Abstract
HIV-1 Tat (transactivator of transcription) protein is the main arsenal of HIV, playing numerous roles during viral infection. This protein is inherently disordered, lacking any secondary structures. This plasticity allows HIV-1 Tat to engage in interaction with multiple proteins and biological molecules, resulting in either collapse of the immune system or severe damage to tissues. Proteomic studies previously revealed p53, commonly cited as the guardian angel of the genome to interact with the Tat protein through its tetramerization domain. As p53 is crucial in terms of whether the cell dies or lives, its interaction with the Tat protein is of broad interest in the pathogenesis of HIV infection. For this reason, we investigated the complexation between the Tat protein and the tetramerization domain of p53 using molecular docking and molecular dynamics simulations. Our results indicate that the N-terminal and C-terminal of Tat exhibit different behaviors in their interactions with p53. The N-terminal domain of Tat favours complexation with p53 thermodynamically, while its C-terminal exerts the opposite effect. These results align very much with the previously reported experimental observations. We believe the results reported in this manuscript are significant for developing novel therapeutic agents targeting the p53/Tat interaction.