Study of enzymatic mechanisms

The increasing computing capacity of today’s computers and our deeper understanding of enzyme structures allow us to calculate enzymatic mechanisms by molecular dynamic simulations and quantum chemical methods. Such approaches enable to work on systems experimentally hard to tackle. Calmodulin, chymotrypsin, trypsin etc. were enzyme the inhibitors of which was studied by NMR-spectroscopy and X-ray diffraction in our group, complemented by MD and QM a decade ago.

More recently, Pseudouridine synthase responsible for the uridine–pseudouridine formation was modelled as well. Pseudouridylation affects several types of RNAs, linked to severe diseases (e.g. cancer, dyskeratosis congenital).

The mutation dependent pathogenicity of podocin can be related to the autosomal-recessive disorder of steroid-resistant nephrotic syndrome type 2. Thus, conformation and dimerization studies of various podocin mutants were completed early on by MD.

Ligand binding (CO, NO and O2) of hemeproteins (e.g. myloglobin) via MD simulations were performed to address the question of diffusion of ligands through the enzyme.