以電腦模擬來探討抑制劑在3CL蛋白酶的結合位置

Studies of inhibitor’s binding site for coronavirus 3CL proteinase

賴易誠(Yi-Cheng Lai)

指導教授 ： 李桂仁

亞洲大學/資訊學院/生物資訊研究所/碩士(2005年)

摘要

本研究是討論如何利用電腦發展的分子結構的應用軟體，與生物科技或分子醫學相關的配合及應用，探討如何利用SARS 冠狀病毒（Coronavirus）複製時所需的主要蛋白酶（main proteinase）1Q2W，與文獻中找到的四種化合物（Compound）AG7088、Fig_4C、Niclosamide與Promazine，及1Q2W解結晶時使用的Ligand用Autodock對虛擬藥物MPD、AG7088、Fig_4C、Niclosamide、Promazine，於MPD結合位置（Binding site ）位置的抑制情形做分析，結果得到Ki，以Ki來說這五個藥物結合狀況都不錯，這部份以Fig_4C為最佳，與Fig_4C是由生物資訊（Bioinformatics）方式取得產生有關，且利用藥物對Ligand結合位置的殘基覆蓋遮蔽的狀況來說，AG7088、Fig_4C有較佳的阻斷性，此結果與兩者取得方式有關，在結合位置作用的Ligand與PRO-108作用為電腦分析所得，之後經過電腦模擬是否與PRO-108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，隨著未來的更完整的分子科學與量子力學等各方面進步下科學，相信在醫療或其他領域下的研發使用會有更迅速的突破。

關鍵字

Autodock ； SARS ； 冠狀病毒 ； 3CL蛋白酶 ； 生物資訊

並列摘要

In this study, the developments of applications of the molecular structure software, using computers with biotechnology or molecular medicines, were discussed. Four compounds, such as AG7088, Fig_4C, Niclosamide, and Promazine, which have been found in the literature, may inhibit the main proteinase of SARS coronavirus duplications. The crystal structure （the PDB code 1Q2W） of SARS main proteinase including ligand MPD through the Autodock analysis revealed the four hypothesized medicines at the binding site of MPD with the position suppressions. From the values of Ki, all of these five medicines binding conditions are quite good, whereas Fig_4C is the best. Based on the binding position to a ligand with a cover camouflage situation, AG7088 and Fig_4C have a good block in the nature, which has a good agreement found in the literature. The function of PRO-108 from the Autodock analysis was obtained. Whether the results obtained from the computer simulation have the hydrogen bonds with PRO-108 is one of reference judgments. 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 ； SARS ； Coronavirus ； 3CL proteinase ； Bioinformatic

參考文獻

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