Biomolecular interactions modulate macromolecular structure and dynamics in atomistic model of a bacterial cytoplasm
Year: 2016
Type: article
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.
Source: eLife
DOI: 10.7554/elife.19274
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,500
Funders: National Science Foundation, Ministry of Education, Culture, Sports, Science and Technology, National Institutes of Health, Japan Society for the Promotion of Science, Japan Science and Technology Agency, RIKEN, National Institute of General Medical Sciences, Core Research for Evolutional Science and Technology
Awards: 分子動力学シミュレーションで探る細胞環境におけるタンパク質フォールディング機構, G180133833, G21022499, G2445101632, G2521286739, G2909878164, Multiscale modeling of supramolecular protein-DNA assemblies, Breakthrough on the high pressure biomolecule reaction with computational chemistry of the volume change, G3288033459, G3512421365, G3935995917, G5893904887, Protein structure refinement through effective sampling and scoring, Signal Transduction Process of G-Protein Coupled Receptor (GPCR) Studied by Molecular Dynamics Simulation, G7509365169, G8179195413, G8226784050, G8294518315, Cellular Crowding Effects of Biomolecular Stability and Dynamics, G8738102781
OpenAlex ID: W2542660070