HIV-1 integrase–DNA interactions investigated by molecular modelling

HIV-1 integrase is the viral enzyme responsible for the insertion of the viral DNA into the host cell chromosome. This process occurs through two distinct biochemical reactions: the 30-processing of the viral DNA and the transesterification reaction. Because experimental structural information on the reaction intermediate is not available, several molecular models have been developed. Unfortunately, none of the models of the enzyme–substrate complex is fully consistent with the available molecular biological data. We have constructed a new theoretical model based on mutagenesis experiments and cross-linking data, using a relatively accurate computational setup. The structural features of the model along with its limitations are discussed here.