Kastelic Miha, Kalyuzhnyi Yurij V, Hribar-Lee Barbara, Dill Ken A, Vlachy Vojko
Faculty of Chemistry and Chemical Technology, University of Ljubljana, 1000 Ljubljana, Slovenia;
Institute for Condensed Matter Physics, 79011 Lviv, Ukraine;
Proc Natl Acad Sci U S A. 2015 May 26;112(21):6766-70. doi: 10.1073/pnas.1507303112. Epub 2015 May 11.
Protein aggregation is broadly important in diseases and in formulations of biological drugs. Here, we develop a theoretical model for reversible protein-protein aggregation in salt solutions. We treat proteins as hard spheres having square-well-energy binding sites, using Wertheim's thermodynamic perturbation theory. The necessary condition required for such modeling to be realistic is that proteins in solution during the experiment remain in their compact form. Within this limitation our model gives accurate liquid-liquid coexistence curves for lysozyme and γ IIIa-crystallin solutions in respective buffers. It provides good fits to the cloud-point curves of lysozyme in buffer-salt mixtures as a function of the type and concentration of salt. It than predicts full coexistence curves, osmotic compressibilities, and second virial coefficients under such conditions. This treatment may also be relevant to protein crystallization.
蛋白质聚集在疾病和生物药物制剂中具有广泛的重要性。在此，我们建立了一个盐溶液中可逆蛋白质 - 蛋白质聚集的理论模型。我们将蛋白质视为具有方阱能量结合位点的硬球，采用韦特海姆热力学微扰理论。这种建模要符合实际所需的必要条件是实验过程中溶液中的蛋白质保持其紧密形式。在这个限制范围内，我们的模型给出了溶菌酶和γIIIa - 晶状体蛋白溶液在各自缓冲液中的准确液 - 液共存曲线。它能很好地拟合溶菌酶在缓冲盐混合物中的浊点曲线，作为盐类型和浓度的函数。然后它预测了在此类条件下的完整共存曲线、渗透压压缩率和第二维里系数。这种处理方法可能也与蛋白质结晶有关。
