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Related papers: Kinetics-Optimized Enhanced Sampling Using Mean Fi…

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We present a method to sample reactive pathways via biased molecular dynamics simulations in trajectory space. We show that the use of enhanced sampling techniques enables unconstrained exploration of multiple reaction routes. Time…

Computational Physics · Physics 2020-07-15 Davide Mandelli , Barak Hirshberg , 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 present a simple and robust technique to extract kinetic rate models and thermodynamic quantities from single molecule time traces. SMACKS (Single Molecule Analysis of Complex Kinetic Sequences) is a maximum likelihood approach that…

Quantitative Methods · Quantitative Biology 2022-03-10 Sonja Schmid , Markus Götz , Thorsten Hugel

Atomistic simulations provide valuable insights into the physical processes governing material behavior. However, their applicability is fundamentally constrained by the limited time scales accessible to brute-force simulations. This…

Computational Physics · Physics 2026-02-16 Michael Kim , Wei Cai

We review a selection of methods for performing enhanced sampling in molecular dynamics simulations. We consider methods based on collective variable biasing and on tempering, and offer both historical and contemporary perspectives. In…

Statistical Mechanics · Physics 2014-01-03 Cameron Abrams , Giovanni Bussi

Atomistic modelling of phase transitions, chemical reactions, or other rare events that involve overcoming high free energy barriers usually entails prohibitively long simulation times. Introducing a bias potential as a function of an…

Computational Physics · Physics 2019-11-06 Federico Giberti , Bingqing Cheng , Gareth Aneurin Tribello , Michele Ceriotti

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

The computer simulation of many molecular processes is complicated by long time scales caused by rare transitions between long-lived states. Here, we propose a new approach to simulate such rare events, which combines transition path…

Computational Physics · Physics 2023-03-23 Sebastian Falkner , Alessandro Coretti , Christoph Dellago

We report new statistical time-series analysis tools providing significant improvements in the rapid, precision extraction of discrete state dynamics from large databases of experimental observations of molecular machines. By building…

Quantitative Methods · Quantitative Biology 2019-10-23 Max A. Little , Bradley C. Steel , Fan Bai , Yoshiyuki Sowa , Thomas Bilyard , David M. Mueller , Richard M. Berry , Nick S. Jones

RNA function is intimately related to its structural dynamics. Molecular dynamics simulations are useful for exploring biomolecular flexibility but are severely limited by the accessible timescale. Enhanced sampling methods allow this…

Biomolecules · Quantitative Biology 2018-02-06 Vojtěch Mlýnský , Giovanni Bussi

Infrequent Metadynamics is a popular method to obtain the rates of long timescale processes from accelerated simulations. The inference procedure is based on rescaling the first-passage times of Metadynamics trajectories using a…

Chemical Physics · Physics 2025-03-04 Ofir Blumer , Shlomi Reuveni , Barak Hirshberg

Empirical force fields employed in molecular dynamics simulations of complex systems can be optimised to reproduce experimentally determined structural and thermodynamic properties. In contrast, experimental knowledge about the rates of…

Statistical Mechanics · Physics 2022-07-12 P. G. Bolhuis , Z. F. Brotzakis , B. G. Keller

Molecular simulations are playing an ever increasing role, finding applications in fields as varied as physics, chemistry, biology and material science. However, many phenomena of interest take place on time scales that are out of reach of…

Computational Physics · Physics 2021-10-07 Michele Invernizzi

Normal molecular dynamics simulations are usually unable to simulate chemical reactions due to the low probability of forming the transition state. Therefore, enhanced sampling methods are implemented to accelerate the occurrence of…

Chemical Physics · Physics 2022-10-14 Yi Sun , Xu Han , Lijiang Yang

Simulations with an adaptive time-dependent bias, such as metadynamics, enable an efficient exploration of the conformational space of a system. However, the dynamic information of the system is altered by the bias. With infrequent…

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

Kinetic parameters such as the turnover number ($k_{cat}$) and Michaelis constant ($K_{\mathrm{M}}$) are essential for modelling enzymatic activity but experimental data remains limited in scale and diversity. Previous methods for…

Quantitative Methods · Quantitative Biology 2025-07-22 Saleh Alwer , Ronan Fleming

Accounting for electrons and nuclei simultaneously is a powerful capability of ab initio molecular dynamics (AIMD). However, AIMD is often unable to accurately reproduce properties of systems such as water due to inaccuracies in the…

Chemical Physics · Physics 2017-01-25 Andrew D. White , Chris Knight , Glen M. Hocky , Gregory A. Voth

Understanding protein conformational dynamics is essential for elucidating biological function but remains challenging due to the wide range of timescales and the complexity of collective motions. Enhanced sampling methods overcome…

Statistical Mechanics · Physics 2026-05-11 Souvik Mondal , Michael A. Sauer , Matthias Heyden