# gst: allosteric lever: toward a principle of specific allosteric response.

<< ️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. >>

<< ️However, a general principle of allostery, i.e., a set of quantitative and transferable “ground rules,” remains elusive. It is neither a set of structural motifs nor intrinsic motions. >>

<< ️Focusing on elastic network models, (AA) here show that an allosteric lever—a mode-coupling pattern induced by the perturbation—governs the directional, source-to-target, allosteric communication: A structural perturbation of an allosteric site couples the excitation of localized hard elastic modes with concerted long-range soft-mode relaxation. >>

<< ️Perturbations of nonallosteric sites instead couple hard and soft modes uniformly. The allosteric response is shown to be generally nonlinear and nonreciprocal, and allows for minimal structural distortions to be efficiently transmitted to specific changes at distant sites. Allosteric levers exist in proteins and “pseudoproteins”—networks designed to display an allosteric response. >>

<< ️Interestingly, protein sequences that constitute allosteric transmission channels are shown to be evolutionarily conserved. >>

Maximilian Vossel, Bert L. de Groot, Aljaž Godec. Allosteric Lever: Toward a Principle of Specific Allosteric Response. Phys. Rev. X 15, 021097. Jun 20, 2025

https://journals.aps.org/prx/abstract/10.1103/wv2k-676p

Also: allostery in FonT https://flashontrack.blogspot.com/search?q=allostery

Also: allosterico in Notes (quasi-stochastic poetry) https://inkpi.blogspot.com/search?q=allosterico

Keywords: gst, allostery, allosteric lever, elasticity, networks, elastic networks.

# evol: emergence of single vs. multi-state allostery

      FIG. 1. The elastic network model

<< Allostery, the change of activity of a  macromolecule in response to a perturbation at a distance from its active site, is thought to be a ubiquitous feature of proteins. Initially described in the context of multimeric proteins, it is now understood to underlie the regulation of proteins with diverse structural architectures, from receptors to signaling proteins and metabolic enzymes. >>️

<< Here, (AA) analyze a simplified model of protein allostery under a range of physical and evolutionary constraints. (They) find that a continuum of mechanisms between two archetypes emerges through evolution. In one limit, a single-state mechanism exists where ligand binding induces a displacement along a single normal mode, and in the other limit, a multi-state mechanism exists where ligand binding induces a switch across an energy barrier to a different stable state. Importantly, whenever the two mechanisms are possible, the multi-state mechanism confers a stronger allosteric effect and thus a selective advantage. >>

️

Eric Rouviere, Rama Ranganathan, Olivier Rivoire. Emergence of Single- versus Multi-State Allostery. PRX Life 1, 023004. Nov 9, 2023.

https://journals.aps.org/prxlife/abstract/10.1103/PRXLife.1.023004

Also: allostery in FonT https://flashontrack.blogspot.com/search?q=allostery

Also: allosterico in Notes 

(quasi-stochastic poetry)

https://inkpi.blogspot.com/search?q=allosterico

Keywords: gst, allostery, elastic, evolution

# s-chem: a strange allosteric regulation by volume fluctuations

<< a typical globular protein [the synaptic protein PSD-95] is able to undergo significant changes in volume under native conditions while exhibiting no additional changes in protein structure.These native state volume fluctuations were found to correlate with changes in internal motions that were previously recognized as a source of allosteric entropy. This finding offers a novel mechanistic basis for allostery in the absence of canonical structural change. >>

Anthony B. Law, Paul J. Sapienza, et al. Native State Volume Fluctuations in Proteins as a Mechanism for Dynamic Allostery. J. Am. Chem. Soc. 2017, 139 (10), pp 3599–3602 doi: 10.1021/jacs.6b12058

http://pubs.acs.org/doi/abs/10.1021/jacs.6b12058

Jeff  Hansen. 'Rosetta Stone' protein offers new mechanism  of allostery.  May 24, 2017

https://m.phys.org/news/2017-05-rosetta-stone-protein-mechanism-allostery.html