生物谷报道：中国科学院上海药物研究所蒋华良与大连理工大学力学系王希诚教授合作，针对寻找药物作用新靶标的需求，带领博士后李洪林和高振霆等，发展了以活性小分子为探针、搜寻潜在结合蛋白质的“反向分子对接”方法，相关结果发表在“Nucl. Acids Res. ”(2006, 34, W219-224)，并建立了相应的公共网络服务器(http://www.dddc.ac.cn/tarfisdock)。目前已有来自50多个国家480多个用户使用该服务器，反馈信息统计，用户已经用该方法发现的10多个候选靶标被实验证实。蒋华良与沈旭和岳建民等合作，用该方法发现了一个抗幽门螺旋杆菌天然产物的作用靶标－PDF蛋白，并测定了天然产物与PDF蛋白复合物的晶体结构，结果发表在“Protein Sci. ”(2006, 2071-2081)。
最近他们又进一步发展了潜在药物靶标库(PDTD)，包含仅1000个重要靶标的信息和三维结构，为用反向对接方法寻找化合物的药物作用靶标提供了技术支撑。结果发表在《BMC生物信息学》（BMC Bioinformatics） （2008, 9:104）后，连续4个月被BioMed Central选为高阅读率文章(Highly accessed article)，发表仅4个月来的总阅读次数已达1953次。PDTD已经建立了网络服务器(http://www.dddc.ac.cn/pdtd/)，得到了广泛的应用，用户数也已经超过400。（生物谷www.bioon.com）
生物谷推荐原始出处：
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.
