A comprehensive mathematical model for three-body binding equilibria.

A comprehensive mathematical model for three-body binding equilibria.
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DOI:
10.1021/ja311795d
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发表时间:
2013-04-24
影响因子:
15
通讯作者:
Spiegel DA
Spiegel DA
中科院分区:
化学1区
文献类型:
--
作者:
Douglass EF Jr;Miller CJ;Sparer G;Shapiro H;Spiegel DA

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三组分体系通常比两组分体系更复杂。虽然溶液中三种组分的可逆缔合对于大量的化学和生物过程至关重要,但还没有出现这种系统的一般物理图像。在这里,我们已经开发了一个通用的,全面的框架来理解三元复杂平衡,它直接涉及到熟悉的概念,如“EC 50”和“IC 50”从简单的(二元复杂)平衡。重要的是,将我们的模型应用于已发表文献的数据,使我们能够对从单克隆抗体的凝血到治疗给药方案的复杂系统获得新的见解。我们还提供了一个Excel电子表格,以帮助读者概念化和应用我们的模型。总的来说,我们的分析有可能使复杂的三组分系统-以前被描述为“分析困难”-容易理解的理论家和实验学家一样。
Three-component systems are often more complex than their two-component counterparts. Although the reversible association of three components in solution is critical for a vast array of chemical and biological processes, no general physical picture of such systems has emerged. Here we have developed a general, comprehensive framework for understanding ternary complex equilibria, which relates directly to familiar concepts such as “EC50” and “IC50” from simpler (binary complex) equilibria. Importantly, application of our model to data from the published literature has enabled us to achieve new insights into complex systems ranging from coagulation to therapeutic dosing regimens for monoclonal antibodies. We also provide an Excel spreadsheet to assist readers in both conceptualizing and applying our models. Overall, our analysis has the potential to render complex three-component systems – which have previously been characterized as “analytically intractable” – readily comprehensible to theoreticians and experimentalists alike.
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