Najdi Tarek S, Yang Chin-Rang, Shapiro Bruce E, Hatfield G Wesley, Mjolsness Eric D
Institute for Genomics and Bioinformatics, Department of Microbiology and Molecular Genetics, College of Medicine, University of California, Irvine, Irvine, California 92697, USA.
J Bioinform Comput Biol. 2006 Apr;4(2):335-55. doi: 10.1142/s0219720006001862.
In our effort to elucidate the systems biology of the model organism, Escherichia coli, we have developed a mathematical model that simulates the allosteric regulation for threonine biosynthesis pathway starting from aspartate. To achieve this goal, we used kMech, a Cellerator language extension that describes enzyme mechanisms for the mathematical modeling of metabolic pathways. These mechanisms are converted by Cellerator into ordinary differential equations (ODEs) solvable by Mathematica. In this paper, we describe a more flexible model in Cellerator, which generalizes the Monod, Wyman, Changeux (MWC) model for enzyme allosteric regulation to allow for multiple substrate, activator and inhibitor binding sites. Furthermore, we have developed a model that describes the behavior of the bifunctional allosteric enzyme aspartate kinase I-homoserine dehydrogenase I (AKI-HDHI). This model predicts the partition of enzyme activities in the steady state which paves the way for a more generalized prediction of the behavior of bifunctional enzymes.
在我们阐明模式生物大肠杆菌系统生物学的过程中，我们开发了一个数学模型，该模型模拟了从天冬氨酸开始的苏氨酸生物合成途径的变构调节。为实现这一目标，我们使用了kMech，它是Cellerator语言的一个扩展，用于描述代谢途径数学建模的酶机制。这些机制由Cellerator转换为可由Mathematica求解的常微分方程（ODEs）。在本文中，我们描述了Cellerator中一个更灵活的模型，该模型将用于酶变构调节的莫诺德、怀曼、尚热（MWC）模型进行了推广，以允许多个底物、激活剂和抑制剂结合位点。此外，我们还开发了一个描述双功能变构酶天冬氨酸激酶I-高丝氨酸脱氢酶I（AKI-HDHI）行为的模型。该模型预测了稳态下酶活性的分配，为更普遍地预测双功能酶的行为铺平了道路。
