Modeling of solvent flow effects in enzyme catalysis under physiological conditions

URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-84862570243&doi=10.1063%2f1.4719539&partnerID=40&md5=ea92730a0cd12672b0e83e66a3795bd6

Keywords:

2, 3 biphosphate, 3 diphosphoglyceric acid, 3 phosphoglyceric acid, 3-biphosphate, 3-phosphoglycerate, Absorbing boundaries, Adenosine Diphosphate, Adenosine Triphosphate, Article, Biocatalysis, Biological, biological model, Catalysis, Catalytic transfer, chemical structure, chemistry, Computer Simulation, Diffusing particles, Diffusion, Diphosphoglyceric Acids, Direct simulation, Dynamics, Elastic network models, Enzymatic catalysis, Enzymatic system, Enzyme catalysis, Enzyme-substrate binding, Enzymes, First-passage-time density, glycerate 1, glyceric acid, Glyceric Acids, Hydrodynamic coupling, Hydrodynamic flows, Hydrodynamics, Intermolecular interactions, Kinetics, metabolism, Models, Molecular, Multi-particle collision dynamics, Multiparticle collisions, Phosphoglycerate Kinase, Phosphoryl groups, Physiological condition, Physiology, Probability densities, Probability density function, Protein Conformation, Reaction cycles, Significant impacts, solvent, Solvent flow, Solvent particles, Solvents, Spherical shell, statistics, Stochastic Processes, Substrate binding, Substrates, Time-scales

Abstract:

A stochastic model for the dynamics of enzymatic catalysis in explicit, effective solvents under physiological conditions is presented. Analytically-computed first passage time densities of a diffusing particle in a spherical shell with absorbing boundaries are combined with densities obtained from explicit simulation to obtain the overall probability density for the total reaction cycle time of the enzymatic system. The method is used to investigate the catalytic transfer of a phosphoryl group in a phosphoglycerate kinase-ADP-bis phosphoglycerate system, one of the steps of glycolysis. The direct simulation of the enzyme-substrate binding and reaction is carried out using an elastic network model for the protein, and the solvent motions are described by multiparticle collision dynamics which incorporates hydrodynamic flow effects. Systems where solvent-enzyme coupling occurs through explicit intermolecular interactions, as well as systems where this coupling is taken into account by including the protein and substrate in the multiparticle collision step, are investigated and compared with simulations where hydrodynamic coupling is absent. It is demonstrated that the flow of solvent particles around the enzyme facilitates the large-scale hinge motion of the enzyme with bound substrates, and has a significant impact on the shape of the probability densities and average time scales of substrate binding for substrates near the enzyme, the closure of the enzyme after binding, and the overall time of completion of the cycle. © 2012 American Institute of Physics.