College of Chemistry and Chemical Engineering, Lanzhou University, South Tianshui Road 222, Lanzhou, Gansu 730000, PR China.
GanSu Computing Center, 42 Qingyang Road, Chengguan District, Lanzhou City, 730030, Gansu Province, China.
J Biochem. 2021 Oct 12;170(3):411-417. doi: 10.1093/jb/mvab053.
With the developments of nanodrugs, some drugs have combined with nanoparticles (NPs) to reduce their side-effects and increase their therapeutic activities. Here, a novel nanodrug platinum nanoparticle-sorafenib (PtNP-SOR) was proposed for the first time. By means of molecular dynamics simulation, the stability and biocompatibility of PtNP-SOR were investigated. Then, the interaction mechanism between PtNP-SOR and vascular endothelial growth factor receptor 2 (VEGFR2) was explored and compared with that of the peptide 2a coated PtNPs. The results showed that PtNP-SOR could bind to VEGFR2 more stably, which was driven by the Coulombic and strong dispersion interaction between PtNP-SOR and VEGFR2. According to their contributions obtained from the decomposition of binding free energies, the key residues in VEGFR2 were identified to form the specific space, which increased the affinity with PtNP-SOR. This study provided useful insights to the design of PtNP-drugs as well as important theoretical proofs to the interaction between PtNP-SOR and VEGFR2 at a molecular level, which can be of large help during the development and optimization of novel nanodrugs.
随着纳米药物的发展，一些药物已经与纳米颗粒（NPs）结合，以减少其副作用并提高其治疗活性。在这里，首次提出了一种新型纳米药物——铂纳米颗粒-索拉非尼（PtNP-SOR）。通过分子动力学模拟，研究了 PtNP-SOR 的稳定性和生物相容性。然后，探索了 PtNP-SOR 与血管内皮生长因子受体 2（VEGFR2）的相互作用机制，并与 2a 肽涂层的 PtNPs 进行了比较。结果表明，PtNP-SOR 与 VEGFR2 的结合更稳定，这是由 PtNP-SOR 与 VEGFR2 之间的库仑和强色散相互作用驱动的。根据从结合自由能分解中获得的贡献，确定了 VEGFR2 中的关键残基形成特定的空间，从而增加了与 PtNP-SOR 的亲和力。这项研究为 PtNP 药物的设计提供了有用的见解，并为分子水平上 PtNP-SOR 与 VEGFR2 的相互作用提供了重要的理论证明，这对新型纳米药物的开发和优化有很大帮助。
