Research

 

Our group holds a remarkable portfolio of biological targets in the areas of inflammatory and metabolic diseases, cancer, and malaria. Our research activities focus on the application of computational methods like homology modelling, docking, screening, pharmacophores, de novo design, molecular dynamics and quantum mechanics to discover, develop and optimise new therapeutic drugs against these targets.

 

 

 

Cancer:

 

Proteasome, APE-1 and HDAC’s

 

 

 

 

Inflammatory Diseases:

Human neutrophil elastase (HNE) is a serine protease that plays an important role in lung disease initiation and progression wherein an excess of extracellular HNE is produced. Our group developed a virtual screening protocol that enabled the identification of novel chemotypes as HNE inhibitors.

 

 

 

One of the hit compounds was subsequently optimized for inhibitory potency and metabolic stability to yield a nM HNE inhibitor.

 

A molecular dynamics study unravelled that HNE operates by an induced-fit mechanism with direct intervention of a surface loop, a finding that enforce the need to account for enzyme flexibility in future virtual screening campaigns.

 

 

Metabolic Diseases:

 

MCAD

 

Antimalarials: 

 

We discovered new antimalarial lead candidates by the use of virtual screening and molecular docking protocols against cytochrome bc1 from P. falciparum and Falcipain-2.