Computational modeling of human dopamine transporter structures, mechanism and its interaction with HIV-1 transactivator of transcription

Yaxia Yuan, Xiaoqin Huang, Jun Zhu, Chang Guo Zhan

Research output: Contribution to journalReview articlepeer-review

15 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2077-2089
Number of pages13
JournalFuture Medicinal Chemistry
Volume8
Issue number17
DOIs
StatePublished - Nov 2016
Externally publishedYes

Keywords

  • drug abuse
  • drug design
  • HIV virus
  • neurocognitive disorder
  • protein-protein interaction
  • transporter

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Drug Discovery

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