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.advisor | Cloete, Ruben Earl Ashley | |
| dc.contributor.author | Isaacs, Matthew Darren | |
| dc.date.accessioned | 2021-08-19T11:14:51Z | |
| dc.date.accessioned | 2024-05-17T07:20:15Z | |
| dc.date.available | 2021-08-19T11:14:51Z | |
| dc.date.available | 2024-05-17T07:20:15Z | |
| dc.date.issued | 2021 | |
| dc.description | Masters of Science | en_US |
| dc.description.abstract | 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. | en_US |
| dc.identifier.uri | https://hdl.handle.net/10566/15247 | |
| dc.language.iso | en | en_US |
| dc.publisher | University of the Western Cape | en_US |
| dc.rights.holder | University of the Western Cape | en_US |
| dc.subject | Retroviruses | en_US |
| dc.subject | HIV | en_US |
| dc.subject | South Africa | en_US |
| dc.subject | Human genome | en_US |
| dc.title | Molecular dynamic simulation studies of the South African HIV-1 Integrase subtype C protein to understand the structural impact of naturally occurring polymorphisms | en_US |