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

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.
Authors:
; ;  [1]
  1. Department of Systems and Computational Biology, Albert Einstein College of Medicine of Yeshiva University, 1300 Morris Park Avenue, Bronx, New York 10461 (United States)
Publication Date:
OSTI Identifier:
22255145
Resource Type:
Journal Article
Resource Relation:
Journal Name: Journal of Chemical Physics; Journal Volume: 140; Journal Issue: 5; Other Information: (c) 2014 AIP Publishing LLC; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
37 INORGANIC, ORGANIC, PHYSICAL AND ANALYTICAL CHEMISTRY; 60 APPLIED LIFE SCIENCES; COMPUTERIZED SIMULATION; DIFFUSION; IN VITRO; IN VIVO; INTERACTIONS; MEMBRANES; REACTION KINETICS; THERMODYNAMIC PROPERTIES