title: PharmMapper server: a web server for potential drug target identification using pharmacophore mapping approach.
abstract: In silico drug target identification, which includes many distinct algorithms for finding disease genes and proteins, is the first step in the drug discovery pipeline. When the 3D structures of the targets are available, the problem of target identification is usually converted to finding the best interaction mode between the potential target candidates and small molecule probes. Pharmacophore, which is the spatial arrangement of features essential for a molecule to interact with a specific target receptor, is an alternative method for achieving this goal apart from molecular docking method. PharmMapper server is a freely accessed web server designed to identify potential target candidates for the given small molecules (drugs, natural products or other newly discovered compounds with unidentified binding targets) using pharmacophore mapping approach. PharmMapper hosts a large, in-house repertoire of pharmacophore database (namely PharmTargetDB) annotated from all the targets information in TargetBank, BindingDB, DrugBank and potential drug target database, including over 7000 receptor-based pharmacophore models (covering over 1500 drug targets information). PharmMapper automatically finds the best mapping poses of the query molecule against all the pharmacophore models in PharmTargetDB and lists the top N best-fitted hits with appropriate target annotations, as well as respective molecule's aligned poses are presented. Benefited from the highly efficient and robust triangle hashing mapping method, PharmMapper bears high throughput ability and only costs 1 h averagely to screen the whole PharmTargetDB. The protocol was successful in finding the proper targets among the top 300 pharmacophore candidates in the retrospective benchmarking test of tamoxifen. PharmMapper is available at http://59.78.96.61/pharmmapper.
authors.affiliation: Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Liu
authors.forename: Sisheng
authors.initials: S
authors.lastname: Ouyang
authors.forename: Biao
authors.initials: B
authors.lastname: Yu
authors.forename: Yabo
authors.initials: Y
authors.lastname: Liu
authors.forename: Kai
authors.initials: K
authors.lastname: Huang
authors.forename: Jiayu
authors.initials: J
authors.lastname: Gong
authors.forename: Siyuan
authors.initials: S
authors.lastname: Zheng
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Li
authors.forename: Honglin
authors.initials: H
authors.lastname: Li
authors.forename: Hualiang
authors.initials: H
authors.lastname: Jiang
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D001665:Binding Sites; D016208:Databases, Factual; D015195:Drug Design; D020407:Internet; D008024:Ligands; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry / Q000187:drug effects; D012984:Software; D013629:Tamoxifen / Q000494:pharmacology; D014584:User-Computer Interface
chemical_list: D018931:Antineoplastic Agents, Hormonal; D008024:Ligands; D004364:Pharmaceutical Preparations; D011506:Proteins; D013629:Tamoxifen