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Metadynamics is a powerful computational tool to obtain the free energy landscape of complex systems. The Monte Carlo algorithm has proven useful to calculate thermodynamic quantities associated with simplified models of proteins, and thus…

Statistical Mechanics · Physics 2007-10-04 F. Marini , C. Camilloni , D. Provasi , R. A. Broglia , G. Tiana

The biological functions of proteins often depend on dynamic structural ensembles. In this work, we develop a flow-based generative modeling approach for learning and sampling the conformational landscapes of proteins. We repurpose highly…

Biomolecules · Quantitative Biology 2024-09-04 Bowen Jing , Bonnie Berger , Tommi Jaakkola

Simple two-state folding kinetics of many small single-domain proteins are characterized by chevron plots with linear folding and unfolding arms consistent with a two-state description of equilibrium thermodynamics. This phenomenon is…

Soft Condensed Matter · Physics 2007-05-23 Huseyin Kaya , Hue Sun Chan

Nested sampling is a Bayesian sampling technique developed to explore probability distributions lo- calised in an exponentially small area of the parameter space. The algorithm provides both posterior samples and an estimate of the evidence…

Biomolecules · Quantitative Biology 2015-03-17 Nikolas S. Burkoff , Csilla Varnai , Stephen A. Wells , David L. Wild

The determination of efficient collective variables is crucial to the success of many enhanced sampling methods. As inspired by previous discrimination approaches, we first collect a set of data from the different metastable basins. The…

Computational Physics · Physics 2026-03-03 Enrico Trizio , Michele Parrinello

We explain the physical basis of a model for small globular proteins with water interactions. The water is supposed to access the protein interior in an "all-or-none" manner during the unfolding of the protein chain. As a consequence of…

Condensed Matter · Physics 2009-10-31 Audun Bakk , Alex Hansen , Kim Sneppen

We present a method for determining the free energy dependence on a selected number of collective variables using an adaptive bias. The formalism provides a unified description which has metadynamics and canonical sampling as limiting…

Statistical Mechanics · Physics 2008-03-31 Alessandro Barducci , Giovanni Bussi , Michele Parrinello

Within the task of collaborative filtering two challenges for computing conditional probabilities exist. First, the amount of training data available is typically sparse with respect to the size of the domain. Thus, support for higher-order…

Information Retrieval · Computer Science 2012-07-19 Lawrence Zitnick , Takeo Kanade

In molecular dynamics simulations, rare events, such as protein folding, are typically studied using enhanced sampling techniques, most of which are based on the definition of a collective variable (CV) along which acceleration occurs.…

Chemical Physics · Physics 2024-07-22 Soojung Yang , Juno Nam , Johannes C. B. Dietschreit , Rafael Gómez-Bombarelli

The sampling problem lies at the heart of atomistic simulations and over the years many different enhanced sampling methods have been suggested towards its solution. These methods are often grouped into two broad families. On the one hand…

Computational Physics · Physics 2020-11-25 Michele Invernizzi , Pablo Miguel Piaggi , Michele Parrinello

To quantify the complexity of a system, entropy-based methods have received considerable critical attentions in real-world data analysis. Among numerous entropy algorithms, amplitude-based formulas, represented by Sample Entropy, suffer…

Signal Processing · Electrical Eng. & Systems 2022-01-12 Hongjian Xiao , Danilo P. Mandic

A statistical mechanical description of flexible and semi-flexible polymer chains in a poor solvent is developed in the constant force and constant distance ensembles. We predict the existence of many intermediate states at low temperatures…

Soft Condensed Matter · Physics 2007-05-23 Sanjay Kumar , Iwan Jensen , Jesper L. Jacobsen , Anthony J. Guttmann

A computational method is developed to work on an inverse equilibrium problem with an interest towards applications with protein folding. In general, we are given a set of equilibrium confgiurations and want to derive the most probable…

Biological Physics · Physics 2007-05-23 John P. Donohue

Umbrella sampling is an efficient method for the calculation of free energy changes of a system along well-defined reaction coordinates. However, when multiple parallel channels along the reaction coordinate or hidden barriers in directions…

Methodology · Statistics 2015-06-16 Mingjun Yang , Lijiang Yang , Yiqin Gao , Hao Hu

Several enhanced sampling methods such as umbrella sampling or metadynamics rely on the identification of an appropriate set of collective variables. Recently two methods have been proposed to alleviate the task of determining efficient…

Computational Physics · Physics 2019-03-27 Yue-Yu Zhang , Haiyang Niu , GiovanniMaria Piccini , Dan Mendels , Michele Parrinello

A new approach for efficiently exploring the configuration space and computing the free energy of large atomic and molecular systems is proposed, motivated by an analogy with reinforcement learning. There are two major components in this…

Chemical Physics · Physics 2018-04-18 Linfeng Zhang , Han Wang , Weinan E

Detecting conformational transitions in molecular systems is key to understanding biological processes. Here, we investigate the force variance in single-molecule pulling experiments as an indicator of molecular folding transitions. We…

Statistical Mechanics · Physics 2023-09-13 Marc Rico , Felix Ritort

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

The development of enhanced sampling methods has greatly extended the scope of atomistic simulations, allowing long-time phenomena to be studied with accessible computational resources. Many such methods rely on the identification of an…

Computational Physics · Physics 2022-06-08 Luigi Bonati , GiovanniMaria Piccini , Michele Parrinello

Variational auto-encoder frameworks have demonstrated success in reducing complex nonlinear dynamics in molecular simulation to a single non-linear embedding. In this work, we illustrate how this non-linear latent embedding can be used as a…

Machine Learning · Statistics 2018-01-03 Mohammad M. Sultan , Hannah K. Wayment-Steele , Vijay S. Pande