Matches in SemOpenAlex for { <https://semopenalex.org/work/W4308804464> ?p ?o ?g. }
- W4308804464 endingPage "4491" @default.
- W4308804464 startingPage "4476" @default.
- W4308804464 abstract "The human L-type amino acid transporter 1 (LAT1; SLC7A5) is a membrane transporter of amino acids, thyroid hormones, and drugs such as the Parkinson’s disease drug levodopa (L-Dopa). LAT1 is found in the blood-brain barrier, testis, bone marrow, and placenta, and its dysregulation has been associated with various neurological diseases, such as autism and epilepsy, as well as cancer. In this study, we combine metainference molecular dynamics simulations, molecular docking, and experimental testing, to characterize LAT1-inhibitor interactions. We first conducted a series of molecular docking experiments to identify the most relevant interactions between LAT1’s substrate-binding site and ligands, including both inhibitors and substrates. We then performed metainference molecular dynamics simulations using cryoelectron microscopy structures in different conformations of LAT1 with the electron density map as a spatial restraint, to explore the inherent heterogeneity in the structures. We analyzed the LAT1 substrate-binding site to map important LAT1-ligand interactions as well as newly described druggable pockets. Finally, this analysis guided the discovery of previously unknown LAT1 ligands using virtual screening and cellular uptake experiments. Our results improve our understanding of LAT1-inhibitor recognition, providing a framework for rational design of future lead compounds targeting this key drug target." @default.
- W4308804464 created "2022-11-15" @default.
- W4308804464 creator A5023404099 @default.
- W4308804464 creator A5048927341 @default.
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- W4308804464 creator A5072791775 @default.
- W4308804464 creator A5080642491 @default.
- W4308804464 creator A5081711330 @default.
- W4308804464 date "2022-12-01" @default.
- W4308804464 modified "2023-10-13" @default.
- W4308804464 title "Describing inhibitor specificity for the amino acid transporter LAT1 from metainference simulations" @default.
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