VIF is one of the six accessory proteins of HIV-1. It has been shown to be necessary for the survival of HIV-1 in the human body and for the retention of viral infectivity. It is strongly expected that a new therapeutic strategy against HIV-1 infection could be realized by blocking the biological pathway to VIF. In this paper, a three-dimensional model of VIF was constructed by comparative modeling based on two templates, VHL and NarL, which were used to construct the C-terminal domain and N-terminal domain of VIF, respectively. A model of the VIF-ElonginB-ElonginC complex was constructed, and molecular dynamics simulations were used to investigate the interactions between VIF and ElonginB-ElonginC. Mutagenesis was used to identify the function of some conserved residues in the putative SOCS-box. The results showed that the mutations of the critical residues led to the disruption of the interactions between VIF and ElonginB-ElonginC, consistent with experimental observations. These novel models of VIF and its complex has therefore provided structural information for investigating the function of VIF at the molecular level.