Molecular Mechanisms: Dysregulation of Monoamine Transporters by HIV-1 Tat and Cocaine

Scope of Work As described in detail in the grant proposal, under this subaward of the multiple-PI NIH R01 grant, the Kentucky team directed by PI Dr. Chang-Guo Zhan is responsible for computational modeling and predictions concerning how human monoamine transporters (hSERT, hDAT, and hNET) interact with HIV-1 Tat, cocaine, and SRI-compounds. The computational predictions will be communicated to other PIs (Contact PI Dr. Jun Zhu and PI Dr. Jay McLaughlin) for experimental design, testing and validation. In light of the actual experimental outcomes obtained from the experimental testing and validation, the Kentucky team will do further computational modeling and simulations to refine the computational models and try to improve the structural and mechanistic understanding of hSERT/hDAT/hNET and their interactions with HIV-1 Tat, cocaine, and SRI-compounds.