title: Diffusional correlations among multiple active sites in a single enzyme.
abstract: Simulations of the enzymatic dynamics of a model enzyme containing multiple substrate binding sites indicate the existence of diffusional correlations in the chemical reactivity of the active sites. A coarse-grain, particle-based, mesoscopic description of the system, comprising the enzyme, the substrate, the product and solvent, is constructed to study these effects. The reactive and non-reactive dynamics is followed using a hybrid scheme that combines molecular dynamics for the enzyme, substrate and product molecules with multiparticle collision dynamics for the solvent. It is found that the reactivity of an individual active site in the multiple-active-site enzyme is reduced substantially, and this effect is analyzed and attributed to diffusive competition for the substrate among the different active sites in the enzyme.
authors.affiliation: Chemical Physics Theory Group, Department of Chemistry, University of Toronto, Toronto, ON M5S 3H6, Canada. rkapral@chem.utoronto.ca.
authors.forename: Carlos
authors.initials: C
authors.lastname: Echeverria
authors.forename: Raymond
authors.initials: R
authors.lastname: Kapral
mesh_terms: D001665:Binding Sites; D020134:Catalytic Domain; D004058:Diffusion; D004798:Enzymes / Q000737:chemistry* / Q000378:metabolism; D007535:Isomerases / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D013379:Substrate Specificity
chemical_list: D004798:Enzymes; C021918:4-oxalocrotonate tautomerase; D007535:Isomerases