(254e) Stochastic Modeling of CTB-GM1 Binding Mechanisms
The goal of this research focuses on modeling and simulation of CTB-GM1 interactions. In this work, GM1 is modeled as an entity constrained to a 2 dimensional host cell membrane, whereas CTB is modeled as an entity capable of binding and detaching from the membrane surface. Three types of microscopic events are considered: 1) molecular attachment, 2) detachment, and 3) migration events on host cell membranes. The implementation of the kinetic Monte Carlo methodology requires knowledge of association, dissociation and migration reaction constants. Previous work computed a range of values to these parameters until satisfactory agreement between the calculated and the experimental binding rates was achieved [2, 3]. Due to the overwhelming likelihood of migration events, migration has been decoupled from the event selection process in order to improve computational efficiency . For molecular attachment, it is assumed that each lattice site is available for attachment, and thus the attachment rate is equal over the lattice. Conversely, for molecular detachment and migration events, the rates are dependent on the local environment. Each local environment comprises up to 6 nearest neighbors. This allows us to classify our local environment into seven classes (zero to six nearest neighbors) in order to increase the computational efficiency when calculating the rates associated with executing a kinetic Monte Carlo event. We will also apply the kinetic Monte Carlo model to examine other host cell receptors such as GM2, which exhibits a distinct CTB binding kinetics. The specific details of how the GM1 concentration affects the CTB-GM1 interactions as well as steric hindrance between the CTB molecules on the membrane surface will be presented.
- de Haan, L.; Hirst , T.R. Cholera toxin: A paradigm for multi-functional engagement of cellular mechanisms. Molecular Membrane Biology 2004, 21, 77-92.
- Lauer, S.; Goldstein, B.; Nolan, R.L.; Nolan, J.P. Analysis of cholera toxin â ganglioside interactions by flow cytometry. Biochemistry 2002, 41, 1742-1751.
- Lin, H.; Kitova, E.N.; Klassen, J.S. Measuring positive cooperativity using the direct ESI-MS Assay. Cholera toxin B subunit homopentamer binding to GM1 pentasaccharide. J. Am. Soc. Mass. Spectrom. 2014, 25, 104-110.
- Crose, M.; Kwon, J.S.; Nayhouse, M.; Ni, D.; Christofides, P.D. Multiscale modeling and operation of PECVD of thin film solar cells. Chem. Eng. Sci. 2015, 136, 50-61.Â