Department of Chemistry, Yale University, New Haven, Connecticut 06520, USA.
J Am Chem Soc. 2013 Apr 24;135(16):6092-9. doi: 10.1021/ja311795d. Epub 2013 Apr 16.
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.
三元系统通常比二元系统更为复杂。尽管三组分在溶液中的可逆缔合对于广泛的化学和生物学过程至关重要，但对于此类系统，尚未出现通用的物理图像。在这里，我们开发了一种用于理解三元复合物平衡的通用综合框架，该框架与从更简单的（二元复合物）平衡中得出的 EC50 和 IC50 等熟悉的概念直接相关。重要的是，将我们的模型应用于文献中已发表的数据，使我们能够深入了解从凝血到单克隆抗体治疗剂量方案等复杂系统。我们还提供了一个 Excel 电子表格，以帮助读者理解和应用我们的模型。总体而言，我们的分析有可能使以前被认为“难以分析”的复杂三元系统，对理论家和实验者来说都变得易于理解。
