以電腦模擬探討抑制劑在半胱氨酸蛋白酶的結合位置

Studies of inhibitor’s binding site for Cysteine protease

劉冠隴(LIOU GUAN LONG)

指導教授 ： 李桂仁

亞洲大學/資訊學院/生物資訊學系碩士班/碩士(2009年)

摘要

中文摘要
本研究是討論如何利用電腦發展的分子結構應用軟體，與生物科技或分子醫學相關的配合及應用，探討如何利用瘧疾惡性瘧原蟲 ( Plasmodium falciparum ) 半胱氨酸蛋白酶的結構 ( Cysteine protease )，和在資料庫中 ( Binding database ) 所找到的十種 Ligands，其中八種為 Phenylurenyl Calcone 衍生物，而另外二種分別為 LEU 和E-64，再加上三種由文獻中所發現的 Compounds ，而這三種化合物則分別為compound1的 N-(1-(cyanomethylcarbamoyl)cyclohexyl)-4-(1-(2-methoxyethyl)piperi-din-4-yl) benzamide，還有compound 2的(S)-N-(1-(cyanomethylamino)-4-methyl-1-oxopentan-2-yl)biphenyl-4-carboxamide，以及compound3 的Leupeptin，於結合位置( binding site ) 的抑制情形做分析，結果得到 Ki，以Ki來說為Phenyurenyl Calcane deriv.23 也就是第一個 Ligand表現較出色，其次為Compound 1 ; 再來分析氫鍵的表現，氫鍵在藥物結合過程中也是非常重要的表現，之後經過電腦模擬是否與ARG-6有氫鍵作用則為本研究分析參考判斷之一，利用分析結合位置與抑制劑間作用關係，隨著未來更完整的分子科學與量子力學等各方面進步之下，相信在醫學或其他領堿下的研發使用會更迅速的發展。

關鍵字

Autodock ； Plasmodium falciparum ； Cysteine protease ； 生物資訊

並列摘要

Abstract
In the study, the developments of application of the molecular medicines, were discussed. Ten ligands which have been found in the database and three compounds have been found in the literature, may inhibit the main proteinase of plasmodium falciparum. The crystal structure ( the cysteine protease ) of plasmodium falciparum main proteinase through the Autodock analysis revealed the thirteen hypothesized ligands and compounds at the binding site with the position suppressions. From the values of Ki, all of these ligands and compounds binding comditions are quite good, whereas ligand 1 is the best, secondarily is the compound 1. In the drug combination, the hydrogen bond is very important process. The function of ARG-6 from the Autodock analysis was obtained. Whether the results obtained from the computer simulation have the hydrogen bond with ARG-6 is one of reference judgment. The analysis unifies the relationships between the position and inhibitors. I believed that this method may have a more rapid breakthrough to find potential drugs or the developments of other domain researches.

並列關鍵字

Autodock ； plasmodium falciparum ； cysteine protease ； bioinformatics

參考文獻

Fighting an Ancient Scourge;

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES;

National Institutes of Health;

National Institute of Allergy and Infectious Diseases NIH

[4] Structural basis for unique mechanisms of folding and hemoglobin binding