title: ACFIS: a web server for fragment-based drug discovery.
abstract: In order to foster innovation and improve the effectiveness of drug discovery, there is a considerable interest in exploring unknown 'chemical space' to identify new bioactive compounds with novel and diverse scaffolds. Hence, fragment-based drug discovery (FBDD) was developed rapidly due to its advanced expansive search for 'chemical space', which can lead to a higher hit rate and ligand efficiency (LE). However, computational screening of fragments is always hampered by the promiscuous binding model. In this study, we developed a new web server Auto Core Fragment in silico Screening (ACFIS). It includes three computational modules, PARA_GEN, CORE_GEN and CAND_GEN. ACFIS can generate core fragment structure from the active molecule using fragment deconstruction analysis and perform in silico screening by growing fragments to the junction of core fragment structure. An integrated energy calculation rapidly identifies which fragments fit the binding site of a protein. We constructed a simple interface to enable users to view top-ranking molecules in 2D and the binding mode in 3D for further experimental exploration. This makes the ACFIS a highly valuable tool for drug discovery. The ACFIS web server is free and open to all users at http://chemyang.ccnu.edu.cn/ccb/server/ACFIS/.
authors.affiliation: Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, P.R.China.
authors.forename: Ge-Fei
authors.initials: GF
authors.lastname: Hao
authors.affiliation: Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, P.R.China.
authors.forename: Wen
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Collaborative Innovation Center of Chemical Science and Engineering, Tianjing 300072, P.R.China.
authors.forename: Yuan-Nong
authors.initials: YN
authors.lastname: Ye
authors.affiliation: Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, P.R.China.
authors.forename: Feng-Xu
authors.initials: FX
authors.lastname: Wu
authors.affiliation: Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, P.R.China.
authors.forename: Xiao-Lei
authors.initials: XL
authors.lastname: Zhu
authors.affiliation: Collaborative Innovation Center of Chemical Science and Engineering, Tianjing 300072, P.R.China fbguo@uestc.edu.cn.
authors.forename: Feng-Biao
authors.initials: FB
authors.lastname: Guo
authors.affiliation: Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, P.R.China Collaborative Innovation Center of Chemical Science and Engineering, Tianjing 300072, P.R.China gfyang@mail.ccnu.edu.cn.
authors.forename: Guang-Fu
authors.initials: GF
authors.lastname: Yang
mesh_terms: D001665:Binding Sites; D003198:Computer Simulation; D055808:Drug Discovery / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D021621:Imaging, Three-Dimensional; D020407:Internet; D008024:Ligands; D011506:Proteins / Q000737:chemistry*; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology; D012984:Software; D014584:User-Computer Interface
chemical_list: D008024:Ligands; D011506:Proteins; D054852:Small Molecule Libraries