Thus, in NMR studies, it was observed that high molecular weight glycoproteins are efficient
molecular seeds for protein aggregation . Such additional effects were also invoked by McGuffee and Elcock , using a simulation model which successfully describes the relative thermodynamic stabilities of proteins measured in E. coli, modeling 50 highly abundant macromolecule types at experimentally Inhibitors,research,lifescience,medical measured concentrations. Morelli et al.  show a simple way to model the effects of macromolecular crowding on biochemical networks. To succeed, they had to scale bimolecular association and dissociation rates correctly. They used kinetic Monte Carlo see more simulations and looked at crowding effects, comparing a constitutively expressed gene, a repressed gene, and a model for the bacteriophage λ genetic switch. Each molecular assembly was modeled both with and without nonspecific binding of transcription factors to genomic DNA. Furthermore, crowding effects shifted association–dissociation Inhibitors,research,lifescience,medical equilibria rather than slowing down protein diffusion, which sometimes had unexpected effects on biochemical network performance. Norris and Malys  show even changes of Michaelis-Menten kinetic constant Km, and rate constant
kcat for the enzyme glucose-6-phosphate dehydrogenase under crowding. kcat increased at very low concentrations of crowding Inhibitors,research,lifescience,medical agent or at high crowded concentrations during heating (45 °C), adding PEG. Simulations applying the Arrhenius equation agree with these observations. More subtle effects of how enzymes are influenced by crowding are apparent in simulations
and only partly supported by experimental data: Adenylate kinase was coarse grain modeled by Echeverria and Inhibitors,research,lifescience,medical Kapral , showing large-scale hinge motions during enzymatic cycles. Multiparticle collision dynamics included effects due to hydrodynamic interactions. A stationary random array of hard spherical objects provided crowding in the simulation. Adenylate kinase prefers Inhibitors,research,lifescience,medical a closed conformation for high volume fractions (smaller obstacle radius and tighter packing). Average enzymatic cycle time and characteristic times of internal conformational motions of the protein change, as do the transport properties. Under crowding, diffusive motion becomes up to ten times slower with longer orientational relaxation time. In general, and according to simulations on from seven different proteins, those experiencing the strongest crowding effects have larger conformational changes between open and closed states . In Brownian dynamic simulations, Ando and Skolnick  modeled a simplified E. coli cytoplasm with 15 different macromolecule types at physiological concentrations and sphere representations using a soft repulsive potential. These authors compare their data with the experiment; at cellular concentrations, the calculated diffusion constant of GFP was shape independent and much larger than in the experiments.