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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

Proteins are essential components of living systems, capable of performing a huge variety of tasks at the molecular level, such as recognition, signalling, copy, transport, ... The protein sequences realizing a given function may largely…

Biomolecules · Quantitative Biology 2016-02-17 John Barton , Arup Chakraborty , Simona Cocco , Hugo Jacquin , Rémi Monasson

Evolution of genetic code is studied as the change in the choice of enzymes that are used to synthesize amino acids from the genetic information of nucleic acids. We propose the following theory: the differentiation of physiological states…

Adaptation and Self-Organizing Systems · Physics 2007-05-23 H. Takagi , K. Kaneko , T. Yomo

Studies of how protein fold have shown that the way protein clumps form in the test tube is similar to how proteins form the so-called ``amyloid'' deposits that are the pathological signal of a variety of diseases, among them the memory…

Condensed Matter · Physics 2009-10-31 R. A. Broglia , G. Tiana , S. Pasquali , H. E. Roman , E. Vigezzi

We seek to understand the interplay between amino acid sequence and local structure in proteins. Are some amino acids unique in their ability to fit harmoniously into certain local structures? What is the role of sequence in sculpting the…

Biomolecules · Quantitative Biology 2021-01-29 Tatjana Škrbić , Amos Maritan , Achille Giacometti , Jayanth R. Banavar

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

We present and implement a distance-based clustering of amino acids within the framework of a statistically derived interaction matrix and show that the resulting groups faithfully reproduce, for well-designed sequences, thermodynamic…

Statistical Mechanics · Physics 2009-10-31 Marek Cieplak , Neal S. Holter , Amos Maritan , Jayanth R. Banavar

Protein folding is the intricate process by which a linear sequence of amino acids self-assembles into a unique three-dimensional structure. Protein folding kinetics is the study of pathways and time-dependent mechanisms a protein undergoes…

Machine Learning · Computer Science 2023-09-19 Vijay Arvind. R , Haribharathi Sivakumar , Brindha. R

Proteins are inherently multiscale physical systems whose functional properties emerge from coordinated structural organization across multiple spatial resolutions, ranging from atomic interactions to global fold topology. However, existing…

Machine Learning · Computer Science 2026-05-13 Viet Thanh Duy Nguyen , John K. Johnstone , Truong-Son Hy

Understanding the observed variability in the number of homologs of a gene is a very important, unsolved problem that has broad implications for research into co-evolution of structure and function, gene duplication, pseudogene formation…

Biomolecules · Quantitative Biology 2007-05-23 Boris Shakhnovich , Eric Deeds , Charles Delisi , Eugene Shakhnovich

The mechanisms by which a protein's 3D structure can be determined based on its amino acid sequence have long been one of the key mysteries of biophysics. Often simplistic models, such as those derived from geometric constraints, capture…

Biological Physics · Physics 2023-01-02 Nora Molkenthin , J. J. Güven , Steffen Mühle , Antonia S. J. S. Mey

The analysis of the three-dimensional structure of proteins is an important topic in molecular biochemistry. Structure plays a critical role in defining the function of proteins and is more strongly conserved than amino acid sequence over…

Applications · Statistics 2015-01-19 Abel Rodriguez , Scott C. Schmidler

Understanding why some cellular components are conserved across species, while others evolve rapidly is a key question of modern biology. Here we demonstrate that in S. cerevisiae proteins organized in cohesive patterns of interactions are…

Genomics · Quantitative Biology 2007-05-23 S. Wuchty , Z. N. Oltvai , A. -L. Barabasi

Variation and selection are the core principles of Darwinian evolution, yet quantitatively relating the diversity of a population to its capacity to respond to selection is challenging. Here, we examine this problem at a molecular level in…

Populations and Evolution · Quantitative Biology 2016-04-27 Sébastien Boyer , Dipanwita Biswas , Ananda Kumar Soshee , Natale Scaramozzino , Clément Nizak , Olivier Rivoire

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

In this study, the distributions of protein structure classes (or folding types) of experimentally determined structures from a legacy dataset and a comprehensive database (SCOP) are modeled precisely with geometric constructs such as…

Biomolecules · Quantitative Biology 2025-10-21 Boryeu Mao

In the course of evolution, proteins undergo important changes in their amino acid sequences, while their three-dimensional folded structure and their biological function remain remarkably conserved. Thanks to modern sequencing techniques,…

Biomolecules · Quantitative Biology 2019-10-07 Simona Cocco , Christoph Feinauer , Matteo Figliuzzi , Remi Monasson , Martin Weigt

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

Interacting proteins coevolve at multiple but interconnected scales, from the residue-residue over the protein-protein up to the family-family level. The recent accumulation of enormous amounts of sequence data allows for the development of…

Biomolecules · Quantitative Biology 2019-06-25 Hendrik Szurmant , Martin Weigt

We propose a principle of superposition to describe protein-folding nuclei and explain an evolutional conservation of a field pattern specifying native-state structure.

Biological Physics · Physics 2009-08-07 S. Nakamura , O. Narikiyo