期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 436, 期 4, 页码 650-654出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2013.06.009
关键词
HIV-1 integrase; Integrase inhibitor; Carbon nanotube; Drug delivery; Molecular dynamics simulation
资金
- HI-tech Research and Development Program of China [2008AA02Z311]
- Shanghai Leading Academic Discipline [B111]
- Shanghai Supercomputer Center (SSC)
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, 5CITEP 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. (c) 2013 Elsevier Inc. All rights reserved.
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