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肌醇1,4,5-磷酸三酯受体(inositol 1,4,5-trisphosphate receptor,IP3R)是内质网钙离子释放的重要通道,对细胞信号的传递至关重要。国内外已经提出一些IP3R通道模型,用来解释拟合IP3R通道膜片钳实验数据,其中的De Young-Keizer模型在数值模拟中应用最为广泛。随着人工免疫系统研究的迅速发展,人工免疫算法已经在多目标优化问题上取得了广泛应用。作者应用混合免疫多目标优化算法,根据爪蟾卵母细胞和草地夜蛾细胞核膜IP3R通道的开放概率、平均开放时间和平均闭合时间的动力学实验数据,对De Young-Keizer通道模型进行参数拟合,获得大量优化的拟合参数,从而得到通道模型参数分布图。通过对比两种细胞的拟合参数分布,指出这两种不同细胞IP3R通道的开关动力学差异,主要来源于抑制Ca2+结合时IP3结合位点和当IP3结合时抑制Ca2+结合位点的结合动力学不同。
Inositol 1,4,5-trisphosphate receptor (IP3R) is an important channel for the release of endoplasmic reticulum calcium, which is crucial for cell signal transmission. At home and abroad, some IP3R channel models have been proposed to explain the experimental data fitting the IP3R channel patch clamp. The De Young-Keizer model is the most widely used in numerical simulation. With the rapid development of artificial immune system, artificial immune algorithm has been widely used in multi-objective optimization. According to the kinetic data of open probability, mean open time and mean closure time of IP3R channel of Xenopus laevis oocytes and S. frugiperda cell nuclei, the authors used the hybrid immune multi-objective optimization algorithm to simulate the De Young-Keizer channel model A large number of optimized fitting parameters are obtained, and the channel model parameter distribution map is obtained. By comparing the distribution of the fitting parameters of the two cells, it is pointed out that the switching dynamics of the IP3R channel of these two different cells are mainly derived from the inhibition of the binding kinetics of the IP3 binding site at Ca2 + binding and the Ca2 + binding site at IP3 binding different.