人肿瘤坏死因子hTNF-α的生物信息学研究

发布时间：2018-05-26 11:01

本文选题：生物信息学 + 人肿瘤坏死因子TNF-α　；参考：《天津科技大学》2009年硕士论文

【摘要】： TNF-a是一类重要的细胞因子,由活化的巨噬细胞和T细胞产生,具有多种生理活性,主要参与炎症反应并能选择性地引起肿瘤组织坏死,有着广泛的临床应用前景。但临床的毒副作用限制了它的进一步应用。现有的研究结果表明,蛋白质的结构与功能有着密切的关系。生物信息学为我们提供了一条可以直接由基因或蛋白质序列进行蛋白质功能预测和结构预测的捷径。本文尝试利用生物信息学的方法和软件对肿瘤坏死因子的蛋白质序列进行研究比对,目的是找到序列和活性之间的联系,以期进一步指导人们合理有效地设计出高效低毒的hTNF-a衍生物,为hTNF-a应用于临床提供一条新路。通过对人肿瘤坏死因子h-TNFA氨基酸序列和与之有不同程度一致性的各物种的TNFA、TNFB、TNFC、CD40L、TNF10、TNF11、TNF13、TNF14等的氨基酸序列进行两两比对结果显示和文献报道的完全一致。此外还有一些新的发现：人肿瘤坏死因子氨基酸序列有一些高度保守的位点,其中102位和104位在文献里鲜有提及；保守性位点多集中于片层中的折叠股内,尤其集中在A4、A5和A3,其次是B2、B2和B3。突变位点多集中与连接折叠股的长环处,特别是在L3和L4内。转角处常非常保守,提示转角处残基有重要作用；人肿瘤坏死因子氨基酸序列N端前10个残基常发生突变,但8位在所有的TNFL6氨基酸序列中非常保守,没有发生任何突变。9位、10位常发生保守性突变。可以断定,人肿瘤坏死因子氨基酸序列中的保守位点和人肿瘤坏死因子的三维结构以及生物活性有着重要的联系。所有这些均证明利用生物信息学的方法研究蛋白质的氨基酸序列和结构、活性之间的联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.
【学位授予单位】：天津科技大学
【学位级别】：硕士
【学位授予年份】：2009
【分类号】：R341

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