Effects of HIV-1 Tat Protein and Methamphetamine on VMAT2-mediated Dopamine Transmission in the Context of NeuroHIV and Drug Abuse

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 vesicular monoamine transporter 2 (VMAT2) interacts with HIV-1 Tat, methamphetamine and related compounds. The computational predictions will be communicated to the other PI (Contact PI Dr. Jun Zhu) 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 VMAT2 and its interactions with HIV-1 Tat, methamphetamine and related compounds.