A measure to quantify the degree of cooperativity in overall titration curves
A measure to quantify the degree of cooperativity in overall titration curves
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DOI：
10.1016/j.jtbi.2017.08.010
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发表时间：
2017-11-07
影响因子：
2
通讯作者：
Martini, Johannes W. R.
中科院分区：
文献类型：
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作者：
Martini, Johannes W. R.
在大规范系综的框架中，配体结合中常用的不同协同性定义并不等同。统一的定义是绑定多项式的非实根的存在。使用这个定性标准，一个悬而未决的问题是如何量化协作程度。在这项工作中，我们引入了一种理论测量来量化滴定曲线的协同程度。它的定义基于最小能量方法，将给定的结合多项式映射到生成它所需的最小相互作用能量。我们表明，如果假设所考虑的分子由能量上相同的结合位点组成，则可以轻松计算协同程度。此外，次乘性的性质使我们能够确定非对称系统中协同程度的上限。该方法与基于绑定多项式非实根存在的协同性定性定义一致，因此有助于将协同性概念置于坚实的理论基础上。它连接了宏观和微观状态，但这里也考虑到无限数量的不同分子可以引起相同的宏观配体结合行为，这意味着不能仅根据滴定曲线唯一地识别底层的微系统。 (C) 2017 Elsevier Ltd. 保留所有权利。
In the framework of the grand canonical ensemble, different definitions of cooperativity commonly used in the context of ligand binding are not equivalent. A unifying definition is the existence of non-real roots of the binding polynomial. Using this qualitative criterion, an open question is how to quantify the degree of cooperativity. In this work, we introduce a theoretical measure to quantify the degree of cooperativity of a titriation curve. Its definition is based on a minimal energy approach mapping a given binding polynomial to the minimal interaction energy which is required to generate it. We show that the degree of cooperativity can be calculated easily, if the molecule under consideration is assumed to consist of energetically identical binding sites. Moreover, the property of sub-multiplicativity allows us to determine upper bounds for the degree of cooperativity in asymmetric systems. The approach is consistent with the qualitative definition of cooperativity based on the existence of non-real roots of the binding polynomial, and thus helps to put the concept of cooperativity on a solid theoretical ground. It connects macro- and microstates, but takes here also into account that an infinite number of different molecules can cause the same macroscopic ligand binding behavior, which means that the underlying microsystem cannot be uniquely identified based on the titration curve only. (C) 2017 Elsevier Ltd. All rights reserved.