title: Computational modeling of human dopamine transporter structures, mechanism and its interaction with HIV-1 transactivator of transcription.
abstract: This is a brief review of computational modeling studies on the detailed structures and mechanism of human dopamine transporter (hDAT), as well as its interaction with HIV-1 transactivator of transcription (Tat). Extensive molecular modeling, docking and dynamics simulations have resulted in reasonable structural models of hDAT in three typical conformational states, its dopamine uptake mechanism and its interaction with Tat. The obtained hDAT models in different conformational states and their complexes with dopamine and Tat have provided novel structural and mechanistic insights concerning how hDAT uptakes dopamine and how Tat affects the dopamine uptake by hDAT. The computational insights, that are consistent with available experimental data, should be valuable for future rational design of novel therapeutic strategies for treatment of HIV-associated neurocognitive disorders.
authors.affiliation: Molecular Modeling & Biopharmaceutical Center, Center for Pharmaceutical Research & Innovation, and Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY 40536, USA.
authors.forename: Yaxia
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Molecular Modeling & Biopharmaceutical Center, Center for Pharmaceutical Research & Innovation, and Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY 40536, USA.
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Drug Discovery & Biomedical Sciences, South Carolina College of Pharmacy, University of South Carolina, 715 Sumter Street, Columbia, SC 29208, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Molecular Modeling & Biopharmaceutical Center, Center for Pharmaceutical Research & Innovation, and Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY 40536, USA.
authors.forename: Chang-Guo
authors.initials: CG
authors.lastname: Zhan
keywords: HIV virus; drug abuse; drug design; neurocognitive disorder; protein–protein interaction; transporter