Elucidation of binding profile similarities across structurally diverse ligands using a 3D dopamine transporter model

COMP 235

Sankar Manepalli1, Jeffry D. Madura, madura@duq.edu2, David J. Lapinsky, lapinskyd@duq.edu3, and Christopher K. Surratt3. (1) Department of Chemistry and Biochemistry, Center for Computational Sciences, Duquesne University, 600 Forbes Avenue, Pittsburgh, PA 15282, (2) Department of Chemistry & Biochemistry, Center for Computational Sciences and Duquesne University, 308 Mellon Hall, 600 Forbes Ave., Pittsburgh, PA 15282, (3) Division of Pharmaceutical Sciences, Duquesne University Mylan School of Pharmacy, 600 Forbes Avenue, Pittsburgh, PA 15282
The dopamine transporter (DAT), a protein belonging to the neurotransmitter sodium symporter (NSS) family, is responsible for the reuptake of dopamine from the synaptic cleft. It is well known that the DAT is the principal target for addictive psychostimulants such as cocaine and amphetamine. Recently LeuTAa, a leucine transporter and distantly related NSS family homologue, was crystallized, providing a template for the construction of 3D DAT homology models. Potential low and high affinity binding pockets were identified using these models. Docking of structurally diverse ligands having different affinities towards the DAT will be used to characterize the low and high affinity binding sites, thus aiding rational design of new DAT-targeted therapeutics.

Poster Session
6:00 PM-8:00 PM, Tuesday, August 18, 2009 Walter E. Washington Convention Center -- Ballroom A, Poster

Division of Computers in Chemistry

The 238th ACS National Meeting, Washington, DC, August 16-20, 2009