乙二醇强烈不利于假异花青染料在拥挤浓度下的低聚,Soft Matter

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乙二醇强烈不利于假异花青染料在拥挤浓度下的低聚
Soft Matter ( IF 2.9 ) Pub Date : 2023-08-01 , DOI: 10.1039/d3sm00564j
Satyendra Rajput ₁ , Roland Pollak ₂ , Klaus Huber ₃ , Simon Ebbinghaus ₂ , Divya Nayar ₁

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细胞内拥挤环境在调节蛋白质聚集中的有趣作用仍然难以捉摸。蛋白质序列依赖性、拥挤的形状和大小以及不同的分子间相互作用等多种因素的交织使得识别系统趋势变得复杂。简化问题的方法之一是研究自组装蛋白质的合成模型。在本研究中，我们研究了阳离子假异氰氯化物 (PIC) 染料的聚集行为，该染料已知在水溶液中自组装并形成原纤维状 J-聚集体，类似于淀粉样蛋白形成的聚集体。先前的实验研究表明，聚乙二醇会阻碍 PIC 染料的自组装，而 Ficoll-400 会促进 PIC 染料的自组装。为了获得分子见解，我们使用广泛的分子动力学模拟研究了乙二醇拥挤对染料低聚成 H 型和 J 型低聚物的溶剂化热力学的影响。结合自由能计算表明，J-低聚物在水中比H-低聚物更有利于形成。H-和J-四聚体和五聚体的稳定性在拥挤的溶液中降低。纯水和乙二醇水溶液中染料-溶剂相互作用能的有利变化支持低聚物的形成，尽管染料-溶剂熵降低则相反。乙二醇作为分子拥挤剂，通过优先结合染料低聚物而不利于 H- 和 J- 低聚。染料-拥挤和染料-染料相互作用能对染料缔合的不利变化使得在拥挤溶液中比在纯水溶液中更不利于H-低聚物的形成。然而，在 J-低聚物的情况下，染料-人群相互作用能的不利变化主要导致染料-溶剂总能量不利。该结果得到等温滴定量热法测量的支持，其中发现乙二醇与 PIC 分子的结合是吸热的。结果提供了一个新的观点，即拥挤的环境可能不利于 PIC 染料通过与低聚状态的相互作用进行自组装。这些发现对于理解拥挤环境在塑造蛋白质自由能景观中的作用具有重要意义。

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Ethylene glycol energetically disfavours oligomerization of pseudoisocyanine dyestuffs at crowded concentrations

The intriguing role of the intracellular crowded environment in regulating protein aggregation remains elusive. The convolution of several factors such as the protein sequence-dependence, crowder's shape and size and diverse intermolecular interactions makes it complex to identify systematic trends. One of the ways to simplify the problem is to study a synthetic model for self-assembling proteins. In this study, we examine the aggregation behaviour of the cationic pseudoisocyanine chloride (PIC) dyestuff which is known to self-assemble and form fibril-like J-aggregates in aqueous solutions, similar to those formed by amyloid-forming proteins. Prior experimental studies have shown that polyethylene glycol impedes and Ficoll-400 promotes the self-assembly of PIC dyes. To achieve molecular insights, we examine the effect of crowding by ethylene glycol on the solvation thermodynamics of oligomerization of dyes into H-type and J-type oligomers using extensive molecular dynamics simulations. The binding free energy calculations show that the formation of J-oligomers is more favourable than that of H-oligomers in water. The stability of H- and J- tetramers and pentamers decreases in crowded solutions. The formation of oligomers is supported by the favourable change in dye–solvent interaction energy in both pure water and aqueous ethylene glycol solution although it is opposed by the reduced dye–solvent entropy. Ethylene glycol, as a molecular crowder, disfavours the H- as well as J-oligomerization via preferential binding to the dye oligomers. An unfavourable change in dye–crowder and dye–dye interaction energy on dye association makes the H-oligomer formation less favourable in crowded solution than in pure water solution. In the case of J-oligomers, however, the unfavourable change in dye–crowder interaction energy primarily contributes to making total dye–solvent energy unfavourable. The results are supported by isothermal titration calorimetry measurements where the binding of ethylene glycol to PIC molecules is found to be endothermic. The results provide an emerging view that a crowded environment can disfavour self-assembly of PIC dyes by interactions with the oligomeric states. The findings have implications in understanding the role of a crowded environment in shaping the free energy landscapes of proteins.

更新日期：2023-08-01

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