本文選題：核糖核苷酸還原酶 + 虛擬篩選��； 參考：《浙江大學(xué)》2012年碩士論文

【摘要】：核糖核苷酸還原酶(RR)是人類體內(nèi)唯一的催化4種核糖核苷酸還原、生成相應(yīng)的脫氧核糖核苷酸的酶。研究表明,人體小亞基R2能促進(jìn)各種致癌基因的轉(zhuǎn)變,提高癌細(xì)胞的入侵能力。因此通過,研究R2抑制劑,抑制腫瘤細(xì)胞的生成和轉(zhuǎn)移,已成為治愈人類癌腫的靶點(diǎn)研究之一,越來越受到關(guān)注。本文從結(jié)構(gòu)生物信息學(xué)的角度研究人體中RR的小亞基R2蛋白質(zhì)。首先,我們應(yīng)用metaPocket2.0找出R2表面上可能的小分子作用位點(diǎn),應(yīng)用AutoDock Vina蛋白質(zhì)與小分子對接軟件對ZINC、DrugBank和PDB數(shù)據(jù)庫中大規(guī)模的小分子進(jìn)行了虛擬篩選,篩選出9個可用于實驗驗證的小分子化合物。我們篩選出一個新的R2抑制劑,格列喹酮,它與2個活性位點(diǎn)的結(jié)合親和力值最好,為下一步實驗驗證提供依據(jù)。接著,我們應(yīng)用ZDOCK蛋白質(zhì)-蛋白質(zhì)對接軟件進(jìn)行R1和R2模擬對接,并利用metaPPI預(yù)測出R1和R2上的蛋白質(zhì)結(jié)合位點(diǎn),構(gòu)造出4種RR全酶模型。最后,通過從結(jié)構(gòu)和序列上比較人類R2與大腸桿菌的R2,以及通過KFC、FlodX、HOTPOINT和HotSpot Wizard4種軟件預(yù)測,得到了R2二聚體結(jié)合表面上的1對熱點(diǎn)氨基酸A_PHE101-D_PHE101,它們在氨基酸序列上和空間結(jié)構(gòu)上都是完全對稱的。本文的結(jié)果可為后續(xù)實驗篩選作用于R2的小分子藥物及研究R2二聚體形成機(jī)制提供可靠的理論依據(jù),具有一定的參考意義。
[Abstract]:Ribonucleotide reductase (RR) is the only enzyme that catalyzes the reduction of 4 ribonucleotides in human body to produce the corresponding deoxyribonucleotide. The study shows that the small subunit R2 can promote the transformation of all kinds of oncogenic genes and improve the invasion ability of cancer cells. Therefore, the development of R2 inhibitors and the inhibition of the formation and metastasis of tumor cells have been developed. In order to cure human cancer target, more and more attention is paid. This paper studies the small subunit R2 protein of RR in human body from the perspective of structural bioinformatics. First, we use metaPocket2.0 to find the possible small molecular action loci on the surface of R2, and use the AutoDock Vina egg white and small molecule docking software for ZINC, DrugBank and PDB. In the database, a large number of small molecules were screened to screen 9 small molecular compounds that could be used for experimental verification. We screened a new R2 inhibitor, Glico - one, which has the best binding affinity with 2 active sites, and provides the basis for the next experimental verification. Then, we apply the ZDOCK protein protein docking. The software carries out R1 and R2 simulative docking, and uses metaPPI to predict protein binding sites on R1 and R2, and constructs 4 RR full enzyme models. Finally, by comparing the R2 of human R2 and Escherichia coli from the structure and sequence, and through the prediction of KFC, FlodX, HOTPOINT, and HotSpot, 1 pairs of heat on the surface of the two polymer are obtained. The amino acid A_PHE101-D_PHE101, both in the amino acid sequence and in the spatial structure, are completely symmetrical. The results of this paper can provide a reliable theoretical basis for the subsequent screening of small molecular drugs acting on R2 and the mechanism of the formation of R2 two polymer, which has some reference meaning.
【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2012
【分類號】：R341

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本文編號：1977901