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Many processes of scientific and technological interest are characterized by time scales that render their simulation impossible if one uses present day simulation capabilities. To overcome this challenge a variety of enhanced simulation…

Statistical Mechanics · Physics 2019-02-26 Z. Faidon Brotzakis , Dan Mendels , Michele Parrinello

The study of the rare transitions that take place between long lived metastable states is a major challenge in molecular dynamics simulations. Many of the methods suggested to address this problem rely on the identification of the slow…

Chemical Physics · Physics 2023-06-07 Dhiman Ray , Enrico Trizio , Michele Parrinello

Designing an appropriate set of collective variables is crucial to the success of several enhanced sampling methods. Here we focus on how to obtain such variables from information limited to the metastable states. We characterize these…

Chemical Physics · Physics 2020-04-08 Luigi Bonati , Valerio Rizzi , Michele Parrinello

Understanding the protein folding process is an outstanding issue in biophysics; recent developments in molecular dynamics simulation have provided insights into this phenomenon. However, the large freedom of atomic motion hinders the…

Computational Physics · Physics 2020-06-18 Takashi Ichinomiya , Ippei Obayashi , Yasuaki Hiraoka

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

In this paper we combine two powerful computational techniques, well-tempered metadynamics and time lagged independent component analysis. The aim is to develop a new tool for studying rare events and exploring complex free energy…

Statistical Mechanics · Physics 2017-12-08 James McCarty , Michele Parrinello

The phenomenon of solidification of a substance from its liquid phase is of the greatest practical and theoretical importance, and atomistic simulations can provide precious information towards its understanding and control. Unfortunately,…

Soft Condensed Matter · Physics 2021-03-25 Tarak Karmakar , Michele Invernizzi , Valerio Rizzi , Michele Parrinello

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

Protein function does not solely depend on structure but often relies on dynamical transitions between distinct conformations. Despite this fact, our ability to characterize or predict protein dynamics is substantially less developed…

Statistical Mechanics · Physics 2026-05-08 Michael A. Sauer , Souvik Mondal , Brandon Neff , Sthitadhi Maiti , Matthias Heyden

Many recently introduced enhanced sampling techniques are based on biasing coarse descriptors (collective variables) of a molecular system on the fly. Sometimes the calculation of such collective variables is expensive and becomes a…

Computational Physics · Physics 2015-09-01 Marco Jacopo Ferrarotti , Sandro Bottaro , Andrea Pérez-Villa , Giovanni Bussi

Disentangling the mechanistic details of a chemical reaction pathway is a hard problem that often requires a considerable amount of chemical intuition and a component of luck. Experiments struggle in observing short-life metastable…

Chemical Physics · Physics 2019-08-01 Valerio Rizzi , Dan Mendels , Emilia Sicilia , Michele Parrinello

While recent advances in AI have transformed protein structure prediction, protein function is also strongly influenced by the thermodynamic and kinetic features encoded in its underlying free-energy surface. Here, we propose a…

Biological Physics · Physics 2026-04-29 Alexander Zhilkin , Muralika Medaparambath , Dan Mendels

Understanding kinetics and thermodynamics profile of biomolecules is necessary to understand their functional roles which has a major impact in mechanism driven drug discovery. Molecular dynamics simulation has been routinely used to…

Biomolecules · Quantitative Biology 2021-12-07 Soumendranath Bhakat

Controlling polymorphism in molecular crystals is crucial in the pharmaceutical, dye, and pesticide industries. However, its theoretical description is extremely challenging, due to the associated long timescales ($ > 1 \, \mu s$). We…

Chemical Physics · Physics 2023-02-09 Oren Elishav , Roy Podgaetsky , Olga Meikler , Barak Hirshberg

The computational study of conformational transitions in RNA and proteins with atomistic molecular dynamics often requires suitable enhanced sampling techniques. We here introduce a novel method where concurrent metadynamics are integrated…

Computational Physics · Physics 2015-09-01 Alejandro Gil-Ley , Giovanni Bussi

A reduced model, which can fold both helix and sheet structures, is proposed to study the problem of protein folding. The goal of this model is to find an unbiased effective potential that has included the effects of water and at the same…

Soft Condensed Matter · Physics 2007-05-23 Nan-yow Chen

A popular way to accelerate the sampling of rare events in molecular dynamics simulations is to introduce a potential that increases the fluctuations of selected collective variables. For this strategy to be successful, it is critical to…

Computational Physics · Physics 2021-01-19 Luigi Bonati

Datasets containing both categorical and continuous variables are frequently encountered in many areas, and with the rapid development of modern measurement technologies, the dimensions of these variables can be very high. Despite the…

Methodology · Statistics 2024-01-03 Binyan Jiang , Chenlei Leng , Cheng Wang , Zhongqing Yang , Xinyang Yu

We introduce a new nonlinear model for classification, in which we model the joint distribution of response variable, y, and covariates, x, non-parametrically using Dirichlet process mixtures. We keep the relationship between y and x linear…

Statistics Theory · Mathematics 2007-05-23 Babak Shahbaba , Radford M. Neal

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
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