title: Thermodynamics of Macromolecular Association in Heterogeneous Crowding Environments: Theoretical and Simulation Studies with a Simplified Model.
abstract: The cytoplasm of a cell is crowded with many different kinds of macromolecules. The macromolecular crowding affects the thermodynamics and kinetics of biological reactions in a living cell, such as protein folding, association, and diffusion. Theoretical and simulation studies using simplified models focus on the essential features of the crowding effects and provide a basis for analyzing experimental data. In most of the previous studies on the crowding effects, a uniform crowder size is assumed, which is in contrast to the inhomogeneous size distribution of macromolecules in a living cell. Here, we evaluate the free energy changes upon macromolecular association in a cell-like inhomogeneous crowding system via a theory of hard-sphere fluids and free energy calculations using Brownian dynamics trajectories. The inhomogeneous crowding model based on 41 different types of macromolecules represented by spheres with different radii mimics the physiological concentrations of macromolecules in the cytoplasm of Mycoplasma genitalium. The free energy changes of macromolecular association evaluated by the theory and simulations were in good agreement with each other. The crowder size distribution affects both specific and nonspecific molecular associations, suggesting that not only the volume fraction but also the size distribution of macromolecules are important factors for evaluating in vivo crowding effects. This study relates in vitro experiments on macromolecular crowding to in vivo crowding effects by using the theory of hard-sphere fluids with crowder-size heterogeneity.
authors: RIKEN Quantitative Biology Center (QBiC), Integrated Innovation Building 7F, 6-7-1 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
authors: Tadashi
authors: T
authors: Ando
authors: RIKEN Theoretical Molecular Science Laboratory and iTHES, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
authors: Isseki
authors: I
authors: Yu
authors: RIKEN Quantitative Biology Center (QBiC), Integrated Innovation Building 7F, 6-7-1 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.|Department of Biochemistry & Molecular Biology, Michigan State University , East Lansing, Michigan 48824, United States.
authors: Michael
authors: M
authors: Feig
authors: RIKEN Quantitative Biology Center (QBiC), Integrated Innovation Building 7F, 6-7-1 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.|RIKEN Theoretical Molecular Science Laboratory and iTHES, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.|RIKEN Advanced Institute for Computational Science (AICS), 7-1-26 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
authors: Yuji
authors: Y
authors: Sugita
mesh_terms: D003593:Cytoplasm / Q000737:chemistry; D046911:Macromolecular Substances / Q000737:chemistry; D056004:Molecular Dynamics Simulation; D045704:Mycoplasma genitalium / Q000737:chemistry; D011506:Proteins / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D046911:Macromolecular Substances; D011506:Proteins