Rigorous sampling of docking poses unveils binding hypothesis for the halogenated ligands of L-type Amino acid Transporter 1 (LAT1).

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 bi

SUBMITTER: Singh N 

PROVIDER: S-EPMC6803698 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature