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We present a statistical mechanics approach to the protein folding problem. We first review some of the basic properties of proteins, and introduce some physical models to describe their thermodynamics. These models rely on a random…

Disordered Systems and Neural Networks · Physics 2008-02-03 T. Garel , H. Orland , E. Pitard

In spite of decades of research, much remains to be discovered about folding: the detailed structure of the initial (unfolded) state, vestigial folding instructions remaining only in the unfolded state, the interaction of the molecule with…

Biological Physics · Physics 2018-11-26 Walter A. Simmons

We present a machine learning approach that leverages persistent homology to classify bacterial flagellar motors into two functional states: rotated and stalled. By embedding protein structural data into a topological framework, we extract…

Biomolecules · Quantitative Biology 2025-12-19 Zakaria Lamine , Abdelatif Hafid , Mohamed Rahouti

Neither of the two prevalent theories, namely thermodynamic stability and kinetic stability, provides a comprehensive understanding of protein folding. The thermodynamic theory is misleading because it assumes that free energy is the…

Biological Physics · Physics 2013-07-22 Ji Xu , Mengzhi Han , Ying Ren , Jinghai Li

The protein folding problem must ultimately be solved on all length scales from the atomic up through a hierarchy of complicated structures. By analyzing the stability of the folding process using physics and mathematics, this paper shows…

Biological Physics · Physics 2015-05-28 Walter Simmons , Joel L. Weiner

Many aspects of the study of protein folding and dynamics have been affected by the recent advances in machine learning. Methods for the prediction of protein structures from their sequences are now heavily based on machine learning tools.…

Biological Physics · Physics 2019-11-25 Frank Noé , Gianni De Fabritiis , Cecilia Clementi

Persistent homology captures the evolution of topological features of a model as a parameter changes. The most commonly used summary statistics of persistent homology are the barcode and the persistence diagram. Another summary statistic,…

Methodology · Statistics 2016-04-01 Violeta Kovacev-Nikolic , Peter Bubenik , Dragan Nikolić , Giseon Heo

Proteins are the most important biomolecules for living organisms. The understanding of protein structure, function, dynamics and transport is one of most challenging tasks in biological science. In the present work, persistent homology is,…

Biomolecules · Quantitative Biology 2014-12-10 Kelin Xia , Guo-Wei Wei

Recently, persistent homology has had tremendous success in biomolecular data analysis. It works by examining the topological relationship or connectivity of a group of atoms in a molecule at a variety of scales, then rendering a family of…

Biomolecules · Quantitative Biology 2019-03-27 David Bramer , Guo-Wei Wei

The thermodynamics of proteins indicate that folding/unfolding takes place either through stable intermediates or through a two-state process without intermediates. The rather short folding times of the two-state process indicate that…

Condensed Matter · Physics 2016-08-31 Audun Bakk , Johan S. Hoye , Alex Hansen , Kim Sneppen , Mogens Hogh Jensen

A phenomenological model hamiltonian to describe the folding of a protein with any given sequence is proposed. The protein is thought of as a collection of pieces of helices; as a consequence its configuration space increases with the…

Soft Condensed Matter · Physics 2009-10-30 Pierpaolo Bruscolini

The folding dynamics of small single-domain proteins is a current focus of simulations and experiments. Many of these proteins are 'two-state folders', i.e. proteins that fold rather directly from the denatured state to the native state,…

Biomolecules · Quantitative Biology 2020-01-08 Thomas R. Weikl

These lectures will address two questions. Is there a simple variational principle underlying the existence of secondary motifs in the native state of proteins? Is there a general approach which can qualitatively capture the salient…

Statistical Mechanics · Physics 2007-05-23 Jay Banavar , Amos Maritan , Cristian Micheletti , Flavio Seno

The principles underlying protein folding remains one of Nature's puzzles with important practical consequences for Life. An approach that has gathered momentum since the late 1990's, looks at protein hetero-polymers and their folding…

Computational Engineering, Finance, and Science · Computer Science 2011-10-05 Susan Khor

Proteins fold using a two-state or multi-state kinetic mechanisms, but up to now there isn't a first-principle model to explain this different behaviour. We exploit the network properties of protein structures by introducing novel…

Molecular Networks · Quantitative Biology 2015-12-04 Giulia Menichetti , Piero Fariselli , Daniel Remondini

The process of protein folding from an unfolded state to a biologically active, folded conformation is governed by many parameters e.g the sequence of amino acids, intermolecular interactions, the solvent, temperature and chaperon…

Soft Condensed Matter · Physics 2010-10-19 Pragya Shukla

How proteins fold remains a central unsolved problem in biology. While the idea of a folding code embedded in the amino acid sequence was introduced more than 6 decades ago, this code remains undefined. While we now have powerful predictive…

Biomolecules · Quantitative Biology 2025-11-04 Carlos Bustamante , Christian Kaiser , Erik Lindahl , Robert Sosa , Giovanni Volpe

Present-day atomistic simulations generate long trajectories of ever more complex systems. Analyzing these data, discovering metastable states, and uncovering their nature is becoming increasingly challenging. In this paper, we first use…

Computational Physics · Physics 2023-06-23 Pietro Novelli , Luigi Bonati , Massimiliano Pontil , Michele Parrinello

Natural protein sequences somehow encode the structural forms that these molecules adopt. Recent developments in structure-prediction are agnostic to the mechanisms by which proteins fold and represent them as static objects. However, the…

Biomolecules · Quantitative Biology 2025-05-26 Ezequiel A. Galpern , Federico Caamaño , Diego U. Ferreiro

Many processes of scientific importance are characterized by time scales that extend far beyond the reach of standard simulation techniques. To circumvent this impediment a plethora of enhanced sampling methods has been developed. One…

Computational Physics · Physics 2018-12-05 Dan Mendels , Giovannimaria Piccini , Z. Faidon Brotzakis , Yi I. Yang , Michele Parrinello
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