An example of the output of PharmMapper. (A) The ranked list of hit target pharmacophore models, which are sorted by fit score indescending order. (B) The pull-down window that illustrates the details of each pharmacophore model candidate and the molecule pharmacophore alignment.(image by SIMM)

Pursuant to the successful joint development of a reverse docking method-TarFisDock, the research team led by Prof. JIANG Hualiang  from Shanghai Institute of Materia Medica, Chinese Academy of Sciences and the research team led by Prof. LI Honglin fom School of Pharmacy, East China University of Science and Technology have jointly constructed PharmTargetDB, a pharmacophore database containing the structure information and pharmacophore models of over 7,000 targets and covering a wide range of 349 biological functions and 110 clinical indications. Using Pharmacophore mapping strategy, Dr. LIU Xiaofeng  from Prof. Jiang’s group developed a reverse pharmacophore mapping method with bioactive small molecules as probes to search for potential drug targets and further predict the bioactivity of target compounds. A public web server has been established based on PharmTargetDB, and related results have been published on the latest issue of Nucleic Acids Researc (2010, 38: W609-W614).

The identification of potential drug target is valuable and significant in the research and development of drug molecules at early stage, safety evaluation and old drugs with new use. Due to the limitation of throughput, accuracy and cost, experimental techniques can not be applied widely, therefore, the development of in silico target identification algorithms, as a stragety with the advantage of fast speed and low cost, has been receiving more and more attention worldwide. It has been of great importance to develop a fast and accurate target identification and prediction method for the discovery of targeted drugs, construction of drug-target interaction network as well as the analysis of small molecule regulating network.

In addition to this new research progress, the collaborative task force has jointly developed a series of computational biology methods and databases for drug target discovery. The reverse docking method they developed and its related web server-TarFisDock have been used by over 1000 users in more than fifty countries and regions, and many new targets predicted by this reverse docking methid have been validated by experiments. As a vital complement to TarFisDock, PharmMapper has significant improvement in computational speed compared with reverse docking methods, and the target prediction results based on PhamMapper can be fulfilled within several to dozens of minutes. Therefore, PharmMapper has proved to be a potent method for new drug target discovery and effectively promoted the drug target identification research. Currently, in cooperation with several other institutions from home and abroad, the cooperative task force has performed target identification and corresponding experimental validation against dozens of natural products, in an attempt to find the potential targets for these compounds from natural products and elucidate their mechanisms based on PhamMapper.  

This program is supported by The People's Republic of China Ministry of Science and Technology, the National Natural Science Foundation of China and Shanghai Science and Technology Commission.

Source:

Xiaofeng Liu, Sisheng Ouyang, Biao Yu, Yabo Liu, Kai Huang, Jiayu Gong, Siyuan Zheng, Zhihua Li, Honglin Li*, and Hualiang Jiang*. PharmMapper server: a web server for potential drug target identification using pharmacophore mapping approach. Nucleic Acids Res., 2010, 38, W609-W614.