A coarse-grained model for the simulations of biomolecular interactions in cellular environments

Zhong Ru Xie, Jiawen Chen, Yinghao Wu

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

The interactions of bio-molecules constitute the key steps of cellular functions. However, in vivo binding properties differ significantly from their in vitro measurements due to the heterogeneity of cellular environments. Here we introduce a coarse-grained model based on rigid-body representation to study how factors such as cellular crowding and membrane confinement affect molecular binding. The macroscopic parameters such as the equilibrium constant and the kinetic rate constant are calibrated by adjusting the microscopic coefficients used in the numerical simulations. By changing these model parameters that are experimentally approachable, we are able to study the kinetic and thermodynamic properties of molecular binding, as well as the effects caused by specific cellular environments. We investigate the volumetric effects of crowded intracellular space on bio-molecular diffusion and diffusion-limited reactions. Furthermore, the binding constants of membrane proteins are currently difficult to measure. We provide quantitative estimations about how the binding of membrane proteins deviates from soluble proteins under different degrees of membrane confinements. The simulation results provide biological insights to the functions of membrane receptors on cell surfaces. Overall, our studies establish a connection between the details of molecular interactions and the heterogeneity of cellular environments.

Original languageEnglish (US)
Article number054112
JournalJournal of Chemical Physics
Volume140
Issue number5
DOIs
StatePublished - 2014

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membranes
Membranes
Membrane Proteins
Intracellular Space
Crowding
proteins
Kinetics
Molecular interactions
simulation
Body Image
Equilibrium constants
Cell Surface Receptors
interactions
Thermodynamics
Rate constants
Carrier Proteins
Thermodynamic properties
molecular diffusion
crowding
kinetics

ASJC Scopus subject areas

  • Physics and Astronomy(all)
  • Physical and Theoretical Chemistry
  • Medicine(all)

Cite this

A coarse-grained model for the simulations of biomolecular interactions in cellular environments. / Xie, Zhong Ru; Chen, Jiawen; Wu, Yinghao.

In: Journal of Chemical Physics, Vol. 140, No. 5, 054112, 2014.

Research output: Contribution to journalArticle

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