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以pleconaril之抑制機制為基礎透過虛擬高速藥物篩選尋找抑制腸病毒71 型之先導藥物
Thesis

以pleconaril之抑制機制為基礎透過虛擬高速藥物篩選尋找抑制腸病毒71 型之先導藥物

李旻晉
Masters, 國立清華大學, 分子醫學研究所
2003

Abstract

虛擬高速藥物篩選 腸病毒 分子對接 電腦輔助藥物設計 同源模擬法 先導藥物 pleconaril enterovirus 71 virtual screening computer-assisted drug design dock x-score homology modeling capsid vp1
Enterovirus had caused 4 epidemic outbreaks, these outbreaks happened in Bulgaria, Hungary, Malaysia and Taiwan. In the 1998 epidemic outbreak of enterovirus in Taiwan, 129,106 cases repor ted, 78 patient s died, 405 patient s with severe disease. Most cases in this outbreak are caused by enterovirus 71. To da te, there is no effective antiviral agent for t reatment of enterovirus 71. Here we t ried to find leads for anti - enterovirus 71 agent s by virtual screening. First, a virtual 3D s t ructure of capsid protein VP1 of enterovirus 71 is built by insightII homology module. Then DOCK and X-Score are combined to build two screening mo del,high - speed screening model and precise screening mo del, based on the mechanism of pleconaril. The precise screening model is fur ther seperated in two ways, corelation screening and binding site screening. We searched Maybridge database with these mo dels. After screening the 59,128 compunds in Maybridge da tabase, we picked out 83 potential compounds. These compounds will be activity tes ted. From the ra tio of active compounds in each screening model, we may conjecture the mechanism of these leads.

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