Dynamic Modeling of Binding Kinetics Between GD1b Ganglioside and Cholera Toxin Subunit B
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© 2018 AACC. Cholera toxin (CTx) has to attach to host cell membrane before it is internalized to initiate infection processes. The attachment of CTx is mediated by cholera toxin subunit B (CTB) to the ganglioside receptors in host cell membrane. Prior studies revealed the complex nature of the CTB-ganglioside binding process by examining the properties of GM1, the major CTB receptor. Other gangliosides (e.g. GD1b) exhibiting moderate binding affinities to CTB also mediate the CTx internalization process. However, due to its intrinsic complexity, the binding mechanisms of other ganglioside receptors still remain elusive. In this work, a new dynamic model is proposed to describe a multistep binding process between CTB and GD1b by considering the cooperative binding effect as well as the GD1b receptor aggregation in a cell membrane. Moreover, in order to quantitatively calibrate the model against the experimental data, a numerical scheme including the local sensitivity under uncertainty and parameter selection method is implemented to identify several important parameters to be estimated. After estimating the selected parameters, the calibrated model agreed well with the experimental measurements, which demonstrated its predictive capability in the CTB-GD1b binding process.
author list (cited authors)
Lee, D., Singla, A., Wu, H., & Kwon, J.