title: HIV-1 integrase binding to its cellular partners: a perspective from computational biology.
abstract: 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.
authors.forename: Vo Cam
authors.initials: VC
authors.lastname: Quy
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Carnevale
authors.forename: Lara
authors.initials: L
authors.lastname: Manganaro
authors.forename: Marina
authors.initials: M
authors.lastname: Lusic
authors.forename: Giulia
authors.initials: G
authors.lastname: Rossetti
authors.forename: Vanessa
authors.initials: V
authors.lastname: Leone
authors.forename: Cristina
authors.initials: C
authors.lastname: Fenollar-Ferrer
authors.forename: Simone
authors.initials: S
authors.lastname: Raugei
authors.forename: Giannino
authors.initials: G
authors.lastname: Del Sal
authors.forename: Mauro
authors.initials: M
authors.lastname: Giacca
authors.affiliation: Computational Biophysics, German Research School for Simulation Sciences, Computational Biomedicine, Institute for Advanced Simulation (IAS-5), Forschungszentrum Jülich, Jülich D-52425, Germany. p.carloni@grs-sim.de.
authors.forename: Paolo
authors.initials: P
authors.lastname: Carloni
mesh_terms: D019295:Computational Biology; D004247:DNA / Q000378:metabolism*; D019427:HIV Integrase / Q000378:metabolism*; D051548:Histone Acetyltransferases / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase / Q000378:metabolism*; D011485:Protein Binding; D016662:Virus Integration
chemical_list: D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D004247:DNA; D051548:Histone Acetyltransferases; D019427:HIV Integrase; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase; C514801:p31 integrase protein, Human immunodeficiency virus 1