Viral DNA integration into the infected cell genome is an essential step in the HIV-1 life cycle. Hence, the viral integrase enzyme
has become an important target for antiviral therapy. The integrase's activity action relies on the binding to its cellular partners,
therefore the knowledge of the structural determinants is very important from a therapeutic perspective. Here we first review published
computer-aided structural predictions of HIV-1 integrase in complex with its interactors. These include DNA and the human HAT protein.
Next, we present a prediction of the complex between HIV-1 integrase with the human prolyl-isomerase-1 (hPin1) enzyme. Interaction
with hPin1 is crucial for efficient HIV-1 infection and it increases integrase stability (Manganaro et. al 2010, Nat. Med. 16, 329). The
modeling presented here, which is validated against experimental data, provides a rationale for a variety of viral protein's mutations
which impair protein function and HIV-1 virus replication in vivo without significantly affecting enzymatic activity.