title: Pharmacophore-Based Virtual Screening of Novel Inhibitors and Docking Analysis for CYP51A from Penicillium italicum.
abstract: Sterol 14α-demethylases from Cytochrome P450 family (CYP51s) are essential enzymes in sterol biosynthesis and well-known as the target of antifungal drugs. The 3D structure of CYP51A fromPenicillium italicum(PiCYP51A) was constructed through homology modeling based on the crystal structure of human CYP51A (PDB: 3LD6). Molecular dynamics (MD) simulation was operated to relax the initial model and followed by quality assessment using PROCHECK program. On the basis of the docking information on the currently available CYP51s with the patent demethylase inhibitors (DMIs), pharmacophore-based virtual screening combined with docking analysis was performed to pick out twelve new compounds from ZINC database. Six hits revealed in the ligand database suggested potential ability to inhibit PiCYP51A. Compared to patent fungicide triazolone, the top three lead compounds had similar or higher affinity with the target enzyme, and accordingly, exhibited comparable or lower EC50values toP. italicumisolates. The results could provide references for de novo antifungal drug design.
authors.affiliation: Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Science, Central China Normal University, Wuhan 430079, China. yuan_yongze@163.com.
authors.forename: Yongze
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Science, Central China Normal University, Wuhan 430079, China. hanrui11473@163.com.
authors.forename: Rui
authors.initials: R
authors.lastname: Han
authors.affiliation: Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Science, Central China Normal University, Wuhan 430079, China. caoqianwen615@163.com.
authors.forename: Qianwen
authors.initials: Q
authors.lastname: Cao
authors.affiliation: Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Science, Central China Normal University, Wuhan 430079, China. j_h_yu@163.com.
authors.forename: Jinhui
authors.initials: J
authors.lastname: Yu
authors.affiliation: Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Science, Central China Normal University, Wuhan 430079, China. jiali93@126.com.
authors.forename: Jiali
authors.initials: J
authors.lastname: Mao
authors.affiliation: Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Science, Central China Normal University, Wuhan 430079, China. zhangtingfu1@126.com.
authors.forename: Tingfu
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Science, Central China Normal University, Wuhan 430079, China. bananatcm@sina.com.cn.
authors.forename: Shengqiang
authors.initials: S
authors.lastname: Wang
authors.affiliation: Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Science, Central China Normal University, Wuhan 430079, China. 15029756722@163.com.
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Niu
authors.affiliation: Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Science, Central China Normal University, Wuhan 430079, China. deliliu2013@163.com.
authors.forename: Deli
authors.initials: D
authors.lastname: Liu
mesh_terms: D000935:Antifungal Agents / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D015195:Drug Design; D005656:Fungal Proteins / Q000378:metabolism; D006801:Humans; D008024:Ligands; D062105:Molecular Docking Simulation / Q000379:methods; D056004:Molecular Dynamics Simulation; D010407:Penicillium / Q000378:metabolism*
chemical_list: D000935:Antifungal Agents; D005656:Fungal Proteins; D008024:Ligands; D003577:Cytochrome P-450 Enzyme System
keywords: Penicillium italicum; PiCYP51A; demethylase inhibitors; molecular docking; pharmacophore; virtual screening