title: Biomolecular interactions modulate macromolecular structure and dynamics in atomistic model of a bacterial cytoplasm.
abstract: Biological macromolecules function in highly crowded cellular environments. The structure and dynamics of proteins and nucleic acids are well characterized in vitro, but in vivo crowding effects remain unclear. Using molecular dynamics simulations of a comprehensive atomistic model cytoplasm we found that protein-protein interactions may destabilize native protein structures, whereas metabolite interactions may induce more compact states due to electrostatic screening. Protein-protein interactions also resulted in significant variations in reduced macromolecular diffusion under crowded conditions, while metabolites exhibited significant two-dimensional surface diffusion and altered protein-ligand binding that may reduce the effective concentration of metabolites and ligands in vivo. Metabolic enzymes showed weak non-specific association in cellular environments attributed to solvation and entropic effects. These effects are expected to have broad implications for the in vivo functioning of biomolecules. This work is a first step towards physically realistic in silico whole-cell models that connect molecular with cellular biology.
authors: iTHES Research Group, RIKEN, Saitama, Japan.|Theoretical Molecular Science Laboratory, RIKEN, Saitama, Japan.
authors: Isseki
authors: I
authors: Yu
authors: iTHES Research Group, RIKEN, Saitama, Japan.|Theoretical Molecular Science Laboratory, RIKEN, Saitama, Japan.
authors: Takaharu
authors: T
authors: Mori
authors: Laboratory for Biomolecular Function Simulation, RIKEN Quantitative Biology Center, Kobe, Japan.
authors: Tadashi
authors: T
authors: Ando
authors: Computational Biophysics Research Team, RIKEN Advanced Institute for Computational Science, Kobe, Japan.
authors: Ryuhei
authors: R
authors: Harada
authors: Computational Biophysics Research Team, RIKEN Advanced Institute for Computational Science, Kobe, Japan.
authors: Jaewoon
authors: J
authors: Jung
authors: iTHES Research Group, RIKEN, Saitama, Japan.|Theoretical Molecular Science Laboratory, RIKEN, Saitama, Japan.|Laboratory for Biomolecular Function Simulation, RIKEN Quantitative Biology Center, Kobe, Japan.|Computational Biophysics Research Team, RIKEN Advanced Institute for Computational Science, Kobe, Japan.
authors: Yuji
authors: Y
authors: Sugita
authors: Laboratory for Biomolecular Function Simulation, RIKEN Quantitative Biology Center, Kobe, Japan.|Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, United States.
authors: Michael
authors: 0000-0001-9380-6422
authors: M
authors: Feig
mesh_terms: D003593:Cytoplasm / Q000737:chemistry*; D046911:Macromolecular Substances / Q000032:analysis*; D056004:Molecular Dynamics Simulation; D045704:Mycoplasma genitalium / Q000737:chemistry*; D062211:Spatio-Temporal Analysis
chemical_list: D046911:Macromolecular Substances
keywords: biophysics; computational biology; crowding effects; diffusion; metabolite dynamics; native state stability; none; quinary interactions; structural biology; systems biology; whole-cell modeling