title: Enzyme kinetics and transport in a system crowded by mobile macromolecules.
abstract: The dynamics of an elastic network model for the enzyme 4-oxalocrotonate tautomerase is studied in a system crowded by mobile macromolecules, also modeled by elastic networks. The system includes a large number of solvent molecules, as well as substrate and product molecules which undergo catalytic reactions with this hexameric protein. The time evolution of the entire system takes place through a hybrid dynamics that combines molecular dynamics for solute species and multiparticle collision dynamics for the solvent. It is shown that crowding leads to subdiffusive dynamics for the protein, in accord with many studies of diffusion in crowded environments, and increases orientational relaxation times. The enzyme reaction kinetics is also modified by crowding. The effective Michaelis constant decreases with crowding volume fraction, and this decrease is attributed to excluded volume effects, which dominate over effects due to reduced substrate diffusion that would cause the Michaelis constant to increase.
authors.affiliation: Chemical Physics Theory Group, Department of Chemistry, University of Toronto, Toronto, ON M5S 3H6, Canada. rkapral@chem.utoronto.ca and CeSiMo, Facultad de Ingeniería, Universidad de Los Andes, Mérida 5101, Venezuela. cecheve@ula.ve.
authors.forename: Carlos
authors.initials: C
authors.lastname: Echeverria
authors.affiliation: Chemical Physics Theory Group, Department of Chemistry, University of Toronto, Toronto, ON M5S 3H6, Canada. rkapral@chem.utoronto.ca.
authors.forename: Raymond
authors.initials: R
authors.lastname: Kapral
mesh_terms: D004058:Diffusion; D007535:Isomerases / Q000737:chemistry / Q000378:metabolism*; D007700:Kinetics; D008958:Models, Molecular
chemical_list: C021918:4-oxalocrotonate tautomerase; D007535:Isomerases