In silico Description of LAT1 Transport Mechanism at an Atomistic Level.

ABSTRACT: The molecular mechanism of transport mediated by LAT1, a sodium-independent antiporter of large neutral amino acids, was investigated through in silico procedures, specifically making reference to two transported substrates, tyrosine (Tyr) and leucine methyl ester (LME), and to 3,5-diiodo-L-tyrosine (DIT), a well-known LAT1 inhibitor. Two models of the transporter were built by comparative modeling, with LAT1 either in an outward-facing (OF) or in an inward-facing (IF) conformation, based, respectively, on the crystal structure of AdiC and of GadC. As frequently classic Molecular Dynamics (MD) fails to monitor large-scale conformational transitions within a reasonable simulated time, the OF structure was equilibrated for 150 ns then processed through targeted MD (tMD). During this p

SUBMITTER: Palazzolo L 

PROVIDER: S-EPMC6117385 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature