本文選題：蛋白-蛋白相互作用 + 分子模擬�。� 參考：《北京協(xié)和醫(yī)學(xué)院》2012年碩士論文

【摘要】：TLR5是一種重要的模式識(shí)別受體,可特異性的識(shí)別細(xì)菌鞭毛蛋白后引起機(jī)體的免疫反應(yīng)和炎癥反應(yīng)。近來(lái)研究發(fā)現(xiàn)鞭毛蛋白通過(guò)結(jié)合TLR5,激活NF-κB信號(hào)通路,調(diào)節(jié)多種細(xì)胞因子的分泌,對(duì)電離輻射及其他刺激引發(fā)的細(xì)胞凋亡具有保護(hù)作用。本文采用同源模建技術(shù)構(gòu)建TLR5的三維結(jié)構(gòu),模型經(jīng)過(guò)優(yōu)化后進(jìn)行構(gòu)象和能量的評(píng)價(jià),表明該TLR5結(jié)構(gòu)模型合理。將TLR5與鞭毛蛋白進(jìn)行分子對(duì)接,采用聚類(lèi)分析,計(jì)算結(jié)合能等手段選出最佳對(duì)接構(gòu)象后進(jìn)行分子動(dòng)力學(xué)模擬,研究TLR5與鞭毛蛋白相互作用機(jī)制及其動(dòng)態(tài)過(guò)程,結(jié)果分析表明范德華作用和靜電作用是TLR5與鞭毛蛋白結(jié)合的主要推動(dòng)力,TLR5上的殘基R392/D393對(duì)于其與配體的結(jié)合至關(guān)重要。 腫瘤抑素是源于人基膜膠原Ⅳ的腫瘤新生血管生成的抑制因子,有明顯的抑制腫瘤新生血管生成和誘導(dǎo)其內(nèi)皮細(xì)胞凋亡的活性,其主要活性片段為T(mén)7肽。T7肽通過(guò)與內(nèi)皮細(xì)胞表面的αvβ3整合素結(jié)合發(fā)揮作用,以其抗腫瘤新生血管生成和抑制腫瘤細(xì)胞增殖的雙重作用機(jī)制使其成為極具潛力的抗腫瘤活性物。本文首先模擬了T7肽的折疊過(guò)程,然后將折疊后的T7肽與αvβ3整合素進(jìn)行分子對(duì)接研究,選出兩個(gè)較好的對(duì)接復(fù)合物進(jìn)行分子動(dòng)力學(xué)模擬,對(duì)比分析得到最優(yōu)的結(jié)合構(gòu)象復(fù)合物,經(jīng)分析發(fā)現(xiàn)T7肽上的殘基：Ser90, Arg91, Asp93, Tyr94是其與受體結(jié)合的關(guān)鍵殘基,且Mn2+對(duì)于結(jié)合至關(guān)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，

本文編號(hào)：1852926