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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

A geometric analysis of protein folding, which complements many of the models in the literature, is presented. We examine the process from unfolded strand to the point where the strand becomes self-interacting. A central question is how it…

Mathematical Physics · Physics 2008-09-13 Walter A. Simmons , Joel L. Weiner

Search for possible relationships between phylogeny and ontogeny is one of the most important issues in the field of evolutionary developmental biology. By representing developmental dynamics of spatially located cells with gene expression…

Populations and Evolution · Quantitative Biology 2015-04-01 Takahiro Kohsokabe , Kunihiko Kaneko

Natural protein molecules are exceptional polymers. Encoded in apparently random strings of amino-acids, these objects perform clear physical tasks that are rare to find by simple chance. Accurate folding, specific binding, powerful…

Biomolecules · Quantitative Biology 2017-10-09 Diego U. Ferreiro , Elizabeth A. Komives , Peter G. Wolynes

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

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

We simulate neutral evolution of proteins imposing conservation of the thermodynamic stability of the native state in the framework of an effective model of folding thermodynamics. This procedure generates evolutionary trajectories in…

Condensed Matter · Physics 2009-11-07 Ugo Bastolla , Markus Porto , H. Eduardo Roman , Michele Vendruscolo

Statistical analysis of alignments of large numbers of protein sequences has revealed "sectors" of collectively coevolving amino acids in several protein families. Here, we show that selection acting on any functional property of a protein,…

Biomolecules · Quantitative Biology 2019-04-26 Shou-Wen Wang , Anne-Florence Bitbol , Ned S. Wingreen

Residue-residue interactions that fold a protein into a unique three-dimensional structure and make it play a specific function impose structural and functional constraints on each residue site. Selective constraints on residue sites are…

Biomolecules · Quantitative Biology 2013-01-18 Sanzo Miyazawa

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

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

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

We describe the results obtained from an improved model for protein folding. We find that a good agreement with the native structure of a 46 residue long, five-letter protein segment is obtained by carefully tuning the parameters of the…

Biomolecules · Quantitative Biology 2009-11-11 Andrea Nobile , Federico Rapuano

Proteins must fold quickly to acquire their biologically functional three-dimensional native structures. Hence, these are mainly stabilized by local contacts, while intricate topologies such as knots are rare. Here, we reveal the existence…

Biomolecules · Quantitative Biology 2019-06-20 Marco Baiesi , Enzo Orlandini , Flavio Seno , Antonio Trovato

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

Natural protein sequences that self-assemble to form globular structures are compact with high packing densities in the folded states. It is known that proteins unfold upon addition of denaturants, adopting random coil structures. The…

Biomolecules · Quantitative Biology 2016-12-02 Himadri S. Samanta , Pavel I. Zhuravlev , Michael Hinczewski , Naoto Hori , Shaon Chakrabarti , D. Thirumalai

Evolutionally conserved quantity that specifies folding nuclei is pursued by a case study for a small protein (PDB code: 1ten). First it is demonstrated that the sequences of amino acids at folding nuclei are not conserved. Then 3D…

Biological Physics · Physics 2007-05-23 S. Nakamura , O. Narikiyo

It is important to understand how protein folding and evolution influences each other. Several studies based on entropy calculation correlating experimental measurement of residue participation in folding nucleus and sequence conservation…

Biomolecules · Quantitative Biology 2007-05-23 Yan Yuan Tseng , Jie Liang

One of the classical questions in evolutionary biology is how evolutionary processes are coupled at the gene and species level. With this motivation, we compare the topological properties (mainly the depth scaling, as a characterization of…

Populations and Evolution · Quantitative Biology 2011-07-26 E. Alejandro Herrada , Víctor M. Eguíluz , Emilio Hernández-García , Carlos M. Duarte

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