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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

In the protein sequence space, natural proteins form clusters of families which are characterized by their unique native folds whereas the great majority of random polypeptides are neither clustered nor foldable to unique structures. Since…

Biomolecules · Quantitative Biology 2018-02-06 Akira R. Kinjo

Predicting protein secondary structures such as alpha helices, beta sheets, and coils from amino acid sequences is essential for understanding protein function. This work presents a transformer-based model that applies attention mechanisms…

Artificial Intelligence · Computer Science 2025-12-10 Manzi Kevin Maxime

Proteins are a matter of dual nature. As a physical object, a protein molecule is a folded chain of amino acids with multifarious biochemistry. But it is also an instantiation along an evolutionary trajectory determined by the function…

Biomolecules · Quantitative Biology 2019-09-04 Jean-Pierre Eckmann , Jacques Rougemont , Tsvi Tlusty

With the help of lattice Monte Carlo modelling of heteropolymers, we show that the necessary condition for a protein to fold on short call is to proceed through partially folded intermediates. These elementary structures are formed at an…

Condensed Matter · Physics 2007-05-23 R. A. Broglia , G. Tiana

Protein structure prediction and folding are fundamental to understanding biology, with recent deep learning advances reshaping the field. Diffusion-based generative models have revolutionized protein design, enabling the creation of novel…

Machine Learning · Computer Science 2025-10-01 Yogesh Verma , Markus Heinonen , Vikas Garg

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

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

The interconnected processes of protein folding, mutations, epistasis, and evolution have all been the subject of extensive analysis throughout the years due to their significance for structural and evolutionary biology. The origin…

Populations and Evolution · Quantitative Biology 2024-04-08 Jorge A. Vila

Emergence of new protein structures has proved difficult to trace in nature and engineer in the laboratory. However, one aspect of structure evolution has proved immensely helpful for determining the three-dimensional structure of proteins…

Populations and Evolution · Quantitative Biology 2017-05-24 Amy I. Gilson , Ahmee Marshall-Christensen , Jeong-Mo Choi , Eugene I. Shakhnovich

We propose a model that explains the hierarchical organization of proteins in fold families. The model, which is based on the evolutionary selection of proteins by their native state stability, reproduces patterns of amino acids conserved…

Statistical Mechanics · Physics 2007-05-23 Nikolay V. Dokholyan , Eugene I. Shakhnovich

We propose a protein model based on a hierarchy of constraints that force the protein to follow certain pathways when changing conformation. The model exhibits a first order phase transition, cooperativity and is exactly solvable. It also…

Condensed Matter · Physics 2015-06-25 Alex Hansen , Mogens H. Jensen , Kim Sneppen , Giovanni Zocchi

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

The ability to absorb mutations while retaining structure and function, or mutational robustness, is a remarkable property of natural proteins. In this Letter, we use a computational model of organismic evolution [Zeldovich et al, PLOS Comp…

Biomolecules · Quantitative Biology 2008-06-25 Konstantin B. Zeldovich , Eugene I. Shakhnovich

Proteins are linear chain molecules that play a central role in life and health. Protein native state folds are modular assemblies of space-filling building blocks of {\alpha}-helices, \{beta}-sheets and tight turns. Here we deduce the…

Biological Physics · Physics 2025-10-09 Jayanth R. Banavar , Achille Giacometti , Trinh X. Hoang , Amos Maritan , Tatjana Škrbić

An all-atom model of proteins is used to show that the same sequence of amino acids can have many alternative structures, that are very distant from, and that can be as stable as, the corresponding native structure. Such alternative…

Biological Physics · Physics 2008-02-11 Leonor Cruzeiro

Many types of peripheral and transmembrane proteins can sense and generate membrane curvature. Laterally isotropic proteins and crescent proteins with twofold rotational symmetry, such as Bin/Amphiphysin/Rvs superfamily proteins, have been…

Soft Condensed Matter · Physics 2024-02-12 Hiroshi Noguchi

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

Novel numerical techniques, validated by an analysis of barnase and chymotrypsin inhibitor, are used to elucidate the paramount role played by the geometry of the protein backbone in steering the folding to the correct native state. It is…

Statistical Mechanics · Physics 2009-10-31 Cristian Micheletti , Jayanth R. Banavar , Amos Maritan , Flavio Seno

Natural protein sequences contain a record of their history. A common constraint in a given protein family is the ability to fold to specific structures, and it has been shown possible to infer the main native ensemble by analyzing…

Biomolecules · Quantitative Biology 2017-03-16 Rocío Espada , R. Gonzalo Parra , Thierry Mora , Aleksandra M. Walczak , Diego U. Ferreiro