The NMR studies and molecular dynamics simulations of ligand-MurD complexes have been performed to obtain the insight into dynamic properties of novel complexes, which can significantly upgrade the drug design studies that are based solely on the static crystal structures. The results have revealed the differing degrees of ligand flexibility and their effect on particular ligand-enzyme contacts. The degree of conformational flexibility depends on the specificity of the ligand molecular structure and can be related to the differences in their inhibitory activities.
COBISS.SI-ID: 4121626
A new type of AT1 antagonists have been designed and synthesized, which have different structural features from the known non-peptide AT1 antagonists and have significant antihypertensive activity. With a combination of experimental and theoretical methods we have determined ligand-membrane and ligand-receptor interactions of new type of AT1 antagonist. We have shown that activity of new antagonists can be improved through the thermodynamic effects on the lipid bilayers and through the stereoelectronic active site requirements.
COBISS.SI-ID: 4385050
A robust method is proposed for identifying the putative bioactive conformation of linear peptide analogues of myelin basic protein, which induce the EAE (experimental autoimmune encephalomyelitis) instructive model for the investigation of multiple sclerosis. Their conformational and binding properties were compared with the properties of EAE antagonist. Specific conformational properties of EAE agonist and antagonist were elucidated, which determine differences in their interactions with T-cell receptor.
COBISS.SI-ID: 3843610
By application of NMR methods we have shown that novel rhodanine MurD inhibitors interact with binding site of UDP substrate and are located in the uracil-binding pocket. The possibility of binding to UDP and ATP binding sites have been proposed, which is based on the molecular structure of rhodanine derivatives and studies of tridimensional structure of UDP and ATP binding sites. Comparison studies of chemical shift perturbations of MurD methyl groups upon binding of known inhibitors, UDP substrate, and AMPPCP have excluded the binding of novel inhibitors to ATP binding site.
COBISS.SI-ID: 2743921
Binding interactions of valsartan, a potent antihypertensive drug, with membrane embedded AT1 receptor have been determined by application of NMR spectroscopy of valsartan in solvent environment and theoretical simulations of molecular dynamics of valsartan-AT1 receptor complex in lipid bilayer environment. Enhancement of binding interactions and stabilization of drug at the active site upon membrane environment have been observed pointing to a crucial role of lipid bilayers in the mechanism of action of AT1 antagonist.
COBISS.SI-ID: 4115994