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The Hydrophobic Ligands Entry and Exit from the GPCR Binding Site-SMD and SuMD Simulations

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dc.abstract.enMost G protein-coupled receptors that bind the hydrophobic ligands (lipid receptors and steroid receptors) belong to the most populated class A (rhodopsin-like) of these receptors. Typical examples of lipid receptors are: rhodopsin, cannabinoid (CB), sphingosine-1-phosphate (S1P) and lysophosphatidic (LPA) receptors. The hydrophobic ligands access the receptor binding site from the lipid bilayer not only because of their low solubility in water but also because of a large N-terminal domain plug preventing access to the orthosteric binding site from the extracellular milieu. In order to identify the most probable ligand exit pathway from lipid receptors CB1, S1P1 and LPA1 orthosteric binding sites we performed at least three repeats of steered molecular dynamics simulations in which ligands were pulled in various directions. For specific ligands being agonists, the supervised molecular dynamics approach was used to simulate the ligand entry events to the inactive receptor structures. For all investigated receptors the ligand entry/exit pathway goes through the gate between transmembrane helices TM1 and TM7, however, in some cases it combined with a direction toward water milieu.
dc.affiliationUniwersytet Warszawski
dc.contributor.authorChawananon, Sathapana
dc.contributor.authorOrzeł, Urszula
dc.contributor.authorFilipek, Sławomir
dc.contributor.authorJakowiecki, Jakub
dc.contributor.authorMiszta, Przemysław
dc.date.accessioned2024-01-26T10:16:30Z
dc.date.available2024-01-26T10:16:30Z
dc.date.copyright2020-04-21
dc.date.issued2020
dc.description.accesstimeAT_PUBLICATION
dc.description.financePublikacja bezkosztowa
dc.description.number8
dc.description.versionFINAL_PUBLISHED
dc.description.volume25
dc.identifier.doi10.3390/MOLECULES25081930
dc.identifier.issn1420-3049
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/122418
dc.identifier.weblinkhttps://www.mdpi.com/1420-3049/25/8/1930/pdf
dc.languageeng
dc.pbn.affiliationchemical sciences
dc.relation.ispartofMolecules
dc.relation.pages1930
dc.rightsCC-BY
dc.sciencecloudnosend
dc.subject.enG protein-coupled receptors
dc.subject.encannabinoid receptors
dc.subject.ensphingosine-1-phosphate receptors
dc.subject.enlysophosphatidic receptors
dc.subject.ensteered molecular dynamics
dc.subject.ensupervised molecular dynamics
dc.titleThe Hydrophobic Ligands Entry and Exit from the GPCR Binding Site-SMD and SuMD Simulations
dc.typeJournalArticle
dspace.entity.typePublication