title: Local elastic constants of LacI and implications for allostery.
abstract: Allostery connects subtle changes in a protein's potential energy surface, induced by perturbations like ligand-binding, to significant changes in its function. Understanding this phenomenon and predicting its occurrence are major goals of current research in biophysics and molecular biology. In this paper we introduce a novel approach for studying complex structural transformations such as those typical for allostery. We show that the calculation and analysis of atomic elastic constants of a known allosterically regulated protein, lac repressor, highlights regions that are particularly prone to suffer structural deformation and are experimentally linked to allosteric function. The calculations are based on a high resolution, all-atom description of the protein. We also show that, for the present system, modifying the description of the system from an all-atom forcefield to an elastic network model yields qualitatively different results, indicating the importance of adequately describing the local environment surrounding the different parts of the protein.
authors.affiliation: Columbia University, Dept. Chemical Engineering, United States.
authors.forename: Andre A S T
authors.initials: AA
authors.lastname: Ribeiro
authors.affiliation: Columbia University, Dept. Chemical Engineering, United States. Electronic address: vortiz@columbia.edu.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Ortiz
mesh_terms: D000494:Allosteric Regulation; D004548:Elasticity; D056968:Lac Repressors / Q000737:chemistry*; D008958:Models, Molecular; D017433:Protein Structure, Secondary; D013314:Stress, Mechanical; D014199:Trehalose / Q000737:chemistry
chemical_list: D056968:Lac Repressors; D014199:Trehalose
keywords: Allostery; Elastic network model; Lac repressor protein; Mechanical properties; Stiffness