Pharmacophore-Based Virtual Screening of Novel Inhibitors and Docking Analysis for CYP51A from Penicillium italicum
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 from Penicillium italicum (PiCYP51A) was constructed through homology modeling based on the crystal structure of huma...
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| Format: | Article |
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MDPI AG
2017-04-01
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| Series: | Marine Drugs |
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| Online Access: | http://www.mdpi.com/1660-3397/15/4/107 |
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| author | Yongze Yuan Rui Han Qianwen Cao Jinhui Yu Jiali Mao Tingfu Zhang Shengqiang Wang Yuhui Niu Deli Liu |
| author_facet | Yongze Yuan Rui Han Qianwen Cao Jinhui Yu Jiali Mao Tingfu Zhang Shengqiang Wang Yuhui Niu Deli Liu |
| author_sort | Yongze Yuan |
| collection | DOAJ |
| description | 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 from Penicillium 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 EC50 values to P. italicum isolates. The results could provide references for de novo antifungal drug design. |
| first_indexed | 2024-04-11T13:06:10Z |
| format | Article |
| id | doaj.art-80b9b57d62e04491bcf2e18116c0ac06 |
| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-04-11T13:06:10Z |
| publishDate | 2017-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-80b9b57d62e04491bcf2e18116c0ac062022-12-22T04:22:46ZengMDPI AGMarine Drugs1660-33972017-04-0115410710.3390/md15040107md15040107Pharmacophore-Based Virtual Screening of Novel Inhibitors and Docking Analysis for CYP51A from Penicillium italicumYongze Yuan0Rui Han1Qianwen Cao2Jinhui Yu3Jiali Mao4Tingfu Zhang5Shengqiang Wang6Yuhui Niu7Deli Liu8Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Science, Central China Normal University, Wuhan 430079, ChinaHubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Science, Central China Normal University, Wuhan 430079, ChinaHubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Science, Central China Normal University, Wuhan 430079, ChinaHubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Science, Central China Normal University, Wuhan 430079, ChinaHubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Science, Central China Normal University, Wuhan 430079, ChinaHubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Science, Central China Normal University, Wuhan 430079, ChinaHubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Science, Central China Normal University, Wuhan 430079, ChinaHubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Science, Central China Normal University, Wuhan 430079, ChinaHubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Science, Central China Normal University, Wuhan 430079, ChinaSterol 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 from Penicillium 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 EC50 values to P. italicum isolates. The results could provide references for de novo antifungal drug design.http://www.mdpi.com/1660-3397/15/4/107Penicillium italicumPiCYP51Apharmacophoredemethylase inhibitorsvirtual screeningmolecular docking |
| spellingShingle | Yongze Yuan Rui Han Qianwen Cao Jinhui Yu Jiali Mao Tingfu Zhang Shengqiang Wang Yuhui Niu Deli Liu Pharmacophore-Based Virtual Screening of Novel Inhibitors and Docking Analysis for CYP51A from Penicillium italicum Marine Drugs Penicillium italicum PiCYP51A pharmacophore demethylase inhibitors virtual screening molecular docking |
| title | Pharmacophore-Based Virtual Screening of Novel Inhibitors and Docking Analysis for CYP51A from Penicillium italicum |
| title_full | Pharmacophore-Based Virtual Screening of Novel Inhibitors and Docking Analysis for CYP51A from Penicillium italicum |
| title_fullStr | Pharmacophore-Based Virtual Screening of Novel Inhibitors and Docking Analysis for CYP51A from Penicillium italicum |
| title_full_unstemmed | Pharmacophore-Based Virtual Screening of Novel Inhibitors and Docking Analysis for CYP51A from Penicillium italicum |
| title_short | Pharmacophore-Based Virtual Screening of Novel Inhibitors and Docking Analysis for CYP51A from Penicillium italicum |
| title_sort | pharmacophore based virtual screening of novel inhibitors and docking analysis for cyp51a from penicillium italicum |
| topic | Penicillium italicum PiCYP51A pharmacophore demethylase inhibitors virtual screening molecular docking |
| url | http://www.mdpi.com/1660-3397/15/4/107 |
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