title: Pharmacophore-Map-Pick: A Method to Generate Pharmacophore Models for All Human GPCRs.
abstract: GPCR-based drug discovery is hindered by a lack of effective screening methods for most GPCRs that have neither ligands nor high-quality structures. With the aim to identify lead molecules for these GPCRs, we developed a new method called Pharmacophore-Map-Pick to generate pharmacophore models for all human GPCRs. The model of ADRB2 generated using this method not only predicts the binding mode of ADRB2-ligands correctly but also performs well in virtual screening. Findings also demonstrate that this method is powerful for generating high-quality pharmacophore models. The average enrichment for the pharmacophore models of the 15 targets in different GPCR families reached 15-fold at 0.5 % false-positive rate. Therefore, the pharmacophore models can be applied in virtual screening directly with no requirement for any ligand information or shape constraints. A total of 2386 pharmacophore models for 819 different GPCRs (99 % coverage (819/825)) were generated and are available at http://bsb.kiz.ac.cn/GPCRPMD.
authors: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, P. R. China phone/fax: + 86 087165199200/+ 86 087165199200.|Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing 100049, P. R. China.
authors: Shao-Xing
authors: SX
authors: Dai
authors: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, P. R. China phone/fax: + 86 087165199200/+ 86 087165199200.|Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing 100049, P. R. China.
authors: Gong-Hua
authors: GH
authors: Li
authors: Kunming Biological Diversity Regional Center of Instruments, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, P. R. China.
authors: Yue-Dong
authors: YD
authors: Gao
authors: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, P. R. China phone/fax: + 86 087165199200/+ 86 087165199200. huangjf@mail.kiz.ac.cn.|Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing 100049, P. R. China. huangjf@mail.kiz.ac.cn.|Kunming Institute of Zoology - Chinese University of Hongkong Joint Research Center for Bio-resources and Human Disease Mechanisms, Kunming 650223, P. R. China. huangjf@mail.kiz.ac.cn.
authors: Jing-Fei
authors: JF
authors: Huang
mesh_terms: D055808:Drug Discovery; D004353:Drug Evaluation, Preclinical; D006801:Humans; D011487:Protein Conformation; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D043562:Receptors, G-Protein-Coupled
keywords: Drug discovery; GPCR; Pharmacophore model