Vilallonga Gabriel D, de Almeida Antônio-Carlos G, Ribeiro Kelison T, Campos Sergio V A, Rodrigues Antônio M
Department of Computer Science, Universidad Nacional de San Luis, San Luis, Argentina.
Department of Biosystems Engineering, Federal University of São João del Rei, São João del Rei, Minas Gerais, Brazil.
R Soc Open Sci. 2018 Mar 21;5(3):172155. doi: 10.1098/rsos.172155. eCollection 2018 Mar.
The sodium-potassium pump (Na/K pump) is crucial for cell physiology. Despite great advances in the understanding of this ionic pumping system, its mechanism is not completely understood. We propose the use of a statistical model checker to investigate palytoxin (PTX)-induced Na/K pump channels. We modelled a system of reactions representing transitions between the conformational substates of the channel with parameters, concentrations of the substates and reaction rates extracted from simulations reported in the literature, based on electrophysiological recordings in a whole-cell configuration. The model was implemented using the UPPAAL-SMC platform. Comparing simulations and probabilistic queries from stochastic system semantics with experimental data, it was possible to propose additional reactions to reproduce the single-channel dynamic. The probabilistic analyses and simulations suggest that the PTX-induced Na/K pump channel functions as a diprotomeric complex in which protein-protein interactions increase the affinity of the Na/K pump for PTX.
钠钾泵（Na/K泵）对细胞生理功能至关重要。尽管在理解这种离子泵系统方面取得了巨大进展，但其机制尚未完全明晰。我们提议使用统计模型检查器来研究岩沙海葵毒素（PTX）诱导的Na/K泵通道。我们基于全细胞配置下的电生理记录，构建了一个反应系统模型，该模型表示通道构象亚态之间的转变，其参数、亚态浓度和反应速率均从文献报道的模拟中提取。该模型使用UPPAAL-SMC平台实现。将随机系统语义的模拟和概率查询与实验数据进行比较，有可能提出额外的反应来重现单通道动态。概率分析和模拟表明，PTX诱导的Na/K泵通道作为一种双聚体复合物发挥作用，其中蛋白质-蛋白质相互作用增加了Na/K泵对PTX的亲和力。
