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Virtual Laboratory

Research that spans the spectrum from gene expression analysis, glycan expression analysis to target discovery and rational lead profiling. Tumour glycome construction for biomarker development

Glycobiology

Research includes the solution structure of simple and complex carbohydrates; the enzymatically catalysed reaction mechanisms that lead to the formation (glycotransferases) and the breakdown (glycosydases) of glycans.

References:

Krishna K. Govender and Kevin J. Naidoo. Evaluating AM1/dCB1 for Chemical Glycobiology AM/MM Simulations. J. Chem. Theor. Comput. 2014, 10, 4708-4717

Venter, G.; Matthews, R. P.; Naidoo, K. J., Conformational flexibility of Sulfur Linked Saccharides a Possible Key to their Glycosidase Inhibitor Activity. Mol. Sim. 2008, 34, 391-402.

Barnett, C. B.; Wilkinson, K. A.; Naidoo, K. J., Pyranose Ring Transition State Is Derived from Cellobiohydrolase I Induced Conformational Stability and Glycosidic Bond Polarization. J. Am. Chem. Soc. 2010, 132, 12800-12803.

Feher, K.; Matthews, R. P.; Kover, K. E.; Naidoo, K. J.; Szilagyi, L., Conformational preferences in diglycosyl disulfides: NMR and molecular modeling studies. Carbohydr. Res. 2011, 346, 2612-21.

Next Generation Antimicrobials

Bacteria are developing resistance against β-lactam antibiotics by various genetic mechanisms of which plasmid acquiring is the most deadly. Amongst others bacteria acquire resistance by degradation or modification of the antibiotic before it reaches the target site, alteration of the antibiotic site and the prevention of access of the antibiotic to the target by forced efflux.

One of the most problematic bacteria known to roam the corridors and wards in hospitals is Staphylococcus aureus, a Gram positive bacterium. We conduct computational structural biology and reaction dynamics studies on S. Aureus to develop lead drugs that may be a new form of antibiotic.

Ian L. Rogers and Kevin J. Naidoo/ Profiling Transition-State Configurations on the Trypanosoma cruzi trans-Sialidase Free-Energy Reaction Surfaces. J. Phys Chem B. 2015. 119, 1192-1201.

Umraan Hendricks, Werner Crous and Kevin J. Naidoo. Computational Rationale for the Selective Inhibition of the Herpes Simplex Virus Type 1 Uracil-DNA Glycosylase Enzyme. J. of Chem Info & Modeling. 2014. 54,3362-3372

Cancer

We use state-of-the-art computational and informatics methods to understanding the molecular level mechanisms important in human biology and disease as it affects cancer. We aim to classify cancer at the genetic and molecular (Glycan) level. Using our mechanistic understanding of glycosylation and glycolysis of tumours we design leads for molecular classes of Cancer. SCRU laboratories collaborate closely with medicinal laboratories as well as human biology laboratories to translate basic research findings into new clinical strategies for diagnosis and therapy.

Ionic Liquid Property Prediction and Design

The most obvious definition of an ionic liquid is a substance in the liquid state, consisting of positive cations and negative anions. Left unmodified, this definition would include simple ionic mixtures such as liquid NaCl as well, as long as it is applied above its melting point of >800°C. Room temperature ionic liquids (RTILs), on the other hand, are ionic mixtures with melting points <100°C. Popular RTILs consist of organic cations such as alkyl substituted imidazoliums, pyridiniums, pyrrolidiniums or ammoniums combined with inorganic or organic cations such as the halides, tetrafluoroborate, triflate, bistriflimide and acetate.

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Ion pairs of ionic liquids 1–ethyl–3–methylimidazolium tetrafluoroborate (left) and 1–ethyl–3–methylimidazolium acetate

Depending on the chosen combination of cation and anion, physical properties such as melting point, viscosity and conductivity vary significantly. Within a family, further changes such as the length of the alkyl chain or functionalisation with e.g. ether groups, can also lead to a host of varying properties.

With a liquidus range of several hundreds of degrees (often the upper temperature limit is not governed by vaporization, but by decomposition) and a wide range of physical properties, the RTILs have numerous exciting applications. With the promise of being able to engineer an ionic liquid that suits the requirements of a specific application, the RTILs make ideal candidates to replace traditional molecular solvents in organic reactions, metal catalysis and electrochemistry.

Simulation and Calculation of RTIL Properties

Whichever application is focused on, a fundamental requirement common to all is a thorough understanding of the nature of the physicochemical properties of the RTILs. The idea of compiling structure-property relationships is intriguing, but rests on a solid understanding and prediction of the intermolecular interactions and related dynamic behaviour of these systems, and it is here where microscopic insight is needed that molecular simulation and calculation becomes a powerful tool. Quantum mechanical (QM) calculations can be used to investigate the electronic stucture of ions and ion pairs. Correctly chosen methods provide accurate descriptions of ion–ion interaction, polarization, hydrogen bonding and dispersion interaction. Molecular dynamics (MD) simulations can be used to integrate over the time evolution of a system, subject to a complete (and accurate) formulation of the intermolecular forces, which can subsequently provide further thermodynamic information and transport properties.

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Hydrogen bonding in a 1–ethyl–3–methylimidazolium chloride ion pair as identified through critical points in the electron density gradient (QTAIM) and the noncovalent index (NCI).


Developing structure–property relationships for room temperature ionic liquids require computational methods (static and polarizable force fields) that accurately describe the range of intermolecular interactions present. Developing such computational methods is one of the aims of this research. Furthermore, important insight into structure–property relationships can be gained through a better understanding of the nature of the interactions, and the effect of strengthening/weakening particular components of it.