Mesoscopic dynamics of diffusion-influenced enzyme kinetics

URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-79551591294&doi=10.1063%2f1.3528004&partnerID=40&md5=8ee0a9ac60440324a31efc5327b140fb

Keywords:

Article, binding site, Binding Sites, Biological, biological model, Catalysis, Catalysts, chemistry, Complex dissociation, Complexation, Concentration (process), Concentration effects, Cooperative effects, Detailed balance, Diffusion, Dynamical regime, Dynamics, Energy conservation law, enzyme, Enzyme concentrations, Enzyme kinetics, enzyme specificity, Enzyme-substrate complexes, Enzymes, Exponential form, Function of time, Hybrid molecular dynamics, Hydrodynamic interaction, Kinetics, Life-time distribution, Mass action, Mesoscopic dynamics, Mesoscopic models, metabolism, Models, Molecular dynamics, Molecular Dynamics Simulation, Multi-particle collision dynamics, Nonmonotonic behaviors, Point particle, Power-law, Power-law behavior, Product production, Rate laws, Reaction kinetics, Reversible reaction, solvent, Solvent molecules, Solvents, Species concentration, Spherical particle, Substrate Specificity, Substrates, Superconducting materials, Time-dependent rate coefficients

Abstract:

A particle-based mesoscopic model for enzyme kinetics is constructed and used to investigate the influence of diffusion on the reactive dynamics. Enzymes and enzyme-substrate complexes are modeled as finite-size soft spherical particles, while substrate, product, and solvent molecules are point particles. The system is evolved using a hybrid molecular dynamics-multiparticle collision dynamics scheme. Both the nonreactive and reactive dynamics are constructed to satisfy mass, momentum, and energy conservation laws, and reversible reaction steps satisfy detailed balance. Hydrodynamic interactions among the enzymes and complexes are automatically accounted for in the dynamics. Diffusion manifests itself in various ways, notably in power-law behavior in the evolution of the species concentrations. In accord with earlier investigations, regimes where the product production rate exhibits either monotonic or nonmonotonic behavior as a function of time are found. In addition, the species concentrations display both t -1/2 and t -3/2 power-law behavior, depending on the dynamical regime under investigation. For high enzyme volume fractions, cooperative effects influence the enzyme kinetics. The time dependent rate coefficient determined from the mass action rate law is computed and shown to depend on the enzyme concentration. Lifetime distributions of substrate molecules newly released in complex dissociation events are determined and shown to have either a power-law form for rebinding to the same enzyme from which they were released or an exponential form for rebinding to different enzymes. The model can be used and extended to explore a variety of issues related concentration effects and diffusion on enzyme kinetics. © 2011 American Institute of Physics.