The capabilities and limitations of NMR methods for the investigation of ligand-receptor interactions were presented. Two of our case-studies of NMR-assisted discovery of novel inhibitors of attractive antibacterial targets were used to explain the application of ligand-based and protein-based NMR methods. Special attention was given to the advantage of NMR spectroscopy for the studies of dynamic processes in molecular complexes. The influence of conformational dynamics on the stability of ligand-receptor interactions and on the inhibitory activities of novel ligands was presented.
B.04 Guest lecture
COBISS.SI-ID: 4174618The investigation of interaction of novel MurD inhibitors with the enzyme was presented. We were focused on the NMR methods, which do not require isotope enrichment of the protein. These methods are based on the observation of ligand signals. We used differential line broadening, longitudinal relaxation time and saturation transfere difference (STD) experiments to determine the ligand dissociation constants (KD). A nonlinear regression analysis was applied to extract the KD values from the NMR parameters. Our results indicate that the most accurate KD values are obtained by the STD method.
B.03 Paper at an international scientific conference
COBISS.SI-ID: 3954202We implemented the NMR methodology for the identification of binding and for the determination of binding interactions of novel MurD ligands with moderate binding affinity, which were synthesized in Lek pharmaceuticals d.d..
F.17 Transfer of existing technologies, know-how, methods and procedures into practice
The NMR studies of configuration and conformation of selected drug derivatives from the LEK pharmaceuticals d.d. were performed to prove the differences in their molecular structure. The application of high magnetic fields and determination of molecular spatial connectivities were crucial for the elucidation of type of molecular framework transformation.
F.17 Transfer of existing technologies, know-how, methods and procedures into practice
COBISS.SI-ID: 4309530I am mentor of two young researchers (M. Simčič and U. Zelenko). I am guiding them in the studies of conformation, dynamics and interactions in complex molecular systems using the NMR methods. M. Simčič is involved in the studies of binding properties of novel muramyl ligase inhibitors. U. Zelenko is participating in the research of novel inhibitors of membrane associated Cyp51 receptor. I was mentor of Špela Klofutar for her master thesis, which is based on the NMR studies of structural and dynamic properties of proteins.
D.09 Tutoring for postgraduate students
COBISS.SI-ID: 23454247