Our groups main research interest is to obtain a fundamental understanding of the parameters underlying regulation of enzymatic function. Enzymes regulate a plethora of vital cellular processes and aberration in their function can result in countless disease states. They are also essential components in multiple industrial applications including drug synthesis and detergent development. Harnessing the biomolecular insights of current single molecule experiments allows us to unmask the structural and functional dynamics of major drug metabolism enzymes. Understanding how these enzymes operate paves the way for the design of novel pharmaceutics.
In spite of their immense importance, current understanding on enzymatic behaviour relies primarily on static pictures and ensemble functional assays and thus dynamic characteristics remain masked due to ensemble averaging. We therefore employ single molecule techniques to interrogate the behaviour of individual enzymes and elicit a detailed understanding of the molecular level details underlying enzymatic function and regulation. Using state of the art fluorescent microscopy techniques, we investigate how the complex protein conformational dynamics facilitate catalysis, as well as the existence and life times of enzymatic functional states and how point mutations, posttranslational modifications or effectors, redistribute them.
Advancing our understanding of functional protein dynamics will lead both to the design of novel pharmaceutics and the in silico design of novel biocatalysts with tailor made functionalities for biotechnological applications.