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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

Stretching of a protein by a fluid flow is compared to that in a force-clamp apparatus. The comparison is made within a simple topology-based dynamical model of a protein in which the effects of the flow are implemented using Langevin…

Biomolecules · Quantitative Biology 2009-11-13 P. Szymczak , Marek Cieplak

Perturbing a Go model towards a realistic protein Hamiltonian by adding non-native interactions, we find that the folding rate is in general enhanced as ruggedness is initially increased, as long as the protein is sufficiently large and…

Disordered Systems and Neural Networks · Physics 2007-05-23 Steven S. Plotkin

Proteins work only if folded in their native state, but changes in temperature T and pressure P induce their unfolding. Therefore for each protein there is a stability region (SR) in the T-P thermodynamic plane outside which the biomolecule…

Soft Condensed Matter · Physics 2017-04-12 Valentino Bianco , Neus Pagès Gelabert , Ivan Coluzza , Giancarlo Franzese

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

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 number of protein structures is far less than the number of sequences. By imposing simple generic features of proteins (low energy and compaction) on all possible sequences we show that the structure space is sparse compared to the…

Soft Condensed Matter · Physics 2009-10-31 D. Thirumalai , D. K. Klimov

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

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

Many protein systems fold in a two-state manner. Random models, however, rarely display two-state kinetics and thus such behavior should not be accepted as a default. To date, many theories for the prevalence of two-state kinetics have been…

Biological Physics · Physics 2015-06-15 Thomas J. Lane , Christian R. Schwantes , Kyle A. Beauchamp , Vijay S. Pande

It has been conjectured that evolution exerted pressure to preserve amino acids bearing thermodynamic, kinetic, and functional roles. In this letter we show that the physical requirement to maintain protein stability gives rise to a…

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

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

A theoretical framework is developed to study the dynamics of protein folding. The key insight is that the search for the native protein conformation is influenced by the rate r at which external parameters, such as temperature, chemical…

Biomolecules · Quantitative Biology 2009-11-13 Gregg Lois , Jerzy Blawzdziewicz , Corey S. O'Hern

Proteins need to selectively interact with specific targets among a multitude of similar molecules in the cell. But despite a firm physical understanding of binding interactions, we lack a general theory of how proteins evolve high…

Biomolecules · Quantitative Biology 2022-09-28 John M McBride , Jean-Pierre Eckmann , Tsvi Tlusty

As an example of topic where biology and physics meet, we present the issue of protein folding and stability, and the development of thermodynamics-based bioinformatics tools that predict the stability and thermal resistance of proteins and…

Biomolecules · Quantitative Biology 2016-03-15 Fabrizio Pucci , Marianne Rooman

Despite the importance of a thermodynamically stable structure with a conserved fold for protein function, almost all evolutionary models neglect site-site correlations that arise from physical interactions between neighboring amino acid…

Populations and Evolution · Quantitative Biology 2013-12-04 Andrew J. Bordner , Hans D. Mittelmann

Protein activity is a significant characteristic for recombinant proteins which can be used as biocatalysts. High activity of proteins reduces the cost of biocatalysts. A model that can predict protein activity from amino acid sequence is…

Quantitative Methods · Quantitative Biology 2018-07-23 X. Han , X. Wang , K. Zhou

Binding of a ligand on a protein changes the flexibility of certain parts of the protein, which directly affects its function. These changes are not the same at each point, some parts become more flexible and some others become stiffer.…

Biomolecules · Quantitative Biology 2015-01-13 Burak Erman

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

We consider the dynamics of a rigid filament in a motor protein assay under external loading. The motor proteins are modeled as active harmonic linkers with tail ends immobilized on a substrate. Their heads attach to the filament…

Biological Physics · Physics 2021-12-23 Amir Shee , Subhadip Ghosh , Debasish Chaudhuri