Juraj Kóňa

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We have demonstrated that the polyethylene glycol (PEG) corona of long-circulating polymeric nanoparticles (NPs) favors interaction with the amyloid-beta (Aβ(1-42)) peptide both in solution and in serum. The influence of PEGylation of poly(alkyl cyanoacrylate) and poly(lactic acid) NPs on the interaction with monomeric and soluble oligomeric forms of(More)
Molecular dynamics (MD) simulations have been performed on the regulatory domain of the Escherichia coli OxyR transcription factor for the different chemical states along the mechanistic cycle for its activation by hydrogen peroxide. Conformational analysis indicates that His198 and Arg220 catalytic residues can be involved in the biochemical process of(More)
Three approaches of computational chemistry [quantum mechanics (QM) calculations, docking, and molecular dynamics (MD) simulations] were used to investigate the redox cycle of bovine erythrocyte glutathione peroxidase from class 1 (GPx1, EC The pKa calculations for two redox states of the active-site selenocysteine of GPx1 (selenol, Sec45-SeH,(More)
Aqueous acid dissociation constants of substituted areneseleninic, areneselenenic, arenesulfinic, and benzoic acids are calculated by ab initio (MP2) and DFT (B3LYP) methods in combination with bulk solvation models (IEFPCM, CRSrad) from appropriate thermodynamic cycles. Mean absolute deviations (MAD) between experimental and calculated pK(a) values are(More)
Hybrid quantum mechanics/molecular mechanics calculations were used to study the catalytic mechanism of the retaining human α-(1,3)-galactosyltransferase (GTBWT) and its E303C mutant (GTBE303C). Both backside (via covalent glycosyl-enzyme intermediate, CGEI) and frontside SNi-like mechanisms (via oxocarbenium-ion intermediate, OCII) were investigated. The(More)
Glycosyltransferases are sugar-processing enzymes that require a specific metal ion cofactor for catalysis. In the presence of other ions the catalysis is often impaired. Here, for the first time, the enzymatic catalysis in the presence of various metal ions was modeled for a glycosyltransferase using a large enzymatic model. The catalytic mechanism of(More)
Two possible mechanisms of the irreversible inhibition of HIV-1 protease by epoxide inhibitors are investigated on an enzymatic model using ab initio (MP2) and density functional theory (DFT) methods (B3LYP, MPW1K and M05-2X). The calculations predict the inhibition as a general acid-catalyzed nucleophilic substitution reaction proceeding by a concerted SN2(More)
Human Golgi α-mannosidase II (hGM) is a pharmaceutical target for the design of inhibitors with anti-tumor activity. Nanomolar inhibitors of hGM exhibit unwanted co-inhibition of the human lysosomal α-mannosidase (hLM). Hence, improving specificity of the inhibitors directed toward hGM is desired in order to use them in cancer chemotherapy. We report on the(More)
Three new triazole conjugates derived from d-mannose were synthesized and assayed in in vitro assays to investigate their ability to inhibit α-mannosidase enzymes from the glycoside hydrolase (GH) families 38 and 47. The triazole conjugates were more selective for a GH47 α-mannosidase (Aspergillus saitoi α1,2-mannosidase), showing inhibition at the(More)
Nucleophilic substitutions by a hydroxide ion at vinylic carbons of methoxyethene (system A), 3-methoxypropenal (system B), 2,3-dihydro-4H-pyran-4-one (system C), and 4H-pyran-4-one (system D) were calculated by Becke's three-parameter hybrid density functional-HF method with the Lee-Yang-Parr correlation functional (B3LYP//B3LYP) and the second-order(More)