Kinetic Monte Carlo modeling of multivalent binding of CTB proteins with GM1 receptors.

Highlights • Development of a kMC model for the CTB-GM1 binding on a cell membrane. • Incorporating detailed surface reactions and the evolution of surface configurations. • The model predictions were accurate and the binding stochasticity was well captured. Abstract The binding mechanism between a cholera toxin subunit B (CTB) protein and ganglioside receptors on a host cell membrane still remains elusive due to multivalent surface binding reactions, dependency on the surface micro-configuration, and intrinsic stochasticity. In this work, a kinetic Monte Carlo (kMC) modeling framework coupled with a continuum model is proposed to incorporate the major characteristics of the binding process between CTB proteins and GM1 gangliosides, which are primary CTB receptors. First, a steady-state diffusion equation is introduced to model the diffusion of CTB proteins in the solution phase. Second, a kMC model is proposed to describe a fluctuation in the surface reaction rates as well as the evolution of surface configurations, and their effects on the binding kinetics. Lastly, the comparison with an experimentally validated deterministic model demonstrates the predictive capability of the proposed modeling framework in describing the kinetics of CTB-GM1 binding systems. [ABSTRACT FROM AUTHOR]