Gag and protease co-evolution modeling for HIV-1

Gag and Protease play important roles in the lifecycle of the HIV-1 virus. Protease is the viral enzyme that cleaves Gag to form functional Gag subunits during the viral maturation. To interfere with the maturation of the HIV virus, Protease Inhibitors or drugs are used to inhibit the Gag-cleaving function of Protease. However, during the viral evolution, while mutations of both Gag and protease that are resistant to most of the current drugs have been reported, co-evolution relationship of Gag and Protease is limitedly studied. Therefore, understanding this relationship between Gag and Protease is crucial for finding a strategy in HIV treatment. In this report, computer simulation and molecular docking were used to help understand the Gag and Protease interactions of both the wild type and the mutated. High Ambiguity Driven Docking (HADDOCK) was used to perform dockings of the Gag and Protease proteins for the wild type as well as the mutated Gag and Protease. Each pair of Gag and Protease interactions was evaluated on 5 cleavage sites of Gag. Swiss-PDB Viewer and PyMOL were then used to analyse the results. Results obtained from all the docking processes were then evaluated and compared with the wild type. It was observed that mutated the Gag and Protease formed more favourable complexes as compared to the wild type. This might suggest that despite the use of Protease Inhibitors, mutations on both Gag and Protease still facilitate their bindings. The results and observations in this report hope to contribute more understanding about Gag and Protease relationship and be helpful in future research.Bachelor of Engineering (Computer Science