生物谷報道：中國科學院上海藥物研究所蔣華良與大連理工大學力學系王希誠教授合作,，針對尋找藥物作用新靶標的需求,，帶領博士后李洪林和高振霆等，發(fā)展了以活性小分子為探針,、搜尋潛在結合蛋白質的“反向分子對接”方法,，相關結果發(fā)表在“Nucl. Acids Res. ”(2006, 34, W219-224)，并建立了相應的公共網絡服務器(http://www.dddc.ac.cn/tarfisdock),。目前已有來自50多個國家480多個用戶使用該服務器,，反饋信息統(tǒng)計,，用戶已經用該方法發(fā)現(xiàn)的10多個候選靶標被實驗證實。蔣華良與沈旭和岳建民等合作,，用該方法發(fā)現(xiàn)了一個抗幽門螺旋桿菌天然產物的作用靶標－PDF蛋白,，并測定了天然產物與PDF蛋白復合物的晶體結構，結果發(fā)表在“Protein Sci. ”(2006, 2071-2081),。
最近他們又進一步發(fā)展了潛在藥物靶標庫(PDTD),，包含僅1000個重要靶標的信息和三維結構，為用反向對接方法尋找化合物的藥物作用靶標提供了技術支撐,。結果發(fā)表在《BMC生物信息學》（BMC Bioinformatics） （2008, 9:104）后,，連續(xù)4個月被BioMed Central選為高閱讀率文章(Highly accessed article)，發(fā)表僅4個月來的總閱讀次數(shù)已達1953次,。PDTD已經建立了網絡服務器(http://www.dddc.ac.cn/pdtd/),，得到了廣泛的應用，用戶數(shù)也已經超過400,。（生物谷www.bioon.com）
生物谷推薦原始出處：
BMC Bioinformatics,，doi:10.1186/1471-2105-9-104，Xicheng Wang,，Hualiang Jiang
PDTD: a web-accessible protein database for drug target identification
Zhenting Gao1,3 , Honglin Li1,2 , Hailei Zhang2 , Xiaofeng Liu1 , Ling Kang2 , Xiaomin Luo1 , Weiliang Zhu1 , Kaixian Chen1 , Xicheng Wang2 and Hualiang Jiang1,3
1Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
2Department of Engineering Mechanics, State Key Laboratory of Structural Analysis for Industrial Equipment, Dalian University of Technology, Dalian 116023, China
3School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China
Abstract
Background
Target identification is important for modern drug discovery. With the advances in the development of molecular docking, potential binding proteins may be discovered by docking a small molecule to a repository of proteins with three-dimensional (3D) structures. To complete this task, a reverse docking program and a drug target database with 3D structures are necessary. To this end, we have developed a web server tool, TarFisDock (Target Fishing Docking) http://www.dddc.ac.cn/tarfisdock webcite, which has been used widely by others. Recently, we have constructed a protein target database, Potential Drug Target Database (PDTD), and have integrated PDTD with TarFisDock. This combination aims to assist target identification and validation.
Description
PDTD is a web-accessible protein database for in silico target identification. It currently contains >1100 protein entries with 3D structures presented in the Protein Data Bank. The data are extracted from the literatures and several online databases such as TTD, DrugBank and Thomson Pharma. The database covers diverse information of >830 known or potential drug targets, including protein and active sites structures in both PDB and mol2 formats, related diseases, biological functions as well as associated regulating (signaling) pathways. Each target is categorized by both nosology and biochemical function. PDTD supports keyword search function, such as PDB ID, target name, and disease name. Data set generated by PDTD can be viewed with the plug-in of molecular visualization tools and also can be downloaded freely. Remarkably, PDTD is specially designed for target identification. In conjunction with TarFisDock, PDTD can be used to identify binding proteins for small molecules. The results can be downloaded in the form of mol2 file with the binding pose of the probe compound and a list of potential binding targets according to their ranking scores.
Conclusion
PDTD serves as a comprehensive and unique repository of drug targets. Integrated with TarFisDock, PDTD is a useful resource to identify binding proteins for active compounds or existing drugs. Its potential applications include in silico drug target identification, virtual screening, and the discovery of the secondary effects of an old drug (i.e. new pharmacological usage) or an existing target (i.e. new pharmacological or toxic relevance), thus it may be a valuable platform for the pharmaceutical researchers. PDTD is available online at http://www.dddc.ac.cn/pdtd/ webcite.
