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Molecular Dynamics (MD) simulations are fundamental computational tools for the study of proteins and their free energy landscapes. However, sampling protein conformational changes through MD simulations is challenging due to the relatively…

Biomolecules · Quantitative Biology 2023-07-20 Diego E. Kleiman , Hassan Nadeem , Diwakar Shukla

Molecular dynamics (MD) simulation is widely used to study protein conformations and dynamics. However, conventional simulation suffers from being trapped in some local energy minima that are hard to escape. Thus, most computational time is…

Quantitative Methods · Quantitative Biology 2022-04-28 Hao Tian , Xi Jiang , Sian Xiao , Hunter La Force , Eric C. Larson , Peng Tao

Using the Dominant Reaction Pathways method, we perform an ab-initio quantum-mechanical simulation of a conformational transition of a peptide chain. The method we propose makes it possible to investigate the out-of-equilibrium dynamics of…

Biomolecules · Quantitative Biology 2010-07-30 S. a Beccara , P. Faccioli , G. Garberoglio , M. Sega , F. Pederiva , H. Orland

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

A wide variety of numerical methods are evaluated and compared for solving the stochastic differential equations encountered in molecular dynamics. The methods are based on the application of deterministic impulses, drifts, and Brownian…

Computational Physics · Physics 2013-05-14 Benedict Leimkuhler , Charles Matthews

The replica exchange method is a powerful tool for overcoming slow relaxation in molecular simulations, but its efficiency depends strongly on the choice of the number and interval of replicas and their exchange probabilities. Here, we…

Statistical Mechanics · Physics 2025-06-04 Akie Kowaguchi , Katsuhiro Endo , Kentaro Nomura , Shuichi Kurabayashi , Paul E. Brumby , Kenji Yasuoka

We introduce a powerful iterative algorithm to compute protein folding pathways, with realistic all-atom force fields. Using the path integral formalism, we explicitly derive a modified Langevin equation which samples directly the ensemble…

Biological Physics · Physics 2017-05-08 S. Orioli , S. A Beccara , P. Faccioli

We introduce a novel multiobjective optimization algorithm based on the conformational space annealing (CSA) algorithm, MOCSA. It has three characteristic features: (a) Dominance relationship and distance between solutions in the objective…

Computational Physics · Physics 2012-09-05 Sangjin Sim , Juyong Lee , Jooyoung Lee

We consider the problem of sampling transition paths between two given metastable states of a molecular system, e.g. a folded and unfolded protein or products and reactants of a chemical reaction. Due to the existence of high energy…

Biomolecules · Quantitative Biology 2023-07-19 Lars Holdijk , Yuanqi Du , Ferry Hooft , Priyank Jaini , Bernd Ensing , Max Welling

Understanding transition pathways between two meta-stable states of a molecular system is crucial to advance drug discovery and material design. However, unbiased molecular dynamics (MD) simulations are computationally infeasible because of…

Machine Learning · Computer Science 2025-01-28 Kiyoung Seong , Seonghyun Park , Seonghwan Kim , Woo Youn Kim , Sungsoo Ahn

Simulated annealing solves global optimization problems by means of a random walk in a cooling energy landscape based on the objective function and a temperature parameter. However, if the temperature is decreased too quickly, this…

Optimization and Control · Mathematics 2025-04-14 Vincent Molin , Axel Ringh , Moritz Schauer , Akash Sharma

Finding complex reaction and transformation pathways, involving many intermediate states, is in general not possible on the DFT level with existing simulation methods due to the very large number of required energy and force evaluations.…

Computational Physics · Physics 2019-11-20 Deb Sankar De , Marco Krummenacher , Bastian Schaefer , Stefan Goedecker

We assess the reliability of the recently developed approach denominated Dominant Reaction Pathways (DRP) by studying the folding of a 16-residue beta-hairpin, within a coarse-grained Go-type model. We show that the DRP predictions are in…

Biomolecules · Quantitative Biology 2008-06-24 Pietro Faccioli

Adapting pre-trained representations has become the go-to recipe for learning new downstream tasks with limited examples. While literature has demonstrated great successes via representation learning, in this work, we show that substantial…

Computer Vision and Pattern Recognition · Computer Science 2021-04-02 Xiao Lin , Meng Ye , Yunye Gong , Giedrius Buracas , Nikoletta Basiou , Ajay Divakaran , Yi Yao

Many natural systems exhibit tipping points where changing environmental conditions spark a sudden shift to a new and sometimes quite different state. Global climate change is often associated with the stability of marine carbon stocks. We…

Dynamical Systems · Mathematics 2024-06-19 Jianyu Chen , Jianyu Hu , Wei Wei , Jinqiao Duan

Finding representative reaction pathways is necessary for understanding mechanisms of molecular processes, but is considered to be extremely challenging. We propose a new method to construct reaction paths based on mean first-passage times.…

Chemical Physics · Physics 2015-06-26 Sanghyun Park , Klaus Schulten

Adaptive gradient methods have been increasingly adopted by deep learning community due to their fast convergence and reduced sensitivity to hyper-parameters. However, these methods come with limitations, such as increased memory…

Machine Learning · Computer Science 2024-12-17 Corrado Coppola , Lorenzo Papa , Irene Amerini , Laura Palagi

We present a one-way shooting algorithm for transition path sampling that accepts every proposed trajectory, yet samples the correct transition path ensemble for systems with overdamped stochastic dynamics. The method is based on two key…

Computational Physics · Physics 2026-03-10 Magdalena Häupl , Sebastian Falkner , Peter G. Bolhuis , Christoph Dellago , Alessandro Coretti

Adaptive simulated annealing (ASA) is a global optimization algorithm based on an associated proof that the parameter space can be sampled much more efficiently than by using other previous simulated annealing algorithms. The author's ASA…

Mathematical Software · Computer Science 2007-05-23 Lester Ingber

Path sampling allows the study of rare events like chemical reactions, nucleation and protein folding via a Monte Carlo (MC) exploration in path space. Instead of configuration points, this method samples short molecular dynamics (MD)…

Chemical Physics · Physics 2023-01-25 Daniel T. Zhang , Enrico Riccardi , Titus S. van Erp