title: Molecular dynamics study of carbon nanotube as a potential dual-functional inhibitor of HIV-1 integrase.
abstract: HIV-1 integrase (IN) plays an important role in integrating viral DNA into human genome, which has been considered as the drug target for anti-AIDS therapy. The appearance of drug-resistance mutants urgently requires novel inhibitors that act on non-active site of HIV-1 IN. Nanoparticles have such unique geometrical and chemical properties, which inspires us that nanoparticles like nanotubes may serve as better HIV-1 IN inhibitors than the conventional inhibitors. To test this hypothesis, we performed molecular dynamics (MD) simulation to study the binding of a carbon nanotube (CNT) to a full-length HIV-1 IN. The results showed that the CNT could stably bind to the C-terminal domain (CTD) of HIV-1 IN. The CNT also induced a domain-shift which disrupted the binding channel for viral DNA. Further MD simulation showed that a HIV-1 IN inhibitor, 5ClTEP was successfully sealed inside the uncapped CNT. These results indicate that the CNT may serve as a potential dual-functional HIV-1 IN inhibitor, not only inducing conformation change as an allosteric inhibitor but also carrying small-molecular inhibitors as a drug delivery system.
authors.affiliation: State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200433, China.
authors.forename: Zhishun
authors.initials: Z
authors.lastname: Zhang
authors.forename: Bingqiang
authors.initials: B
authors.lastname: Wang
authors.forename: Bo
authors.initials: B
authors.lastname: Wan
authors.forename: Long
authors.initials: L
authors.lastname: Yu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Huang
mesh_terms: D019428:HIV Integrase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D015497:HIV-1 / Q000201:enzymology; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D037742:Nanotubes, Carbon
chemical_list: D019428:HIV Integrase Inhibitors; D037742:Nanotubes, Carbon
keywords: Carbon nanotube; Drug delivery; HIV-1 integrase; Integrase inhibitor; Molecular dynamics simulation