A hybrid (QM/MM) approach was utilized, to evaluate three reaction pathways leading to the tetrahedral intermediate formation. Geometries of the starting structures and tetrahedral intermediates were studied as well as the role of crucial amino acids and water molecules. The QM/MM replica path method was used to generate the reaction pathways between the starting structures and the tetrahedral reaction intermediates, producing reaction pathways which were in agreement with in a sequential kinetic mechanism. The D-Glu moiety most likely enters the enzyme reaction in its deprotonated form.
COBISS.SI-ID: 3978778
Binding free energies were calculated for a series of MurD N-sulphonyl-glutamic acid inhibitors using the Linear Interaction Energy method. Analysis of interaction energy revealed non-polar van der Waals interactions as the main driving force for the binding of these inhibitors, and excellent agreement with the experimental free energies was obtained. Analysis of fragment contribution to binding free energies for selected inhibitor moieties in this structural class substantiated the insight into the source of inhibitory activity.
COBISS.SI-ID: 4090650
Based on the available structural data for the MurD and MurE enzymes (both from E. coli) a virtual screening campaign was performed, combining three-dimensional structure-based pharmacophores and molecular docking calculations, resulting in the identification of a novel class of glutamic acid surrogates - benzene 1,3-dicarboxylic acid derivatives possessing dual MurD and MurE inhibitory activity.
COBISS.SI-ID: 2534001
- Carcinogenicity of the styren ultimate carcinogen was studied by quantum chemical methods. We studied chemical reaction between styrene-7,8-oxide and DNA, in particular guanine at position N7. Calculations were performed by Hartree-Fock and DFT methods in conjunction with flexible basis sets. Effects of solvation were considered using the Langevin dipoles method. The calculated activation free energies are in good agreement with the experimental value of 26.52 kcal/mol.
COBISS.SI-ID: 4186650
A detailed insight into the mechanism of propene epoxidation reaction by hydrogen peroxide – one of the most important reactions catalysed by the zeolite catlayst TS-1 – is essential for the understanding of factor that govern catalytic activity. We modeled the propene epoxidation reaction in the gas phase, evaluated the reaction mechanism, and studied the influence of water molecules, solvent reaction field, electric field and explicit zeolite environment on the activation barrier and reaction pathway.
COBISS.SI-ID: 4121370