title: Allostery without conformation change: modelling protein dynamics at multiple scales.
abstract: The original ideas of Cooper and Dryden, that allosteric signalling can be induced between distant binding sites on proteins without any change in mean structural conformation, has proved to be a remarkably prescient insight into the rich structure of protein dynamics. It represents an alternative to the celebrated Monod-Wyman-Changeux mechanism and proposes that modulation of the amplitude of thermal fluctuations around a mean structure, rather than shifts in the structure itself, give rise to allostery in ligand binding. In a complementary approach to experiments on real proteins, here we take a theoretical route to identify the necessary structural components of this mechanism. By reviewing and extending an approach that moves from very coarse-grained to more detailed models, we show that, a fundamental requirement for a body supporting fluctuation-induced allostery is a strongly inhomogeneous elastic modulus. This requirement is reflected in many real proteins, where a good approximation of the elastic structure maps strongly coherent domains onto rigid blocks connected by more flexible interface regions.
authors.affiliation: Biophysical Sciences Institute, Durham University, South Road, Durham DH1 3LE, UK.
authors.forename: T C B
authors.initials: TC
authors.lastname: McLeish
authors.forename: T L
authors.initials: TL
authors.lastname: Rodgers
authors.forename: M R
authors.initials: MR
authors.lastname: Wilson
mesh_terms: D000494:Allosteric Regulation; D004548:Elasticity; D008962:Models, Theoretical; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D011506:Proteins