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One of the most puzzling and unsolved challenges in molecular biology is understanding how proteins fold. Despite having advanced predictive tools that can accurately estimate the native structures of proteins, we still lack a comprehensive…

Biomolecules · Quantitative Biology 2026-01-13 Jorge Vila

In 1999 Wright and Dyson highlighted the fact that large sections of the proteome of all organisms are comprised of protein sequences that lack globular folded structures under physiological conditions. Since then the biophysics community…

Biological Physics · Physics 2024-09-05 Zi Hao Liu , Maria Tsanai , Oufan Zhang , Julie Forman-Kay , Teresa Head-Gordon

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

Globular proteins are expected to assume folds with fixed secondary structures, alpha-helices and beta-sheets. Fold-switching proteins challenge this expectation by remodeling their secondary and/or tertiary structures in response to…

Biomolecules · Quantitative Biology 2025-07-16 Devlina Chakravarty , Lauren L. Porter

Understanding protein folding has been one of the great challenges in biochemistry and molecular biophysics. Over the past 50 years, many thermodynamic and kinetic studies have been performed addressing the stability of globular proteins.…

Biomolecules · Quantitative Biology 2014-04-01 Ernesto A. Roman , F. Luis Gonzalez Flecha

Over the years, advances in experimental and computational methods have helped us to understand the role of thermodynamic, kinetic and active (chaperone-aided) effects in coordinating the folding steps required to achieving a knotted native…

Biomolecules · Quantitative Biology 2016-10-20 Sophie E. Jackson , Antonio Suma , Cristian Micheletti

What are the molecular mechanisms that dictate protein-protein binding stability and whether those are related to the ones behind protein fold stability are still largely open questions. Indeed, despite many past efforts, we still lack…

Biological Physics · Physics 2023-11-28 Fausta Desantis , Mattia Miotto , Lorenzo Di Rienzo , Edoardo Milanetti , Giancarlo Ruocco

A protein's function depends critically on its conformational ensemble, a collection of energy weighted structures whose balance depends on temperature and environment. Though recent deep learning (DL) methods have substantially advanced…

Biomolecules · Quantitative Biology 2026-01-09 Myeongsang Lee , Lauren L. Porter

Folding and aggregation of proteins, the interaction between proteins and membranes, as well as the adsorption of organic soft matter to inorganic solid substrates belong to the most interesting challenges in understanding structure and…

Soft Condensed Matter · Physics 2007-12-06 Michael Bachmann , Wolfhard Janke

Repeat proteins are made with tandem copies of similar amino acid stretches that fold into elongated architectures. Due to their symmetry, these proteins constitute excellent model systems to investigate how evolution relates to structure,…

Biomolecules · Quantitative Biology 2022-10-12 Ezequiel A. Galpern , Jacopo Marchi , Thierry Mora , Aleksandra M. Walczak , Diego U. Ferreiro

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

This paper presents a method of reconstruction a primary structure of a protein that folds into a given geometrical shape. This method predicts the primary structure of a protein and restores its linear sequence of amino acids in the…

Quantitative Methods · Quantitative Biology 2017-01-04 Andrii Riazanov , Mikhail Karasikov , Sergei Grudinin

The binding of a ligand molecule to a protein is often accompanied by conformational changes of the protein. A central question is whether the ligand induces the conformational change (induced-fit), or rather selects and stabilizes a…

Biomolecules · Quantitative Biology 2008-09-04 Thomas R. Weikl , Carola von Deuster

Predicting the three-dimensional (3D) functional structures of proteins remains an important computational milestone in molecular biology to be achieved. This feat is hinged on a clear understanding of the mechanism which proteins use to…

Biomolecules · Quantitative Biology 2019-11-28 Samuel Nkrumah

Binding interactions between proteins and other molecules mediate numerous cellular processes, including metabolism, signaling, and regulation of gene expression. These interactions evolve in response to changes in the protein's chemical or…

Populations and Evolution · Quantitative Biology 2015-02-19 Michael Manhart , Alexandre V. Morozov

The motion involved in barrier crossing for protein folding are investigated in terms of the chain dynamics of the polymer backbone, completing the microscopic description of protein folding presented in the previous paper. Local reaction…

Soft Condensed Matter · Physics 2009-10-31 John J. Portman , Shoji Takada , Peter G. Wolynes

During the last decade, network approaches became a powerful tool to describe protein structure and dynamics. Here we review the links between disordered proteins and the associated networks, and describe the consequences of local,…

Peripheral membrane proteins can reversibly and specifically bind to biological membranes to carry out functions such as cell signalling, enzymatic activity, or membrane remodelling. Structures of these proteins and of their lipid-binding…

Biological Physics · Physics 2023-11-14 Andreas Haahr Larsen , Laura H. John , Mark S. P. Sansom , Robin A. Corey

The paradigm that the primary amino acid sequence prescribes structure and thus function has for a long time been central to the understanding of protein science. Though the theory is supported by the behaviour of most structured proteins,…

Biological Physics · Physics 2022-12-19 Rickie Xian , Sarah Rauscher

How do protein structure prediction models fold proteins? We investigate this question by tracing how ESMFold folds a beta hairpin, a prevalent structural motif. Through counterfactual interventions on model latents, we identify two…

Machine Learning · Computer Science 2026-02-10 Kevin Lu , Jannik Brinkmann , Stefan Huber , Aaron Mueller , Yonatan Belinkov , David Bau , Chris Wendler