Zuse Institute Berlin, Takustraße 7, 14195, Berlin, Germany.
Sci Rep. 2022 Aug 4;12(1):13402. doi: 10.1038/s41598-022-17188-x.
The Wiseman fitting can be used to extract binding parameters from ITC data sets, such as heat of binding, number of binding sites, and the overall dissociation rate. The classical Wiseman fitting assumes a direct binding process and neglects the possibility of intermediate binding steps. In principle, it only provides thermodynamic information and not the kinetics of the process. In this article we show that a concentration dependent dissociation constant could possibly stem from intermediate binding steps. The mathematical form of this dependency can be exploited with the aid of the Robust Perron Cluster Cluster Analysis method. Our proposed extension of the Wiseman fitting rationalizes the concentration dependency, and can probably also be used to determine the kinetic parameters of intermediate binding steps of a multivalent binding process. The novelty of this paper is to assume that the binding rate varies per titration step due to the change of the ligand concentration and to use this information in the Wiseman fitting. We do not claim to produce the most accurate values of the binding parameters, we rather present a novel method of how to approach multivalent bindings from a different angle.
Wiseman 拟合可用于从 ITC 数据集提取结合参数，如结合热、结合位点数和整体离解速率。经典的 Wiseman 拟合假设直接结合过程，忽略了中间结合步骤的可能性。原则上，它仅提供热力学信息，而不是过程的动力学信息。在本文中，我们表明，浓度相关的离解常数可能源自中间结合步骤。这种依赖性的数学形式可以借助稳健的 Perron 聚类分析方法来利用。我们对 Wiseman 拟合的扩展合理化了浓度依赖性，并且可能也可用于确定多价结合过程中中间结合步骤的动力学参数。本文的新颖之处在于假设由于配体浓度的变化，结合速率在每个滴定步骤中都有所不同，并在 Wiseman 拟合中使用此信息。我们不声称能得到最准确的结合参数值，而是提出了一种从不同角度研究多价结合的新方法。
