TY  - JOUR
AU  - Sgobba, Miriam
AU  - Olubiyi, Olujide
AU  - Ke, Song
AU  - Haider, Shozeb
TI  - Molecular dynamics of HIV1-integrase in complex with 93del - a structural perspective on the mechanism of inhibition.
JO  - Caryologia
VL  - 29
IS  - 5
SN  - 1538-0254
CY  - Abingdon, Oxon
PB  - Taylor & Francis63883
M1  - FZJ-2015-04385
SP  - 863 - 877
PY  - 2012
AB  - HIV1 integrase is an important target for the antiviral therapy. Guanine-rich quadruplex, such as 93del, have been shown to be potent inhibitors of this enzyme and thus representing a new class of antiviral agents. Although X-ray and NMR structures of HIV1 integrase and 93del have been reported, there is no structural information of the complex and the mechanism of inhibition still remains unexplored. A number of computational methods including automated protein-DNA docking and molecular dynamics simulation in explicit solvent were used to model the binding of 93del to HIV1 integrase. Analysis of the dynamic behaviour of the complex using principal components analysis and elastic network modelling techniques allow us to understand how the binding of 93del aptamer and its interactions with key residues affect the intrinsic motions of the catalytic loops by stabilising them in catalytically inactive conformations. Such insights into the structural mechanism of inhibition can aid in improving the design of anti-HIV aptamers.
KW  - Aptamers, Nucleotide (NLM Chemicals)
KW  - HIV Integrase Inhibitors (NLM Chemicals)
KW  - p31 integrase protein, Human immunodeficiency virus 1 (NLM Chemicals)
KW  - HIV Integrase (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:22292948
UR  - <Go to ISI:>//WOS:000300074600002
DO  - DOI:10.1080/07391102.2012.10507418
UR  - https://juser.fz-juelich.de/record/202096
ER  -