Masters of Science / The 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.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:uwc/oai:etd.uwc.ac.za:11394/8368 |
| Date | January 2021 |
| Creators | Isaacs, Matthew Darren |
| Contributors | Cloete, Ruben Earl Ashley |
| Publisher | University of the Western Cape |
| Source Sets | South African National ETD Portal |
| Language | English |
| Detected Language | English |
| Rights | University of the Western Cape |
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