Computational Modeling of Human Dopamine Transporter Structures, Mechanism and Its Interaction with HIV-1 Transactivator of Transcription
Year: 2016
Type: article
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.
Source: Future Medicinal Chemistry
Authors: Yaxia Yuan, Xiaoqin Huang, Jun Zhu, Chang-Guo Zhan
Institutions: University of Kentucky, University of South Carolina
Language: English
Subfield: Computational Theory and Mathematics
Field: Computer Science
Domain: Physical Sciences
Open Access status: green
Awards: Development of a Cocaine-Metabolizing Enzyme for Drug Overdose Treatment, High-activity mutants of cocaine esterase for treatment of drug addiction, Kentucky Center for Clinical and Translational Science, Long-lasting cocaine-metabolizing enzyme for cocaine addiction treatment, Redesign of Butyrylcholinesterase for Cocaine Metabolism, Molecular mechanisms: Dysregulation of monoamine transporters by HIV-1Tat and cocaine
OpenAlex ID: W2530153806