Identification of Small Molecular Chaperones Binding P23H Mutant Opsin through an In Silico Structure-Based Approach
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
36367985
DOI
10.1021/acs.jcim.2c01040
Knihovny.cz E-zdroje
- MeSH
- lidé MeSH
- molekulární chaperony genetika metabolismus terapeutické užití MeSH
- opsiny * genetika MeSH
- reprodukovatelnost výsledků MeSH
- retinopathia pigmentosa * farmakoterapie genetika metabolismus MeSH
- tyčinkové opsiny chemie genetika metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- molekulární chaperony MeSH
- opsiny * MeSH
- tyčinkové opsiny MeSH
N-terminal P23H opsin mutation accounts for most of retinitis pigmentosa (RP) cases. P23H functions and folding can be rescued by small chaperone ligands, which contributes to validate mutant opsin as a suitable target for pharmacological treatment of RP. However, the lack of structural details on P23H mutant opsin strongly impairs drug design, and new chemotypes of effective chaperones of P23H opsin are in high demand. Here, a computational-boosted workflow combining homology modeling with molecular dynamics (MD) simulations and virtual screening was used to select putative P23H opsin chaperones among different libraries through a structure-based approach. In vitro studies corroborated the reliability of the structural model generated in this work and identified a number of novel chemotypes of safe and effective chaperones able to promote P23H opsin trafficking to the outer cell membrane.
Department of Chemistry Faculty of Science and Engineering Swansea University Swansea SA2 8PP UK
School of Biosciences Cardiff University Cardiff CF10 3AX UK
School of Pharmacy and Pharmaceutical Sciences Cardiff University Cardiff CF10 3NB UK
Vysoká Škola Chemicko Technologiká Praha Prague 166 28 Czech Republic
Citace poskytuje Crossref.org
