Abstract

In this work binding properties and conformational changes in alpha lactalbumin (α-LA) upon interaction with sorafenib were investigated by spectrofluorimetry, UV-Vis spectroscopy, Fourier transform infrared spectroscopy and molecular modeling methods. The fluorescence spectroscopic results revealed that sorafenib could effectively quench the intrinsic fluorescence of alpha lactalbumin through a static quenching mechanism. Evaluation of the thermodynamic parameters (ΔH₀ = –120.167 kJ mol^–1, ΔS₀ = –309.507 J mol^–1 K^–1) suggested that the binding process was spontaneous while hydrogen bonds and van der Waals forces played a major role in this interaction. The fluorescence, UV-absorption and FT-IR spectra showed that conformational changes occurred in alpha lactalbumin structure after interaction with sorafenib. The molecular docking studies showed one binding site in alpha lactalbumin which most of its interactions are hydrophobic. The value of calculated docking ΔG₀ (–27.11232 kJ mol^–1) (is in agreement with those obtained from fluorescence spectroscopy measurement. Finally, molecular dynamics simulation was performed on the best docked complex by considering the permanence and flexibility of α-LA–sorafenib complex in the binding site.

中文翻译：

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索拉非尼与 ​​α-乳清蛋白相互作用的研究：光谱和分子建模

摘要

在这项工作中，通过荧光分光光度法、紫外-可见光谱法、傅里叶变换红外光谱法和分子建模方法研究了与索拉非尼相互作用后 α 乳清蛋白 (α-LA) 的结合特性和构象变化。荧光光谱结果表明，索拉非尼可以通过静态猝灭机制有效猝灭α乳清蛋白的固有荧光。热力学参数评估（Δ H ₀ = –120.167 kJ mol ^–1，Δ S ₀ = –309.507 J mol ^–1 K ^–1) 表明结合过程是自发的，而氢键和范德华力在这种相互作用中起主要作用。荧光、紫外吸收和 FT-IR 光谱表明，与索拉非尼相互作用后，α 乳清蛋白结构发生了构象变化。分子对接研究显示α乳清蛋白中有一个结合位点，其大部分相互作用是疏水的。计算的对接Δ G ₀ (–27.11232 kJ mol ^–1 ) 值（与荧光光谱测量得到的值一致。最后，考虑到α-LA的持久性和灵活性，对最佳对接复合物进行了分子动力学模拟-结合位点的索拉非尼复合物。