Receptor-Based Discovery of a Plasmalemmal Monoamine Transporter Inhibitor via High Throughput Docking and Pharmacophore Modeling.

ABSTRACT: Recognition of psychostimulants such as cocaine and the amphetamines by the dopamine transporter (DAT) protein is principally responsible for the euphoria and addiction associated with these drugs. Using as a template the crystal structure of a distantly related bacterial leucine transporter, 3-D DAT computer molecular models have been generated. Ligand docking to such models has revealed potential substrate and inhibitor binding pockets, subsequently confirmed by in vitro pharmacology. An inhibitor pocket defined by the DAT model to be within the "extracellular vestibule", just to the extracellular side of the external gate of the primary substrate pocket, was used for virtual screening of a structural library of compounds. High-throughput docking and application of pharmacophore constrai

SUBMITTER: Indarte M 

PROVIDER: S-EPMC2843925 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature