Research

Dr Cloete's research is mainly focused on molecular modeling and drug design, with special focus on Structural Bioinformatics. His PhD dissertation investigated Mycobacterium tuberculosis metabolic pathways to identify drug targets in the genome of Mycobacterium tuberculosis. This research led to successful identification of nine Mycobacterium tuberculosis drug targets that is currently being exploited in drug discovery attempts and structure elucidation. Ongoing research projects include understanding mechanisms of drug resistance in HIV-1 integrase and Catalase peroxidase (KatG) as well as prioritizing polymorphisms in human drug metabolizing enzymes (NAT1 and NAT2). Another research project involves identifying disease causal variants of Parkinson's disease in South African families. His research area has also expanded to RNA-aptamer based technology development to diagnose Tuberculosis and Ebola infection and more recently understanding the effects of haplotype variation in the solute carrier transporter gene (SLC22A2) within the South African Xhosa population diagnosed with type 2 diabetes mellitus and its effects on drug transport. He has recently formed part of the SAMRC RCDI grant project as Co-PI that focuses on the use of computational methods to exploit SARS-COV2 coronavirus proteins to identify novel drugs to kill this deadly pathogen.


Research Interest

  • 3D structural predictions of proteins, peptides and RNA

  • Molecular dynamic simulations of protein-ligand and protein-protein interactions

  • Docking studies of small molecules and peptides/proteins to protein receptors

  • Automated pipeline development to interrogate HIV and Mycobacterium tuberculosis drug resistance

Ongoing projects

  • Genetic variation: Simulating the functional effects of single nucleotide polymorphisms on human NAT1 gene and understanding the effects of haplotype variation on the solute carrier transporter gene (SLC22A2) ability to transport diabetes drugs in South African Xhosa populations with type 2 diabetes mellitus.

  • Drug discovery: In silico identification and testing of novel small molecules against Mycobacterium tuberculosis and more recently against SARS-COV-2 coronavirus

  • Resistance mechanisms: Simulating the functional effects of mutations on HIV-1 integrase drug binding and DNA binding, Structural investigations of KatG mutations associated with Isonaizid resistance

  • Candidate gene prioritization: Prioritizing co-segregating variants in South African families with Parkinson's disease

  • Biomarker discovery: Development of RNA-aptamers for rapid flow diagnosis of Tuberculosis infection and Ebola virus infection