ArticleScientific reports2019
Rigorous sampling of docking poses unveils binding hypothesis for the halogenated ligands of L-type Amino acid Transporter 1 (LAT1).
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed, 33 citations in OpenAlex.
- Insight into telomere regulation: road to discovery and intervention in plasma drug-protein targets.BMC genomics · 2024Article
- The human LAT1-4F2hc (SLC7A5-SLC3A2) transporter complex: Physiological and pathophysiological implications.Basic & clinical pharmacology & toxicology · 2023Review
- In Vitro, In Vivo, and In Silico Analyses of Molecular Anti-Pigmentation Mechanisms of Selected Thai Rejuvenating Remedy and Bioactive Metabolites.Molecules (Basel, Switzerland) · 2023Article
- Docking-Based Prediction of Peptide Binding to MHC Proteins.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Discovery of new potent lysine specific histone demythelase-1 inhibitors (LSD-1) using structure based and ligand based molecular modelling and machine learning.RSC advances · 2022Article
- Describing inhibitor specificity for the amino acid transporter LAT1 from metainference simulations.Biophysical journal · 2022Article
- Homology Modeling and Molecular Docking Approaches for the Proposal of Novel Insecticides against the African Malaria Mosquito (Molecules (Basel, Switzerland) · 2022Article
- Mechanism of substrate transport and inhibition of the human LAT1-4F2hc amino acid transporter.Cell discovery · 2021Article
- ATP modulates SLC7A5 (LAT1) synergistically with cholesterol.Scientific reports · 2020Article
- L-Type amino acid transporter 1 as a target for drug delivery.Pharmaceutical research · 2020Review
- Glutamine transporters as pharmacological targets: From function to drug design.Asian journal of pharmaceutical sciences · 2020Review
- Demystifying the Molecular Basis of Pyrazoloquinolinones Recognition at the Extracellular α1+/β3- Interface of the GABAFrontiers in pharmacology · 2020Article
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
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Abstract
L-type Amino acid Transporter 1 (LAT1) plays a significant role in the growth and propagation of cancer cells by facilitating the cross-membrane transport of essential nutrients, and is an attractive drug target. Several halogen-containing L-phenylalanine-based ligands display high affinity and high selectivity for LAT1; nonetheless, their molecular mechanism of binding remains unclear. In this study, a combined in silico strategy consisting of homology modeling, molecular docking, and Quantum Mechanics-Molecular Mechanics (QM-MM) simulation was applied to elucidate the molecular basis of ligand binding in LAT1. First, a homology model of LAT1 based on the atomic structure of a prokaryotic homolog was constructed. Docking studies using a set of halogenated ligands allowed for deriving a binding hypothesis. Selected docking poses were subjected to QM-MM calculations to investigate the halogen interactions. Collectively, the results highlight the dual nature of the ligand-protein binding mode characterized by backbone hydrogen bond interactions of the amino acid moiety of the ligands and residues I63, S66, G67, F252, G255, as well as hydrophobic interactions of the ligand's side chains with residues I139, I140, F252, G255, F402, W405. QM-MM optimizations indicated that the electrostatic interactions involving halogens contribute to the binding free energy. Importantly, our results are in good agreement with the recently unraveled cryo-Electron Microscopy structures of LAT1.
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