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Understanding the link between structure and function in proteins is fundamental in molecular biology and proteomics. A central question in this context is whether allostery - where the binding of a molecule at one site affects the activity…

Statistical Mechanics · Physics 2025-06-02 Giulio Costantini , Lorenzo Caprini , Umberto Marini Bettolo Marconi , Fabio Cecconi

A growing number of experimental evidence shows that it is general for a ligand binding protein to have a potential for allosteric regulation and for further evolution. In addition, such proteins generically change their conformation upon…

Biomolecules · Quantitative Biology 2019-05-09 Anton S. Zadorin

Allosteric regulation is found across all domains of life, yet we still lack simple, predictive theories that directly link the experimentally tunable parameters of a system to its input-output response. To that end, we present a general…

Subcellular Processes · Quantitative Biology 2017-06-23 Manuel Razo-Mejia , Stephanie L. Barnes , Nathan M. Belliveau , Griffin Chure , Tal Einav , Mitchell Lewis , Rob Phillips

Allosteric regulation is often viewed as thermodynamic in nature. However protein internal motions during an enzymatic reaction cycle can be slow hopping processes over numerous potential barriers. We propose that regulating molecules may…

Biological Physics · Physics 2009-11-13 Jianhua Xing

Many signalling functions in molecular biology require proteins bind to substrates such as DNA in response to environmental signals such as the simultaneous binding to a small molecule. Examples are repressor proteins which may transmit…

Biomolecules · Quantitative Biology 2009-11-10 Rhoda J. Hawkins , Thomas C. B. McLeish

Allosteric signaling in biological molecules, which may be viewed as specific action at a distance due to localized perturbation upon binding of ligands or changes in environmental cues, is pervasive in biology. Phenomenological MWC and KNF…

Soft Condensed Matter · Physics 2022-02-28 D. Thirumalai , Changbong Hyeon , Pavel I. Zhuravlev , George H. Lorimer

Allostery, the phenomenon by which the perturbation of a molecule at one site alters its behavior at a remote functional site, enables control over biomolecular function. Allosteric modulation is a promising avenue for drug discovery and is…

Biological Physics · Physics 2025-05-15 Maximilian Vossel , Bert L. de Groot , Aljaž Godec

Interactions between a protein and a ligand are often accompanied by a redistribution of the population of thermally accessible conformations. This dynamic response of the protein's functional energy landscape enables a protein to modulate…

Biological Physics · Physics 2016-03-15 Prithviraj Nandigrami , John J. Portman

Allostery refers to the puzzling phenomenon of long-range communication between distant sites in proteins. Despite its importance in biomolecular regulation and signal transduction, the underlying dynamical process is not well understood.…

Biological Physics · Physics 2024-08-28 Ahmed A. A. I. Ali , Emanuel Dorbath , Gerhard Stock

Although the importance of protein dynamics in protein function is generally recognized, the role of protein fluctuations in allosteric effects scarcely has been considered. To address this gap, the Kullback-Leibler divergence (Dx) between…

Biomolecules · Quantitative Biology 2009-11-13 Michael E. Wall

Allostery is a fundamental property of proteins that represents the functional coupling between distantly located sites. In different manifestations, this property underlies signal transduction, gene expression, and regulation -- elementary…

Biomolecules · Quantitative Biology 2024-11-14 Eric Rouviere , Olivier Rivoire , Rama Ranganathan

Allostery is a fundamental mechanism of protein regulation and is commonly interpreted as modulating enzymatic activity or product abundance. Here we show that this view is incomplete. Using a stochastic model of allosteric regulation…

Molecular Networks · Quantitative Biology 2026-01-08 Pedro Pessoa , Steve Pressé , S. Banu Ozkan

In allosteric proteins, binding a ligand can affect function at a distant location, for example by changing the binding affinity of a substrate at the active site. The induced fit and population shift models, which differ by the assumed…

Biological Physics · Physics 2019-10-28 Riccardo Ravasio , Solange Flatt , Le Yan , Stefano Zamuner , Carolina Brito , Matthieu Wyart

Thermodynamic bulk measurements of binding reactions critically rely on the validity of the law of mass action and the assumption of a dilute solution. Yet important biological systems such as allosteric ligand-receptor binding,…

Biological Physics · Physics 2017-03-31 Joan Camunas-Soler , Anna Alemany , Felix Ritort

Several physical mechanisms have been proposed to explain allostery in proteins. They differ by the number of internal states that they assume a protein to occupy, leaving open the question of what controls the emergence of these distinct…

Biomolecules · Quantitative Biology 2021-11-19 Eric Rouviere , Rama Ranganathan , Olivier Rivoire

Allostery, the intriguing phenomenon of long-range communication between distant sites in proteins, plays a central role in biomolecular regulation and signal transduction. While it is commonly attributed to conformational rearrangements,…

Atomic and Molecular Clusters · Physics 2026-04-29 Emanuel Dorbath , Fabian Rudolf , Adnan Gulzar , Gerhard Stock

Proteins display generic properties that are challenging to explain by direct selection, notably allostery, the capacity to be regulated through long-range effects, and evolvability, the capacity to adapt to new selective pressures. An…

Biomolecules · Quantitative Biology 2019-10-02 Olivier Rivoire

Allosteric regulation in proteins is often accompanied by conformational changes that facilitate transmission of mechanical signals between distant ligand binding sites. Typically, these deformations are classified in terms of specific…

Soft Condensed Matter · Physics 2024-01-26 Jason W. Rocks , Eleni Katifori , Andrea J. Liu

Protein dynamics has been investigated on a wide range of time scales. Nano- and picosecond dynamics have been assigned to local fluctuations, while slower dynamics have been attributed to larger conformational changes. However, it is…

Allosteric effects are often underlying the activity of proteins and elucidating generic design aspects and functional principles which are unique to allosteric phenomena represents a major challenge. Here an approach which consists in the…

Biological Physics · Physics 2017-02-28 Holger Flechsig
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