Rajendran Vijayakumar, Kandasamy Saravanan, Gunalan Seshan, Kanagaraj Sekar, Kothandan Gugan
Laboratory for Structural Biology and Biocomputing, Computational and Data Sciences, Indian Institute of Science, Bangalore, India.
Computational Biology Laboratory, Biological and Chemical Research Centre, University of Warsaw, Warszawa, Poland.
J Mol Recognit. 2025 Jan;38(1):e3112. doi: 10.1002/jmr.3112.
Bovine serum albumin (BSA) plays a crucial role as a carrier protein in plasma, binding various ligands, including drugs. Understanding the interaction between BSA and saquinavir, an antiretroviral drug, is essential for predicting its pharmacokinetics and pharmacodynamics. We employed spectroscopic approaches, including circular dichroism spectrometry and fluorescence spectroscopy, to investigate the binding of saquinavir to BSA. CD studies revealed conformational changes upon saquinavir mesylate binding, and the complex was stable up to 45°C during thermal denaturation. Saquinavir quenched the intrinsic fluorescence of BSA, indicating static quenching due to complex formation. Additionally, molecular docking simulations were performed to elucidate the favored binding site and interactions. The molecular docking results revealed that Subdomains IIA and IIB, which are proximal to Sudlow Site I, are the principal binding sites for the antiviral drug saquinavir. The ligand-bound pose of BSA also revealed that residue Trp213, which is adjacent to saquinavir, further validated the results of the fluorescence quenching assay, suggesting that residue Trp213 is quenched upon binding with saquinavir. MD simulations allowed us to explore the dynamic behavior of the BSA-saquinavir complex over time. We observed conformational fluctuations, solvent exposure, flexibility of binding pockets, free energy landscape, and binding energy. This study enhances our understanding of drug-protein interactions and contributes to drug development and optimization.
牛血清白蛋白（BSA）作为血浆中的一种载体蛋白发挥着关键作用，它能结合包括药物在内的各种配体。了解BSA与抗逆转录病毒药物沙奎那韦之间的相互作用对于预测其药代动力学和药效学至关重要。我们采用了包括圆二色光谱法和荧光光谱法在内的光谱学方法来研究沙奎那韦与BSA的结合。圆二色性研究揭示了甲磺酸沙奎那韦结合后构象的变化，并且在热变性过程中该复合物在45°C以下是稳定的。沙奎那韦淬灭了BSA的内在荧光，表明由于复合物形成导致静态淬灭。此外，进行了分子对接模拟以阐明有利的结合位点和相互作用。分子对接结果表明，靠近Sudlow位点I的IIA和IIB亚结构域是抗病毒药物沙奎那韦的主要结合位点。BSA与配体结合的构象还表明，与沙奎那韦相邻的色氨酸残基Trp213进一步验证了荧光淬灭试验的结果，表明色氨酸残基Trp213在与沙奎那韦结合时被淬灭。分子动力学模拟使我们能够探索BSA-沙奎那韦复合物随时间的动态行为。我们观察到了构象波动、溶剂暴露、结合口袋的灵活性、自由能景观和结合能。这项研究增进了我们对药物-蛋白质相互作用的理解，并有助于药物开发和优化。
