The effect of site-to-site variability in ultrasensitive dose responses

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• 作者：German A. Enciso ; Shane Ryerson
• 关键词：Multisite system ; Phosphorylation ; Signal transduction ; Ultrasensitivity ; Cooperativity ; Allostery
• 刊名：Journal of Mathematical Biology
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：74
• 期：1-2
• 页码：23-41
• 全文大小：
• 刊物类别：Mathematics and Statistics
• 刊物主题：Mathematical and Computational Biology; Applications of Mathematics;
• 出版者：Springer Berlin Heidelberg
• ISSN：1432-1416
• 卷排序：74

文摘

In this paper we study the ultrasensitive behavior of multisite phosphorylation or ligand binding systems, under site-to-site variations in the modification rates. Using computational methods and mathematical analysis, we prove that the Hill coefficient reaches its maximum value when all sites are identical to each other. This is shown for a non-cooperative multisite system with arbitrary activation function as well as for the well known MWC model. We also show that the Hill coefficient of the dose response is locally robust to variations in individual modification rates. The results suggest that maximal ultrasensitivity is reached when sites are similar to each other but not necessarily identical, a conformation found in unstructured modification domains present in many experimental systems.