been adopted in a variety of ambitious proposals that aim to characterize all adaptive, sentient, and cognitive systems within a unifying framework. Judging by the amount of attention it has…

Neurons and Cognition · Quantitative Biology 2024-01-18 Zahra Sheikhbahaee , Adam Safron , Casper Hesp , Guillaume Dumas

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

The Free-Energy-Principle (FEP) is an influential and controversial theory which postulates a deep and powerful connection between the stochastic thermodynamics of self-organization and learning through variational inference. Specifically,…

Artificial Intelligence · Computer Science 2021-10-05 Beren Millidge , Anil Seth , Christopher L Buckley

The high-temperature atom exchange and dissociation reaction dynamics of the O($^3$P) + O$_2(^3\Sigma_g^{-} )$ system are investigated based on a new reproducing kernel-based representation of high-level multi-reference configuration…

Chemical Physics · Physics 2025-06-09 JingChun Wang , Juan Carlos San Vicente Veliz , Meenu Upadhyay , Markus Meuwly

The Targeted Free Energy Perturbation (TFEP) method aims to overcome the time-consuming and computer-intensive stratification process of standard methods for estimating the free energy difference between two states. To achieve this, TFEP…

Chemical Physics · Physics 2023-02-24 Soo Jung Lee , Amr H. Mahmoud , Markus A. Lill

The minimum energy path (MEP) describes the mechanism of reaction, and the energy barrier along the path can be used to calculate the reaction rate in thermal systems. The nudged elastic band (NEB) method is one of the most commonly used…

Numerical Analysis · Mathematics 2025-03-24 Xuanyu Liu , Huajie Chen , Christoph Ortner

Sampling the free energy surface, namely, the distribution of collective variables (CVs), is a crucial problem in statistical physics, as it underpins a better understanding of chemical reactions and conformational transitions. Traditional…

Machine Learning · Computer Science 2026-05-04 Zichen Liu , Tiejun Li

In this work, we propose a multi-scale protocol for routine theoretical studies of chemical reaction mechanisms. The initial reaction paths of our investigated systems are sampled using the Nudged-Elastic Band (NEB) method driven by a cheap…

Chemical Physics · Physics 2023-07-26 Tomislav Piskor , Peter Pinski , Thilo Mast , Vladimir V. Rybkin

We present a new method to compute free energies at a quantum mechanical (QM) level of theory from molecular simulations using cheap reference potential energy functions, such as force fields. To overcome the poor overlap between the…

Computational Physics · Physics 2023-11-13 Andrea Rizzi , Paolo Carloni , Michele Parrinello
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