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几类重要蛋白—蛋白相互作用的分子模拟

发布时间:2018-05-06 15:52

  本文选题:蛋白-蛋白相互作用 + 分子模拟 ; 参考:《北京协和医学院》2012年硕士论文


【摘要】:TLR5是一种重要的模式识别受体,可特异性的识别细菌鞭毛蛋白后引起机体的免疫反应和炎症反应。近来研究发现鞭毛蛋白通过结合TLR5,激活NF-κB信号通路,调节多种细胞因子的分泌,对电离辐射及其他刺激引发的细胞凋亡具有保护作用。本文采用同源模建技术构建TLR5的三维结构,模型经过优化后进行构象和能量的评价,表明该TLR5结构模型合理。将TLR5与鞭毛蛋白进行分子对接,采用聚类分析,计算结合能等手段选出最佳对接构象后进行分子动力学模拟,研究TLR5与鞭毛蛋白相互作用机制及其动态过程,结果分析表明范德华作用和静电作用是TLR5与鞭毛蛋白结合的主要推动力,TLR5上的残基R392/D393对于其与配体的结合至关重要。 肿瘤抑素是源于人基膜胶原Ⅳ的肿瘤新生血管生成的抑制因子,有明显的抑制肿瘤新生血管生成和诱导其内皮细胞凋亡的活性,其主要活性片段为T7肽。T7肽通过与内皮细胞表面的αvβ3整合素结合发挥作用,以其抗肿瘤新生血管生成和抑制肿瘤细胞增殖的双重作用机制使其成为极具潜力的抗肿瘤活性物。本文首先模拟了T7肽的折叠过程,然后将折叠后的T7肽与αvβ3整合素进行分子对接研究,选出两个较好的对接复合物进行分子动力学模拟,对比分析得到最优的结合构象复合物,经分析发现T7肽上的残基:Ser90, Arg91, Asp93, Tyr94是其与受体结合的关键残基,且Mn2+对于结合至关重要。
[Abstract]:TLR5 is an important pattern recognition receptor which can specifically recognize bacterial flagellin and induce immune and inflammatory responses. Recently, it has been found that flagellin activates NF- 魏 B signaling pathway by binding TLR5, regulates the secretion of many cytokines, and has protective effect on apoptosis induced by ionizing radiation and other stimuli. In this paper, the conformation and energy of TLR5 are optimized by using the homologous modeling technique, which shows that the TLR5 structure model is reasonable. The molecular docking of TLR5 with flagellin was carried out. The optimal conformation was selected by cluster analysis and binding energy. The interaction mechanism and dynamic process between TLR5 and flagellin were studied. The results show that van der Waals interaction and electrostatic interaction are the main driving force for the binding of TLR5 to flagellin. The residue R392/D393 on TLR5 is very important for its binding to ligand. Tumor endostatin is a tumor angiogenesis inhibitor derived from human basement membrane collagen 鈪,

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