Structural analysis of proteases from South African HIV-1 (subtype C) patients undergoing Lopinavir treatment, using comparative modeling, ligand-docking and molecular dynamics
- Authors: Sheik-Amamuddy, Olivier
- Date: 2017
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/4931 , vital:20744
- Description: HIV is regarded as one of the most devastating infectious diseases of the last few decades, and has a high prevalence in South Africa, subtype C being the most common. Palliative measures used to fight HIV involve the use various types of inhibitors, including the use of HIV protease inhibitors. Representatives from this class of inhibitors are gradually losing their efficacy due to development of resistance mutations from HIV-1. In this study, compounds from the South African Natural Compound Database (SANCDB) were screened against HIV-1 protease models generated from protease protein sequences belonging to 11 South African HIV patients before and after treatment with Lopinavir. The effect of Lopinavir on the alteration of drug-binding affinity before and after treatment is investigated by molecular docking of the protease against other FDA-approved drugs and detection of mutation types using the HIVdb tool. A network representation of hydrogen bonding between docked ligands and their receptor proteases has been developed and a profiling method of visualizing receptor-ligand docking energies at the local level is presented. Four potential HIV-1 protease inhibitors were identified from the list of 599 natural compounds on the basis of receptor conformation and binding free energy. Ligand stabilities were monitored by 20ns molecular dynamics runs using the GROMACS software.
- Full Text:
- Date Issued: 2017
The life history of a minnow, Barbus Anoplus, in a man-made lake in South Africa
- Authors: Cambray, James Alfred
- Date: 1982
- Subjects: Minnows -- South Africa
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:5346 , http://hdl.handle.net/10962/d1006861
- Description: Aspects of the life history strategy of Barbus anoplus Weber were studied in a turbid man-made lake (P.K. Ie Roux impoundment, Orange River system, South Africa). The minnow has successfully colonized the shoreline of the P.K. Ie Roux impoundment, where the preferred habitats of the chubbyhead barb are flooded stream beds, erosion gullies and flooded ruderal communities. B. anoplus reaches sexual maturity in one year, at a length of about 40mm FL. They have a multiple spawning habit, with the first spawn in November or December and the second spawn in February or March. A part of the adult population undertakes a spawning migration up inflowing tributaries, while the other part breeds along the shoreline. The eggs and young develop rapidly and a proportion of the protolarvae float near the water surface, where they are probably dispersed by water currents. Most of the males die off after their second summer, whereas many females live into a third summer. Females also attain a larger maximum size (73mm FL) than males (60mm FL). The importance of increasing the reproductive potential of B. anoplus by multiple spawning is discussed. Feeding studies indicate that B. anoplus are opportunistic predators on invertebrates. The feeding habits of minnows collected from four different habitats varied. Minnows collected in the open water fed mainly on zooplankton, while shoreline populations fed on chironomid larvae and zooplankton. The most varied diet was found in fish living in a well-vegetated tributary of the impoundment which was not subject to inundation. B. anoplus is basically an r-strategist (i.e. it is small in size, shortlived, males have bright colouration, high seasonal reproductive potential). These characteristics enable the species to colonize and successfully inhabit unstable environments and probably accounts for the fact that it is the most widespread species south of the Limpopo River system. It is recommended that B. anoplus be considered as a candidate in southern Africa for further studies on life history strategies.
- Full Text:
- Date Issued: 1982