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咪唑噠嗪類似物作為抗瘧疾靶標PfCDPK1抑制劑的分子設計研究

時間:2019-04-05 21:08來源:畢業論文
建立的3D-QSAR模型具有明確、良好的預測能力。此外還通過分子對接的方法,計算配體與受體結合的模式和親和力,并對新分子結果進行打分,評判結合程度

摘要:瘧疾是世界許多地區的一個主要殺手。 咪唑噠嗪衍生物是一系列芳香雜環化合物,具有殺蟲、殺菌、調節植物生長、抗病毒、抗驚厥、抗癌等高度的生物活性,此外還能作為有機液晶因為其具有良好的介晶性。經研究表明可作為抗瘧疾標靶PfCDPK1抑制劑的分子。本文主要使用了比較分子力場分析方(CoMFA)和比較分子相似性指數分析法(CoMSIA),對一系列新型咪唑噠嗪類似物的結構參數和從文獻上得到的pIC50值進行分析,以102個總分子數量中的90個分子的結構和pIC50值作為訓練集。并且使用三維定量構效關系(3D-QSAR)方法建立模型和采用抽一法(leave one out,LOO) 得到交叉驗證系數q2與相關系數R2的值來檢測模型的可靠性,之后選出18個線性不好的咪唑噠嗪類似物組成測試集,依此來驗證模型的預測能力。通過從CoMFA、CoMSIA等勢圖的結果進行分析,根據色塊圖設計新的抑制活性更高的化合物。實驗結果證明本文所建立的3D-QSAR模型具有明確、良好的預測能力。此外還通過分子對接的方法,計算配體與受體結合的模式和親和力,并對新分子結果進行打分,評判結合程度。并且本文基于一系列已知化學結構的咪唑噠嗪類似物,構建了其三維藥效團模型。挑選出構效關系最好的藥效團模型,通過虛擬篩選的方式找出配體與受體蛋白相結合的部分氨基酸。34260
畢業論文關鍵詞: 三維定量構效關系(3D-QSAR);新型咪唑噠嗪類似物;pIC50值;CoMFA;CoMSIA
 Study on the molecular design of anti malaria target PfCDPK1 as inhibitors of imidazole pyridazine analogues 源`自*六)維[論*文'網www.mmeqir.tw
Abstract:Malaria is a major killer in many parts of the world. Imidazole pyridazine derivatives are a series of aromatic heterocyclic compounds, with insecticidal, sterilization, regulating plant growth, antivirus, anticonvulsants, anti-cancer, such as high biological activity, and also can be used as organic liquid crystal because of its good structure. Studies show that the target can be used as antimalarial PfCDPK1 inhibitor molecules. This article mainly USES the comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA), for a series of novel imidazole pyridazine analogue structure parameters and pIC50 values from the literature were analyzed, and in 102 the total number of 90 molecules structure and pIC50 value as the training set. And using three-dimensional quantitative structure-activity relationship (3 d - QSAR) method to establish model and use smoke a method (leave one out, LOO) gain coefficient of cross-validation q2 and correlation coefficient R2 values to the reliability of the test model, then select 18 linear bad imidazole pyridazine analogue test set of validation according to the predictive ability of the model. Through from CoMFA, CoMSIA equipotential chart the results of the analysis, according to the color piece figure design new higher inhibitory activity of compounds. Experimental results prove the established 3 d - QSAR model is clear and good prediction ability. Also, by using the method of molecular docking computation model and the affinity ligand and receptor, and the result of the new molecular scores, judge bonding degree. And this article is based on a series of known chemical structures of imidazole pyridazine analogues, build the 3 d pharmacophore model. Pick out the structure-activity relationship of the best pharmacophore model, find out by means of virtual screening combined part of  ligand and receptor protein amino acids.
Key Words:Three-dimensional quantitative structure-activity relationship (3D-QSAR);new Imidazole pyridazine analogues ;pIC50 value;CoMFA;CoMSIA
源`自*六)維[論*文'網www.mmeqir.tw

 目錄
第一章    1
1.1 研究的背景與目的    1
1.2 研究現狀和進展    3
1.3 主要研究內容    5 咪唑噠嗪類似物作為抗瘧疾靶標PfCDPK1抑制劑的分子設計研究:http://www.mmeqir.tw/huaxue/20190405/31723.html
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