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Spatially proximate amino acids in a protein tend to coevolve. A protein's three-dimensional (3D) structure hence leaves an echo of correlations in the evolutionary record. Reverse engineering 3D structures from such correlations is an open…

Quantitative Methods · Quantitative Biology 2013-01-15 Magnus Ekeberg , Cecilia Lövkvist , Yueheng Lan , Martin Weigt , Erik Aurell

A complete time-parameterized statistical model quantifying the divergent evolution of protein structures in terms of the patterns of conservation of their secondary structures is inferred from a large collection of protein 3D structure…

Quantitative Methods · Quantitative Biology 2023-08-15 Sandun Rajapaksa , Lloyd Allison , Peter J. Stuckey , Maria Garcia de la Banda , Arun S. Konagurthu

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

Proteins encode diverse functions within complex three-dimensional structures, yet most deep learning representations remain highly entangled, obscuring the biophysical signals that underlie function. Here we introduce ProtDiS, a…

Biomolecules · Quantitative Biology 2026-05-26 Mingqing Wang , Zhiwei Nie , Athanasios V. Vasilakos , Yonghong He , Zhixiang Ren

Protein evolution involves mutations occurring across a wide range of time scales. In analogy with disordered systems in statistical physics, this dynamical heterogeneity suggests strong correlations between mutations happening at distinct…

Biomolecules · Quantitative Biology 2025-07-15 Saverio Rossi , Leonardo Di Bari , Martin Weigt , Francesco Zamponi

We perform an exhaustive analysis of genome statistics for organisms, particularly extremophiles, growing in a wide range of physicochemical conditions. Specifically, we demonstrate how the correlation between the frequency of amino acids…

Genomics · Quantitative Biology 2013-09-19 Benjamin Greenbaum , Pradeep Kumar , Albert Libchaber

Composed of amino acid chains that influence how they fold and thus dictating their function and features, proteins are a class of macromolecules that play a central role in major biological processes and are required for the structure,…

Quantitative Methods · Quantitative Biology 2022-07-15 Aaron Wang

Life on earth is distinguished by long-lived correlations in time. The patterns of material organization that characterize living organisms today are contingent on events that occurred billions of years ago. This contingency is a necessary…

Soft Condensed Matter · Physics 2021-01-06 Peter M. Tzelios , Kyle J. M. Bishop

Protein interaction networks aim to summarize the complex interplay of proteins in an organism. Early studies suggested that the position of a protein in the network determines its evolutionary rate but there has been considerable…

Molecular Networks · Quantitative Biology 2007-05-23 Ino Agrafioti , Jonathan Swire , James Abbott , Derek Huntley , Sarah Butcher , Michael P. H. Stumpf

In the course of evolution, proteins show a remarkable conservation of their three-dimensional structure and their biological function, leading to strong evolutionary constraints on the sequence variability between homologous proteins. Our…

Quantitative Methods · Quantitative Biology 2014-04-07 Carlo Baldassi , Marco Zamparo , Christoph Feinauer , Andrea Procaccini , Riccardo Zecchina , Martin Weigt , Andrea Pagnani

Proteins, by virtue of their central role in most biological processes, represent one of the key subjects of the study of molecular evolution. Inherent to the indispensability of proteins for living cells is the fact that a given protein…

Biomolecules · Quantitative Biology 2007-05-23 Eric J. Deeds , Eugene I. Shakhnovich

Protein is linked to almost every life process. Therefore, analyzing the biological structure and property of protein sequences is critical to the exploration of life, as well as disease detection and drug discovery. Traditional protein…

Machine Learning · Computer Science 2021-12-08 Yijia Xiao , Jiezhong Qiu , Ziang Li , Chang-Yu Hsieh , Jie Tang

Introduction: While the origin and evolution of proteins remain mysterious, advances in evolutionary genomics and systems biology are facilitating the historical exploration of the structure, function and organization of proteins and…

Quantitative Methods · Quantitative Biology 2026-02-20 Gustavo Caetano-Anollés , M. Fayez Aziz , Fizza Mughal , Derek Caetano-Anollés

The protein folding problem has attracted an increasing attention from physicists. The problem has a flavor of statistical mechanics, but possesses the most common feature of most biological problems -- the profound effects of evolution. I…

Statistical Mechanics · Physics 2009-10-31 Chao Tang

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

Two processes can influence the evolution of protein interaction networks: addition and elimination of interactions between proteins, and gene duplications increasing the number of proteins and interactions. The rates of these processes can…

Statistical Mechanics · Physics 2007-05-23 A. Wagner

Although rare, an increasing number of proteins have been observed to contain entanglements in their native structures. To gain more insight into the significance of protein knotting, researchers have been investigating protein knot…

Biomolecules · Quantitative Biology 2022-11-08 Isabel K. Darcy , Garrett Jones , Puttipong Pongtanapaisan

Protein domains are found on genomes with notable statistical distributions, which bear a high degree of similarity. Previous work has shown how these distributions can be accounted for by simple models, where the main ingredients are…

Genomics · Quantitative Biology 2008-07-14 M. Cosentino Lagomarsino , A. L. Sellerio , P. D. Heijning , B. Bassetti

Functional protein-protein interactions are crucial in most cellular processes. They enable multi-protein complexes to assemble and to remain stable, and they allow signal transduction in various pathways. Functional interactions between…

Biomolecules · Quantitative Biology 2018-11-14 Anne-Florence Bitbol

Natively unfolded proteins exist as an ensemble of flexible conformations lacking a well defined tertiary structure along a large portion of their polypeptide chain. Despite the absence of a stable configuration, they are involved in…

Genomics · Quantitative Biology 2008-07-14 Antonio Deiana , Andrea Giansanti