Structural requirements for potential HIV-integrase inhibitors identified using pharmacophore-based virtual screening and molecular dynamics studies

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dc.contributor.author Islam, Md Ataul
dc.contributor.author Pillay, Tahir S.
dc.date.accessioned 2016-05-05T14:09:31Z
dc.date.issued 2016
dc.description.abstract Acquired immunodeficiency syndrome (AIDS) is a life-threatening disease which is a collection of symptoms and infections caused by a retrovirus, human immunodeficiency virus (HIV). There is currently no curative treatment and therapy is reliant on the use of existing anti-retroviral drugs. Pharmacoinformatics approaches have already proven their pivotal role in the pharmaceutical industry for lead identification and optimization. In the current study, we analysed the binding preferences and inhibitory activity of HIV-integrase inhibitors using pharmacoinformatics. A set of 30 compounds were selected as the training set of a total 540 molecules for pharmacophore model generation. The final model was validated by statistical parameters and further used for virtual screening. The best mapped model (R = 0.940, rmsd = 2.847, Q2 = 0.912, se = 0.498, R2 pred = 0.847 and r2 m (test) = 0.636) explained that two hydrogen bond acceptor and one aromatic ring features were crucial for the inhibition of HIV-integrase. From virtual screening, initial hits were sorted using a number of parameters and finally two compounds were proposed as promising HIV-integrase inhibitors. Drug-likeness properties of the final screened compounds were compared to FDA approved HIV-integrase inhibitors. HIV-integrase structure in complex with the most active and final screened compounds were subjected to 50ns molecular dynamics (MD) simulation studies to check comparative stability of the complexes. The study suggested that the screened compounds might be promising HIV-integrase inhibitors. The new chemical entities obtained from the NCI database will be subjected to experimental studies to confirm potential inhibition of HIV integrase. en_ZA
dc.description.department Chemical Pathology en_ZA
dc.description.embargo 2017-01-31
dc.description.librarian hb2016 en_ZA
dc.description.sponsorship University of Pretoria Vice Chancellor’s post-doctoral fellowship and National Research Foundation (NRF), South Africa. en_ZA
dc.description.uri http://www.rsc.orgmolecularbiosystems en_ZA
dc.identifier.citation Islam, MA & Pillay, TS 2016, 'Structural requirements for potential HIV-integrase inhibitors identified using pharmacophore-based virtual screening and molecular dynamics studies', Molecular BioSystems, vol. 12, no. 3, pp. 982-993. en_ZA
dc.identifier.issn 1742-206X (print)
dc.identifier.issn 1742-2051 (online)
dc.identifier.other 10.1039/C5MB00767D
dc.identifier.uri http://hdl.handle.net/2263/52495
dc.language.iso en en_ZA
dc.publisher Royal Society of Chemistry en_ZA
dc.rights © The Royal Society of Chemistry 2016 en_ZA
dc.subject Acquired immune deficiency syndrome (AIDS) en_ZA
dc.subject Life-threatening disease en_ZA
dc.subject Human immunodeficiency virus (HIV) en_ZA
dc.title Structural requirements for potential HIV-integrase inhibitors identified using pharmacophore-based virtual screening and molecular dynamics studies en_ZA
dc.type Postprint Article en_ZA


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