發(fā)布時間：2018-05-26 11:01

  本文選題：生物信息學(xué) + 人腫瘤壞死因子TNF-α��； 參考：《天津科技大學(xué)》2009年碩士論文

【摘要】： TNF-a是一類重要的細胞因子,由活化的巨噬細胞和T細胞產(chǎn)生,具有多種生理活性,主要參與炎癥反應(yīng)并能選擇性地引起腫瘤組織壞死,有著廣泛的臨床應(yīng)用前景。但臨床的毒副作用限制了它的進一步應(yīng)用�，F(xiàn)有的研究結(jié)果表明,蛋白質(zhì)的結(jié)構(gòu)與功能有著密切的關(guān)系。生物信息學(xué)為我們提供了一條可以直接由基因或蛋白質(zhì)序列進行蛋白質(zhì)功能預(yù)測和結(jié)構(gòu)預(yù)測的捷徑。 本文嘗試利用生物信息學(xué)的方法和軟件對腫瘤壞死因子的蛋白質(zhì)序列進行研究比對,目的是找到序列和活性之間的聯(lián)系,以期進一步指導(dǎo)人們合理有效地設(shè)計出高效低毒的hTNF-a衍生物,為hTNF-a應(yīng)用于臨床提供一條新路。 通過對人腫瘤壞死因子h-TNFA氨基酸序列和與之有不同程度一致性的各物種的TNFA、TNFB、TNFC、CD40L、TNF10、TNF11、TNF13、TNF14等的氨基酸序列進行兩兩比對結(jié)果顯示和文獻報道的完全一致。此外還有一些新的發(fā)現(xiàn)：人腫瘤壞死因子氨基酸序列有一些高度保守的位點,其中102位和104位在文獻里鮮有提及；保守性位點多集中于片層中的折疊股內(nèi),尤其集中在A4、A5和A3,其次是B2、B2和B3。突變位點多集中與連接折疊股的長環(huán)處,特別是在L3和L4內(nèi)。轉(zhuǎn)角處常非常保守,提示轉(zhuǎn)角處殘基有重要作用；人腫瘤壞死因子氨基酸序列N端前10個殘基常發(fā)生突變,但8位在所有的TNFL6氨基酸序列中非常保守,沒有發(fā)生任何突變。9位、10位常發(fā)生保守性突變�？梢詳喽�,人腫瘤壞死因子氨基酸序列中的保守位點和人腫瘤壞死因子的三維結(jié)構(gòu)以及生物活性有著重要的聯(lián)系。所有這些均證明利用生物信息學(xué)的方法研究蛋白質(zhì)的氨基酸序列和結(jié)構(gòu)、活性之間的聯(lián)系是非常方便而又行之有效的方法。
[Abstract]:TNF-a is a kind of important cytokines, which is produced by activated macrophages and T cells. It has many physiological activities. It mainly participates in inflammatory reaction and can cause tumor necrosis selectively. However, clinical side effects limit its further application. The present research results show that the structure and function of proteins are closely related. Bioinformatics provides us with a shortcut to predict protein function and structure directly from gene or protein sequence. This paper attempts to use bioinformatics methods and software to study the alignment of tumor necrosis factor protein sequences in order to find out the relationship between sequence and activity. In order to further guide people to design efficient and effective hTNF-a derivatives, and provide a new way for the clinical application of hTNF-a. By comparing the amino acid sequence of human tumor necrosis factor (h-TNFA) with the amino acid sequence of TNF10, TNF11, TNF13 and TNF14 of different species, the results were consistent with those reported in the literature. The amino acid sequences of TNF10, TNF11, TNF13 and TNF14 were identical to those reported in the literature. In addition, there are some new findings: there are some highly conserved sites in the amino acid sequence of human tumor necrosis factor, of which 102 and 104 are rarely mentioned in the literature. In particular, A4, A5 and A3 were concentrated, followed by B _ 2, B _ 2 and B _ 3. The mutation sites were mainly located at the long loop of the folded strands, especially in L 3 and L 4. The corner is often very conserved, suggesting that the corner residue plays an important role, and that the first 10 residues of the N-terminal of the human tumor necrosis factor amino acid sequence often mutate, but 8 are very conserved in all TNFL6 amino acid sequences. There was no mutation at the 9. 9 position and the 10 position was often conserved. It can be concluded that the conserved sites in the amino acid sequence of human tumor necrosis factor are closely related to the three-dimensional structure and biological activity of human tumor necrosis factor. All these prove that bioinformatics is a convenient and effective method to study the amino acid sequence and structure of protein.
【學(xué)位授予單位】：天津科技大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2009
【分類號】：R341

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本文編號：1936990