Welcome to the Research laboratory of Dr Ruben Cloete

The research focus of my lab is on the use and development of computational structural tools in understanding protein structure and function. The methods we employ include molecular protein structure modelling to determine a protein’s three dimensional shape using homology or fold recognition predictions and molecular docking studies to identify novel drug molecules to inhibit enzyme function. Other approaches we employ in my group is molecular dynamic simulation studies to understand protein thermodynamic and kinetic properties. Current research projects include; understanding drug resistance in Mycobacterium tuberculosis and in the Human Immune deficiency virus (HIV-1) integrase protein and the identification of causal variants in Parkinson’s disease development.

Rationale for research projects:

Tuberculosis and HIV-1 drug resistance is a huge problem in South Africa and calls for the identification of newer drugs to curb the spread of these diseases. Computational methods can help in speeding up the drug discovery process and is an important tool that can reduce the cost and time spend pursuing drugs that later fail in clinical trials. We have developed computational pipelines within my laboratory to interrogate drug targets to screen for inhibitors that can be purchased and tested in vitro for activity against Mycobacterium tuberculosis. We also use computational methods to validate mutations and their effects on protein structure and function. This is also very useful to determine if a drug remains within an enzyme active pocket and if the mutation results in reduced binding. The result of this research may provide improve treatment regimens for South African populations to combat infectious diseases and non-communicable diseases.

Lab members:

Msc students

Mr Darren Isaacs,

Miss Rumbidzai Chitongo,

Miss Maryam Hassan.

Research Collaborations

Prof Alan Christoffels – SANBI, UWC

Dr Melanie Grobbelaar – Stellenbosch University

Prof Samantha Samson – Stellenbosch University

Prof Sarel Malan – School of Pharmacy, UWC

Prof Jacque Joubert – School of Pharmacy, UWC

Mrs Erika Kapp – School of Pharmacy, UWC

Prof Soraya Bardien – Stellenbosch University

Dr Graeme Jacobs – Stellenbosch University

Prof Rob Warren – Stellenbosch University

Prof Chandra Verma – A-star Bioinformatics Institute, Singapore


1) van der Merwe L, Cloete R, Revera M, Heradien M, Goosen A, Corfield VA, Brink PA, Moolman-Smook JC. (2008) Genetic variation in angiotensin-converting enzyme 2 gene is associated with extent of left ventricular hypertrophy in hypertrophic cardiomyopathy. Hum Genet. 2008 Aug;124(1):57-61. Epub 2008 Jun 17. PMC2469277

2) McEvoy C.R.E., Cloete R, Muller B, Schurch A.C, van Helden P.D, Gagneux S, Warren R.M, Gey van Pittius N.C. (2012) Comparative analysis of mycobacterium tuberculosis pe and ppe genes reveals high sequence variation and an apparent absence of selective constraints. PLoS One. 2012;7(4):e30593. Epub 2012 Apr 4. PMC3319526

3) Cloete R, Oppon E, Murungi E, Schubert W-D, Christoffels A. Resistance related metabolic pathways for drug target identification in Mycobacterium tuberculosis. BMC Bioinformatics. 2016;17:1–10. PMC4745158.

4) Ruben Cloete, Wisdom A Akurugu, Cedric Werely and Alan Christoffels. Structural and functional effects of nucleotide variation on the human TB drug metabolizing enzyme arylamine N-acetyltransferase 1. J Mol Graph Model. 2017 Aug;75:330-339. doi: 10.1016/j.jmgm.2017.04.026. Epub 2017 Jun 10. PMID:28628859 DOI:10.1016/j.jmgm.2017.04.026

5) du Plessis, J., Cloete, R., Burchell, L., Sarkar, P., Warren, R.M., Christoffels, A., Wigneshweraraj, S. and Sampson, S.L., 2017. Exploring the potential of T7 bacteriophage protein Gp2 as a novel inhibitor of mycobacterial RNA polymerase. Tuberculosis. PMID: 28802409.

6) Gurwitz KT, Aron S, Panji S, Maslamoney S, Fernandes PL, Judge DP, Ghouila A, Domelevo Entfellner JB, Guerfali FZ, Saunders C, Alzohairy AM, Salifu SP, Ahmed R, Cloete R, Kayondo J, Ssemwanga D, Mulder N. (2017). Designing a course model for distance-based online bioinformatics training in Africa: The H3ABioNet experience. PloS Comput Biol 13(10): e1005715. https://doi.org/10.1371/journal.pcbi.1005715. PMID: 28981516, PMCID: PMC5628786.

7) Brado, D., Obasa, A. E., Ikomey, G. M., Cloete, R., Singh, K., Engelbrecht, S., Neogi, U., Jacobs, G. B. (2018). Analyses of HIV-1 integrase sequences prior to South African national HIV-treatment program and available of integrase inhibitors in Cape Town, South Africa. Scientific Reports, 8(1), 4709. PMID: 29549274, PMC5856838.

8) Cloete R, Kapp E, Joubert J, Christoffels A, Malan S. (2018). Molecular modelling and simulation studies of the Mycobacterium tuberculosis multidrug efflux pump protein Rv1258c. PloS One.

Link to personal website:


Available projects: Dependent on funding

1) Molecular dynamic simulation studies of Mycobacterium tuberculosis protein drug targets.

2) Developing T7 bacteriophage (GP2) into Mycobacterium tuberculosis RNA polymerase inhibitor

3) Pharmacophore and docking based studies to discover novel drugs against Mycobacterium tuberculosis and HIV-1 integrase.

4) Prioritising disease causative variants in Parkinson’s disease families.

5) Comparative studies of different HIV-1 subtype integrase (HIV-1C, HIV-1AG and HIV-1E) proteins using structural methods.

6) 2D interaction map open source stand-alone tool development using python.

Contact details:

Physical Address:

South African National Bioinformatics Institute

5th Floor, Life Sciences Building

University of Western Cape

Modderdam Road

Bellville 7530

South Africa

Phone: +27(0) 21 959 3573





twitter: ruben@sanbi.ac.za