2023/11/20 by Maximilian Vossel, Bert L. de Groot, Vossel, Maximilian +3
Biochemistry, Genetics and Molecular Biology · Physics and Astronomy · #Biological Physics (physics.bio-ph) #Biomolecules (q-bio.BM) #Cellular Mechanics and Interactions #Chemical Physics (physics.chem-ph) #FOS: Biological sciences #FOS: Physical sciences #Force Microscopy Techniques and Applications #Mechanical and Optical Resonators #Soft Condensed Matter (cond-mat.soft)
paper · pdf · doi:10.48550/arxiv.2311.12025
openalex publication_date 2023/11/20 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/28
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 employed in the design of mechanical metamaterials. 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, we 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 non-allosteric sites instead couple hard and soft modes uniformly. The allosteric response is shown to be generally non-linear and non-reciprocal, 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. To illustrate how the results may be applied in drug design, we use them to successfully predict known allosteric sites in proteins.