Faculty of Chemistry and Chemical Technology , University of Ljubljana , Večna pot 113 , SI-1000 Ljubljana , Slovenia.
J Phys Chem B. 2018 May 31;122(21):5400-5408. doi: 10.1021/acs.jpcb.7b11458. Epub 2018 Jan 27.
This study presents the theory for liquid-liquid phase separation for systems of molecules modeling monoclonal antibodies. Individual molecule is depicted as an assembly of seven hard spheres, organized to mimic the Y-shaped antibody. We consider the antibody-antibody interactions either through Fab, Fab' (two Fab fragments may be different), or Fc domain. Interaction between these three domains of the molecule (hereafter denoted as A, B, and C, respectively) is modeled by a short-range square-well attraction. To obtain numerical results for the model under study, we adapt Wertheim's thermodynamic perturbation theory. We use this model to calculate the liquid-liquid phase separation curve and the second virial coefficient B. Various interaction scenarios are examined to see how the strength of the site-site interactions and their range shape the coexistence curve. In the asymmetric case, where an attraction between two sites is favored and the interaction energies for the other sites kept constant, critical temperature first increases and than strongly decreases. Some more microscopic information, for example, the probability for the particular two sites to be connected, has been calculated. Analysis of the experimental liquid-liquid phase diagrams, obtained from literature, is presented. In addition, we calculate the second virial coefficient under conditions leading to the liquid-liquid phase separation and present this quantity on the graph B versus protein concentration.
本研究提出了用于模拟单克隆抗体的分子的液-液相分离理论。单个分子被描绘为七个硬球的组装，组织起来以模拟 Y 形抗体。我们考虑通过 Fab、Fab'（两个 Fab 片段可能不同）或 Fc 结构域来进行抗体-抗体相互作用。分子的这三个结构域（以下分别表示为 A、B 和 C）之间的相互作用通过短程方阱吸引来模拟。为了获得所研究模型的数值结果，我们采用了 Wertheim 的热力学微扰理论。我们使用该模型来计算液-液相分离曲线和第二维里系数 B。研究了各种相互作用情况，以观察位点位相互作用的强度及其范围如何影响共存曲线。在不对称情况下，两个位之间的吸引力受到青睐，而其他位的相互作用能量保持不变，临界温度首先增加，然后强烈降低。还计算了一些更微观的信息，例如，特定两个位连接的概率。呈现了从文献中获得的实验液-液相相图的分析。此外，我们在导致液-液相分离的条件下计算了第二维里系数，并将该量表示在 B 与蛋白质浓度的关系图上。
