Identification of a Non-Retinoid Opsin Ligand Through Pharmacophore-Guided Virtual Screening—A Novel Potential Rhodopsin-Stabilizing Compound
Rhodopsin, a G-protein-coupled receptor (GPCR) comprising the protein opsin covalently linked to the chromophore 11-cis retinal, is pivotal in visual phototransduction. Mutations in the gene encoding rhodopsin (RHO) can cause opsin misfolding or reduce its stability, resulting in retinal degenerativ...
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MDPI AG
2025-05-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/30/11/2328 |
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| author | Miriana Di Stefano Maria Ghilardi Clarissa Poles Lisa Piazza Gian Carlo Demontis Giulio Poli Tiziano Tuccinardi Marco Macchia |
| author_facet | Miriana Di Stefano Maria Ghilardi Clarissa Poles Lisa Piazza Gian Carlo Demontis Giulio Poli Tiziano Tuccinardi Marco Macchia |
| author_sort | Miriana Di Stefano |
| collection | DOAJ |
| description | Rhodopsin, a G-protein-coupled receptor (GPCR) comprising the protein opsin covalently linked to the chromophore 11-cis retinal, is pivotal in visual phototransduction. Mutations in the gene encoding rhodopsin (RHO) can cause opsin misfolding or reduce its stability, resulting in retinal degenerative disorders such as retinitis pigmentosa (RP). Current therapeutic strategies employing retinoid-based chaperones partially rescue the folding and trafficking of mutant rhodopsin, but are limited by inherent toxicity and instability due to photoinduced isomerization. In the present work, a pharmacophore-based virtual screening protocol combined with molecular docking and molecular dynamics simulations was employed, leading to the identification of a novel non-retinoid opsin ligand that can potentially act as a pharmacological chaperone. Biological validation confirmed that the compound <b>VS1</b> binds opsin effectively, representing a valuable starting point for structure-based optimization studies aimed at identifying new opsin stabilizers. |
| format | Article |
| id | doaj-art-5fa3ea8521d44d7d8a1e75301dd83b95 |
| institution | OA Journals |
| issn | 1420-3049 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj-art-5fa3ea8521d44d7d8a1e75301dd83b952025-08-20T02:23:00ZengMDPI AGMolecules1420-30492025-05-013011232810.3390/molecules30112328Identification of a Non-Retinoid Opsin Ligand Through Pharmacophore-Guided Virtual Screening—A Novel Potential Rhodopsin-Stabilizing CompoundMiriana Di Stefano0Maria Ghilardi1Clarissa Poles2Lisa Piazza3Gian Carlo Demontis4Giulio Poli5Tiziano Tuccinardi6Marco Macchia7Department of Pharmacy, University of Pisa, 56126 Pisa, ItalyDepartment of Pharmacy, University of Pisa, 56126 Pisa, ItalyTelethon Institute of Genetics and Medicine, 80078 Naples, ItalyDepartment of Pharmacy, University of Pisa, 56126 Pisa, ItalyDepartment of Pharmacy, University of Pisa, 56126 Pisa, ItalyDepartment of Pharmacy, University of Pisa, 56126 Pisa, ItalyDepartment of Pharmacy, University of Pisa, 56126 Pisa, ItalyDepartment of Pharmacy, University of Pisa, 56126 Pisa, ItalyRhodopsin, a G-protein-coupled receptor (GPCR) comprising the protein opsin covalently linked to the chromophore 11-cis retinal, is pivotal in visual phototransduction. Mutations in the gene encoding rhodopsin (RHO) can cause opsin misfolding or reduce its stability, resulting in retinal degenerative disorders such as retinitis pigmentosa (RP). Current therapeutic strategies employing retinoid-based chaperones partially rescue the folding and trafficking of mutant rhodopsin, but are limited by inherent toxicity and instability due to photoinduced isomerization. In the present work, a pharmacophore-based virtual screening protocol combined with molecular docking and molecular dynamics simulations was employed, leading to the identification of a novel non-retinoid opsin ligand that can potentially act as a pharmacological chaperone. Biological validation confirmed that the compound <b>VS1</b> binds opsin effectively, representing a valuable starting point for structure-based optimization studies aimed at identifying new opsin stabilizers.https://www.mdpi.com/1420-3049/30/11/2328rhodopsinmolecular chaperonesconsensus dockingvirtual screening |
| spellingShingle | Miriana Di Stefano Maria Ghilardi Clarissa Poles Lisa Piazza Gian Carlo Demontis Giulio Poli Tiziano Tuccinardi Marco Macchia Identification of a Non-Retinoid Opsin Ligand Through Pharmacophore-Guided Virtual Screening—A Novel Potential Rhodopsin-Stabilizing Compound Molecules rhodopsin molecular chaperones consensus docking virtual screening |
| title | Identification of a Non-Retinoid Opsin Ligand Through Pharmacophore-Guided Virtual Screening—A Novel Potential Rhodopsin-Stabilizing Compound |
| title_full | Identification of a Non-Retinoid Opsin Ligand Through Pharmacophore-Guided Virtual Screening—A Novel Potential Rhodopsin-Stabilizing Compound |
| title_fullStr | Identification of a Non-Retinoid Opsin Ligand Through Pharmacophore-Guided Virtual Screening—A Novel Potential Rhodopsin-Stabilizing Compound |
| title_full_unstemmed | Identification of a Non-Retinoid Opsin Ligand Through Pharmacophore-Guided Virtual Screening—A Novel Potential Rhodopsin-Stabilizing Compound |
| title_short | Identification of a Non-Retinoid Opsin Ligand Through Pharmacophore-Guided Virtual Screening—A Novel Potential Rhodopsin-Stabilizing Compound |
| title_sort | identification of a non retinoid opsin ligand through pharmacophore guided virtual screening a novel potential rhodopsin stabilizing compound |
| topic | rhodopsin molecular chaperones consensus docking virtual screening |
| url | https://www.mdpi.com/1420-3049/30/11/2328 |
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