Bahena-Culhuac Erick, Bello Martiniano
Laboratorio de Diseño y Desarrollo de Nuevos Fármacos e Innovación Biotecnológica, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Salvador Diaz Mirón s/n, Casco de Santo Tomás, Miguel Hidalgo, Ciudad de México 11340, Mexico.
Faculty of Biology and Medicine, University of Lausanne, 1015 Lausanne, Switzerland.
Pharmaceuticals (Basel). 2025 Jul 17;18(7):1048. doi: 10.3390/ph18071048.
: Understanding the molecular interactions between small bioactive compounds and serum albumins is essential for drug development and pharmacokinetics. Noraucuparin, a biphenyl-type phytoalexin with promising pharmacological properties, has shown a strong binding affinity to bovine serum albumin (BSA), a model protein for drug transport. This study aims to elucidate the structural and energetic characteristics of the noraucuparin-BSA complex under physiological and slightly elevated temperatures. : Microsecond-scale molecular dynamics (MD) simulations and Molecular Mechanics Generalized Born Surface Area (MMGBSA)-binding-free energy calculations were performed to investigate the interaction between noraucuparin and BSA at 298 K and 310 K. Conformational flexibility and per-residue energy decomposition analyses were conducted, along with interaction network mapping to assess ligand-induced rearrangements. : Noraucuparin preferentially binds to site II of BSA, near the ibuprofen-binding pocket, with stabilization driven by hydrogen bonding and hydrophobic interactions. Binding at 298 K notably increased the structural mobility of BSA, affecting its global conformational dynamics. Key residues, such as Trp213, Arg217, and Leu237, contributed significantly to complex stability, and the ligand induced localized rearrangements in the protein's intramolecular interaction network. : These findings offer insights into the dynamic behavior of the noraucuparin-BSA complex and enhance the understanding of serum albumin-ligand interactions, with potential implications for drug delivery systems.
了解小生物活性化合物与血清白蛋白之间的分子相互作用对于药物开发和药代动力学至关重要。降紫堇灵，一种具有良好药理特性的联苯型植物抗毒素，已显示出对牛血清白蛋白（BSA）具有很强的结合亲和力，BSA是一种药物转运的模型蛋白。本研究旨在阐明生理温度和略高温度下降紫堇灵 - BSA复合物的结构和能量特征。：进行了微秒级分子动力学（MD）模拟和分子力学广义玻恩表面积（MMGBSA）结合自由能计算，以研究298K和310K下降紫堇灵与BSA之间的相互作用。进行了构象灵活性和每个残基的能量分解分析，以及相互作用网络映射以评估配体诱导的重排。：降紫堇灵优先结合到BSA的II位点，靠近布洛芬结合口袋，由氢键和疏水相互作用驱动稳定。在298K时的结合显著增加了BSA的结构流动性，影响其全局构象动力学。关键残基，如Trp213、Arg217和Leu237，对复合物稳定性有显著贡献，并且配体在蛋白质分子内相互作用网络中诱导了局部重排。：这些发现为降紫堇灵 - BSA复合物的动态行为提供了见解，并增强了对血清白蛋白 - 配体相互作用的理解，对药物递送系统具有潜在意义。
