Back to Search
Start Over
Thermodynamics of Macromolecular Association in Heterogeneous Crowding Environments: Theoretical and Simulation Studies with a Simplified Model
- Source :
- J Phys Chem B
- Publication Year :
- 2016
-
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 non-specific 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.
- Subjects :
- 0301 basic medicine
Cytoplasm
genetic structures
Chemistry
Macromolecular Substances
Thermodynamics
Proteins
Mycoplasma genitalium
Molecular Dynamics Simulation
Crowding
Article
Surfaces, Coatings and Films
03 medical and health sciences
Molecular dynamics
030104 developmental biology
Materials Chemistry
Brownian dynamics
Protein folding
Physical and Theoretical Chemistry
Macromolecular crowding
Macromolecule
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- J Phys Chem B
- Accession number :
- edsair.doi.dedup.....5f91fc92ecc3cdf5bd350c4815fd3519