Molecular dynamic simulation studies of the South African HIV-1 Integrase subtype C protein to understand the structural impact of naturally occurring polymorphisms

dc.contributor.advisorCloete, Ruben Earl Ashley
dc.contributor.authorIsaacs, Matthew Darren
dc.date.accessioned2021-08-19T11:14:51Z
dc.date.accessioned2024-05-17T07:20:15Z
dc.date.available2021-08-19T11:14:51Z
dc.date.available2024-05-17T07:20:15Z
dc.date.issued2021
dc.descriptionMasters of Scienceen_US
dc.description.abstractThe viral Integrase (IN) protein is an essential enzyme of all known retroviruses, including HIV-1. It is responsible for the insertion of viral DNA into the human genome. It is known that HIV-1 is highly diverse with a high mutation rate as evidenced by the presence of a large number of subtypes and even strains that have become resistant to antiretroviral drugs. It remains inconclusive what effect this diversity in the form of naturally occurring polymorphisms/variants exert on IN in terms of its function, structure and susceptibility to IN inhibitory antiretroviral drugs. South Africa is home to the largest HIV-1 infected population, with (group M) subtype C being the most prevalent subtype. An investigation into IN is therefore pertinent, even more so with the introduction of the IN strand-transfer inhibitor (INSTI) Dolutegravir (DTG). This study makes use of computational methods to determine any structural and DTG drug binding differences between the South African subtype C IN protein and the subtype B IN protein. The methods employed included homology modelling to predict a three-dimensional model for HIV-1C IN, calculating the change in protein stability after variant introduction and molecular dynamics simulation analysis to understand protein dynamics. Here we compared subtype C and B IN complexes without DTG and with DTG.en_US
dc.identifier.urihttps://hdl.handle.net/10566/15247
dc.language.isoenen_US
dc.publisherUniversity of the Western Capeen_US
dc.rights.holderUniversity of the Western Capeen_US
dc.subjectRetrovirusesen_US
dc.subjectHIVen_US
dc.subjectSouth Africaen_US
dc.subjectHuman genomeen_US
dc.titleMolecular dynamic simulation studies of the South African HIV-1 Integrase subtype C protein to understand the structural impact of naturally occurring polymorphismsen_US

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