Balazs Jojart

• Ph.D.
• Professor (Associate) at University of Szeged

Cationic antimicrobial peptide PGLa gets into close contact with the anionic bacterial cell membrane, facilitating cross-membrane transport phenomena and membrane disruption depending on the concentration. The mechanisms of action are closely associated with the tilted insertion geometry of PGLa. Therefore, we aimed to understand the interaction be...

The negative membrane potential of bacterial cells influences crucial cellular processes. Inspired by the molecular scaffold of the antimicrobial peptide PGLa, we have developed antimicrobial foldamers with a computer-guided design strategy. The novel PGLa analogues induce sustained membrane hyperpolarization. When co-administered as an adjuvant, t...

EDTA is commonly used as an efficient chelator of metal ion enzyme cofactors. It is highly soluble, optically inactive and does not interfere with most chemicals used in standard buffers making EDTA a common choice to generate metal-free conditions for biochemical and biophysical investigations. However, the controversy in the literature on metal-f...

Metabotropic glutamate receptor 5 (mGluR5) is a class C G protein-coupled receptor (GPCR) with both an extracellular ligand binding site and an allosteric intrahelical chamber located similarly to the orthosteric ligand binding site of Class A GPCRs. Ligands binding to this ancestral site of mGluR5 can act as positive (PAM), negative (NAM) or silen...

In order to study the effects of peptide exposure to oxidative attack, we chose a model reaction in which the hydroxyl radical discretely abstracts a hydrogen atom from the α-carbon of each residue of a highly amyloidogenic region in the human calcitonin hormone, hCT 15-19 . Based on a combined Molecular Mechanics / Quantum Mechanics approach, the...

Computer simulations of four lipid membranes of different compositions, namely neat DPPC and PSM, and equimolar DPPC-cholesterol and PSM-cholesterol mixtures, are performed in the presence and absence of the general anesthetics diethylether and sevoflurane both at 1 and 600 bar. The results are analyzed in order to identify membrane properties that...

DJ-1 (PARK7) is a multifunctional protein linked to the onset and progression of a number of diseases, most of which are associated with high oxidative stress. The oxidation state of Cys106 of DJ-1 is believed to determine the specific functions of the protein in normal and disease conditions. Here we report molecular dynamics simulation and biophy...

dUTPases catalyze the hydrolysis of dUTP into dUMP and pyrophosphate to maintain the proper nucleotide pool for DNA metabolism. Recent evidence suggests dUTPases may also represent a selective drug target in mycobacteria because of these enzymes' crucial role in maintaining DNA integrity. Nucleotide-hydrolyzing enzymes typically harbor a buried lig...

In order to identify molecular models of the human 5-HT6 receptor suitable for virtual screening, homology modeling and membrane-embedded molecular dynamics simulations were performed. Structural requirements for robust enrichment were assessed by an unbiased chemometric analysis of enrichments from retrospective virtual screening studies. The two...

Molecular dynamics simulations of the liquid-vapor interface of acetone-water mixtures of different compositions, covering the entire composition range have been performed on the canonical (N,V,T) ensemble at 298 K, using a model combination that excellently describes the mixing properties of these compounds. The properties of the intrinsic liquid...

A kémiai rendszerek szerveződését különböző szinteken figyelhetjük meg, a szerveződés minden szintjén új fizikai, kémiai (és biológiai) tulajdonságok jelennek meg. Két alapvető szemlélet alakult ki az összetett rendszerek megismerésére. A redukcionista elmélet a rendszerek egy jellemző vagy különleges részének vizsgálatára törekszik, míg a holiszti...

The global minimum (GM) structure of opiorphin (QRFSR) and its seven derivatives (qRFSR, QrFSR, QRfSR, QRFsR QRFSr, QRYSR, QRySR) were explored using molecular mechanics method. Based on STRIDE analysis, most of the conformers possessed no secondary structures. Amongst global minima, only QrFSR epimer contained a β-turn formed between glutamine (Q1...

The energetics of peptide bond formation is an important factor not only in the design of chemical peptide synthesis but also has a role in protein biosynthesis. In this work quantum chemical calculations at ten different levels of theory including G3MP2B3 were performed on the energetics of glutathione formation. The strength of the peptide bond i...

n this paper the impurity distribution is computed in an axis-symmetric (2D) domain, which represents the meniscus and a part of the capillary channel. The model takes into account the pulling rate, thermal convection, molecular diffusion and thermo diffusion. Numerical illustration is given for Al doped cylindrical Si tube wall and the contributio...

Micellisation process for sodium dodecyl sulphate and sodium cholate in 1∶1 molar ratio was investigated in a combined approach, including several experimental methods and coarse grained molecular dynamics simulation. The critical micelle concentration (cmc) of mixed micelle was determined by spectrofluorimetric and surface tension measurements in...

The epimerization of amino acid residues increases with age in living organisms. In the present study, the structural consequences and thermodynamic functions of the epimerization of thymopentin (TP-5), the active site of the thymic hormone thymopoietin, were studied using molecular dynamics and density functional theory methods. The results show t...

Molecular dynamics simulations of the liquid–vapour interface of acetone have been performed in the canonical (N, V, T) ensemble at 298 K with two different molecular models, belonging to the transferable potential for phase equilibria (TraPPE) and Chemistry at Harvard Molecular Mechanics 27 (CHARMM27) force fields, respectively. The first three mo...

Bursopentin (BP(5), H-Cys(1)-Lys(2)-Arg(3)-Val(4)-Tyr(5)-OH), found in the bursa Fabricius of the chicken, is a pentapeptide that protects the organism from oxidative stress by reducing the intracellular generation of reactive oxygen species. Hydrogen abstraction, a common oxidative reaction occurring in proteins, often results in the formation of...

In spite of recent investigations into the potential pharmaceutical importance of bile acids as drug carriers, the structure of bile acid aggregates is largely unknown. Here, we used global optimization techniques to find the lowest energy configurations for clusters composed between 2 and 10 cholate molecules, and evaluated the relative stabilitie...

We report the identification of novel histamine H4 receptor ligands by ensemble docking on homology model conformers derived from molecular dynamics simulations. Selected receptor models from the trajectories demonstrated superior virtual screening performance compared to the initial models. The ensemble of the best models was able to retrieve a di...

Selective cyclo-oxygenase-2 inhibitors (COXIBs) are prominent members of the nonsteroidal anti-inflammatory drugs. The neutral and protonated COXIB scaffold has been subjected to molecular computations in the gas phase and implicit solvent to measure the relative changes in the thermodynamic functions, enthalpy (Hrel), potential energy (Urel), Gibb...

Formation of ligand-protein complexes requires simultaneous adaptation of the binding partners. In structure based virtual screening high throughput docking approaches typically consider the ligand flexibility but the conformational freedom of the protein is usually taken into account in limited way. The goal of this study is to elaborate a methodo...

Non-reactive, comparative (2×1.2 μs) molecular dynamics simulations were carried out to characterize the interactions between glutathione (GSH, host molecule) and hydroxyl radical (OH(•), guest molecule). From this analysis, two distinct steps were identified in the recognition process of hydroxyl radical by glutathione: catching and steering, base...

Penicillin, travels through bodily fluids, targeting and acylatively inactivating enzymes responsible for cell-wall synthesis in gram-positive bacteria. Somehow, it avoids metabolic degradation remaining inactive en route. To resolve this ability to switch from a non-active, to a highly reactive form, we investigated the dynamic structure-activity...

The recently solved crystal structure of the human adenosine A2A receptor (hA2AR) shows the characteristics of a partially activated state. Experimental data suggests that high sodium chloride concentration shifts hA2AR to the inactive state. We found that molecular dynamics simulations at high sodium chloride concentration result in an inactive fo...

Recent studies using ab initio calculations have-shown that C-alpha-centered radical formation by H-abstraction from the backbone of peptide residues has dramatic effects on peptide structure and have suggested that this reaction may contribute to the protein misfolding observed in Alzheimer's and Parkinson's diseases. To enable the effects of C-al...

Haplopine-3,3′-dimethylallyl ether (HAP) was isolated from a Sudanese herb (El-hazha), characterized and tested on isolated rat uterus rings pre-contracted with KCl by means of in vitro and in silico docking studies on a customized rat β2-adrenoceptor (β2-AR). The in vitro results revealed that HAP produces uterus-relaxant effects similar to those...

Galactokinase is responsible for the phosphorylation of α-d-galactose, which is an important step in the metabolism of the latter. Malfunctioning of galactokinase due to a single point mutation causes cataracts and, in serious cases, blindness. This paper reports a study of the Pro28Thr point mutation using a variety of theories including molecular...

6-Methoxykaempferol-3-O-glucoside (6-MKG) was isolated from a Sudanese herb (El-hazha). The pharmacological effects of 6-MKG were tested on isolated non-pregnant or late-pregnant rat uteri in vitro, whilst docking studies were carried out modelling of the binding of 6-MKG to the rat beta(2)-adrenoceptor in silico. In vitro studies revealed that 6-M...

All possible X-H (where X can be C, N, O or S) bond dissociation energies (BDEs) of glutathione (γ-L-glutamyl-L-cysteinyl-glycine, GSH) and its fragments have been calculated by first principle methods, and the antioxidant potential of GSH was revealed to be higher than expected in earlier studies. Electron delocalization was found to have an impor...

6-Methoxykaempferol-3-O-glucoside (6-MKG) was isolated from a Sudanese herb (El-hazha). The pharmacological effects of 6-MKG were tested on isolated non-pregnant or late-pregnant rat uteri in vitro, whilst docking studies were carried out modelling of the binding of 6-MKG to the rat β(2)-adrenoceptor in silico. In vitro studies revealed that 6-MKG...

This study reports first principle calculations and molecular mechanics calculations of glutathione and its fragments with the goal of determining whether the conformational nature of this tripeptide can be inferred based on the geometries of its constituents. Although the size of a molecule usually predetermines the applicable computational method...

It has always been a question of considerable scientific interest why amino acids (and other biomolecule building blocks) formed and accumulated in the prebiotic ocean. In this study, we suggest an answer to this question for the simplest amino acid, glycine. We have shown for the first time that classical equilibrium thermodynamics can explain the...

Fabry disease is an X-linked recessive hereditary disorder due to a defect of a lysosomal hydrolase alpha-galactosidaseA (EC.3.2.1.22). There is high degree molecular heterogenity of alpha-galactosidase A gene (GLA) deficiency. In thispaper we report the mutation of the alpha-galactosidase A gene detected in a Hungarian Fabry patient. Mutationanaly...

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Molecular dynamics (MD) simulations in a membrane-embedded environment were carried out on the homology model of the human histamine H4 receptor (hH4R) alone and in complex with its endogenous activator histamine and with the first reported selective hH4R antagonist JNJ7777120. During the simulation of the histamine-hH4R complex, considerable chang...

The oxytocin receptor belongs to class A receptors within the great family of G protein-coupled receptors. The endogenous ligand oxytocin is a nonapeptide hormone that induces the uterine contractions at parturition and is used to induce the labor. The peptide oxytocin and, even more, its non-peptide antagonist, could be valuable tools in tocolysis...

Three-dimensional structure-activity relationship studies of alpha2a-adrenoceptor agonists were carried out by Distance Comparison (DISCOthech) and Comparative Molecular Field Analysis (CoMFA) methods to define the pharmacophore and a quantitative model, respectively, of this class of compounds. The statistical validation of the CoMFA model indicat...

The aim of this work was to answer the question of whether the general amber force field (GAFF) is good enough to simulate fully hydrated POPC membrane bilayers. The test system contained 128 POPC and 2985 TIP3P water molecules. The equilibration was carried out in a nonarbitrary manner to reach the stable liquid-crystalline phase. The simulations...

In the present study, QSAR calculations were performed on the receptor-based alignment of 58 non-peptide human oxytocin receptor antagonists. With the aid of different scoring functions (AutoDock 3.05 built-in and X-Score 1.2) the evolved receptor-ligand complexes were characterized. By means of various datasets it was confirmed that the scoring fu...

In this study, we performed a molecular docking and dynamics simulation for a benzoxazinone–human oxytocin receptor system to determine the possible hydrophobic and electrostatic interaction points in the dynamic complex. After the homology modeling, the ligand was docked into the putative active using AutoDock 3.05. After the application of energe...

Three aromatic disulfides and their two selected congeners were studied in order to see if they could be initiators or catalysts in a process that aims to tie together the two strands of a DNA double helix. Thermodynamic functions were calculated from first principle molecular computations on deoxyribose models and the disulfide congener. The gas r...

In this study, eight oxytocin (OT) antagonists were subjected to conformational analysis. By means of simulated annealing, 2,000 structures were generated to sample the conformational space. The preferred main-chain and side-chain dihedral angles, intramolecular H-bond interactions (types 1<--4 and 1<--3), and secondary-structure elements (beta-tur...

The pathways of the conformational transitions in flexible molecular systems were studied by the DDRP (Dynamically Determined Reaction Path) method implemented in TINKER molecular modelling package. Our first model systems were conformational transitions in small organic molecules (determination of rotational transitions, boat-chair transitions, et...

Molecular docking and 3D-QSAR studies were performed to determine the binding mode for a series of benzoxazine oxytocin antagonists taken from the literature. Structural hypotheses were generated by docking the most active molecule to the rigid receptor by means of AutoDock 3.05. The cluster analysis yielded seven possible binding conformations. Th...