title: Molecular dynamics of HIV1-integrase in complex with 93del - a structural perspective on the mechanism of inhibition.
abstract: 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.
authors.affiliation: Centre for Cancer Research and Cell Biology, Queen's University of Belfast, 97 Lisburn Road, BT9 7BL, Belfast, UK. s.haider@qub.ac.uk
authors.forename: Miriam
authors.initials: M
authors.lastname: Sgobba
authors.forename: Olujide
authors.initials: O
authors.lastname: Olubiyi
authors.forename: Song
authors.initials: S
authors.lastname: Ke
authors.forename: Shozeb
authors.initials: S
authors.lastname: Haider
mesh_terms: D016880:Anisotropy; D052157:Aptamers, Nucleotide / Q000737:chemistry*; D054856:G-Quadruplexes; D019427:HIV Integrase / Q000737:chemistry* / Q000378:metabolism*; D019428:HIV Integrase Inhibitors / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D016011:Normal Distribution; D025341:Principal Component Analysis; D011487:Protein Conformation; D055672:Static Electricity
chemical_list: D052157:Aptamers, Nucleotide; D019428:HIV Integrase Inhibitors; D019427:HIV Integrase; C514801:p31 integrase protein, Human immunodeficiency virus 1