Ligand discovery for LAT1 with molecular dynamics simulation and virtual screening

Abstract

The human Large neutral amino acids transporter small subunit 1 (LAT1 or SLC7A5), mediates the import of large neutral amino acids, thyroid hormones, and pharmaceutical drugs in a 1:1 exchange for intracellular amino acids (e.g., glutamine). LAT1 is found in the blood-brain-barrier (BBB), testis, bone marrow and placenta, where multiple genetic variations of LAT1 have been associated with numerous diseases and disorders. For example, LAT1 is overexpressed in numerous cancer types, where LAT1’s ability to transport amino acids in particular leucine, is hijacked to activate the mechanistic target of rapamycin (mTOR) pathway, promoting cancer cell growth and the Warburg Effect.