Developing a new drug costs up to US$2.6B and 13.5 years. To save money and time, we have developed a toolset for computer-aided drug discovery, and utilized our toolset to discover drugs for the treatment of cancers and influenza. / We first implemented a fast protein-ligand docking tool called idock, and obtained a substantial speedup over a popular counterpart. To facilitate the large-scale use of idock, we designed a heterogeneous web platform called istar, and collected a huge database of more than 23 million small molecules. To elucidate molecular interactions in web, we developed an interactive visualizer called iview. To synthesize novel compounds, we developed a fragment-based drug design tool called iSyn. To improve the predictive accuracy of binding affinity, we exploited the machine learning technique random forest to re-score both crystal and docked poses. To identify structurally similar compounds, we ported the ultrafast shape recognition algorithms to istar. All these tools are free and open source. / We applied our novel toolset to real world drug discovery. We repurposed anti-acne drug adapalene for the treatment of human colon cancer, and identified potential inhibitors of influenza viral proteins. Such new findings could hopefully save human lives. / 開發一種新藥需要多至26億美元和13年半的時間。為節省金錢和時間，我們開發了一套計算機輔助藥物研發工具集，並運用該工具集尋找藥物治療癌症和流感。 / 我們首先實現了一個快速的蛋白與配體對接工具idock，相比一個同類流行軟件獲得了顯著的速度提升。為輔助idock 的大規模使用，我們設計了一個異構網站平台istar，收集了多達兩千三百萬個小分子的大型數據庫。為在網頁展示分子間相互作用，我們開發了一個交互式可視化軟件iview。為生成全新的化合物，我們開發了一個基於分子片段的藥物設計工具iSyn。為改進結合強度預測的精度，我們利用了機器學習技術隨機森林去重新打分晶體及預測構象。為尋找結構相似的化合物，我們移植了超快形狀識別算法至istar。所有這些工俱全是免費和開源。 / 我們應用了此創新工具集至現實世界藥物尋找中。我們發現抗痤瘡藥阿達帕林可用於治療人類結腸癌，亦篩選出流感病毒蛋白的潛在抑制物。這些新發現可望拯救人類生命。 / Li, Hongjian. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2015. / Includes bibliographical references (leaves 340-394). / Abstracts also in Chinese. / Title from PDF title page (viewed on 15, September, 2016). / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only.
| Identifer | oai:union.ndltd.org:cuhk.edu.hk/oai:cuhk-dr:cuhk_1290642 |
| Date | January 2015 |
| Contributors | Li, Hongjian (author.), Leung, Kwong Sak , 1955- (thesis advisor.), Chinese University of Hong Kong Graduate School. Division of Computer Science and Engineering. (degree granting institution.) |
| Source Sets | The Chinese University of Hong Kong |
| Language | English, Chinese |
| Detected Language | English |
| Type | Text, bibliography, text |
| Format | electronic resource, electronic resource, remote, 1 online resource (xxi, 394 leaves) : illustrations (some color), computer, online resource |
| Rights | Use of this resource is governed by the terms and conditions of the Creative Commons "Attribution-NonCommercial-NoDerivatives 4.0 International" License (http://creativecommons.org/licenses/by-nc-nd/4.0/) |
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