In silico analysis of plasmodium falciparum Hsp70-x for potential binding sites and hits
- Authors: Amusengeri, Arnold
- Date: 2017
- Subjects: Uncatalogued
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/59136 , vital:27435
- Description: Restricted access-thesis embargoed for 1 year - release date April 2019
- Full Text:
- Authors: Amusengeri, Arnold
- Date: 2017
- Subjects: Uncatalogued
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/59136 , vital:27435
- Description: Restricted access-thesis embargoed for 1 year - release date April 2019
- Full Text:
Phenomenology: preconceptions and experiences of non-chemists at Rhodes University using milk paint
- Authors: Kelly, Kelvin Leigh
- Date: 2017
- Subjects: Phenomenology , Art and science , Casein , Paint , Chemistry -- Study and teaching , Science -- Study and teaching -- Philosophy
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/37942 , vital:24711
- Description: There exists an ever-increasing crisis in science education where students experience disinterest because of an inability to grasp true understanding of scientific subjects, and therefore there should be a call to increase the research of phenomenology in combination with science education. A rebalance and paradigm shift in the focus of the modes of teaching could result in a great improvement in the learning, comprehension, and intellectual self-confidence of students interested in the sciences. To study this, three research questions were established: How is chemistry perceived by non-chemists; what is the experience of the participants’ during the chemistry practical in a laboratory and; do the participants’ perspectives about chemistry change during the experience. The performed study consisted of a chemistry practical, two art works and, in some cases, an interview. Nine participants were asked to create the art under specific instructions of points of focus, namely their preconceptions prior to the practical (Artwork 1) and their lived experience during the practical (Artwork 2). Participants’ artworks were examined using methods of visual semiotics and classical art analysis techniques, looking at line, shape, and colour choice. The iterative analysis of the interviews from participants 1, 2, 7, and 9 coded with ATLAS.ti 7 software, led to the emergence of themes that constitute the core of the participants’ experience. This phenomenological study presents a path to engage the non-chemist with processes taking place in the laboratory by using ‘Kitchen Chemistry’ and illustrates how a phenomenological engagement with chemistry can make the subject more applicable to the general population of non-chemists.
- Full Text:
- Authors: Kelly, Kelvin Leigh
- Date: 2017
- Subjects: Phenomenology , Art and science , Casein , Paint , Chemistry -- Study and teaching , Science -- Study and teaching -- Philosophy
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/37942 , vital:24711
- Description: There exists an ever-increasing crisis in science education where students experience disinterest because of an inability to grasp true understanding of scientific subjects, and therefore there should be a call to increase the research of phenomenology in combination with science education. A rebalance and paradigm shift in the focus of the modes of teaching could result in a great improvement in the learning, comprehension, and intellectual self-confidence of students interested in the sciences. To study this, three research questions were established: How is chemistry perceived by non-chemists; what is the experience of the participants’ during the chemistry practical in a laboratory and; do the participants’ perspectives about chemistry change during the experience. The performed study consisted of a chemistry practical, two art works and, in some cases, an interview. Nine participants were asked to create the art under specific instructions of points of focus, namely their preconceptions prior to the practical (Artwork 1) and their lived experience during the practical (Artwork 2). Participants’ artworks were examined using methods of visual semiotics and classical art analysis techniques, looking at line, shape, and colour choice. The iterative analysis of the interviews from participants 1, 2, 7, and 9 coded with ATLAS.ti 7 software, led to the emergence of themes that constitute the core of the participants’ experience. This phenomenological study presents a path to engage the non-chemist with processes taking place in the laboratory by using ‘Kitchen Chemistry’ and illustrates how a phenomenological engagement with chemistry can make the subject more applicable to the general population of non-chemists.
- Full Text:
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:
- 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:
Synthesis and bioassay of rationally designed DXR inhibitors as potential antimalarial lead compounds
- Authors: Nokalipa, Iviwe Cwaita
- Date: 2017
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/4888 , vital:20740
- Description: Globally, the eradication of malaria has been challenging due to the problem of resistance that past and currently available drugs exhibit. This is exacerbated by the inherent need for anti-malarial drugs to be affordable to the poverty-stricken majority that is primarily affected by this burden. This research has focused on the development of potential inhibitors of 1-deoxy-D- xylulose-5 phosphate reductoisomerase (DXR), an essential enzyme in the mevalonate- independent pathway for the biosynthesis of isoprenoids in Plasmodium falciparum. DXR mediates the isomerisation and reduction of 1-deoxy-D-xylulose-5-phosphate into 2-C- methyl-D-erithrytol 4-phosphate. This enzyme has been determined to be a target for the development of novel antimalarial agents and extensive molecular modelling has been undertaken to develop inhibitors that fit into the DXR active site. The in silico docking data have been used to inform the design and synthesis of various N-benzyl-substituted phosphoramidate ligands that were determined to have potential as novel substrate mimics of fosmidomycin, a known DXR inhibitor. Synthesis of the N-benzyl-substituted phosphoramidate ligands involved a nine-step sequence commencing from diethyl phosphoramidate. In all, some 40 compounds have been prepared, some of them new, and were fully characterized using NMR. Attention has also been given to the mass spectrometric fragmentation patterns exhibited by selected intermediates. Four of the final products were evaluated for in vitro antimalarial activity using a PLDH assay and exhibited IC50 values < 100 µM.
- Full Text:
- Authors: Nokalipa, Iviwe Cwaita
- Date: 2017
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/4888 , vital:20740
- Description: Globally, the eradication of malaria has been challenging due to the problem of resistance that past and currently available drugs exhibit. This is exacerbated by the inherent need for anti-malarial drugs to be affordable to the poverty-stricken majority that is primarily affected by this burden. This research has focused on the development of potential inhibitors of 1-deoxy-D- xylulose-5 phosphate reductoisomerase (DXR), an essential enzyme in the mevalonate- independent pathway for the biosynthesis of isoprenoids in Plasmodium falciparum. DXR mediates the isomerisation and reduction of 1-deoxy-D-xylulose-5-phosphate into 2-C- methyl-D-erithrytol 4-phosphate. This enzyme has been determined to be a target for the development of novel antimalarial agents and extensive molecular modelling has been undertaken to develop inhibitors that fit into the DXR active site. The in silico docking data have been used to inform the design and synthesis of various N-benzyl-substituted phosphoramidate ligands that were determined to have potential as novel substrate mimics of fosmidomycin, a known DXR inhibitor. Synthesis of the N-benzyl-substituted phosphoramidate ligands involved a nine-step sequence commencing from diethyl phosphoramidate. In all, some 40 compounds have been prepared, some of them new, and were fully characterized using NMR. Attention has also been given to the mass spectrometric fragmentation patterns exhibited by selected intermediates. Four of the final products were evaluated for in vitro antimalarial activity using a PLDH assay and exhibited IC50 values < 100 µM.
- Full Text:
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